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WO1997007993A1 - Procedes et articles ameliorant l'adsorption des proteines et la gestion des liquides sur des surfaces - Google Patents

Procedes et articles ameliorant l'adsorption des proteines et la gestion des liquides sur des surfaces Download PDF

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Publication number
WO1997007993A1
WO1997007993A1 PCT/US1996/013895 US9613895W WO9707993A1 WO 1997007993 A1 WO1997007993 A1 WO 1997007993A1 US 9613895 W US9613895 W US 9613895W WO 9707993 A1 WO9707993 A1 WO 9707993A1
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WIPO (PCT)
Prior art keywords
protein
group
article
solid phase
etching
Prior art date
Application number
PCT/US1996/013895
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English (en)
Inventor
Robert F. Zuk
Jeffrey A. Pierce
Original Assignee
First Medical, 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 First Medical, Inc. filed Critical First Medical, Inc.
Priority to AU69602/96A priority Critical patent/AU6960296A/en
Publication of WO1997007993A1 publication Critical patent/WO1997007993A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
    • C07K17/02—Peptides being immobilised on, or in, an organic carrier
    • C07K17/08—Peptides being immobilised on, or in, an organic carrier the carrier being a synthetic polymer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
    • G01N33/545—Synthetic resin

Definitions

  • the present invention relates generally to the production of test articles used for determining the presence of analyte in biological samples. More particularly, the present invention relates to a method for treating test articles to promote protein adsorption and in some cases to enhance surface hydrophobicity to provide fluid control in the article.
  • many specific binding assays employ a solid phase surface having a protein specific binding substance, such an antibody, antibody fragment, avidin, or a derivatized protein carrier, immobilized on the surface.
  • the surface may then be utilized to capture analyte through direct or indirect binding of the immobilized specific binding substance to the target analyte.
  • Such solid phase surfaces used for performing immunoassays are frequently the most costly component in a commercial immunoassay kit .
  • Procedures and protocols for immobilizing proteins onto a solid phase often require multiple steps and are thus time-consuming and expensive. While the cost can be reduced by employing batch manufacturing processes, the batch size (and hence cost advantage) is limited by the need to carefully control the characteristics of each solid phase being produced.
  • U.S. Patent No. 5,316,784 describes a two-step process for attaching immunologically active substances, such as antibodies, antigens, and binding proteins, to solid phase surfaces by applying a mixture of the active substance and a linking group having photoactivable groups to the surface. After allowing the mixture to absorb into the surface, the active substance is covalently attached by activating the linking group.
  • U.S. Patent No. 5,258,041 describes the use of spacer arms having hydrophobic guiding groups for attaching biomolecules to solid phase supports. The inventors of the present application have filed an earlier application with a third co-inventor on related subject matter. See, application serial no. 08/374,265, filed on January 18, 1995, the full disclosure of which is incorporated herein by reference.
  • the present invention provides an improved method for the non-covalent immobilization of proteins to a solid phase surface to produce articles which are particularly useful in the performance of immunoassays and other biological procedures.
  • the improvement comprises plasma etching with a reactant gas and under conditions selected to provide such enhanced protein binding. While the mechanism is not understood in detail, it is presently believed that the reactant gas chemically modifies the surface and/or leaves residual moieties on the surface which promote the desired binding via one or more binding forces, including hydrophobic hydrogen bonding, Van der Waals forces, and other interactions.
  • Exemplary reactant gases include hydrocarbons (e.g., CH 4 and C 2 H 6 ) , halocarbons (e.g., CF 4 , CC1 4 , CF 3 C1, CF 3 Br) , other halogen-containing gases (e.g., S 2 F 6 ) , and combinations thereof.
  • halocarbons e.g., CF 4 , CC1 4 , CF 3 C1, CF 3 Br
  • other halogen-containing gases e.g., S 2 F 6
  • Preferred is the use of halocarbons, with the most preferred gas being carbon tetrafluoride (CF 4 )
  • exemplary conditions include a treatment time in the range from 1 to 20 minutes, a treatment pressure in the range from 0.1 to 1 Torr, at a power level from 100 W to 1000 W.
