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WO2003034041A1 - Systeme de mesure de particules utilisant un transformateur temps-frequence - Google Patents

Systeme de mesure de particules utilisant un transformateur temps-frequence Download PDF

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Publication number
WO2003034041A1
WO2003034041A1 PCT/GB2001/004552 GB0104552W WO03034041A1 WO 2003034041 A1 WO2003034041 A1 WO 2003034041A1 GB 0104552 W GB0104552 W GB 0104552W WO 03034041 A1 WO03034041 A1 WO 03034041A1
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WO
WIPO (PCT)
Prior art keywords
particles
migration channel
detection region
driven
migration
Prior art date
Application number
PCT/GB2001/004552
Other languages
English (en)
Inventor
Andreas Manz
Yien Chian Kwok
Original Assignee
Imperial College Innovations Limited
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 Imperial College Innovations Limited filed Critical Imperial College Innovations Limited
Priority to PCT/GB2001/004552 priority Critical patent/WO2003034041A1/fr
Publication of WO2003034041A1 publication Critical patent/WO2003034041A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1456—Optical investigation techniques, e.g. flow cytometry without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/01—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N2015/0042—Investigating dispersion of solids
    • G01N2015/0053—Investigating dispersion of solids in liquids, e.g. trouble

Definitions

  • the present invention relates to a measurement system for and method of characterizing particles of a fluid sample, in particular measuring velocities of particles in a fluid medium and numbers of particles.
  • the characterization of particles of a fluid sample is of increasing importance, in particular in biology and industrial processes.
  • the measurement of the velocities of cells moving under the influence of an electric field is important.
  • the intrinsic electrophoretic mobilities (EPMs) of cells could reveal whether cells under different physiological conditions or exposed to different physiologically- active agents would have an altered net surface charge as reflected by their different EPMs.
  • the present invention provides a measurement system for characterizing particles of a fluid sample, comprising: a microfluidic chip including a migration channel through which particles of a fluid sample are driven in a fluid medium; an illumination unit for illuminating at least a plurality of spaced sections in a detection region of the migration channel; an optical detector for detecting optical emission from at least the plurality of spaced sections in the detection region of the migration channel; an acquisition unit for generating a time-domain signal from the optical emission as detected; and a processing unit operably coupled to the acquisition unit for receiving the time-domain signal and transforming the time-domain signal to a frequency-domain signal, which frequency-domain signal provides for characterization of the particles.
  • the system provides for measurement of velocities of particles in a fluid medium.
  • the system provides for measurement of numbers of particles.
  • the particles are transported in a fluid flow through the migration channel.
  • the particles are driven through a fluid medium in the migration channel.
  • the particles are pressure driven through the migration channel.
  • the particles are driven through the migration channel by hydrodynamic chromatography.
  • the particles are driven through the migration channel by flow-field fractionation.
  • the particles are driven through the migration channel by electrophoresis.
  • the electrophoresis is dielectrophoresis.
  • the particles are driven through the migration channel by hydrodynamic pumping.
  • the hydrodynamic pumping is electrohydrodynamic pumping.
  • the hydrodynamic pumping is magnetohydrodynamic pumping.
  • the optical detector is a fluorescence detector for detecting fluorescence of the particles.
  • the optical detector is a light-scattering detector for detecting light scattering from the particles.
  • the optical detector is an absorption detector for detecting optical absorption by the particles .
  • the illumination unit includes a slit array comprising a plurality of spaced windows disposed in registration with the plurality of spaced sections in the detection region of the migration channel, and a light source for providing a light beam directed onto the slit array.
  • the slit array is integrated with the microfluidic chip.
  • the light source is a laser.
  • the illumination unit comprises a plurality of spaced light elements for illuminating the plurality of spaced sections in the detection region of the migration channel.
  • the illumination unit comprises at least one light source and a plurality of light-transmitting elements coupled to the at least one light source and disposed in spaced relation to the detection region in the migration channel such as to illuminate respective ones of the plurality of spaced sections in the detection region of the migration channel.
  • the light-transmitting elements are integrated with the microfluidic chip.
  • the light-transmitting elements comprise holographic lenses.
  • the light-transmitting elements comprise waveguides.
  • the light-transmitting elements comprise optical fibers.
  • the at least one light source is a laser.
  • the illumination unit comprises a plurality of light sources, each coupled to a respective one of the light-transmitting elements.
