+

WO2017031369A1 - Dispositifs de concentration d'échantillon - Google Patents

Dispositifs de concentration d'échantillon Download PDF

Info

Publication number
WO2017031369A1
WO2017031369A1 PCT/US2016/047642 US2016047642W WO2017031369A1 WO 2017031369 A1 WO2017031369 A1 WO 2017031369A1 US 2016047642 W US2016047642 W US 2016047642W WO 2017031369 A1 WO2017031369 A1 WO 2017031369A1
Authority
WO
WIPO (PCT)
Prior art keywords
accumulator
fluid
interface surface
sink
self
Prior art date
Application number
PCT/US2016/047642
Other languages
English (en)
Inventor
Keith A. Oberg
Anthony SPENCE
Ivan RUEDA
Mark D. DOBBS
Milton Lee
Original Assignee
Monolythix, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Monolythix, Inc. filed Critical Monolythix, Inc.
Priority claimed from US15/240,978 external-priority patent/US20170051274A1/en
Publication of WO2017031369A1 publication Critical patent/WO2017031369A1/fr

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0631—Purification arrangements, e.g. solid phase extraction [SPE]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0689—Sealing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16—Reagents, handling or storing thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0672—Integrated piercing tool
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/069—Absorbents; Gels to retain a fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0478—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/405—Concentrating samples by adsorption or absorption