  • the present invention further provides for improving the management of the flow of aqueous solutions on the surfaces of test articles, particularly those used in immunoassays and other biological assays.
  • plasma treatment as described above can enhance surface hydrophobicity on surfaces which are generally rather hydrophilic in their native (unmodified) state, such as acrylates, e.g., methylmethacrylate surfaces.
  • the methods comprise a solid phase surface having at least one flow path or test chamber formed therein.
  • the solid phase surfaces will typically comprise naturally hydrophilic organic polymers, such as acrylates, which have been molded or machined to include surface cavities which define the flow paths and/or test chambers.
  • the flow paths and test chambers will be treated in order to enhance their hydrophobicity.
  • Such enhanced hydrophobicity will limit the flow of aqueous fluids through such flow paths and within such test chambers.
  • Such procedures will be particularly useful in the preparation of analytical rotors, where it is desired to be able to introduce or transfer aqueous fluids to the rotor and have the fluids remain within a fixed location on the rotor prior to transfer, usually by rotation of the rotor above a desired threshold rotational speed.
  • the methods of the present invention for imparting enhanced hydrophobicity to flow paths and test chambers will find use with any test article where it is desired to be able to selectively effect fluid transfer within the test article and through such flow paths and test chambers, usually by application of an outside force to the fluid.
  • the preferred method for imparting a greater degree of hydrophobicity is plasma treatment according to the methods described above.
  • the present invention further provides improved test articles prepared by the methods described above.
  • Fig. 1 is a schematic illustration of a test article which may be prepared using the methods of the present invention.
  • Fig. 2 is a schematic illustration of a plasma treatment apparatus useful for performing a method according to the principles of the present invention.
  • Methods are provided for attaching proteins to solid phase surfaces to form test articles useful for detecting target analytes in biological and other assays.
  • the methods of the present invention are in some cases also useful for modifying the flow characteristics of flow paths and test chambers on such solid phase surfaces in order to improve the usefulness of the test articles in performing immunoassays .
  • plasma etching the entire solid phase surface or selected portions thereof both protein attachment and flow management of test liquids and reagents may be improved.
  • the target analyte will usually be a member of a specific binding pair (SBP) , including compounds, compositions, aggregations, and virtually any other substance which may be detected or reacted by immunological or equivalent techniques. That is, the analyte, or a portion thereof, will usually be antigenic or haptenic, defining at least one epitopic site, or will be a member of a naturally- occurring binding pair (e . g. , carbohydrate and lectin, hormone and hormone receptor, ligand and anti-ligand, and the like) .
  • Analytes of particular interest include antigens, antibodies, proteins, glycoproteins, carbohydrates, macromolecules, toxins, bacteria, tumor markers, and the like, which define a plurality of epitopic sites.
  • analytes of interest include haptens, drugs, and other small molecules, which usually define only a single epitopic binding site.
  • a non- exhaustive list of exemplary analytes is set forth in U.S. Patent No. 4,366,241, at column 19, line 7, through column 6, line 42, the disclosure of which is incorporated herein by reference.
  • cardiac markers such as troponin I, troponin T, myoglobin, and creatine kinase isozymes.
  • the analytes may be present in a wide variety of samples, where the sample is liquid, can be liquified, or can be suspended in a liquid.
  • the methods of the present invention will find their greatest use with biological specimens such as blood, serum, plasma, urine, cerebral fluid, spinal fluid, ocular lens liquid (tears) , saliva, sputum, semen, cervical mucus, scrapings, swab samples, and the like, which are frequently employed in the diagnosis and monitoring of disease and therapeutic treatments.
  • biological specimens such as blood, serum, plasma, urine, cerebral fluid, spinal fluid, ocular lens liquid (tears) , saliva, sputum, semen, cervical mucus, scrapings, swab samples, and the like, which are frequently employed in the diagnosis and monitoring of disease and therapeutic treatments.