  • the optical detector comprises a single detector for detecting optical emission from each of the plurality of spaced sections in the detection region of the migration channel.
  • the optical detector comprises a plurality of spaced detector elements for detecting optical emission from respective ones of the plurality of spaced sections in the detection region of the migration channel.
  • the detector elements comprise photodetectors.
  • the illumination unit comprises a single light source for illuminating the detection region of the migration channel
  • the optical detector comprises a plurality of spaced detector elements for detecting optical emission from a plurality of spaced sections in the detection region of the migration channel.
  • the light source is a laser.
  • the detector elements comprise photodetectors.
  • the system further comprises: a dilution stage for performing dilution of the fluid sample such that the concentration of particles is less than a predetermined concentration.
  • the dilution stage is configured to provide that the concentration of particles is such that the average spacing of particles driven through the migration channel is not less than the center-to-center spacing of adjacent ones of the plurality of spaced sections in the detection region of the migration channel.
  • the dilution stage is configured to provide that the concentration of particles is such that the average spacing of particles driven through the migration channel is not less than about 0.5 mm.
  • the dilution stage is configured to provide that the concentration of particles is such that the average spacing of particles driven through the migration channel is not less than about 1 mm.
  • the dilution stage is operably controlled by the processing unit such as to provide for the necessary dilution of the fluid sample.
  • the transform is a Fourier transform.
  • the transform is a wavelet transform.
  • the transform is a continuous wavelet transform.
  • the particles comprise single molecules.
  • the particles comprise particles of a particle-based assay.
  • the assay is an immunoassay.
  • the particles comprise biological cells.
  • the particles comprise blood cells, namely red or white blood cells.
  • the particles comprise viruses.
  • the particles comprise bacteria.
  • the present invention also provides a method of characterizing particles of a fluid sample, comprising the steps of: driving particles of a fluid sample through a migration channel of a microfluidic chip; illuminating at least a plurality of spaced sections in a detection region of the migration channel; detecting optical emission from at least the plurality of spaced sections in the detection region of the migration channel; generating a time-domain signal from the optical emission as detected; and transforming the time- domain signal to a frequency-domain signal, which frequency-domain signal provides for characterization of the particles.
  • the characterization provides for measurement of velocities of particles in a fluid medium.
  • the characterization provides for measurement of numbers of particles.
  • the particles are transported in a fluid flow through the migration channel.
  • the particles are driven through a fluid medium in the migration channel.
  • the particles are pressure driven through the migration channel. In another preferred embodiment the particles are driven through the migration channel by hydrodynamic chromatography.
  • the particles are driven through the migration channel by flow-field fractionation.
  • the particles are driven through the migration channel by electrophoresis.
  • the electrophoresis is dielectrophoresis.
  • the particles are driven through the migration channel by hydrodynamic pumping.
  • the hydrodynamic pumping is electrohydrodynamic pumping.
  • the hydrodynamic pumping is magnetohydrodynamic pumping.
  • the step of detecting optical emission comprises the step of detecting fluorescence of the particles.
  • the step of detecting optical emission comprises the step of detecting light scattering from the particles.
  • the step of detecting optical emission comprises the step of detecting optical absorption by the particles.
  • the step of illuminating at least a plurality of spaced sections in the detection region of the migration channel comprises the step of illuminating a plurality of spaced sections in the detection region of the migration channel.
  • illumination is from a laser.
  • the step of detecting optical emission comprises the step of detecting optical emission from each of the plurality of spaced sections in the detection region of the migration channel using a single detector.
  • the step of detecting optical emission comprises the step of detecting optical emission from the plurality of spaced sections in the detection region of the migration channel using a plurality of spaced detector elements, each detecting optical emission from a respective one of the plurality of spaced sections in the detection region of the migration channel.
  • the step of illuminating at least a plurality of spaced sections in the detection region of the migration channel comprises the step of illuminating the detection region of the migration channel
  • the step of detecting optical emission comprises the step of detecting optical emission from a plurality of spaced sections in the detection region of the migration channel using a plurality of spaced detector elements, each detecting optical emission from a respective one of the plurality of spaced sections in the detection region of the migration channel.
  • illumination is from a laser.
  • the method further comprises the step of: diluting the concentration of particles in the fluid sample such that the concentration of particles is less than a predetermined concentration.