Definitions

  • the present disclosure relates to a concentrator for concentrating, purifying or otherwise isolating one or more target analytes in a fluid matrix, and related methods, using self-wicking materials, such as monoliths.
  • the present disclosure can be used as a point-of need sample preparation device.
  • the self-contained device can be used for the extraction and concentration of specific target molecules, such as nucleic acids.
  • genomic DNA extraction necessarily begins with the lysis of cells that contain the DNA to be analyzed. After lysis, only two commonly used DNA isolation procedures exist One is phenol-chloroform extraction followed by DNA precipitation. This process is time consuming, requires multiple manipulations of the sample, requires refrigeration, cerrtrifugation and evaporation, and finally, generates toxic waste. The other involves DNA adsorption on a silica matrix.
  • DNA sources such as saliva and buccal swabs, are less invasive to collect than blood but are much more variable in matrix composition and DNA content All of these samples tend to yield dilute DNA or DNA extracts contaminated with inhibitors mat interfere with downstream processing, e.g., enzymological reactions.
  • Sdf-wicking materials can include a number of different materials, including monoliths, absorbent pads, etc.
  • Macroporous monolithic materials are used in the field of separations science, most commonly as chromatographic media.
  • the two most common base materials for monoliths are silica gel and acrylic polymers. Both can be made with the mechanical strength necessary to withstand the extreme pressure of HPLC or the mechanical stresses of industrial- scale purification processes.
  • Polymeric monoliths are also frequently used in solid-phase extraction consumables and in microfluidic devices. For example, polymeric monoliths are popular components in microfluidic chips because they can be cured-in-place with masked UV irradiation to generate integrated microscale chromatography columns.
  • U.S. Patent Publication No.2014/0127669 describes the use of polymeric monoliths in the field of sample preservation as an alternative to paper-based dry blood-spot (DBS) DNA preservation matrices. Blood spots spiked with small molecule pharmaceuticals dried on a monolith film were treated to recover the pharmaceuticals.
  • DBS dry blood-spot
  • the concentrator and related methods of the present disclosure can provide a simple, stand-alone target analyte isolation and concentration system that minimizes the need for hazardous chemicals and specialized equipment
  • the concentrator of the present disclosure can provide the ability to extract adequate amounts of biological targets, e.g., nucleic acid, from typical clinical samples and increase the concentration of nucleic acid in these samples to increase the efficiency of various testing methods, e.g., DNA sequencing.
  • the concentrator of the present disclosure can also reduce the chemicals and equipment needed to obtain a concentrated target analyte, e.g., DNA sample.
  • the present disclosure relates to a concentrator for concentrating, purifying or otherwise isolating one or more target analytes in a fluid matrix, and related methods, using self-wicking materials, such as monoliths.
  • the present disclosure can be used as a point-of need sample preparation device.
  • the self-contained device can be used for the extraction and concentration of specific target molecules, such as nucleic acids.
  • the present disclosure describes a self-contained, simple-to-use, and optionally disposable device mat can be constructed for target analyte, e.g., nucleic acid, extraction from a sample matrix (e.g., biological sample, such as lysed cells) with a self-wicking material, such as macroporous monolithic polymers, as the central fluidic components.
  • a sample matrix e.g., biological sample, such as lysed cells
  • a self-wicking material such as macroporous monolithic polymers
  • die present disclosure relates to a method for concentrating an analyte in a fluid matrix, the method including providing an accumulator comprising a first self- wicking porous polymer monolith, the accumulator having at plurality of interface surfaces, and a fluid capacity volume (Vac), and wicldng the fluid matrix containing the analyte into the accumulator through any interface surface of the accumulator, and capturing the analyte in the accumulator.
  • the method can further include providing a sink comprising a second self-wicking porous polymer monolith, the sink having an interface surface, and a fluid capacity volume (Vfs), and coupling any interface surface of the accumulator to the interface surface of the sink. wherein the interface surface of the accumulator and the interface surface of the sink are in fluid communication and configured to facilitate wicldng of fluid across the coupling.
  • the method can further include uncoupling the accumulator from the sink, providing an elution fluid source, coupling the elution fluid source to any selected interface surface of the accumulator wherein the elution fluid source and the interface surface of the accumulator are in fluid communication, introducing an elution fluid having a volume Vef from the elution fluid source into the accumulator through the selected interface surface of the accumulator, wherein Vef is greater than Vac, and wherein the elution fluid releases the analyte from the accumulator, and collecting the analyte from any other interface surface of the accumulator.
  • the method can utilize a matrix absorber.
  • the elution fluid can be introduced in portions wherein each portion can generate a corresponding volume of eluate, referred to as fractions by those skilled in the art of chromatography, where at least one of the portions contains the released and eluted analyte.
  • the present disclosure relates to a concentrator for concentrating an analyte in a fluid matrix, the concentrator including an accumulator comprising a first self- wicking porous polymer monolith, the accumulator having a plurality of interface surfaces, and a fluid capacity volume (Vac), wherein the accumulator has an affinity for the analyte.
  • an accumulator comprising a first self- wicking porous polymer monolith, the accumulator having a plurality of interface surfaces, and a fluid capacity volume (Vac), wherein the accumulator has an affinity for the analyte.
  • the concentrator can further comprise a sink, wherein the sink includes a second self- wicking porous polymer monolith, the sink having at least one interface surface, and a fluid capacity volume (Vfs), wherein the at least one interface surface of the sink and any interface surface of the accumulator are coupled together in fluid communication and configured to facilitate wicking of fluid across the coupling.
  • the accumulator, sink or both can be contained in a sleeve or housing.
  • the sleeve or housing can form a water-tight seal with the accumulator, sink or bom.
  • the sleeve or housing can be coupled with an elution syringe wherein the junction between the monolith(s) and the syringe is water tight
  • the concentrator can further include an elution fluid dispenser, the elution fluid dispenser having an elution fluid reservoir, and an elution fluid pressurizer wherein the elution fluid dispenser is configured to attach to the interface port of the housing and to establish fluid communication between the elution fluid reservoir and the at least one interface surface of the accumulator.
  • the concentrator can farther include a cutter -which can be configured to separate the accumulator and the sink such that the accumulator and sink are no longer in fluid
  • the present disclosure relates to a method for concentrating an analyte in a fluid matrix, the method includes providing a first concentrator having a first self- wicking porous polymer monolith, the monolith includes a first accumulator, the first accumulator having a plurality of interface surfaces, and a fluid capacity volume (Vacl), providing a first sink having a second self-wicking porous polymer monolith, the sink having an interface surface, and a fluid capacity volume (Vfsl ); coupling any interface surface of the first accumulator to the LTDerface surface of the first sink, wherein at least one interface surface of the first accumulator and the interface surface of the first sink are in fluid communication and configured to facilitate wicking of fluid across the coupling, wicking the fluid matrix containing the analyte into die first accumulator through any interface surface of the first accumulator, and capturing the analyte in the first accumulator.
  • a fluid capacity volume Vinl
  • Vfsl fluid capacity volume
  • the method can further include wicking the fluid matrix in excess of the Vacl from the first accumulator into the first sink, and retaining the excess fluid matrix in the first sink.
  • the method can further include wicking a wash fluid having a volume Vwl into the first accumulator through any interface surface of the first accumulator, wherein Vwl is greater than Vacl .
  • a second concentrator can also be used.
  • the method can further include uncoupling the first accumulator from the first sink, providing a second concentrator including a third self- wicking porous polymer monolith, the monolith having an second accumulator and a second sink, the second accumulator having at plurality of interface surfaces, and a fluid capacity volume (Vac2), the second sink having a fourth self-wicking porous polymer monolith, the second sink having an interface surface, and a fluid capacity volume (Vfs2), and coupling any interface surface of the first accumulator to any interface surface of the second accumulator, wherein the interface surface of the first accumulator and the interface surface of the second accumulator are in fluid communication.
  • a second concentrator including a third self- wicking porous polymer monolith, the monolith having an second accumulator and a second sink, the second accumulator having at plurality of interface surfaces, and a fluid capacity volume (Vac2)
  • the second sink having a fourth self-wicking porous polymer mono
  • a first elution fluid can be provided by coupling a first elution fluid source to any selected interface surface of the first accumulator, introducing a first elution fluid having a volume Vefl from the first elution fluid source through the selected interface surface of the first accumulator through the second accumulator and into the second sink, wherein Veil is greater than Vac 1 + Vac2, and wherein the first elution fluid releases the analyte from the first accumulator, and capturing the analyte in the second accumulator.
  • the method can further include uncoupling the first accumulator from the second accumulator, uncoupling the second accumulator from the second sink, providing a source of a second elution fluid, coupling the second elution fluid source to any selected interface surface of the second accumulator, introducing a second elution fluid having a volume Vef2 from the second elution fluid source into the second accumulator through the selected interface surface of the second accumulator, wherein Vef2 is greater than Vac2, and wherein the second elution fluid releases the analyte from the second accumulator, and collecting the analyte from any other interface surface of the second accumulator.
  • the method can also include a matrix absorber having an interface surface, a bypass channel with an outlet, and a fluid capacity volume (Vma), wherein Vma is smaller than or equal to Vac2; coupling the interface surface of the matrix absorber to any selected interface surface of the second accumulator, wherein the interface surface of the matrix absorber and the selected interface surface of the second accumulator are in fluid communication, providing a source of a second elution fluid, coupling the second elution fluid source to any other interface surface of the second accumulator, introducing a second elution fluid having a volume Vef2 from the second elution fluid source into the second accumulator through the any other interface surface of the second accumulator, wherein Vef2 is greater than Vac2, and wherein the second elution fluid releases the analyte from the second accumulator, and collecting the analyte from the bypass channel outlet of the matrix absorber.
  • Vma fluid capacity volume
  • the present disclosure relates to a system for concentrating an analyte in a fluid matrix
  • a second accumulator having a third self- wicking porous polymer monolith, the second accumulator having a plurality of interface surfaces, and a fluid capacity volume (Vac2)
  • a second sink having a fourth self-wicking porous polymer monolith the second sink having an interface surface, and a fluid capacity volume (Vfs2)
  • Vfs2 fluid capacity volume
  • the system can also include a first elution fluid configured to release the analyte from the first accumulator, a second elution fluid configured to release the analyte from the second accumulator, or bom.
  • the system can also include a matrix absorber having a fifth self-wicking porous polymer monolith, the matrix absorber having an interface surface, a bypass channel, and a fluid capacity volume (Vma), wherein Vma is smaller than or equal to Vac2, wherein the interface surface of the matrix absorber is configured for fluid communication with any interface surface of the accumulator of the second concentrator.
  • Figures 1A-1C show a block diagram of an embodiment of a system configured to concentrate a target analyte from a fluid sample.
  • Figure 2 shows a flowchart for an exemplary method of concentrating a target analyte in a system shown in Figures 1 A-l C.
  • Figures 3A-3D show a block diagram of an embodiment of a system configured to concentrate analyte from a fluid sample.
  • Figure 4 shows a flowchart for an exemplary method of concentrating a target analyte in a system shown in Figures 3A-3D.
  • Figures 5 A-SD show a block diagram of an embodiment of a system configured to concentrate a target analyte from a fluid sample.
  • Figure 6 shows a flowchart for an exemplary method of concentrating a target analyte in a system shown in Figures SA-SD.
  • Figures 7A-7E show a block diagram of an embodiment of a system configured to concentrate a target analyte from a fluid sample.
  • Figure 8 shows a flowchart for an exemplary method of concentrating a target analyte in a system shown in Figures 7A-7E.
  • Figures 9A-9D show a block diagram of an embodiment of a system configured to concentrate a target analyte from a fluid sample.
  • Figure 10 shows a flowchart for an exemplary method of concentrating a target analyte in a system shown in Figures 9A-9D.
  • Figures 11A-11H show an exemplary step by step method for the operation of an embodiment of an analyte concentrator.
  • Figures 12A-12H show another exemplary step by step method for the operation of an embodiment of an analyte concentrator.
  • Figure 13 shows an exemplary view of an accumulator monolith having a tapered shape in a housing or sleeve. A portion of the accumulator monolith extends past or out of one of the housing openings and can be used to form a fluidic junction with another monolith.
  • Figure 14 shows another exemplary view of an accumulator monolith having a tapered shape in a housing or sleeve.
  • Figure IS shows an exemplary combination of an accumulator monolith in fluid communication with a two-piece sink monolith. A portion of the accumulator monolith extends past or out of one of the housing openings.
  • Figure 16 shows another exemplary view of the combination of an accumulator monolith in fluid communication with a two-piece sink monolith.
  • Figures 17A-17D show different exemplary configurations from the sequence of use protocol steps for an exemplary ' device containing an accumulator monolith and a sink monolith for concentrating a target analyte from a fluid sample.
  • Figure 18A-18D show different exemplary configurations from the sequence of use protocol steps for another exemplary device containing an accumulator monolith and a sink monolith for concentrating a target analyte from a fluid sample.
  • Figure 19 shows a comparison of % DNA recovery of the same sample tested using different DNA concentration devices, as provided in Example 3.
  • Figure 20 showB a conipariaon of gel electrophoresis results for pre-loaded vs. collected DNA samples, as provided in Example 3.
  • Figure 21 shows a comparison of PCR results from collected enterobacteria phage Lambda DNA digests, as provided in Example 3.
  • Figures 22A-22D show an exemplary embodiment of an analyte in a fluid sample being concentrated in one concentrator (2200) and thereafter being further concentrated on a second concentrator (2230).
  • Figure 23 shows a flowchart for an exemplary method of concentrating a target analyte in a system shown in Figures 22A-22D.
  • the present disclosure relates to a concentrator for concentrating one or more analytes in a fluid matrix, and related methods, using one or more self-wicking materials, such as monoliths.
  • the composition whether described as a device, system, apparatus, concentrator, etc., can be used to extract, concentrate, purify, isolate or combinations thereof, whether described as only performing one of these functions.
  • the present disclosure relates to a method for concentrating an analyte in a fluid matrix, the method including providing an accumulator comprising a first self- wicking porous polymer monolith, the accumulator having a plurality of interface surfaces, and a fluid capacity volume (Vac); wi eking the fluid matrix containing the analyte into the
  • Different target analytes that can be concentrated by the methods and compositions of the present disclosure including DNA, RNA, PNA, proteins, metabolites, pharmaceuticals, toxins, viruses, bacteria, spores, eukaryotic cells, amoeba, plankton, pollutants, heavy metals, environmental contaminants, pathogens, food additives, colorants, and polymers.
  • the methods and compositions of the present disclosure are applicable to the diagnostics industry, genetic analysis industry, pharmaceutical industry, law enforcement, environmental monitoring, hospitals, clinics, food manufacturing, and quality control organizations.
  • DNA, RNA and related small molecules, such as toxins or pharmaceuticals can be concentrated from forensic samples.
  • antibodies specific to a wide variety of target analytes can be coupled to monolith and capture the antibody specific targets for epidemiological research.
  • accumulator elements can be fabricated from molecularly imprinted monolith.
  • analyte and target analyte can describe molecules of interest contained within a sample.
  • the terms may refer to the chemical species of interest in a sample mat is desired for use or analysis.
  • the target analyte can be a biological molecule, including a nucleic acid.
  • the target analyte can include DNA.
  • the fluid matrix, or sample mat contains the target analyte can be a biological sample, including blood, saliva, urine, stool, colostrum, milk, sputum, cerebrospinal fluid, amniotic fluid, plasma, semen, vaginal secretion, or serum.
  • the biological fluid can be artificially cultured, for example, it can be a recombinant enzyme, a virus, fermentation medium, a vaccine, or similar.
  • the biological fluid can also be associated with a plant, such as a plant exudate or an extract of a plant
  • a sample may be a fluid derived by the treatment or extraction of a portion of water, biological material, soil, a swab, blood, a suspension or a solution with a 'conditioning solution' or a process capable of extracting target analyte or capable of making die target analyte capable of being extracted from the sample by adsorption to the accumulator.
  • the fluid matrix can refer to all other materials in a sample mat are not the target analyte.
  • the fluid matrix can contain particulates or solids that can be removed by filtration or it may be an extract, containing non-analyte and potentially analyte also, of a solid sample.
  • Spent fluid matrix can refer to the components of the fluid matrix mat remain after the analyte has been captured by an accumulator element
  • the fluid sample can also be obtained from swabbing or otherwise extracting material from surfaces, such as medical equipment personal protective equipment furniture, counters, or floors.
  • the fluid sample can also be water samples, cosmetics, extracts from soil, foods, pharmaceuticals or raw materials.
  • the fluid sample can be an environmental sample, for example, it may be a water sample or an extract of a solid of interest, for example, a soil extract, an ash extract, or similar.
  • a water sample can include samples taken at various stages in water purification processing, for example, the water sample may be raw sewage or processed sewage.
  • the fluid sample can be a sample of interest for molecular diagnostics or analytics.
  • the processing of the fluid sample can include a detection/analysis step to determine the presence or absence of the target analyte(s).
  • the sample can be a solid sample, e.g., a dried or lyophilized sample.
  • the solid sample can be reconstituted in a liquid, e.g., an aqueous diluent
  • the aqueous diluent can be a salt, a buffer, a surfactant solution, an enzyme solution, an acidic solution or a basic solution.
  • the fluid sample containing target analyte, or sample can be purified or partially purified using an industry standard purification process.