  • the methods of the present invention may be used with industrial, environmental, and food samples, such as water, process streams, milk, meat, poultry, fish, conditioned media, and the like.
  • the sample may be desirable to pretreat the sample, such as by liquification, separation, solubilization, concentration, filtration, chemical treatment, or a combination of these steps, in order to improve the compatibility of the sample with the remaining steps of the assay, as described hereinafter.
  • the selection and pretreatment of biological, industrial, and environmental samples prior to immunological testing is well known in the art and need not be further described.
  • the samples will usually be in the form of an aqueous solution, suspension, or the like.
  • the flow characteristics of such aqueous media can be advantageously controlled on the solid phase surfaces which are prepared according to the method of the present invention.
  • Exemplary proteins which may be adsorbed onto the modified surfaces of the present invention include those which are conventionally attached to unmodified surfaces, e . g. , immunoglobulins, avidin, streptavidin, albumins, thyroglobins, ferritin, and the like.
  • the adsorbed proteins may be directly useful in the immunoassays, i.e., they may comprise the cognate member of a specific binding pair which includes the analyte of interest.
  • directly useful proteins include antibodies raised against the analyte, receptor proteins used to detect hormones and other small molecules, and the like.
  • the adsorbed protein may comprise a carrier molecule attached to a hapten or other binding moiety selected to participate in a particular binding protocol.
  • the haptens will provide for high affinity binding to another molecule, where the hapten-binding molecule pair provides an intermediate binding reaction in the assay protocol.
  • Exemplary haptens which may be attached, usually covalently attached, to the surface-adsorbed protein of the present invention include biotin (which binds to avidin, streptavidin, and anti-biotin antibody with very high affinity) , fluorescein (which binds with high affinity to anti-fluorescein antibody) , dinitrophenol (which binds with very high affinity to anti- dinitrophenol antibody) , digoxin (which binds with very high affinity to anti-digoxin antibody) , luminol (which binds with very high affinity to anti-luminol antibody) , theophylline (which binds with very high affinity to anti-theophylline antibody) , morphine (which binds with very high affinity to anti-morphine antibody), and the like.
  • biotin which binds to avidin, streptavidin, and anti-biotin antibody with very high affinity
  • fluorescein which binds with high affinity to anti-fluorescein antibody
  • the preparation of hapten-protein conjugates which could be used in the methods and articles of the present invention are well described in the patent and scientific literature. Specific techniques are described in copending application serial no. 08/374,265, the full disclosure of which has previously been incorporated herein by reference.
  • the surface to be treated and modified to adsorb proteins according to the method of the present invention may be composed of any material that can be formed into a test article or device having a reaction zone, including organic polymers, glass, ceramics, metals, and the like.
  • the surface may be composed of an organic polymer having a natural hydrophilic surface (i.e., a surface which is hydrophilic (has a small water contact angle, usually below 100°) prior to treatment according to the present invention) , such as an acrylate, in which case, plasma etching will enhance protein binding and will also impart hydrophobicity to modify the surface flow characteristics.
  • a natural hydrophilic surface i.e., a surface which is hydrophilic (has a small water contact angle, usually below 100°) prior to treatment according to the present invention
  • the material may be naturally more hydrophobic, e.g., polystyrene, in which case plasma etching only enhances protein binding.
  • Particularly preferred materials for forming a solid phase surface according to the present invention are methylmethacrylate polymer and polystyrene.
  • the surface will usually be formed on or as a part of a substrate which is at least part of a test article which may be employed in an immunological or other assay protocol.
  • exemplary substrate configurations include disks, strips, plates, tubes, wells, particles, microspheres, magnetic particles, and the like.
  • the substrate will be composed entirely of the surface material, but this is not necessary.
  • the substrate may also be formed by coating a desired organic polymer or other material over a portion thereof, by forming a laminate, composite, or other structure comprising two or more materials. At least a portion of the solid phase surface will be treated according to the method of the present invention to enhance binding prior to protein adsorption.