  • the concentration of particles is such that the average spacing of particles driven through the migration channel is not less than the center-to-center spacing of adj acent ones of the plurality of spaced sections in the detection region of the migration channel.
  • the concentration of particles is such that the average spacing of particles driven through the migration channel is not less than about 0.5 mm.
  • the concentration of particles is such that the average spacing of particles driven through the migration channel is not less than about 1 mm.
  • the dilution of the fluid sample is in response to the generated time-domain signal.
  • the transform is a Fourier transform.
  • the transform is a wavelet transform.
  • the transform is a continuous wavelet transform.
  • the particles comprise single molecules.
  • the particles comprise particles of a particle-based assay.
  • the assay is an immunoassay.
  • the particles comprise biological cells.
  • the particles comprise blood cells, namely red and white blood cells.
  • the particles comprise viruses.
  • the particles comprise bacteria.
  • the fluid sample comprises a single fluid sample including a plurality of particles of different kind, whereby the method provides for characterization of each different kind of particle.
  • the spaced sections in the detection region of the migration channel are equi-spaced.
  • the wavelength of the illuminating radiation is in the visible spectrum.
  • the wavelength of the illuminating radiation is outside the visible spectrum.
  • Figure 1 schematically illustrates a measurement system in accordance with a preferred embodiment of the present invention
  • Figure 2 illustrates the relative positions of the light source and the optical detector of the measurement system of Figure 1 ;
  • Figure 3 illustrates a plan view of the layout of the chip of the microfabricated particle migration unit of the measurement system of Figure 1;
  • Figure 4 illustrates in enlarged scale the slit array of the chip of Figure 3;
  • Figure 5 illustrates part of the time-domain signal as acquired by the measurement system of Figure 1 in the described Example
  • Figure 6(a) illustrates the frequency-domain magnitude plot of the Fourier transform of the time-domain signal as acquired by the measurement system of Figure 1 in the described Example;
  • Figure 6(b) illustrates in enlarged scale the frequency-domain magnitude plot encompassing the fundamental peak at 7.1 Hz;
  • Figure 7(a) illustrates the time-domain signal as acquired by the measurement system of Figure 1 in the described Example
  • Figure 7(b) illustrates a plot of the wavelet transform in the frequency region about 7 Hz of the time-domain signal as acquired by the measurement system of Figure 1 in the described Example
  • Figure 8 illustrates part of a modified optical detector for the measurement system of Figure 1.
  • the measurement system comprises a microfabricated particle migration unit 1, in this embodiment fabricated as a substrate chip, through which particles of a fluid sample, in this embodiment a liquid sample, are driven.
  • the particle migration unit 1, in this embodiment an electrophoresis chip includes a migration channel 5, in this embodiment an elongate linear channel having a length of 57 mm, through which particles of a fluid sample are driven, a sample reservoir 7 for receiving a volume of a fluid sample, a sample reservoir channel 8, in this embodiment having a length of 5 mm, fluidly connecting the sample reservoir 7 and one end of the migration channel 5, a buffer reservoir 9 for receiving a volume of a buffer solution, a buffer reservoir channel 10, in this embodiment having a length of 37 mm, fluidly connecting the buffer reservoir 9 and the one end of the migration channel 5, a sample waste reservoir 11 for receiving a volume of waste fluid sample, a sample waste channel 12, in this embodiment having a length of 43 mm, fluidly connecting the sample waste reservoir 11 and the one end of the migration channel 5, and a buffer waste reservoir 13 for receiving a volume of waste buffer solution fluidly connected to the other end of the migration channel 5.
  • a migration channel 5 in this embodiment an elongate linear channel having a length of 57
  • the particle migration unit 1 is fabricated from three planar substrate plates, in this embodiment a first, lower plate composed of microsheet glass, a second, intermediate plate composed of poly (dimethylsiloxane) (PMDS), and a third, upper plate composed of microsheet glass.
  • the first plate was etched to form wells which define the migration channel 5, the sample reservoir channel 8, the buffer reservoir channel 10 and the sample waste channel 12.
  • the wells have a depth of 10.5 ⁇ m, a width of 15 ⁇ m at the bottom thereof and a width of 36 ⁇ m at the top thereof.
  • a slit array 15 was fabricated on the third plate, in this embodiment having a thickness of 2.5 mm.