  • the sample can be contain, or can be purified or partially purified to contain, about or lees that about 500000, 100000, 50000, 10000, 5000, 1000, 500, 100, 50, 10, S, 1, 0.5, 0.1, 0.0S, 0.01, 0.005 or 0.001 ppra of non-DNA components.
  • the volume amount of the fluid matrix, or the amount of the fluid matrix tested can be about, more man about, or less than about 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, 4000, 4100, 4200, 4300, 4400, 4500, 4600, 4700, 4800, 4900, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500 or about 10000 uL.
  • the concentration of the target analyte in the fluid matrix, or fluid matrix to be tested can be about, or greater man about, or less man about 0.00001, 0.00005, 0.0001, 0.0005, 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.S, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90 or about 100 ng/uL.
  • These vales can also define a range, such as about 0.001 to about 0.1 ng/uL.
  • the concentration of the target analyte in the fluid matrix, or fluid matrix to be tested can be about, or greater than about, or less than about 0.00001, 0.00005, 0.0001, 0.0005, 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, ,0.04, ,0.05, ,0.06, ,0.07, ,0.08, ,0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9 or about 10 oiM.
  • These vales can also define a range, such as about 0.01 to about 1 mM.
  • the pH of the fluid matrix, or the pH of the fluid matrix tested can affect performance.
  • the pH of me fluid matrix, or the pH of the fluid matrix tested can be about, more than about, or less than about 1, 2, 3, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 11 or about 12. These values can define a range, such as about a pH of about 2 to about 8, or about 5.5 to about 7.5.
  • the ionic strength of the sample, or combined sample in the loading solution can vary depending on the analysis, the analyte, the monolith, etc. The ionic strength of the fluid matrix, or the combined sample, can affect performance.
  • the ionic strength of the fluid matrix, or the fluid matrix tested can be about, more than about, or less than about 0.1, 0.5, 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 500, 750, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500 or about 10000 mM. These values can define a range, such as about 5 to about 30 mM, or about 150 to about 500 mM, or about 2000 to about 4000 mM.
  • the concentration of the target analyte in the fluid matrix, or the fluid matrix tested can be increased using the methods and compositions of the present disclosure.
  • the amount or degree of the concentration can be about, more man about, or less than about 2x, 3x, 4x, 5x, 6x, 7x, 8x, 9x, lOx, 20x, 3 Ox, 40x, 5 Ox, 60x, 70x, 80x, 90x, lOOx, SOOx or about lOOOx. These values can be used to define a range, such as about 5x to about 50x.
  • the elution volume from the system can be fixed.
  • the degree of sample concentration can, therefore, be inversely proportional to the volume of sample loaded. For example, a 500 ⁇ , sample volume reduced to 50 ]iL provides a 1 Ox level of concentration.
  • Pre-dilution of the sample can reduce the net level of concentration.
  • pre-dilution is not necessary.
  • pre-dilution is optional for samples, such as environmental water samples, urine, or beverages.
  • Other sample can be pin-diluted, such as saliva, stool, or body lotion.
  • the recovery of the target analytc from the system can be 100%, or less. A full recovery, or a recovery greater than about 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15 or about 10%, of the target analyte can be obtained. In some embodiments, the recovery can be affected by the concentration of the analyte.
  • a full recovery, or a recovery greater than about 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15 or about 10% can be obtained from a sample having a concentration of about, or greater than about, or less than about 0.00001, 0.00005, 0.0001, 0.0005, 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90 or about 100 ng/uL.
  • a recovery of about 50% or greater for analytes concentrations between 0.005 and 0.5 ng/uL can be greater than about 90% for concentrations greater than about 1 ng ⁇ L.
  • An accumulator is provided and can be used to filter out, retain or capture the target analyte from the fluid matrix or sample.
  • the accumulator can be a self-wicking material, such as a self-wicking monolith, or "accumulator” or “accumulator material” or “accumulator monolith.”
  • the self-wicking material can be any material that has sufficient self-wicking properties, can be designed or modified to have an affinity for one or more analytes, can be formed into different geometries, or combinations thereof.
  • the self-wicking material can be a self- wicking monolith as described in U.S. Patent Application Serial No.: 14/549,055, the disclosure of which is incorporated by reference in its entirety.
  • the accumulator can contain a self-wicking monolith mat can be designed or modified to have an affinity for one or more target analytes.
  • each accumulator, sink, and matrix absorber can be formed from a self-wicking material.
  • the self-wicking material is a monolith which is used herein and in the examples as an exemplary self-wicking material.
  • Other non-monolith accumulators, sinks and matrix absorber, can be used with the methods and compositions of the present disclosure.
  • the self-wicking material can be any material that can provide self-wicking action, such as having a wick rate of about 1 cm or more, can be configured to form a coupling in fluid communication with at least one other material, and has a fluid capacity.
  • self- wicking materials include absorbent pads, such as those used for lateral flow tests, cellulose fiber, such as woven and non-woven sheets, high-density cellulose which can be provided in a number of different thicknesses and densities, micro-patterned plastics, molecular sieve, superabsorbent materials, such as starch-acrylonitrile copolymer, sodium polyacrylate, polyacrylamide, CM-celhilose and PVA copolymers.
  • the accumulator in a concentrator is a volume of chromatographic stationary phase made from a self-wicldng macroporous monolith.
  • the interior pore surfaces of the accumulator can include hydrophilic groups that cause wicking and one or more types of functional side-chains that can adsorb one or more target analytes from a sample as the sample flows through the accumulator.
  • the functional molecules can be incorporated into the accumulator pore structure as monomers during polymerization, or they can be grafted onto the pore surfaces after the monolith has been formed using various chemical processes well known to those skilled in the art.
  • Some example functional groups include primary amines, secondary amines, tertiary amines, sulfates, phosphates, acetates, benzene, phenol, benzoate, alkyl, amino alkyl, lectins, antibodies, apoproteins, avidins, polynucleotides, amphiphiles, chelators, toxins, pharmaceuticals, sugars, chiral molecules or cyano groups.
  • the accumulator may have any shape mat can be cured in a mold including disk, rod, truncated cone, star, or complex geometry..
  • the accumulator can have multiple internal zones, each containing a different functional chemistry.
  • the accumulator can be any size and can have multiple surfaces capable of interfacing with other components in a concentrator device.
  • the accumulator monolith can wick the fluid, e.g., the fluid matrix containing the analyte, wash fluid, elution fluid, etc., that is in fluid communication with any of its interface surfaces.
  • the term "self-wi eking" refers to the effect of capillary action by the monolith pores on a liquid. This is the property of the monoliths that causes a liquid sample to flow spontaneously from a first portion of the monolith to another portion spaced from the first without the need for an external pressure differential to be applied (as is used, for example, in conventional column chromatography). It is mis self-wicking ability mat can alone provide motility to the fluids applied during the target analyte concentration and optional washing.
  • Sclf-wicking can be independent of the orientation of the monolith in space. It can occur vertically, for example up the monolith, or laterally, that is, along the monolith, depending on the method of application of the fluid.
  • sclf-wicking refers to a material exhibiting a wicking
  • Fluid flow through the monolith can occur without the need for externally applied pressure. Accordingly, self-wicking monoliths as described herein can be used in methods wherein the fluid flows with no externally applied pressure gradient across the monolith.
  • a favorable interfacial energy between the fluid and the monolith material can cause the wicking action by pulling fluid into the material until all of the monolith has been wetted.
  • the free energy of mis interaction can create a hydrostatic pressure at the fluid front below ambient pressure.
  • the back pressure of the fluid wicking through the monolith can be less man ambient pressure at any elevation, and therefore less than mean sea level pressure.
  • the following wicking test measures the distance water travels up a monolith cured with dimensions: 1.27 cm wide, 6.35 cm long, 0.30 cm thickness. Prior to testing, the monolith is stored in atmospheric conditions (temperature: 18-22 °C, RH 10-40%). The test involves (i) 3 mm of the monolith is submerged in de-ionized water with the monolith in the upright orientation, (ii) water moves up the length of the monolith due to wicking action, and (iii) the distance traveled by the water over the course of 2.0 * min is measured at the corner of the monolith having the greatest measurement The measurement may be made visually, simply by observing the solvent front. Alternatively, a dye may be added to aid measurement The dye can be a dye that travels with the water without being significantly retarded by the monolith.
  • Suitable examples include FD&C Yellow number 1 and fluorescein.
  • Red 40 and Blue 1 can be also be used for some monoliths as described herein, although the dyes may interact with particular functionalities in the matrix (for example, free amino groups) of certain monoliths as described herein, thereby causing retardation.
  • Very large dyes, such as blue dextran, may be retarded by the pore size of the monolith. Similarly, charged dyes may move along the monolith at different rates.
  • Wicking rate can also be measured in units of s/4cm.
  • a comparison Table equating measurements according to the wicking test as described herein and a wicking value in s/4cm is provided below..
  • the monolith can be made from any material(s) that can be used to form a sclf-wicking monolith mat can selectively capture a target analyte.
  • the sclf-wicking monolith can include a hydrophilic monomer and a linker monomer, such as those described in U.S. Patent Application Serial No.: 14/549,055, the disclosure of which is incorporated by reference in its entirety.
  • the linker monomer can have two polymerizable groups spaced apart by a linker including at least one— C(R) 2 0- group.
  • one or more further monomers can be included.
  • Each R can be hydrogen, or can be any organic group.
  • the linker can include an alkyl or substituted alkyl chain - ⁇ C(R)2)ir in which at least one or two of the -C(R) 2 - groups can be replaced by oxygen, n can be 3 to 20, for examplci 5 to IS, for example, 5 to 13.
  • the R groups can include further polymerizable groups.
  • the linker can be a polyether, for example, a polyethylene glycol or similar.
  • the linker can include a polyethylene glycol chain, for example
  • Suitable linker monomers include ethyleneglycol diacrylate, ethyleneglycol dimethacrylate, tetra(ethylene glycol) dimethacrylate, tetra(ethylene glycol) diacrylate, and di(ethylene glycol) dimethacrylate.
  • Suitable hydrophilic monomers include an acrylate or methacrylate, for example, the hydrophilic monomer can be 2-hydroxyethyl methacrylate (HEM A), 2-hydroxyacrylate, 2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate or 2-hydroxypropyl acrylate. In some preferred embodiments, it can be 2-hydroxyethyl methacrylate.
  • Combinations of linker monomers can include ethylene glycol dimethacrylate and tetraefhylene glycol dimethacrylate, or ethylene glycol dimethacrylate and tetraethylene glycol diacrylate.
  • a combination of linker monomers can be ethylene glycol
  • dimethacrylate and tetraethylene glycol diacrylate for example, in a ratio of 4:3 to 1 :3, for example in a ratio of 1:1 to 1:3, for example, in a ratio of 2:3 to 7:10.
  • a combination of linker monomers can be ethylene glycol dimethacrylate and tetraethylene glycol dimethacrylate, for example in a ratio of, 5:1 to 1:1, for example, in a ratio of around 3:1.
  • the ratio of tetraethylene glycol dimethacrylate to hydrophilic monomer can be about 20:1; 18:1; 16:1; 14:1; 12:1, 10:1; 8:1; 6:1; 4:1; 2:1; or about 1:1. These values can be used to define a range, such as about 10:1 to 1:3, or, 5:1 to 2:1.
  • the ratio of tetraethylene glycol dimethacrylate to hydrophilic monomer can be about 3:1; 2:1; 1.5:1; 1.4:1; 1.3:1; 1.2:1; 1.1:1; 1:1; 0.9:1; 0.8:1; 0.7:1; 0.6:1; 0.5:1; 0.4:1; or about 0.3:1.
  • These values can be used to define a range, such as about 1:1 to 0.7: 1.
  • the ratio of tetraethylene glycol diacrylate to hydrophilic monomer, for example, HEMA can be 5:2 to 1 :3, for example, 2:1 to 1 :1.
  • the total linker monomer to total hydrophilic monomer ratio can be from 1 : 1 to 10:1, from 1:1 to 7:1, or from 1:1 to 5:1, or from 2:1 to 4:1.
  • the total linker monomer to total other monomer content can from 1 : 1 to 10: 1 , or from 1:1 to 7:1, or from 1:1 to 4:1.
  • the hydrophilic monomer refers to a monomer with a polar side-chain capable of ionization or hydrogen bonding in an aqueous environment.
  • polymers with high content of hydrophilic monomers are wettable or will absorb water.
  • hydrophilic side chains include, without limitation, hydroxyl, amino, acetate, guanidate, amide, sulfate, nitrate, or nitrile.
  • the hydrophilic monomer can include a free hydroxyl group.
  • the hydrophilic monomer can be hydroxyacrylate, 2-hydroxyethyl methacrylate (HEMA), 2-hydroxyethyl aery late, 2-hydroxypropyl methacrylate or 2-hydroxypropyl acrylate; or acrylic acid. In some embodiments, it is 2-hydroxyethyl methacrylate (HEMA).
  • HEMA 2-hydroxyethyl methacrylate
  • the linker monomer can also include hydroxyl groups.
  • a linker monomer can be a hydrophilic monomer.
  • it can be 3-(aoyloyloxy)-2-hydroxypropyl methacrylate or glycerol 1 ⁇ -diglycerolate diacrylate.
  • These linker monomers including a free hydroxyl group can serve as a linker monomer and / or as a hydrophilic monomer in monoliths and methods as described herein.
  • the linker monomer refers to a polymerizable compound having at least two
  • the two polymerizable groups can include vinylic moieties, and can for example be acryl or methacryl groups.
  • the linker monomer can be an acrylate or a methacrylate, for example, a diacrylate or dimethacrylate.
  • Each R can be hydrogen, or any organic group.
  • the linker can be an alkyl or substituted alkyl chain -(C(R)2)n- in which at least one, preferably at least two, -C(R)2- groups are replaced by oxygen.
  • the R groups may themselves include further polymerizable groups, and may be the same or different.
  • each R group is H.
  • the linker can be an ethylene glycol, for example, ethylene glycol, diethylene glycol, or polyethylene glycol.
  • the linker can be a glycerol, for example glycerol 1-3-diglycerolate or 3-acryloyloxy-2- hydroxypropylrnethacrylate.
  • a linker monomer can include mixtures of two or more different such monomers.
  • a linker monomer may refer to single linker monomer as described above, or to a combination of two or more such linker monomers. Exemplary linker monomers are provided in the Table below.
  • the accumulator monolith can have a variable fluid capacity volume.
  • the fluid capacity volume (Vac) of the accumulator monolith can be about, more than about, or less than about 5, 10, IS, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 85, 90, 95, 100, 110. 120, 130, 140, 150, 200, 300, 400 or about 500 ⁇ L ⁇
  • These values can also define a range, such as about 20 to about 50 uL.
  • the fluid capacity volume of the accumulator can be equal to or less than me sample volume.
  • the fluid capacity of the accumulator can be about 2x, 1.5x, lx ditch 0.5x, O.lx, O.OSx, O.Olx, 0.005x or about 0.001 x of the sample volume. These values can be used to define a range, such as about lx to about O.lx.
  • the rate of absorption of the fluid matrix, or the amount of the fluid matrix tested, into die accumulator monolith can vary depending on self-wicking ability of the monolith, the sample composition, etc.
  • the rate of absorption into the accumulator monolith can be about, more than about, or less than about 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900 or about 1000 ⁇ . These values can define a range, such as about 20 to about 50 ⁇ .
  • the absorption time of the system can be about, more man about, or less than about 0.1 , 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170 or about 180 minutes. These values can define a range, such as about 2 and about 20 minutes.
  • the accumulator monolith can be designed, produced, functional ized or otherwise modified to capture or retain specific target analytes in the accumulator.
  • the accumulator monolith can have specific surface chemistry that can capture a target analyte from a cell lysate and release it when treated with an elution solution that has different properties than the lysate solution. Some of die different properties being a different pH, ionic strength, or die
  • the monolith can include DEAE for a specific solute.
  • the monolith can include DEAE for a specific solute.
  • the monoliths can be functional ized with lectins to capture sugars, or, functionalized with proteinase K to digest away proteins from a sample, or functionalized with antibodies to capture bacteria or viruses, or other materials specific to the antibodies.
  • the monolith can include amino groups such as aminoethyl methacrylate to capture species with negative charge such as lipid-membrane fragments, DNA, and proteins.
  • Amino groups are chemically reactive; they can be used for permanently immobilizing other chemicals on the interior surfaces of the monolith after initial fabrication. This bonding can be direct, or it can be via added linkers (e.g. caibodiimide). Amino groups can also be used as the anchor for capture chemistry (for example, to immobilize molecules such as antibodies and/or lectins), and for immobilizing proteinases.
  • Negatively charged groups such as carboxy or sulfate can be used to capture species with positive charge such as proteins.
  • Carboxy 1 groups are chemically reactive; they can be used for permanently immobilizing other chemicals on the interior surfaces of the monolith after initial fabrication. This bonding can be direct, or h can be via an added linker.
  • Long chain alkyl groups for example, incorporated through use of a monomer having such a chain during polymerization (for example, lauryl methacrylate, or amino-lauryl methacrylate, or sulfo-lauryl methacrylate), can be used to capture oils and fatty chain molecules, for example, detergents, triglycerides, lecithins, lipid-membrane fragments and lipoproteins.
  • a monomer having such a chain during polymerization for example, lauryl methacrylate, or amino-lauryl methacrylate, or sulfo-lauryl methacrylate
  • oils and fatty chain molecules for example, detergents, triglycerides, lecithins, lipid-membrane fragments and lipoproteins.
  • the capacity of the accumulator can vary depending the size of the accumulator monolith, the surface area, the volume, the affinity for the target analytes, etc.
  • the capacity of the accumulator can be measured in the amount of target analyte captured.
  • the binding capacity of the system for a target analyte can be about, more man about, or less than about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90 or about 100
  • These values can be used to define a range, such as about 1 to about 5 ⁇ &
  • the capacity of the system for a target analyte can also be defined in terms of analyte mass per monolith mass.
  • the capacity can be about, more than about, or less man about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550600, 650, 700, 750, 800, 850, 900, 950, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900 or about 2000 ng/mg.
  • These values can be used to define a range, such as about 100 to about 800 ng/mg.
  • a DNA capture monolith can hold between 100 to about 800 ng of DNA per mg monolith.
  • a DNA capture monolith can hold about 3500 ng of DNA in a 7 mg (33 uL total volume, 25% solids) accumulator.
  • the various monoliths of the present disclosure can have a bulk density of about, more than about, or less than about 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75 or about 0.8 g/cc. These values can define a range, such as about 0.15 to about 0.50 g/cc, or about 0.20 to about 0.40 g/cc.
  • the various monoliths of the present disclosure can have a porosity of about, more than about, or less than about 40, 45, 50, 55, 65, 70, 75, 80, 85, 90 or about 95% . These values can define a range, such as about 50 to about 85%, or about 60 to about 80%
  • the accumulator monolith can be formed into various shapes and can have a plurality of interface surfaces.