  • two or more discrete regions or zones on the surface may be treated where it is desired to adsorb protein only within . such zones.
  • An exemplary disk substrate which could be prepared using the method of the present invention is described in copending application serial no. 08/374,265, the full disclosure of which has previously been incorporated herein by reference. It will be appreciated that the treatment method of the present invention could be utilized as an improvement in the method of this earlier application.
  • the surface to be treated according to the present invention may also include flow paths, test chambers, and other fluid-receiving geometries thereon.
  • analytical rotors of the type described in copending application serial no. 08/521,615, the full disclosure of which has previously been incorporated herein by reference.
  • fluid retention and management can be enhanced by imparting a hydrophobic surface to such chambers, flow paths, and other portions of the test surface which will contact the liquid.
  • the hydrophobic surface will cause the aqueous test sample, reagent, or other fluid, to bead (have a water contact angle in the range from 100° to 120°) on the surface and not flow from the point of application until the external force is applied, e . g. , through rotation of an analytical rotor.
  • An exemplary rotor 10 is illustrated in Fig. 1.
  • the rotor includes inlet chambers 12, 14, and 16, which are connected to a test chamber 18 by flow paths 20, 22, and 24, respectively.
  • test chamber 18 illustrates reaction zones 30, 32, 34, and 36, each of which may include an adsorbed protein, where protein adsorption is enhanced by the method of the present invention as described above. Further details of the construction of the exemplary rotor 10 are described in copending application serial no. 08/521,615, the full disclosure of which has previously been incorporated herein by reference.
  • the solid phase surface may be treated by a variety of etching techniques, particularly including dry etching techniques.
  • Suitable dry etching techniques include plasma etching, reactive ion etching, and ion milling, where the surface is exposed to highly reactive chemical species produced by energizing a gas or other ion source.
  • Particularly preferred are plasma etching techniques where a very low pressure reactant gas, typically having pressure in the range from 0.1 to 1 Torr, is exposed to radio frequency energy to produce ions, free radicals, and neutral species, all having high kinetic energies.
  • Preferred reactive gases include hydrocarbons, such as CH 4 and C 2 H 6 ; halocarbons, such as CF 4 , CC1 4 , CF 3 C1, and CF 3 Br; and other halogen-containing gases, such as S 2 F 6 .
  • the RF energy will be applied at a power level in the range from 1 W to 1000 W, for a time sufficient to impart the desired level of hydrophobicity, usually from 1 minute to 20 minutes, preferably from 1 minute to 10 minutes.
  • Plasma etching may be performed in conventional plasma reactors, such as reactor 10 illustrated in Fig. 2.
  • the process gas is continually introduced through an inlet 12 and flows between electrodes 14 and 16 to produce a glow discharge within the reactant gas.
  • Process gas is withdrawn through an exit port 18 to a vacuum system which maintains the desired low pressure level within the reactor 10.
  • Reactor 10 as illustrated is an isotropic reactor, where etching occurs at a uniform rate in all directions.
  • the substrate 20 which is treated within the reactor 10 may be oriented in any convenient orientation.
  • a preferred plasma etching protocol comprises initial plasma etching with an inert gas, such as Argon, followed by etching with the hydrocarbon or halogen-containing reactant gas .
  • protein will be adsorbed to the surface in the generally conventional manner.
  • the adsorption process will generally be much shorter than that required by otherwise equivalent processes where the surface has not been pretreated by plasma etching. That is, it will require much longer protein adsorption times in order to achieve an equivalent strength of protein adsorption on surfaces which have not been treated to enhance hydrophobicity. Moreover, even prolonged adsorption times will not always achieve an equivalent strength of protein adsorption.
  • the pretreatment methods of the present invention can provide protein adsorption having a higher resistance to desorption under denaturing conditions than that achieved with conventional adsorption procedures, regardless of the length of time of the adsorption step.