  • the shape of the accumulator monolith can help facilitate self-wi eking, can allow for coupling to additional system components, monoliths or both.
  • One shape of the accumulator can be a truncated cone with dimensions of, for example, a diameter about, more than about, or less than about 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9 or about 10 mm at the tip.
  • the base can have an increased diameter by about 1, 2, 3, 4, 5, 6, 7, 8, 9 or about 10 additional mm.
  • the length of the cone can be about 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18 or about 20 mm.
  • the values for each dimension can form individual ranges for each dimension, such as about 2 to about 5 mm for tip, about 3 to about 7 for the base and about 3 to about 9 for the length.
  • the tip is 2 mm
  • the base is 3 mm and the length is 5 mm.
  • the tip is 1 mm
  • the base is 6 mm and the length is 12 mm.
  • the cross-section shape of the cone may be any shape, for example square, triangular, trapezoidal or irregular.
  • the cross section shape of the accumulator element may change over the length of the accumulator.
  • the shape can also be a cylindrical rod of monolith or a combination of a cylindrical rod section and a truncated cone section.
  • the shape can be any that includes a taper, such as a cone.
  • a taper can improve the formation of a seal between the accumulator monolith and a housing or casing surrounding, covering or attached to a surface of the accumulator monolith.
  • An accumulator monolith can swell and shrink at various stages in the fabrication process. As a result of the size variability, the taper can promote a sea) between a sleeve and at least one portion of the accumulator monolith.
  • the formed seal can also reduce or prevent the migration of fluid around the monolith during use.
  • the taper angle of the accumulator monolith can be about, more than about, or less than about 5, 6, 7, 8, 9, 10, 12, IS, 20, 30, 45 or about 60 degrees. For a range, 8 to about 12 degrees.
  • the taper angle of the casing, housing or sleeve can be the same as the accumulator, or can differ by less than about 5, 4, 3, 2, 1, 0.S, 0.2S, 0.2, 0.1S, 0.1, 0.0S, 0.02 or less than about 0.01 degrees.
  • the accumulator and the sleeve (or housing) have at least one section of intimate contact such that a fluidic seal is made.
  • the method can further include providing a sink including a second self-wicking porous polymer monolith, the sink having an interlace surface, and a fluid capacity volume (Vfs); and coupling any interface surface of the accumulator to the interface surface of the sink, wherein the interface surface of the accumulator and the interface surface of the sink are in fluid
  • fluid connection or fluidic junction can be used to indicate any assembly that allows fluid to move from one element in a concentrator to another element.
  • a fluidic connection can withstand the pressure used in the system and can prevent fluid from leaking out of its intended path.
  • fluidic connections can be fully surrounded by a solid enclosure mat is non-permeable to the fluids mat are used in the system. Further, fluidic connections can form fluid-impervious seals with the elements mat they connect. Fluidic connections between wicking elements can require that the two elements are held in close enough proximity mat fluid contained in a first element can be wicked into the second without breaking the fluid column. Generally, this means mat the two elements must be in physical contact with each other. Fluidic connections in a wicking system can be made by bringing wicking elements into physical contact with each other. Fluidic connections in a wicking system can be broken by separating wicking elements mat were previously in physical contact
  • a sink is provided and can be used to hold or contain excess fluid, e.g., sample matrix fluid, wash fluid, after it has passed through the accumulator monolith.
  • the sink can be a self- wicking monolith, or "sink monolith.”
  • the self-wicking monolith can be any monolith mat has sufficient self-wicking properties and can be formed into different geometries, or combinations thereof.
  • the monolith can be a monolith as described in U.S. Patent Application Serial No.: 14/549,055, the disclosure of which is incorporated by reference in its entirety.
  • the sink can be a volume of absorbent material made from self- wicking macroporous monolith or other suitable material with a high wick rate.
  • the sink can be any size and can have multiple interface surfaces capable of forming fhridic connections with other components in a concentrator device.
  • one or more sink elements in a concentrator can provide the motive force for drawing samples through concentrator elements. After absorbing spent fluid matrix, sink elements can serve to sequester and hold the fluid matrix within mem.
  • the sink monolith can be coupled to the accumulator monolith.
  • the coupling can establish fluid communication between the sink and accumulator, such that fluid can be wicked from one monolith to the other.
  • the sink can "pull" fluid through the accumulator monolith by wicking.
  • the wi eking action of the accumulator, the sink or the combination of both can eliminate the need for an external force or pressure to move fluid, e.g., sample matrix fluid, through the accumulator.
  • the sink monolith can wick the fluid, e.g., fluid from the accumulator monolith, that is in fluid communication with one or more of its interface surfaces.
  • the sink monolith can have a self-wicking rate that is the same as, greater man, or less than the accumulator monolith.
  • the self-wicking rate of the sink can be about 50%, 100%, 200%, 300%, 400% or about 500% of the wicking rate of the accumulator monolith.
  • the wick rate of the sink is higher than the accumulator to counteract the effect that any decrease in fluid transport through the accumulator would have on the time required to fully absorb a sample or wash solution.
  • the sink monolhh can have a variable fluid capacity volume.
  • the fluid capacity volume (Vfs) of the sink monolith can be about, more than about, or less than about 0.1 , 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, IS, 20, 25, 30, 35, 40, 45 or about 50 mL. These vales can also define a range, such as about 1 to about 10 mL.
  • the sink monolith fluid capacity volume can be equal to greater that the sample volume, the accumulator monolith or both.
  • the sink fluid capacity volume can be about 2x, 3x, 4x, 5x, 6x, 7x, 8x, 9x, lOx, 20x, 3 Ox, 40x, or about 5 Ox of the sample volume, the accumulator monolith or both. These values can be used to define a range, such as about 2x to about 20x.
  • the sink monolith can draw into and maintain lysate and wash fluids in volumes much greater man those applied to the accumulator monolith.
  • the sink monolith can be formed into various shapes and can have a plurality of interface surfaces. At least one of the interface surfaces of the sink monolith is configured to couple to an interface surface of the accumulator monolith. The coupling of the two interface surfaces can facilitate wicldng of fluid across die coupling.
  • the coupling of two monoliths can be achieved by placing two pieces of wicldng monolith into physical contact with each other.
  • the amount of fluid mat can move through such an interface can be roughly proportional to the area of the interface in physical contact
  • the area of the interface can be about, more than about, or less than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, IS or about 20% of the surface area of the accumulator monolith. These values can be used to define a range, such as about S to 10%.
  • the sink is larger man the accumulator so die relative percent area of the sink interface can be smaller than the relative percent rea of the accumulator interface.
  • the coupling of two monoliths can include compressing the monoliths together.
  • the compression of the accumulator and sink together can form a mechanical junction.
  • the amount of compressive force can be small, such as the equivalent of a few pounds of force.
  • the weight of one 10 mg monolith placed on top of another monolith is sufficient compression.
  • slightly more pressure is required:
  • the surfaces of the monoliths forming the coupling can also be smooth.
  • the surface variations across an interface of a monolith can be less than about S mm, 4, 3, 2, 1, 0.8, 0.6, 0.S or 0.3 mm. These values can be used to define a range, such as about 1 to about 0.5 mm.
  • the mechanical junction between any interface surface of the accumulator and the interface surface of the sink can be formed by interiocking surface geometries of the accumulator and the sink. See, e.g., Figure 15.
  • the method and compositions of the present disclosure can further include wicking the fluid matrix in excess of the Vac from the accumulator into die sink, and retaining the excess fluid matrix in the sink.
  • a sample volume of about 500 ⁇ * can be wicked into an accumulator with a 30 ⁇ iL fluid capacity.
  • the 470 uL of excess fluid matrix is wicked into the sink.
  • the sink can have a fluid capacity of about, greater than about, or less than about 0.1, 0.2, 0.3, 0.4, 0.S, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or about 20 mL. These values can be used to define a range, such as about 0.2 to 10 mL.
  • the monoliths can be regenerated. In other embodiments, the monolith cannot be regenerated and are intended for one-time use.
  • the housing for the sink is not completely sealed.
  • the housing can allow displaced air to escape as die sink fills with fluid.
  • the methods and compositions of the present disclosure can further include wicking a wash fluid having a volume Vw into the accumulator through any interface surface of the accumulator, wherein Vw is greater man Vac.
  • the wash fluid can be water or a dilute buffer.
  • the wash fluid can be any fluid that (i) does not dislodge an appreciable amount of target analyte, and/or (ii) does not contain anything that would be considered a "contaminant" in the final output of the concentrator.
  • a wash fluid can be any liquid mat can-be used to physically displace liquid such as spent fluid matrix or a previous wash fluid from die accumulator without displacing the target analyte.
  • a wash fluid can also ' serve the function of dislodging or desorbing unwanted species from an accumulator element that may have adsorbed in addition to the target analyte.
  • the final wash fluid before elution can be compatible with subsequent processes such as characterization, identification or sequencing to be performed on the target analyte.
  • the wash fluid can be wicked into the system and can be pulled into the sink, or a wash fluid can be introduced using pressure in the same manner as the elution fluid.
  • the monoliths can stop wicking when die input fluid is exhausted or removed, in particular when no other external force or pressure is applied. When wicking is stopped, the monolith pores can remain filled with fluid. When a wash fluid is wicked through the accumulator h can displace die sample matrix and any non-captured or retained material or analytes. In some monoliths where mixing features have not been deliberately incorporated, die fluids do not mix or essentially do not mix as they are wicked. As such, the mtroduction of a wash fluid can effectively displace the sample matrix fluid from the accumulator with a wash volume mat is equal to die fluid capacity of die accumulator. [00115] To ensure complete removal of the sample matrix fluid, a wash volume of 2x, 3, 4, 5.
  • an 8x value can provide a balance between wash effectiveness and time.
  • a DNA extraction uses a 200 ⁇ *L h/sate sample with a 25 ⁇ LL fluid capacity accumulator. After the lysate is loaded, a wash fluid is used using three different 200 ⁇ , solutions.
  • the fluid capacity of me sink is about 1800 ⁇ L ⁇ In other examples, 1, 4, or 8 mL samples can be used with either 50, 500 or 1000 ⁇ . accumulators.
  • the method of die present disclosure can further include uncoupling the accumulator from the sink, providing an elution fluid source, coupling the elution fluid source to any selected interface surface of the accumulator wherein the elution fluid source and the interface surface of the accumulator are in fluid communication, mtroducing an elution fluid having a volume Vef from the elution fluid source into the accumulator through the selected mterface surface of the accumulator, wherein Vef is greater than Vac, and wherein the elution fluid releases the analyte from the accumulator, and collecting the analyte from any other interface surface of the accumulator.
  • the accumulator and the sink can be uncoupled. Uncoupling involves eliminating the fluid communication, such as removing die physical contact, between die monolith elements.
  • the two monoliths can be uncoupled by physically moving diem apart, e.g,. mechanical means.
  • the coupling can include the removal of the portion of die accumulator containing the bound or captured target analyte, such as being cut and moved away.
  • a guillotine mechanism can be used, such as a blade or barrier that can be forced into the monolith to separate two portions of monolith and prevent the flow of liquid between the two separated portions during later steps of processing such as the elution step.
  • guillotines may be a tube or a straight blade.
  • the uncoupling can be performed using a cutter configured to separate the accumulator and the sink and to discontinue the accumulator and sink from being in fluid communication.
  • the separated portion can then be placed in contact with other monolith components.
  • the separated portion can be transferred to an elution component which ejects its fluid contents into a collection container.
  • the accumulator element filled with target molecule can also be cut into two or more separate sections that each are transferred to supply analyte to different downstream processing systems.
  • One of the separated components can be used as an archival medium. For example, in the case of DNA capture, the size of the excised piece of monolith can be controlled to deliver a specific amount of DNA to downstream processes that require the amount of DNA to be in a particular range.
  • the monolith can also be divided into slices progressing away from the sample introduction face. Elution from each of these can allow for the DNA concentration to be controlled or held at a selected threshold. If there was insufficient DNA to saturate the accumulator element, only those fractions containing DNA can be selected for pooling to give the required concentration.
  • the separated portion, or portions, of the accumulator containing analyte can be transported using a shuttle mechanism that can break the junction between the sink monolith and the concentrator monolith.
  • the shuttle can additionally bring a fluid reservoir and the concentrator monolith into contact and form a fluidic junction between the concentrator monolith and the outlet of the fluid reservoir.
  • the shuttle mechanism can be a container holding the entire accumulator monolith or only a specific portion of accumulator monolith from the total fluid system. It can break or cut away a select portion of the accumulator monolith and shuttle it to one of the device components described above.
  • An elution fluid and an elution fluid reservoir can be provided.
  • the elution fluid can be any fluid that can efficiently release the target analyte from the accumulator.
  • An elution fluid can be any solution that disrupts the attractive forces between the analyte and the accumulator's interior surfaces causing the analyte to desorb or 'fall off of the accumulator pore surfaces and be elutable.
  • DNA can be released from some of the monolith described herein with any solution having a pH greater than about 8.5.
  • an elution fluid can be any liquid that can cause the target analyte to deaorb from the accumulator monolith pore surfaces after capture and optional washing. The elution fluid can physically transport the desorbed target analyte out of the accumulator monolith.
  • the elution fluid can be compatible with subsequent processes such as ⁇ characterization, identification or sequencing to be performed on the target analyte.
  • the elution fluid can preferentially cause analyte to desorb but will leave contaminant molecules adsorbed on the accumulator.
  • the eluate can be the fluid ejected from an accumulator element as the result of introducing fluid into the accumulator element. In an elution step, the initial eluate that can be recovered from an accumulator is the fluid mat was most recently introduced into the
  • the eluate can contain analyte and elution fluid.
  • Eluate from a concentrator can contain purified and concentrated analyte. Eluate is the solution mat can used for subsequent processes such as characterization, identification or sequencing.
  • the elution fluid can be contained in an elution source.
  • the elution source can be out of fluid communication or not in fluid communication while the target analyte is being loaded and wicked into and captured by the accumulator.
  • the elution fluid source can be coupled to any selected interface surface of the accumulator wherein the elution fluid source interface surface of the accumulator are in fluid communication
  • the elution source, or elution fluid dispenser can include an elution fluid reservoir, an elution fluid pressurizer and an output fitting configured to make a fluidic coupling to any interface surface of the accumulator.
  • the elution fluid dispenser is a syringe filled with the elution fluid.
  • the syringe can be capped or otherwise not in fluid contact with the accumulator.
  • the syringe is capped with a heat-seal foil.
  • the elution volume from the accumulator monolith can vary depending on the size of the accumulator, the amount of analyte required, and the concentration required.
  • the elution volume from the accumulator containing the analyte can be about, more man about, or less than about 1, 5, 10, IS, 20, 25, 30, 35.40, 45, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600.700, 800, 900 or about 1000 uL. These values can be used to define a range, such as about 20 to about 120 ⁇ ,.
  • the elution fluid can be designed to release the target analyte from the accumulator monolith.
  • the elution fluid can have a different pH, ionic strength, contain a specific solute, or combinations thereof.
  • Tbe elution fluid can also be a non-aqueous solution.
  • the ionic strength of a solution is a measure of the concentration of ions in mat solution in molality (mol/kg)
  • the elution fluid can have a pH value mat differs from the fluid matrix of the sample fluid matrix, wash solution or both by about, or more than about, 0.1, 0.2, 0.3, 0.4, 0.S, 0.6, 0.7, 0.8, 0.9, 1, 1.S, 2, 2.S, 3, 3.5, 4, 4.S, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or about 10 pH units. These values can define a range, such as about 1 to about 3 pH units, or about 9 to about 11 pH units.
  • the elution fluid can have an ionic strength mat differs from the fluid matrix of the sample fluid matrix, wash solution or both by about, or more than about, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or about 10 molality (mol/kg). These values can define a range, such as about 0.5 to about 2 molality (mol/kg).
  • the elution fluid can have concentration of a specific solute mat differs from the fluid matrix of the sample fluid matrix, wash solution or bom by about, or more than about, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90 or about 95 wt%. These values can define a range, such as about 30 to about 60 wr%.
  • the specific solute can be one (hat has the same or higher affinity to be captured by or in the accumulator monolith, e.g., the specific solute can have a higher affinity man the target analyte to binding sites in the accumulator monolith.
  • the specific solute can have a 2, 5, 10, 100, 1000, 10,000, 100,000, 1,000,000, 10,000,000, or about 100,000,000 fold greater affinity for binding sites in the accumulator monolith that tbe target analyte.
  • the specific solute can also increase the solubility of the target analyte in the elution fluid.
  • the elution fluid can be introduced to, or into, the accumulator.
  • the volume of the elution fluid can be greater than the volume capacity of the accumulator, i.e., wherein Vef is greater man Vac. Because the fluids can move through monolith in bands, a well-defined boundary between two different fluids can be created and contained within the pores of the accumulator.
  • the analyte typically does not elute from the accumulator until the elution fluid boundary reaches the outlet.
  • the elution fluid volume, Vef can be about 2x, 3x, 4x, 5x, 6x, 7x, 8x, 9x or up to lOx of the accumulator monolith capacity, Vac..
  • the elution fluid containing the analyte is collected from a surface of the accumulator.
  • the elution fluid can be collected after a defined amount of elution fluid has been passed into the accumulator, such as about SO, 60, 70, 80, 90, 100, 110, 120, 130, 140, ISO, 160, 170, 180, 190 or about 200% of the accumulator capacity volume. These values can be used to define a range, such as about 90% to about 110%.
  • the elution fluid can be collected in fractions over mis range. The fractions can be individually tested for target analyte, and/or pooled to reconstitute the sample.
  • the elution fluid can contain a dye or other visible or detectable signature to indicate where the elution fluid is and when to begin collecting the elution fluid exiting die accumulator monolith.