  • protein adsorption will comprise applying a liquid medium containing the protein of interest to the solid phase surface, by a variety of techniques, including pipetting, dipping, spraying, inkjet printing (as described in detail in copending application serial no. 08/374,265, the full disclosure of which has previously been incorporated herein by reference) , and the like.
  • the present invention generally allows for protein adsorption to occur at room temperature, for relatively short period of time, usually less than 1 hour, preferably in the range from 1 minute to 20 minutes, more preferably in the range from 2 minutes to 10 minutes.
  • the surface will usually be washed to remove non-bound proteins and other contaminants. After such washing, the solid phase surfaces will generally be ready for use in an immunoassay or other biological test procedure.
  • proteins adsorbed as described above may, however, be subjected to additional treatment in order to even further enhance binding.
  • proteins may be heated to a relatively high temperature, often above 50°C, sometimes above 90°C, or higher, to accelerate and further enhance adherence of the protein to the surface.
  • heat treatment methods will generally only be possible with hapten- protein carrier combinations, where the hapten is not denatured by the heating.
  • 35 mm (dia.) methacrylate disks used for substrate material were obtained from the Germanow-Simon company. They were machined from Hesalite HTC material and were 1.1 or 1.4 mm thick. This material has optical properties that are sufficient for interferometric, fluorescent, or other types of interrogation. Disks were shipped from the vendor laminated on both sides to minimize scratching during machining, transport, and storage. Prior to plasma etching, protein adsorption and assay, laminates were removed, and the disks were rinsed with deionized water and in some instances washed with mild detergents both to quench static electricity build- up and to remove debris remaining from the machining process.
  • Plasma etching with various gases was used to modify the surface characteristics from those of native acrylic, either in the direction of a more hydrophilic surface or a more hydrophobic one.
  • Etchants included C0 2 , (Plasmaline lab etcher, 10 min exposure, 200-300 W forward RF, 0.1-0.5 Torr) , H 2 0 vapor (Gasonics Pilot Test Etcher, 5 min exposure, 600 W, 0.4 Torr) , CF 4 (Gasonics Pilot Test Etcher, 10 min exposure, 600 W, 0.35 Torr) , and a H 2 (5%)/N 2 combination (Gasonics Pilot Test Etcher, 10 min exposure, 600@, 0.35 Torr) .
  • Etching with C0 2 , H 2 0 vapor, and the H 2 (5%)/N 2 combination enhanced the hydrophilicity of the acrylic surface, decreasing the H 2 0 contact angle.
  • Etching with CF 4 in contrast, enhanced the hydrophobicity of the plastic surface, markedly decreasing the H 2 0 contact angle.
  • a suitable system for performing plasma etching is illustrated in Fig. 2.
  • BSA bovine serum albumin
  • biotin moieties biotinylated
  • PBS phosphate buffered saline
  • the BSA was then conjugated at a molar ratio of ca. 10:1 NHS-LC-biotin to BSA.
  • 4.1 mg of NHS-LC-Biotin was dissolved in 60 ⁇ L of DMF (Pierce #931026155) and added to the 6 mL of BSA in PBS.
  • This reaction mixture was placed in an ice bath for 2 hours followed by placing the mixture in a 12,000 MWCO dialysis tubing and dialyzing against 0.1 M phosphate buffer (pH 7.0, with at least two 1 L changes) at 4°C to remove unreacted biotin. Following dialysis and hapten number assessment, 0.1% NaN 3 was added to the concentrated biotin-BSA (B-BSA) to discourage microbial growth. Hapten numbers in the range from 2 to 9 were obtained.
  • Table 1 contains data illustrating that CF 4 plasma etching (which renders the acrylic test surface more hydrophobic) both (1) enhances binding at short contact times (ca. 5 minutes) to a level that is normally achievable on a non-etched disk only after a much longer contact time and (2) renders the binding effectively irreversible, i.e., resistant to desorption.