  • the accumulator monolith can have fluid pass through in more man one direction.
  • a target can be captured in a first volume of fluid to pass through the monolith.
  • the target analyte can then be modified, detected, and/or released in subsequent fluid volumes passed through the monolith in any direction, such as using multiple fluid sources and/or multiple sinks flowing in multiple directions.
  • the monolith can capture DNA by wicking a sample fluid matrix into the accumulator monolith through a first surface interface.
  • the DNA can be eluted out of the same surface interface by passing an elution fluid into a different surface interface on the accumulator monolith, such as an opposite face or an orthogonal face.
  • a different surface interface on the accumulator monolith such as an opposite face or an orthogonal face.
  • Numerous configurations of il iridic connections can be created including flipping the accumulator to introduced the sample fluid matrix to an accumulator monolith and flipping the accumulator over again to collect the eluted analyte from the same surface wherein the eluate is collected.
  • analyte fluid path through the accumulator is substantially the same, such that the analytea can be captured or retained on a portion of me accumulator and thereafter edited in narrow band.
  • the analyte inlet and elution fluid inlet can have a majority of the monolith between them.
  • a monolith acting as a cell-capture element may have a suspension of harvested cells introduced from the 'top' so that they are captured by the monolith while the suspending solution is washed through the accumulator element and into a sink.
  • the sink may then be replaced with a solvent reservoir and the fluid driven through the monolith in the opposite direction such that at least some of the captured cells are ejected from the monolith.
  • a dilute target molecule solution may be introduced from the 'top* and flowed through an accumulator element, and then eluted by fluid from a different reservoir that is attached to the 'side* of the accumulator element
  • a large volume sample may be flowed through a accumulator element by introduction from the 'top' with the depleted carrier fluid absorbed by a sink element on the 'bottom'
  • a second sink, or other processing zones may be attached to the 'side' of the accumulator element and additional fluid added from the top' or another location.
  • analyte may be concentrated to increase the efficiency or sensitivity of subsequent steps.
  • a large sample may be flowed through an accumulator element with a large volume. The captured analyte could then be eluted into a smaller accumulator element to further increase its concentration. This second accumulator element has a different type of affinity for the target analyte.
  • the method of the present disclosure can further include uncoupling the accumulator from the sink, providing a matrix absorber comprising a third self-wicking porous polymer monolith, the matrix absorber having an interface surface, a bypass channel, and a fluid capacity volume (Vma), wherein Vma is smaller man or equal to Vac, coupling the interface surface of the matrix absorber to any selected interface surface of the accumulator, wherein the interface surface of the matrix absorber intersects the output path of the accumulator such that it can contact and absorb the initial fluid volume Vma that elutes from the accumulator, providing an elution fluid source, coupling the elution fluid source to any other interface surface of the accumulator wherein the elution fluid source and the interface surface of the accumulator are in fluid communication, introducing an elution fluid having a volume Vef from the elution fluid source into the accumulator through any other interface surface of the accumulator, wherein Vef is greater than Vac, and wherein the
  • a matrix absorber can be used.
  • a matrix absorber is an additional self-wi eking monolith positioned near or in contact with an outlet surface of the accumulator monolith after the sample and wash fluids have been wicked through the accumulator.
  • the matrix absorber's self-wicking monolith can be any monolith mat has sufficient self-wicking properties and can be formed into different geometries, or combinations thereof.
  • the monolith can be a monolith as described in U.S. Patent Application Serial No.: 14/549,055, the disclosure of which is incorporated by reference in its entirety.
  • the accumulator can have an exit site that flows past or around the matrix absorber, i.e.
  • the bypass can be a tube that passes through the center of a monolith ring.
  • the matrix absorber monolith can be in contact with an outlet tube. The matrix absorber can absorb the first fluid to flow into the tube, but after it is full, all other fluid bypasses it.
  • the matrix absorber has a fluid capacity volume, e.g., Vma, and can have all or a portion of the Vma being unused or dry.
  • Vma fluid capacity volume
  • the matrix absorber can wick me first fluid, or soak up the first fluid, exiting the accumulator.
  • the absorbed fluid is typically the sample matrix fluid or the wash fluid in the accumulator.
  • a small volume of fluid elutes (eluate) containing a high concentration of the released target analyte.
  • the small volume of fluid can be about 2, 3, 4, S, 6, 7, 8, 9, 10, 11, 12, 13, 14, IS, 20, or about 25% of the accumulator capacity volume, or Vac.
  • This small volume is similar to an eluted "peak'' in chromatography.
  • the fractions of fluid eluting before and after this small volume can contain much less concentrations of analyte. If these fractions containing no target analyte are collected together with the analyte peak, the target analyte is diluted. The dilution can be substantial and is undesirable if high analyte concentration is required
  • the matrix absorber is a volume of absorbent material made from self-wicking macroporous monolith or other suitable absorbent material.
  • the matrix absorber can be placed in the outlet fluid path of a concentrator and can absorb a well-defined initial volume of eluate.
  • the matrix absorber can have at least one internee surface which can be coupled to any selected internee surface of the accumulator monolith or placed in contact with an outlet tube or channel.
  • the fluid capacity of the matrix absorber can be less than the fluid capacity of the accumulator monolith, e.g., the fluid capacity volume (Vma) is smaller than or equal to Vac.
  • the fluid capacity of the matrix absorber can be 110, 105, 102, 101, 100, 99, 98, 95, 92, 90, 88, 85, 82, 80 or about 75% that of the accumulator capacity. These values can define a range, such as about 80 to about 95%.
  • the matrix absorber can have a fluid capacity of about, more than about, or less than about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 85, 90, 95, 100, 110. 120, 130, 140, 150, 200, 300, 400 or about 500 uL. These values can define a range, such as about 10 to about 30 ⁇ ,. In some embodiments, the absorber can absorb fluid only until it is full.
  • the matrix absorber does not absorb additional fluid and the fluid exiting the accumulator, e.g., the eluate, can flow around die matrix absorber, through die bypass channel for example, as opposed to flowing through it
  • the matrix absorber can also have an outlet port at die end of a bypass channel for die elution fluid, or eluate, or both that have not been absorbed, to flow around die matrix absorber after it has filled.
  • the outlet port can be configured to allow die eluate to be transferred or flow directly into a collection vial.
  • the elution fluid can be introduced in more than one portion, e.g., 2, 3 4, or more portions.
  • the elution fluid can be introduced in a first portion having a volume Vefl from an elution fluid source into the accumulator through one interface surface of the accumulator, wherein Vefl is less than or equal to Vac.
  • the fluid that elutes from die accumulator, i.e., is displaced from die accumulator by this first portion of elution fluid can be absorbed in die matrix absorber and therein trapped.
  • a second portion of elution fluid can be introduced having a volume Vef2 from the elution fluid source into die accumulator through the same or any other interface surface of the accumulator, wherein Vefl + Vef2 is greater than Vac
  • the fluid that elutes from the accumulator can include a small volume of fluid or cluate that contains the released target analyte mat does get absorbed in the matrix absorber.
  • the volume of eluted fluid from Ve£2 that does not get absorbed in the matrix absorber can be collected from the bypass channel outlet of the matrix absorber.
  • the eluate fraction of the fluid can also be collected.
  • a first portion, or portions, of the elution fluid can be introduced into the accumulator to displace a similar first volume, or volumes, of fluid from the accumulator where the displaced fluid touches and can be wicked into the matrix absorber and trapped therein, wherein the first volume, or volumes, of displaced fluid can contain less than about 20, IS, 10, 5, 2 or about 1% of the analyte contained in the accumulator.
  • a second portion, or further portions, of the elution fluid can be introduced into the accumulator to displace a second volume, or further volumes, of fluid from the accumulator, this second volume, or further volumes, can be not absorbed by the saturated matrix absorber and can therefore pass through the output of the matrix absorber, wherein the second volume, or further volumes, of displaced fluid can contain more than about SO, 60, 70, 80, 90, 95, 99 or about 100% of the analyte contained in the accumulator.
  • the present disclosure also relates to a concentrator.
  • the concentrator can be a device that can accept a sample containing a target analyte as input.
  • the output of the concentrator can be a solution containing the target analyte at a higher concentration and in a higher purity than it was present in the sample.
  • the total amount of target analyte in the output solution can be equal to or less than the amount in the sample.
  • the volume of the output solution can be less than the volume of the sample.
  • the process of concentration can include
  • the present disclosure relates to a concentrator for
  • the concentrator including an accumulator comprising a first self-wicking porous polymer monolith, the accumulator having a plurality of interface surfaces, and a fluid capacity volume (Vac), wherein the accumulator has an affinity for the analyte.
  • the concentrator can further include a sink, wherein the sink comprises a second self- wicking porous polymer monolith or other suitable absorbent' material, the sink having at least one interface surface, and a fluid capacity volume (Vfs), wherein the at least one interface surface of the sink and any interface surface of the accumulator are coupled together in fluid communication and configured to facilitate wi eking of fluid across the coupling.
  • the coupling between die accumulator and sink can be a mechanical junction.
  • Fluid junctions between monolith zones do not necessarily have to be covalent.
  • a zone does not necessarily need to be comprised of a single piece of monolith.
  • Monolith blocks can be held together by external compression or by interlocking geometries, e.g., See Figure 15.
  • the monolith surfaces within the interface can be held together such that there is physical contact along at least part of the interface surface.
  • the contact area should be at least equal to the cross sectional area of the smallest monolith piece at the junction.
  • the extent of contact can be increased by using molds with smooth surfaces, which monolith pieces closely match during curing.
  • Smooth surfaces can also be generated by other means such as cutting with blades, die cutter, laser, water knife or other methods that do not exert crushing force at the edge of the cut
  • the extent of contact can also be increased by using a monolith with sufficient flexibility that it will conform to the interface surface of the other monolith without crushing or other detreimental effects.
  • the concentrator can further include an elution fluid reservoir configured to store elution fluid until the time of use.
  • the reservoir can form a fluidic coupling with die
  • the pressured elution fluid can be delivered with a force of less than 1 or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, SO or about 100 psi. These values can be used to define a range, such as about 2 to about 5 psi.
  • the concentrator can further include an inlet and outlet, which may be the same port, for use introduction of sample and the collection of concentrated target analyte.
  • the elution fluid dispenser can be configured to attach to the interface port of the housing and to establish fluid communication between the elution fluid reservoir and at least one interface surface of the accumulator.
  • the concentrator can further include a housing, sleeve or both, wherein the housing or sleeve can be configured to form a fluid-tight mechanical seal with a surface of the
  • a monolith element may be held in a sleeve made of an elastomeric material, such as silicone rubber.
  • the outer surface of the sleeve can be shaped to interface with the monolith enclosure.
  • the sleeve can be made with an internal surface geometry mat matches, or nearly matches, the shape of the monolithic accumulator and can include the accumulator being in contact with at least some portion of the inner surface of the sleeve along the length of the accumulator, except for the locations of at least two of the interface surfaces.
  • the accumulator can be positioned within the sleeve such mat the tip is flush or recessed in the sleeve.
  • the accumulator-sleeve interface can be tapered and matched such that mere is a tight junction between die two of mem along the entire interface surface that prevents the migration of fluid around the accumulator element during use.
  • the angle of the taper can be oriented such that any net force created upon the accumulator by die injection of pressurized fluid, such as elution fluid, can be directed such that the sleeve-monolith interface is strengthened. In other words, the accumulator can be pushed deeper into the conical shape of die sleeve and contact can be increased.
  • the sleeve is preferably made of a material with some compliance so that, when the accumulator .is pushed into die sleeve during elution with pressurized fluid, geometric irregularities in the accumulator surface will not create gaps around the accumulator that fluid could migrate through.
  • die accumulator can be sealed by the sleeve and/or housing such that die elution fluid inlet and eluate/elution fluid outlet are the interfaces capable of fluid flow.
  • the inlet and outlet are die only interfaces capable of fluid flow into and out of the concentrator.
  • the strength of the seal can be such that die resistance to flow through the monolith is less than resistance to flow through any gap between the
  • accumulator and seal For non-pressurized flow, e.g., wicking, no sleeve or housing seal is required.
  • pressurized fluid can exit the accumulator. The flow can exit and reenter the accumulator closer to the outlet. Any accumulator material between the exit and re-entry point not exposed to the pressurized fluid can reduce the efficiently of the concentrator.
  • the sleeve may be made using hydrophobic material, such as polyvinyl chloride or fluorosilicone, such that water will be less likely to migrate along the accumulator-sleeve interface.
  • a monolith element can be held in a sleeve that is made from a material that is similar to the monolith, e.g., a polymer.
  • the sleeve is made from an incompletely cured acrylic polymer.
  • the acrylic part can be fabricated using stereo-lithography.
  • the polymer based sleeve can react with the monolith as it polymerizes such that the monolith and sleeve are cross-linked or mechanically interlaced when the polymerization was complete. Suitable sleeve materials could be methacrylate-based.
  • the housing can be covalently bonded to the first self-wi eking porous polymer monolith, or accumulator monolith.
  • the housing can further include an external port at, near or adjacent to one of the interface surfaces of the accumulator for receiving fluids.
  • the accumulator is configured to selectively capture and release polynucleic acids.
  • the capacity of the accumulator can have a capacity of at least 1
  • the collection container may be another piece of monolith, a vial, or the inlet of another fluidic system.
  • a system can use one or more of the concentrators to selectively purify, concentrate, etc. one or more target analytes.
  • a first accumulator can be selective to a class of compounds.
  • a second accumulator can be selective for a subset of the compounds.
  • a first accumulator can be selective for a target analyte but can also bind non-target andyte components.
  • a second accumulator can be selective for the target analyte and not the non-target analyte components which bind to the first accumulator.
  • first and socond concentrators in series can be used to achieve a higher net concentration factor, purity, etc. than a single concentrator would be capable of while still maintaining a practical sample absorption rate.
  • the first accumulator can have a large Vacl and a relatively large cross-sectional area to allow for rapid flow rate.
  • the first concentrator can achieve, for example, a concentration factor of 2x, 3x, 4x, Sx, 6x, 7x, 8x, 9x or about lOx.
  • An amount of elution fluid Veil smaller man the sample size can be used to elute the analyte to second accumulator.
  • the second accumulator can have a smaller capacity volume, Vac2 « Vacl .
  • the second concentrator can achieve, for example a concentration factor of 2x, Sx, 7x, lOx, lSx, 20x, 30x, 40x, SOx or about lOOx.
  • the present disclosure relates to a method for concentrating an analyte, or a class of analytes, in a fluid matrix including providing a first concentrator comprising a first self-wicking porous polymer monolith, the monolith comprising a first accumulator, the first accumulator including a plurality of interface surfaces, and a fluid capacity volume (Vacl), providing a first sink comprising a second self-wicking porous polymer monolith, die sink having an interface surface, and a fluid capacity volume (Vfsl), coupling any interface surface of the first accumulator to the interface surface of the first sink, wherein at least one interface surface of the first accumulator and the interface surface of the first sink are in fluid communication and configured to facilitate wicking of fluid across the coupling, wicking the fluid matrix containing the analyte into the first accumulator through any interface surface of the first accumulator; and capturing the analyte in the first accumulator.
  • the method can further include wicking the fluid matrix in excess of the Vacl from the first accumulator into the first sink, and retaining the excess fluid matrix in the first sink.
  • the method can also former include wicking one or more wash fluids each having a volume Vwl into the first accumulator through any interface surface of the first accumulator, wherein Vwl is greater man Vacl .
  • the target analyte(s) can be further processed using one or more additional accumulators.
  • the method can further include uncoupling the first accumulator from the first sink, providing a second concentrator comprising a third self-wicking porous polymer monolith, the monolith including a second accumulator and a second sink, the second accumulator including a plurality of interface surfaces, and a fluid capacity volume (Vac2), the second sink comprising a fourth self-wicking porous polymer monolith, the second sink having an interface surface, and a fluid capacity volume (Vfs2), and coupling any interface surface of the first accumulator to any interface surface of the second accumulator, wherein the interface surface of the first accumulator and the interface surface of the second accumulator are in fluid communication.
  • the selection of the third and/or fourth self-wicldng porous polymer monolith is similar to the monoliths as provided herein, including, for example,
  • a first elution fluid can be used to transfer the target analyte(s) to the second accumulator.
  • the method can further include providing a source of a first elution fluid, coupling the first elution fluid source to any selected interface surface of the first accumulator, introducing (or dispensing or injecting) a first elution fluid having a volume Vefl from the first elution fluid source through the selected interface surface of the first accumulator through the second accumulator and into the second sink, wherein Vefl is greater than Vacl + Vac2, and wherein the first elution fluid releases the analyte from the first accumulator, and capturing the analyte in the second accumulator.
  • the first accumulator can thereafter be removed and the second accumulator can be optionally washed.
  • the target analyte(s) can then be removed using a second elution fluid.
  • the method further including uncoupling the first accumulator from the second accumulator, uncoupling the second accumulator from the second sink, providing a source of a second elution fluid, coupling the second elution fluid source to any selected interface surface of the second accumulator, introducing a second elution fluid having a volume Vef2 from the second elution fluid source into the second accumulator through the selected interface surface of the second accumulator, wherein Vef2 is greater than Vac2, and wherein the second elution fluid releases the analyte from the second accumulator, and collecting the analyte from any other interface surface of the second accumulator.
  • the selection of the second elution fluid is similar to the first elution fluid as provided herein, including, for example, the fluid volumes and
  • the first and the second sink can be the same sink.
  • the sink can be coupled / uncoupled to the different accumulators.
  • the first and the second elution fluid is the same fluid.
  • the monolith binding properties may be different.
  • a matrix absorber can also be used.
  • the method can further include uncoupling the first accumulator from the second accumulator, uncoupling the second accumulator from the second sink, providing a matrix absorber including a fifth self-wicking porous polymer monolith, the matrix absorber having an interface surface, a bypass channel with an outlet, and a fluid capacity volume (Vma), wherein Vma is smaller than or equal to Vac2, coupling the interface surface of the matrix absorber to any selected interface surface of the second accumulator, wherein the interface surface of the matrix absorber and the selected interface surface of the second accumulator, providing a source of a second elution fluid, coupling the second elution fluid source to any other interface surface of the second accumulator, introducing a second elution fluid having a volume Vef2 from the second elution fluid source into the second accumulator through the any other interface surface of the second accumulator, wherein Vef2 is greater than Vac2, and wherein the second elution fluid
  • the present disclosure also relates to a method and system for concentrating an analyte in a fluid matrix including two or more concentrators or accumulators.
  • the system can include a first accumulator including a first self-wicking porous polymef monolith, the accumulator having a plurality of interface surfaces, and a fluid capacity volume (Vacl ); a first sink including a second self-wicking porous polymer monolith, the sink having an interface surface, and a fluid capacity volume (Vfsl), a second accumulator including a third self-wicking porous polymer monolith, the second accumulator having a plurality of mterface surfaces, and a fluid capacity volume (Vac2), a second sink including a fourth self-wicking porous polymer monolith, the second sink having an mterface surface, and a fluid capacity volume (Vfs2), wherein at least one interface surface of the first accumulator and the interface surface of the first sink, at least one interface surface of the second accumulator and the
  • the system can further include a first edition fluid configured to release the analyte from the first accumulator.
  • the system can further include a second elution fluid configured to release the analyte from the second accumulator.
  • the system can further include a niatrix absorber, the matrix absorber having a fifth self-wicking porous polymer monolith, the matrix absorber having an interface surface, a bypass channel, and a fluid capacity volume (Vma), wherein Vma is smaller man or equal to Vac2, wherein the interface surface of the niatrix absorber is configured for fluid communication with any interface surface of the accumulator of the second concentrator.
  • Vma fluid capacity volume
  • the accumulator and the sink can be contained in a single monolith having different zone, i.e., an accumulator zone and a sink zone.
  • Multi-zone monoliths, and the preparation thereof, is disclosed in U.S. Patent Application Serial No.:
  • FIG. 1 A shows a block diagram of concentrator 100 made of accumulator 110 coupled to sink 120 configured to concentrate analyte from a fluid sample ISO.
  • Accumulator 110 is made of a functionalized or derivatized self-wicking porous polymer monolith having an interface surface 112, an interface surface 114 and a fluid capacity volume equal to Vac.
  • Sink 120 is made of self-wicking porous polymer monolith having an interface surface 122 and a fluid capacity volume equal to Vfs.
  • Fluid sample 150 consisting of analyte 152 and fluid matrix 154 is wicked into accumulator 110 via interface surface 112 and continues wicking through the accumulator 110 and into sink 120.
  • the coupling between accumulator 110 and sink 120 is configured to facilitate wicking from the accumulator 110 to the sink 120 by a fluid sample 150 and can be held in this configuration by a compressive force.
  • the analyte is captured on the internal pore surfaces of the accumulator 110.
  • the analyte and some fluid matrix 152 are contained within the monolith pores of accumulator 110.
  • the volume of fluid sample 150 is greater man the fluid capacity volume of accumulator 110 and is less than the fluid capacity volume Vfs of sink 120.
  • Most of the fluid matrix wicks into the sink 120, which can be several fluid volumes larger than accumulator 110 and is typically able to absorb at least the portion of fluid matrix volume 154 exceeding the capacity of accumulator 110.
  • the sink 120 is uncoupled from accumulator 110 and elution fluid 1S6 is injected into accumulator 110.
  • the injection of elution fluid 1S6 into the accumulator 110 elutes the analyte 152 as part of output fluid 160, which also contains elution fluid 156 and fluid matrix 154.
  • the volume of elution fluid Vef is greater than the fluid capacity Vac of accumulator 110.
  • FIG. 2 shows a flowchart for a method 200 of concentrating analyte for the system shown in Figures 1 A-1C.
  • accumulator 110 made of self-wicking porous polymer monolith having an interface surface 112, an interface surface 114 and a fluid capacity Vac is provided.
  • a sink 120 made of a self-wicking porous polymer monolith having an interface surface 122 with a fluid capacity Vis is also provided.
  • the interface surface 114 of accumulator 110 is coupled to the interface surface 122 of the sink 120 to form a fluidic junction and forming concentrator 100.
  • a compressive force can be applied to form the junction.
  • fluid sample 150 of volume Vs containing analyte 152 and fluid matrix 154 is wicked into concentrator 100 via interface surface 112 of accumulator 110, through the body of accumulator 110 and into sink 120, where Vs > Vac.
  • analyte 152 from fluid sample ISO is captured in accumulator 110 as the sample 150 passes through accumulator 110.
  • Fluid matrix 154 in excess of accumulator 110 fluid capacity Vac is wicked into sink 120 but first passes through accumulator 110.
  • sink 120 is uncoupled from accumulator 110.
  • a source of elution fluid 156 is coupled to any surface of accumulator 110 as shown in Figure 1 C.
  • elution fluid 156 of volume Vef is injected or introduced into accumulator 110 via coupling to the accumulator 110, where Vef > Vac.
  • analyte 152 and elution fluid 156 are ejected as output 160 from accumulator 110.
  • FIG. 3A-3D show a block diagram of an embodiment of a system configured to concentrate analyte from a fluid sample. The description of the components and operation of Figures 1 A and IB also apply to Figures 3A and 3B.
  • Figure 3C shows wash fluid 158 being dispensed into concentrator 100 via interface surface 112 resulting in wash fluid 158 displacing fluid matrix 154 out of accumulator 110 and into sink 120. After the dispensing of wash fluid 158 into concentrator 100, then sink 120 is uncoupled from accumulator 110 , as shown in Figure 3D.
  • Figure 3D shows elution fluid 156 being injected into accumulator 110 resulting in at least some of the analyte 152 in accumulator 110 being ejected in output 160, which will include elution fluid 156 and wash fluid 158.
  • Figure 4 shows a flowchart for a method 400 of concentrating analyte for the system shown in Figures 3A-3D. Method steps 202-210 from method 200 from Figure 2 are performed with respect to Figures 3A and 3B before proceeding to block 412.
  • a volume Vw of wash fluid 158 is wicked into accumulator 110 via interface surface 112, where Vw > Vac.
  • the fluid matrix 154 in accumulator 110 is displaced into sink 120. Wash fluid 158 in excess of accumulator 110 fluid capacity Vac is wicked into sink 120.
  • sink 120 is uncoupled from accumulator 110.
  • a source of elution fluid 156 is coupled to any surface of accumulator 110.
  • elution fluid 156 of volume Vef is injected into accumulator 110 via the coupling to the accumulator 110, wherein Vef > Vac.
  • analyte 152 and elution fluid 156 are ejected from accumulator 110.
  • Figures 5A-5D show a block diagram of an embodiment of a system configured to concentrate analyte from a fluid sample.
  • the description of the components and operation of Figures 1 A and IB also apply to Figures 5A and 5B.
  • Matrix absorber 540 is made of a self-wicking porous polymer monolith having an interface surface 542 and a bypass channel 544 and forming concentrator 530. Matrix absorber 540 mterface surface 542 and interface surface 112 of accumulator 110 are coupled by a fluidic junction. Elution fluid 156 is to be injected into any other surface of accumulator 110. The volume of elution fluid Vef is greater than or equal to the fluid capacity Vac of accumulator 110.
  • Figure 6 shows a flowchart for a method 600 of concentrating analyte for the system shown in Figures 5A-5D. Method steps 202-210 from method 200 from Figure 2 are performed with respect to Figures 5A and 5B before proceeding to block 612.
  • sink 120 is uncoupled from accumulator 110.
  • matrix absorber 540 made of a self-wicking porous polymer monolith is provided having an interface surface 542 and a bypass channel 544.
  • interface surface 542 of matrix absorber 540 is coupled to interface surface 112 of accumulator 110.
  • a source of elution fluid 156 is coupled to any other surface of accumulator 110.
  • elution fluid 156 of volume Vef is injected via the elution fluid coupling into accumulator 110, where Vef > Vac.
  • analyte 154 and elution fluid 156 are ejected from accumulator 110 via bypass channel 544 of matrix absorber 540.
  • Figures 7A-7E show a block diagram of an embodiment of a system configured to concentrate analyte from a fluid sample.
  • the description of the components and operation of Figures 1 A and IB also apply to Figures 7A and 7B.
  • Figure 7C shows wash fluid 158 being dispensed into accumulator 110.
  • Figure 7D shows matrix absorber 740 made of a third self- wicking porous polymer monolith having an interface surface 742 and bypass channel outlet 744.
  • Figure 8 shows a flowchart for a method 800 of concentrating analyte for the system shown in Figures 7A-7E.
  • Method steps 202-210 from method 200 from Figure 2 are performed with respect to Figures 7A and 7B before proceeding to block 812.
  • a volume Vw of wash fluid 158 is wicked into accumulator 110 via the interface surface 112, where Vw > Vac.
  • fluid matrix 154 in accumulator 110 is displaced into sink 120. Wash fluid 158 in excess of accumulator 110 fluid capacity Vac is wicked into sink 120.
  • sink 120 is uncoupled from accumulator 110.
  • matrix absorber 740 made of a self-wicking porous polymer monolith is provided having an interface surface 742 and a bypass channel 744.
  • interface surface 742 of matrix absorber 740 is coupled to interface surface 112 of accumulator 110.
  • a source of elution fluid 156 is coupled to any other surface of accumulator 110.
  • elution fluid 156 of volume Vef is injected via the elution fluid coupling into accumulator 110, where Vef > Vac.
  • analyte 152 and elution fluid 156 are ejected from accumulator 110 via bypass channel outlet 744 of matrix absorber 740.
  • Figures 9A-9D show a block diagram of an embodiment of a system configured to concentrate analyte from a fluid sample.
  • the description of the components and operation of Figures 1 A and IB also apply to Figures 9A and 9B.
  • Figure 9C shows a first portion of elution fluid 156 to be injected into accumulator 110.
  • Figure 9D shows a second portion of elution fluid 156 to be injected into accumulator 110.
  • Figure 10 shows a flowchart for a method 1000 of concentrating analyte for the system shown in Figures 9A-9D. Method steps 202-210 from method 200 from Figure 2 are performed with respect to Figures 9A and 9B before proceeding to block 1012.
  • sink 120 is uncoupled from accumulator 110.
  • a source of elution fluid 156 is coupled to any surface of accumulator 110.
  • a first portion of elution fluid 156 of volume Veil is injected via the elution fluid coupling into accumulator 110, where Vefl ⁇ Vac.
  • fluid matrix 154 of volume Vefl is ejected from accumulator 110 and collected separately or discarded.
  • a second portion of elution fluid 156 of volume Vef2 is injected via the elution fluid coupling into accumulator 110, where Vefl + Ve£2 > Vac.
  • analyte 152 and elution fluid 156 with volume Vef2 is ejected from accumulator 110 and collected separately.
  • Figures 11 A-l 1 H show a series of diagrams for the operation of a system of self- wicking monoliths for analyte cleanup and concentrator.
  • accumulator 110 is coupled with sink 120 to form a fluidic coupling.
  • Accumulator housing or sleeve 1116 forms a liquid-tight seal with the loading cup 1130.
  • Fluid sample 150 consisting of analyte 152 and fluid matrix 154 is contained in a transfer device 1140 such as a pipettor.
  • fluid sample 150 is transferred into sample cup 1130 and is wicked into the inlet surface of accumulator 110.
  • the sample 150 passes through accumulator 110, where analyte 152 is bound to the interior surfaces.
  • Matrix fluid depleted of analyte 1151 is further wicked into sink 120. Wicking will continue until the sample fluid 150 is exhausted or until the sink 120 is full.
  • a wash solution 1S8 is added to die sample cup 1130.
  • wash fluid 158 carries any matrix fluid, 1151 out of accumulator 110 and into sink 120, and leaves analyte 152 bound to accumulator 110 interior pore surfaces. As wash fluid 158 wicks into sink 120 and pushes matrix fluid 1151 further into sink 120, the portion 1159 of sink 120 closest to accumulator 110 receives wash fluid 158.
  • accumulator 110 in housing 1116 is coupled with outlet fitting 1190 and elution fluid dispenser 1170, similar to a syringe.
  • the elution fluid dispenser includes elution fluid 156 held in a container 1160 which can be ejected by plunger 1180.
  • the outlet fitting 1190 is optional, but serves the role of generating small droplets that can readily be collected.
  • a coupling is formed between the housing 1116 and the elution fluid dispenser 1170.
  • a coupling is also formed between the housing 1116 and the outlet 1190, if present
  • the elution fluid dispenser plunger is depressed, injecting elution fluid 156 into accumulator 110.
  • Eluate 160 droplets form on the tip of outlet 1190 and drip into collection tube 1165.
  • Figures 12A-12H show a series of diagrams for the operation of a system of self- wicking monoliths for analyte concentration.
  • the description and operation of the coriccntrator shown in Figures 12A and 12B is the same as previously discussed with regard to Figures 11 A and 1 IB.
  • sample cup 1130 is uncoupled from accumulator 110.
  • Sink 120 is uncoupled from accumulator 110.
  • accumulator 110 in housing 1116 is brought into proximity with the elution fluid dispenser 1170 and the matrix absorber 1290.
  • Elution fluid dispenser 1170 includes elution fluid 156 held in a container 1160 which can be ejected by depressing plunger 1180.
  • the matrix absorber 1290 has a fluid capacity Vma about the same or smaller than the fluid capacity Vac of accumulator 110 and includes bypass channel 1292 (shown in Figure 12F).
  • a coupling is formed between accumulator housing 1116 and elution fluid dispenser 1170.
  • the outlet of accumulator 110 is coupled with the matrix absorber 1290.
  • elution fluid 1S6 is injected into accumulator 110 by depressing plunger 1180.
  • the initial eluate contains residual matrix fluid 154 and little or no analyte 152.
  • the initial eluate is absorbed by matrix absorber 1290 until the fluid capacity of matrix absorber 1290 is reached.
  • elution fluid 156 continues to be injected through accumulator 110 after matrix absorber 1290 is saturated. This eluate 160 moves through the bypass channel 1292 in matrix absorber 1290 and drips into collection tube 1265.
  • Figure 13 shows a cross sectional view of an accumulator and sleeve assembly.
  • Accumulator 110 is partially covered by sleeve 116.
  • Fluid barrier 105 between accumulator 110 and sleeve 116 provides a liquid tight fluid barrier so that no fluid can flow in between accumulator 110 and sleeve 116.
  • Interface surface 112 of accumulator 110 is the point of introduction for a fluid sample.
  • Portion 103 of accumulator 110 mat protrudes above the sleeve 116 is available to form a fluidic junction with a sink element or other portion of a wicldng fluidic system.
  • Portion 103 of accumulator 110 can play a mechanical role and may not capture analyte unless the amount of analyte loaded exceeds the capacity of the lower part of
  • accumulator 110 After accumulator 110 has captured analyte from a fluid sample wicked into the accumulator via interface surface 112, then the upper portion 103 of accumulator 110 can be sheared off at break point 118, adjacent to surface 107. Surface 107 can form a fluidic seal with an elution assembly, such as the one shown in Figures 17A-17D, before elution fluid is injected into the top of accumulator 110.
  • an elution assembly such as the one shown in Figures 17A-17D
  • Figure 14 shows a perspective view of an accumulator and seal assembly, such as the one shown in Figure 13.
  • Figure 15 shows a cross sectional view of a sink coupled to an accumulator, such as used in the shuttle-design concentrator of Figures 17A-17D.
  • Accumulator 100 may be the same or similar to accumulator 110 shown in Figures 13 and 14.
  • Junction or interface 145 is a fluidic junction between sink 120 and accumulator 100. Interface 145 requires physical contact between the separate monolith components. Fluid mat wicks into accumulator 100 will continue into sink 120. As sink 120 wicks up additional fluid, it passes through accumulator 110 before entering sink 120.
  • Figure 16 shows a perspective view of a sink coupled to an accumulator, such as the one shown in Figure IS.
  • Figures 17A-17D show the elements of a self-contained wicking concentrator 1700. This single-use, disposable unit does not use electrical power. The unit is used as described in Examples 1 and 2.
  • Figure 17A shows the concentrator orientation as the sample 1750 is introduced via loading cup 1722 and absorbed through accumulator 1710 and into sink 1720.
  • Accumulator 1710 is partially covered by sleeve 1716, and the sample cup forms a fluidic coupling with the sleeve 1716, preventing leakage of fluid sample 17S0.
  • Figure 17B shows the system in the elution orientation with the shuttle 1712 moved from the loading position on the sink side to the elution position on the other side of the system.
  • the accumulator 1710 has been cut into two parts.
  • the upper portion 1711 of accumulator 1710 is still coupled to sink 1720 and is no longer involved in further processing.
  • Pierceable seal 1726 is positioned above tubular blade 1728.
  • Activator knob 1724 is in the upper position.
  • Figure 17C shows the positon of the fluid reservoir after activation.
  • the activator knob 1724 and the fluid reservoir 1758 have been lowered to seal against the sleeve 1716, and the tubular blade 1728 has pierced the pierceable seal 1726.
  • Figure 17D shows the system after elution is complete.
  • the plunger assembly 1730 has been depressed to force the elution fluid 1756 through accumulator 1710.
  • the initial eluate has also wicked into matrix absorber 1740.
  • eluate 1760 will flow through the bypass channel 1744 of matrix absorber 1740, emerge from the outlet tube 1745, and be collected in collection tube 1770.
  • Figures 18A-18D show the key design elements of a self-contained wicking concentrator 1800.
  • This single-use, disposable unit does not use electrical power.
  • the unit is used as described in Example 4.
  • This design contains an alternative mechanical system to the one shown in Figures 17A-17D mat uses a ' guillotine ' mechanism to isolate the accumulator from the sink.
  • the components including 1802, sample vial; 1805, tubular steel cutter, 1807, elution fluid; 1810, accumulator, 1820, sink; 1822, hollow shaft within sink; 1820, sink; 1825 sink frame; 1826, pierceable seal; 1830, seal piercer, 1845, mechanical fluid junction; 1860, output; 1865, collection tube; 1880, plunger, and 1890, elution fluid reservoir housing.
  • Figure 18A shows the loading orientation after the sample, contained in the sample vial 1802, has been wicked into the device through the accumulator 1810 and into the sink 1820.
  • Figure 18B shows die system in the elution orientation before activation.
  • Figure 18C demonstrates the positon of the fluid reservoir after activation.
  • the elution fluid reservoir housing 1890 has been lowered and locked into its activated position and the tubular steel cutter 180S has been lowered to cut through the edges of the accumulator 1810 and seal against the sink frame 1825 to form a fluidic junction 1845 that isolates the accumulator 1810 from the sink 1820.