  • Assav Diluent 0.1% BSA (Pentax) , 0.05% Tween ® 20
  • SA-HRP Conjugate Streptavidin-horse radish peroxidase (SA-HRP, Pierce, Product #21127) was reconstituted to 1 mg/mL and frozen. Prior to use, the stock was further diluted in the 1:1000 to 1:1000000 range with Assay Diluent.
  • OPD o- Phenyl enediamine Dihydrochloride
  • a solution of 0.4 mg/mL OPD was made by dissolving a 15 mg tablet of OPD (Sigma) into 37 mL of 0.1 M citrate-phosphate buffer, pH 5.0. Immediately prior to use, 10 mM hydrogen peroxide was added (37 ⁇ L of 30% solution, Sigma) as an activating agent. Sulfuric acid (2N) was added in an equal volume to OPD to stop the reaction at the desired time.
  • Teflon rings (themselves plasma etched with C0 2 to enhance binding to the double stick tape) several millimeters thick and 0.25 inches in inner diameter were affixed to the clean, unspotted, 35 mm acrylic test articles (Germanow-Simon) with double-stick tape to facilitate containment of liquid materials above the test surface. After the protein adsorption step in the assay, the rings were removed and a fresh ring and double-stick tape was affixed to the original double-stick tape. This eliminates assay activity due to "wall effects.”
  • Acrylic test articles either virgin or those previously etched with one of the test etchants, with teflon rings affixed had 100 ⁇ L of biotinylated BSA added to each well and contacted for either 5 minutes or overnight (ca. 12 hours) .
  • test articles were washed for 10 minutes in wash buffer (2 L for 10 disks) in an automated washer rotating at 46 rpm to remove excess biotinylated BSA and then the wells were rinsed several times manually with deionized water and stored for assay. The other half of the 5 minute contact disks were washed for an additional 12 hours with Wash Buffer in the automated washer (46 rpm) to stimulate desorption. After this stress test, the test articles were also rinsed several times with deionized water, dried, and stored.
  • the freshly-prepared OPD substrate was then added to the wells. (75 ⁇ L) and allowed to react for 10 minutes without agitation.
  • a Molecular Devices microplate reader (E ⁇ ) was used to determine absorbance at 405 nm after 140 ⁇ L of the reaction mixture from each teflon well was transferred to the microplates.

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Abstract

Un procédé de préparation d'articles de tests comprend l'adsorption d'une protéine sur une surface en phase solide, cette surface ayant subi un traitement préalable d'attaque au plasma. Habituellement, l'opération de traitement préalable comprend l'attaque de la surface en phase solide dans un réacteur classique d'attaque au plasma. Un tel traitement préalable de la phase solide réduit le temps nécessaire à la réalisation d'une adsorption adéquate de protéines et améliore celle-ci dans le cas où les conditions sont dénaturantes, comme la présence de détergents. Un traitement préalable de ce genre augmente aussi le caractère hydrophobe de matières qui sont naturellement hydrophiles, afin de limiter l'écoulement des liquides à la surface, généralement par des voies d'écoulement, des chambres et autres.
PCT/US1996/013895 1995-08-31 1996-08-27 Procedes et articles ameliorant l'adsorption des proteines et la gestion des liquides sur des surfaces WO1997007993A1 (fr)

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US08/522,435 1995-08-31

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US9388325B2 (en) 2012-06-25 2016-07-12 Ross Technology Corporation Elastomeric coatings having hydrophobic and/or oleophobic properties
US9546299B2 (en) 2011-02-21 2017-01-17 Ross Technology Corporation Superhydrophobic and oleophobic coatings with low VOC binder systems
US9914849B2 (en) 2010-03-15 2018-03-13 Ross Technology Corporation Plunger and methods of producing hydrophobic surfaces
US10317129B2 (en) 2011-10-28 2019-06-11 Schott Ag Refrigerator shelf with overflow protection system including hydrophobic layer
US11786036B2 (en) 2008-06-27 2023-10-17 Ssw Advanced Technologies, Llc Spill containing refrigerator shelf assembly

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Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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