  • Figure 18D illustrates the system during elution.
  • the plunger 1880 has been depressed to force the seal piercer 1830 through the pierceable seal 1826 and to pressurize the elution fluid 1807 so it flows through the steel tubing 1805, through the accumulator 1810 and into the collection tube 1865.
  • Figure 22A shows a block diagram of a first concentrator 2200 made of a self- wi eking monolith accumulator 2210 and a monolith sink 2220 held together to create a fluidic junction between them.
  • a fluid sample 2250 is introduced to the accumulator 2210.
  • Figure 22B shows the state of the components after fluid sample 2250 has been wicked into the first concentrator 2200. As the fluid sample 2250 wicks through the first accumulator 2210 and into the first sink, 2220, analyte 2252 is captured in the first accumulator 2210 and the spent fluid matrix 2254 wicks into sink #1 2220.
  • FIG 22C shows a block diagram of a second concentrator 2230 made of a self- wi eking monolith accumulator #22232 and a monolith sink #22234 held together to create a fluidic junction between mem.
  • Accumulator #1 2210 has been separated from sink #1 2220 and is coupled to concentrator #22230.
  • An elution fluid source 2204 containing an elution fluid 2256 can be coupled to accumulator #1 2210.
  • Figure 22D shows the state of the components after elution fluid 2256 has been wicked through accumulator zone 2210 and released analyte 2252.
  • Accumulator #1 2210 is shown removed. The analytes were carried into accumulator #22232 of concentrator #22230 and adsorbed to the pore surfaces. Depleted elution fluid 2256 continued through accumulator #22232 and into sink #22234. After the transfer of analyte 2252 into accumulator zone 2232, concentrator #22230 is ready for further processing, such as washing or isolation of accumulator zone 2232 by cutting it away from sink #22234.
  • Figure 23 shows an exemplary flowchart for an exemplary method of concentrating a target analyte in a system shown in Figures 22A-22D.
  • a first concentrator 2200 made of a first monolith accumulator 2210 and a first monolith sink 2220 are provided.
  • a fluid sample 2250 is wicked through accumulator 2210 of concentrator 2200.
  • a target analyte 2252 is captured from the fluid sample 2250 in accumulator 2210 of concentrator 2200.
  • accumulator 2210 is uncoupled from sink 2220 and further processing can continue without sink 2220.
  • a second concentrator 2230 made of a second monolith with an accumulator 2232 and a monolith sink 2234 are provided.
  • accumulator 2232 of concentrator 2230 is coupled to the first accumulator 2210 of the first concentrator 2200.
  • a source of elution fluid 2250 is coupled to the first accumulator 2210 of concentrator 2200.
  • elution fluid 2250 is wicked through the first accumulator 2210 of concentrator 2200, through the second accumulator 2232 of the second concentrator 2230 and into the second sink 2234 of concentrator 2230.
  • analyte is captured in
  • a DNA sample was concentrated using a manual concentrator apparatus.
  • a SOO uL DNA sample was obtained from extraction of a buccal cell sample.
  • the sample matrix contained 20 mM TRIS pH 7.5.
  • the concentration of DNA in the sample was about 1 ng/uL.
  • the sample had been prepared using an industry standard purification process.
  • the concentrator apparatus included a concentrator cartridge for containing the accumulator monolith, etc., a cartridge stand to hold the apparatus in place (not shown for clarity), and a collection tube, as shown in Figures 17A-17D.
  • the concentrator apparatus was assembled in stages. For example, the accumulator monolith was rjolymerized, washed, and dried in a separate process.
  • the monolith was prepared by polymerization of a polymer mixture of EGDMA:HEMA 2:1 with 1.5% TBAMA and 1% DMAP by weight This mixture was combined at a 1 :3 ratio with a mixture of 19:1 octanolrwater. 50 ul of this mixture was dispensed into a 1000 ⁇ .
  • the mixture was polymerized for 20 minutes under UV irradiation at a power of 0.6 -0.7 mW/cm 2 for 20 minutes. After polymerization, the polymer was washed extensively with isopropanol, methanol and water drawn through by vacuum and men dried at -26 mM Hg vacuum at 40°C for 16 hours.
  • the accumulator has an affinity to DNA and can capture and retain DNA from the sample by electrostatic interaction.
  • the volume capacity of the accumulator monolith was about 37 ⁇ L ⁇ About 60% of the total space, e.g., 33 ⁇ , or about 25 uL of fluid capacity, was used for DNA capture.
  • the portion of the total space used for fluid capacity can be about, more than about, or less than about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 85, 90% or about %. These values can also define a range, such as about 50 to about 70%.
  • the remainder of the space, if any, forms the fluid interface with the sink.
  • the sleeve is sufficiently soft or pliable to allow the sleeve to expand to accommodate, securely fit and seal the accumulator monolith.
  • the sleeve was men inserted into a shuttle. The portion of me accumulator that extends beyond the sleeve will be broken away when the shuttle is used to move the accumulator from sample capture to sample elution.
  • the sink monolith was polymerized, washed, and dried in a separate process.
  • the sink was fabricated in two symmetrical halves by polymerization of a polymer mixture of EODMA:HEMA 2: 1 with 1% DMAP by weight. This mixture was combined at a 1 :3 ratio with a mixture of 19: 1 octanol water. 800 ⁇ , of this mixture was dispensed into an open-face fluorosUicone mold and irradiated with 365 ran UV light for 20 minutes at an intensity of about 1 uW/cm 2 . After polymerization, the sink halves were extensively washed by soaking in IP A, and then Methanol bams. The total fluid capacity of the sink was about 1.2 mL.
  • the apparatus was built up by placing half of the sink in the concentrator base.
  • the shuttle-sleeve-accumulator was men placed in the base.
  • the portion of the accumulator that sticks out of the sleeve fits into a recess in the sink-half.
  • the second half of the sink was placed on top, and finally a cover was glued on top of the sink & shuttle to hold it all together.
  • Figure 15 shows how the three monolith pieces fit together inside the rest of the apparatus.
  • a multi- cavity sink mold was used to prepare multiple sinks at one time.
  • the mold was made from fluorosilicone rubber of medium hardness (70 d urometer, Shore A).
  • the mold is designed to create the recesses for the tapered accumulator as two pieces of sink can be used to sandwich around the accumulator.
  • a matrix absorber (optional) was available, but was not used.
  • the matrix absorber was prepared separately in the same method as the sink halves.
  • the fluid capacity of the matrix absorber was about 20 uL.
  • the matrix absorber when used, can be attached to the accumulator prior to the elution fluid introduction (as shown in Figure 12).
  • the matrix absorber can be held in place by a compression fit in the housing or system.
  • a rod-shaped monolith element with the appropriate fluid capacity ( ⁇ 20 uL) can be inserted into a bole drilled beside the outlet tube, as shown in Figures 17A-17D. If this piece of monolith is in fluid communication with the outlet tube, it can also act as a matrix absorber.
  • the specific shape of the matrix absorber has no significant influence on its function.
  • the elution portion of the apparatus includes a syringe prepared by cutting the barrel and plunger from a commercial, plastic syringe.
  • the barrel-plunger was assembled, filled with the elution fluid, and sealed with foil using an inductive heat-seal system.
  • the filled assembly was dropped into the base.
  • An activator was screwed down on top of it.
  • a retainer U-shaped piece was glued on to keep it from being removed. Finally, the plunger was threaded through the center of the activator.
  • the elution fluid was 25 mM ammonium hydroxide.
  • the syringe was filled with about 60 ⁇ , of the elution fluid.
  • the elution fluid is designed to elute or eject the DNA from the accumulator by deprotonating the amino groups on the monolith and mere by eliminating the electrostatic attraction between charged amine groups and DNA.
  • Figures 17A-17D shows an overview of the apparatus and method.
  • the apparatus, or cartridge, was supported on a stand with the sample cup facing up.
  • a 4S0 uL aliquot of the DNA sample was combined with 50 ⁇ L ⁇ loading buffer concentrate and sufficient water to bring the sample volume to 500 ⁇ L.
  • the loading buffer was 20 mm THIS pH 7.5
  • the 10X loading buffer was 200 mM TRIS pH 7.5 which was diluted 10-fold for use.
  • the combination was loaded on to the apparatus.
  • the sample was dispensed into the cup and was wicked through the accumulator and into the sink.
  • the total volume of the combined sample and loading buffer was wicked through the accumulator.
  • the DNA present in the sample is captured by the accumulator.
  • the "spent" sample matrix or fluid is wicked through the accumulator and into the sink.
  • the absorption of the DNA solution took between 5 and 15 minutes.
  • the absorption of the sample can vary depending on the volume, wicking capacity of the monolith(s) and the size of the apparatus.
  • the sink is designed to have excess fluid capacity to ensure the sample, or combined sample and loading buffer, can be wicked into, and contained within, the sink. Once it has been absorbed, it remains within the sink and is discarded when the device is disposed of.
  • the shuttle is moved from the loading position into the elution position. Upon this movement, the portion of the accumulator that was positioned inside of the sink breaks away from the active portion of the accumulator and remains trapped between the two halves of the sink. The portion of the accumulator that is contained within the sleeve and shuttle moves to the elution side of the apparatus. To ensure that no DNA is lost in the portion of the accumulator broken away, the accumulator capacity was higher than the amount of DNA in the sample.
  • the capacity can be 2x, 3x, 4x, 5x, 6x, 7x, 8x, 9x or up to 1 Ox of the expected sample amount In doing so, the DNA that enters the accumulator gets captured by the initial monolith surface area it encounters (not already containing bound DNA).
  • the apparatus was turned over to elute and coiled the DNA.
  • the syringe barrel was pushed down against the piercer.
  • the foil seal was broken.
  • the syringe barrel forms a seal against the upper surface of the sleeve (through the cutter support shown in Figures 17A-17D) and a sealed fluidic channel from the syringe directly to the interface surface of the DNA-filled accumulator is formed.
  • the seal piercer is a sharp piece of steel tubing supported in a die-cut piece of silicone sheeting.
  • the concentrated DNA flowed out of the apparatus through the elution tube and was collected in the attached vial.
  • the amount of DNA collected and eluted was about 480 ng.
  • the concentration of ehited DNA solution was about 9.6 ug/mL, representing a concentration factor increase of about 9.6, and a yield greater than 95% .
  • Analysis of the eluted DNA showed no significant fragmentation.
  • the Purity of the concentrated DNA, measured by A260/A280nm was comparable to mat of the original DNA stock solution.
  • Protocol - Caution Do not manipulate shuttle, activation knob or collection screw until instructed to do so. Sample should contain DNA that has been extracted and is relatively pure. The DNA binding capacity of the concentrator cartridge is 2.S ⁇ %. These values can define a range, such as about 1 and about 5 ⁇ g.
  • the pH of the diluted sample should be ⁇ about pH 8.0. If uncertain, check a droplet of the sample with pH paper. The ionic strength of the loading solution should not exceed 30 mM. At 40 mM, recovery is reduced to 40% of maximum. At 50 mM, recovery is reduced to 30% of maximum.
  • a DNA concentration device as shown in Figure 17A-D, having an accumulator monolith, as described in Examples 1 and 2, was used.
  • the accumulator monolith was identical to the accumulator described in Example 1.
  • a 200 uL sample of 10 mM TRIS buffer, pH 7.3, containing 200 ng of human genomic DNA was placed into the receiving cup of the DNA concentrator device. The sample was allowed to absorb completely into the device. The DNA was captured and retained on the accumulator monolith.
  • the shuttle containing the accumulator monolith was moved from the loading position to the elution position. This movement disconnected the accumulator monolith from the sink monolith and positioned the accumulator between the device outlet port and the elution syringe.
  • SO mM TRIS buffer, pH 10 small drops of fluid emerged from the outlet and were collected in a 200 ⁇ . microfuge tube attached to the outlet port of the device. The microfuge tube was removed from the device, closed and stored.
  • the concentrated DNA was characterized by UV absorbance, gel electrophoresis, and quantitative PCR. Aside from the change in concentration, the data obtained from the concentrated DNA was iiidistinguishable from mat of the original DNA.
  • Figure 19 shows a comparison of % DNA recovery of the same sample tested using a set of 10 of the DNA concentration devices built from each of 5 different monolith fabrication batches, for a total of 1 S tests. The recovery of pure DNA is essentially quantitative for all test lots and demonstrates an A260/A280 ratio of approximately 1.8 which is the same as the ratio before application to the matrix.
  • Figure 20 shows gel electrophoresis results from pre-concentration vs. 3 different collected DNA concentrates.
  • Lane 2 is pre-concentration Aral digested DNA and lanes 3-5 are the concentrated Alul digests. No differences are observed.
  • Lane 6 is pre-concentration BamHI digested DNA and lanes 7-9 are the concentrated BamHI digests. No differences are observed.
  • Table 2 and Figure 21 show the PCR results from collected Lambda DNA digests.
  • Table 2 shows the DNA concentrated by the device amplifies the same as input DNA over 5 orders of magnitude.
  • Figure 21 shows a plot of Cq versus log ng of DNA, pre-concentration versus post-concentration for 3 devices. The results indicate an absence of PCR inhibitors in the concentrates and a recovery of DNA of similar quality as the input DNA.
  • Example 4 Alternate DNA concentration system configuration
  • a concentrator monolith system as shown in Figures 18A-18D, can be used having an accumulator monolith (1810) inserted within sink monolith (1820).
  • An empty sink frame made from acrylic with a thickness of 6 mm was clamped between two pieces of borosilicate glass.
  • a fluid-tight plug was inserted in the outlet bole, and the frame was filled with 1600 sink monolith mixture containing 1 :3:1 TEGDMA: EGDMA:HEMA with 1% DMAP by weight thoroughly mixed 1:3 with a solvent solution containing 2:1 n-octano]:l,5 pentane diol.
  • the wick rate for this material was measured to be 2.60 cm.
  • a PVC rod was inserted in the top port of the mold and pushed down until it rested against the outlet plug.
  • the sink (1820) was cured for 25 minutes from both sides with 365 nm UV irradiation of about 0.7 mW/cm 2 intensity. After curing was complete, the glass slides, rod and plug were removed.
  • the cured, but unwashed, accumulator is used to plug the sink frame outlet hole.
  • the sink monomer is then added and the PVC rod inserted. Before polymerization the sink mixture can penetrate slightly into the accumulator. When the sink is finally polymerized, h forms a crosslinked fluidic connection to the
  • the elution assembly was constructed by heat-sealing a pierceable membrane ( 1826) to the inside of the elution fluid reservoir housing (1890).
  • the tubular steel cutter (1805) was fabricated by sharpening one end of a stainless steel tube and flaring the other, and snapping the flare into a seat in the housing.
  • the elution assembly was completed by filling the hollow plunger with elution fluid consisting of 30 mM TRIS buffer pH 9 and then snapping the assembled reservoir housing on to it.
  • Figures 18A-18D show an overview of die apparatus at key points in a typical method of use.
  • a 10 - 1000 uL aliquot of sample containing nucleic acids, such as cell lysate, is combined with an appropriate amount of 10X loading buffer concentrate.
  • This solution is placed in the sample tube (1802) and snapped onto the clip at the inlet The device is then inverted to the orientation shown in Figure 18 A, and the sample falls to contact the tip of the accumulator (1810) which initiates the process of wicking the sample into the monolith assembly through the accumulator.
  • sample tube (1802) is filled with a wash solution (100 - 200 ⁇ , is a typical volume for each wash) such as 10 mM TRIS pH 7.5, snapped back onto the concentrator inlet, and wicked into the monolith through the accumulator. Additional washes with, for example, isopropanol solutions or other buffers can be performed up to a total of 1100 uL.
  • a wash solution 100 - 200 ⁇ , is a typical volume for each wash
  • isopropanol solutions or other buffers can be performed up to a total of 1100 uL.
  • the sample vial is replaced with a clean collection vial (1865) and the concentrator is flipped into the orientation shown in Figure 18 B.
  • the accumulator (1810) is separated from the sink (1820) and isolated by unlocking and then moving the elution fluid reservoir housing (1890) down towards the outlet.
  • the tubular steel cutter (1805) cuts through the periphery of the accumulator as it moves down and finally cuts into the sink frame, forming a water-tight seal.
  • the position of mis assembly after activation is shown in Figure 18C.
  • the plunger (1880) is unlocked and depressed. It is locked again when it reaches the folly depressed position. This is shown in Figure 18D.
  • There can be an air pocket in the syringe assembly mat can be compressed by movement of the plunger and served to pressurize the elution fluid (1807) to about 3 psi.
  • the elution fluid (1807) travels down the steel tube ( 1805) and is forced through the accumulator by this pressure.
  • the micron-scale pores of the accumulator prevents air from passing through the accumulator at the pressure generated within the device. Because of this, elution occurs only after die elution fluid (1807) has trickled down the steel tube and contacts the accumulator. Eluate drips out of the accumulator (1810) and into the elution tube (1865).
  • Example S Protocol for the concentration of DNA from a cell tysate sample
  • a concentrator monolith system can be used to purify and concentrate DNA from a cell lysate sample.
  • the concentrator monolith can include a sink and an accumulator monolith.
  • a sink material is provided that is identical to the material used in either Example 1 or Example 4.
  • either apparatus described in Example 1 or Example 4 can be used with pH 11 NaOH as the elution solution.
  • the accumulator monolith is fabricated from a monomer mixture of 3 : 17:3
  • TEGDA:EGDMA:HEMA with 3% TBAMA and 1.5% DMAP, by weight This is mixed 1:3 with a solution of 90% Methanol and 10% water.
  • 50 fiL of the accumulator monomer solution is dispensed into a 1000 uL pipette tip with the outlet capped.
  • the solution is irradiated from the top and both sides with 365 nm UV light for 20 minutes.
  • the light intensity from the sides is about 0.6 mW/cm 2 and die intensity from above is about 0.4 mW/cm 2 .
  • the self-wicking rate of this monolith ranges from 4 to 6 cm.
  • mat top iUumination provided a smoother top surface.
  • the monoliths of the present disclosure can be irradiated on one or more of the intended surface interfaces which can be configured to couple to other materials.
  • the monoliths of the present disclosure can also be held or contained in the mold during irradiation with one or more of the intended surface interfaces not in contact with the mold.
  • the smoother surfaces can effect a better coupling and improved fluid communication.
  • [00261] Harvest buccal cells from donor by swabbing cheek for 20 s. (Puritan Purflock Ultra, Puritan Diagnostic 25-3606-U). [00262] 3. Place swab with cells into a 2 mL microtube with buffer. Break off the swab handle at the indentation and seal the tube with the swab inside. The sample may be stored for up to 1 hour before lysis.
  • vortex sample When ready for extraction and concentration, vortex sample briefly ( ⁇ 1 s) three tunes at maximum and remove the swab from the tube. Squeeze out the remaining fluid using the rim of the microtube and discard.
  • the cell lysis included the following steps
  • the DNA capture and concentration included the following steps
  • wash with wash solution 1 by removing the sample tube, adding 200 uL of wash 1 solution (30 mM TRIS pH 7.6), men attaching me sample tube to concentrator unit and inverting, and allowing the wash to wick into the concentrator.
  • wash with wash solution 2 by removing the sample tube, adding 200 ⁇ . of wash 2 solution (20% 1PA, 30 mM MOPS pH 7.6), then attaching the sample tube to concentrator unit and inverting, and allowing the wash to wick into the concentrator.
  • the DNA quality can be evaluated by the following steps
  • the DNA fragmentation can be measured by agarose gel
  • electrophoresis There can be a dominant high molecular weight band with traces of smaller fragments that arc formed during the digestion step.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

La présente invention concerne un concentrateur permettant de concentrer, de purifier ou encore d'isoler un ou plusieurs analytes cibles dans une matrice fluidique, et des procédés associés, au moyen de matériaux à auto-capillarité tels que des monolithes. La présente invention peut être utilisée comme un dispositif de préparation d'échantillon répondant à un besoin précis. Le dispositif autonome peut être utilisé pour l'extraction et la concentration de molécules cibles spécifiques, telles que des acides nucléiques.
PCT/US2016/047642 2015-08-18 2016-08-18 Dispositifs de concentration d'échantillon WO2017031369A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201562206749P 2015-08-18 2015-08-18
US62/206,749 2015-08-18
US15/240,978 US20170051274A1 (en) 2015-08-18 2016-08-18 Sample concentration devices
US15/240,960 2016-08-18
US15/240,960 US10570439B2 (en) 2015-08-18 2016-08-18 Sample concentration devices
US15/240,978 2016-08-18

Publications (1)

Publication Number Publication Date
WO2017031369A1 true WO2017031369A1 (fr) 2017-02-23

Family

ID=56851699

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2016/047642 WO2017031369A1 (fr) 2015-08-18 2016-08-18 Dispositifs de concentration d'échantillon

Country Status (1)

Country Link
WO (1) WO2017031369A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040161788A1 (en) * 2003-02-05 2004-08-19 Shuqi Chen Sample processing
WO2011082449A1 (fr) * 2010-01-08 2011-07-14 University Of Tasmania Monolithes de polymère poreux, leurs procédés de préparation et d'utilisation
WO2011137533A1 (fr) * 2010-05-05 2011-11-10 The Governing Council Of The University Of Toronto Procédé de traitement d'échantillons séchés utilisant un dispositif microfluidique numérique
WO2013006904A1 (fr) * 2011-07-12 2013-01-17 University Of Tasmania Utilisation de matériaux polymères poreux pour le stockage d'échantillons biologiques
US20140017672A1 (en) * 2007-10-31 2014-01-16 Rebecca HOLMBERG Method and kit for purifying nucleic acids

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040161788A1 (en) * 2003-02-05 2004-08-19 Shuqi Chen Sample processing
US20140017672A1 (en) * 2007-10-31 2014-01-16 Rebecca HOLMBERG Method and kit for purifying nucleic acids
WO2011082449A1 (fr) * 2010-01-08 2011-07-14 University Of Tasmania Monolithes de polymère poreux, leurs procédés de préparation et d'utilisation
WO2011137533A1 (fr) * 2010-05-05 2011-11-10 The Governing Council Of The University Of Toronto Procédé de traitement d'échantillons séchés utilisant un dispositif microfluidique numérique
WO2013006904A1 (fr) * 2011-07-12 2013-01-17 University Of Tasmania Utilisation de matériaux polymères poreux pour le stockage d'échantillons biologiques
US20140127669A1 (en) 2011-07-12 2014-05-08 University Of Tasmania Use of porous polymer materials for storage of biological samples

Similar Documents

Publication Publication Date Title
US20220111389A1 (en) Sample preparation device
CN107202727B (zh) 用于分离和/或纯化生物分子的装置
US11299728B2 (en) Sample extraction and preparation device
EP2215103B1 (fr) Procédé de purification d'acides nucléiques
US8726744B2 (en) Portable concentrator
JP6041448B2 (ja) 試料調製デバイスおよび方法
JP2020190560A (ja) 核酸サンプルを収集するためのシステム及び方法
US10518196B2 (en) Devices for separation of particulates, associated methods and systems
US20140179909A1 (en) Microfluidic device for nucleic acid extraction and fractionation
CN203389364U (zh) 一种层析柱
US20230227888A1 (en) Point of need diagnostic device and methods of use thereof
EP1820552B1 (fr) Support poreux
EP1903110B1 (fr) Dispositif pour recouvrir un acide nucléique et procédé pour récupérer un acide nucléique
KR20240027088A (ko) 범용 분석 카트리지 및 사용 방법
US10570439B2 (en) Sample concentration devices
WO2017031369A1 (fr) Dispositifs de concentration d'échantillon
CN101649317A (zh) 一种硅胶膜型dna快速提取及保存的方法
RU2595374C2 (ru) Способ автоматизированного выделения с одновременной очисткой нуклеиновых кислот из нескольких биологических образцов
Stachowiak et al. Automated Sample Preparation System for Rapid Biological Threat Detection

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16758331

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 16758331

Country of ref document: EP

Kind code of ref document: A1

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载