  • the slit array 15 was fabricated by depositing a chromium film having a thickness of 100 nm onto the third plate and patterning the chromium film to provide 375 equi-spaced detection windows 17, each having a width w of 40 ⁇ m and a center-to-center spacing d of 70 ⁇ m.
  • the plates were assembled such that the openings in the second plate were aligned with the wells in the first plate and the slit array 15 on the third plate was aligned with substantially the mid point of the migration channel 5.
  • the measurement system further comprises a light source 19 for providing a light beam, and a lens arrangement 21 for expanding the light beam, in this embodiment as a linear beam, and directing the expanded light beam onto a region of the migration channel 5 in the particle migration unit 1 ; this region of the migration channel 5 being the detection region.
  • the light source 19 comprises an argon ion laser (line at 488 nm; model 532-B-A01, OmNichrome; Melles Griot, Chino, California, US).
  • a single lens a Powell- 10-0.75 lens (Elliot Scientific, Hertfordshire, UK)
  • the light source 19, the lenses 23, 25 of the lens arrangement 21 and the particle migration unit 1 are supported on a vertically-mounted optical rail (not illustrated) (lens mounts and posts on a 2 m X-95 rail and carrier system; Newport, Irvine, California, US).
  • the measurement system further comprises an optical detector 27 for detecting the migration of particles through the migration channel 5 of the particle migration unit 1, in this embodiment by detecting the optical emission of the particles.
  • the optical detector 27 is disposed at an angle from the plane of the expanded light beam, here 30 degrees, and spaced from the detection region of the particle migration unit 1, here by 3.5 cm.
  • the optical detector 27 comprises a photomultiplier tube (PMT), specifically a 5.1 cm diameter head-on PMT (R550 PMT, El 198-11 socket, C3830 power supply; Hamamatsu Photonics, Middlesex, UK), and associated filters, specifically at least one high-pass interference filter, in this embodiment three high-pass interference filters (505EFLP; Omega Optical, Brattleboro, NT, US), at least one Schott filter, in this embodiment three high-pass Schott filters (OG515; Edmund Scientific, Barrington, New Jersey, US), and at least one emission band-pass filter, in this embodiment one fluoroscein emission band-pass filter (520DF15; Omega Optical); the latter filter being disposed downstream of the other filters.
  • the edges of the filters and the PMT are foil wrapped to prevent unfiltered light from reaching the PMT.
  • the measurement system further comprises a data acquisition unit 29 which is connected to the optical detector 27 for logging the output signal thereof.
  • the data acquisition unit 29 comprises a PICO analog-to-digital converter data acquisition unit (ADC; Pico Instruments) having a scan rate set at 100 Hz, and the current signal output from the PMT biased at -1000 V is filtered with a low-pass filter (NBF21 M; Kemo, Kent, UK) set at a 40 Hz cut-off frequency.
  • ADC PICO analog-to-digital converter data acquisition unit
  • NPF21 M Low-pass filter
  • the measurement system further comprises a power supply 31 for applying potentials at the electrodes in each of the sample reservoir 7, the buffer reservoir 9, the sample waste reservoir 11 and the buffer waste reservoir 13.
  • the power supply 31 comprises four multiplexed discrete dc-dc converters.
  • the measurement system further comprises a sample dilution stage 33 for diluting a fluid sample to be measured as necessary; no dilution being necessary where the concentration of particles in the fluid sample is sufficiently low.
  • a sample dilution stage 33 for diluting a fluid sample to be measured as necessary; no dilution being necessary where the concentration of particles in the fluid sample is sufficiently low.
  • the measurement system further comprises a processing unit 35, in this embodiment a personal computer, for controlling the power supply 31 and the dilution stage 33, in this embodiment from a LabNiew program (National Instruments, Austin, Texas, US), and operating on the acquired data.
  • the dilution stage 33 is controlled by a continuous feedback loop such as to increasingly dilute the fluid sample where the acquired time-domain signal does not have the required resolution.
  • FFTs Fast Fourier transforms
  • Igor Pro 3 Widemetrics, Lake Oswego, Oregon, US
  • WTs Wavelet transforms
  • Matlab The Mathworks Inc., Natick, MA, US).
  • the components of the measurement system are disposed in a light-tight box, in this embodiment a galvanized steel box.
  • Tris-Borate-EDTA (TBE) buffer solution was prepared at O.lx concentration (8.9 mM each of tris-(methoxy)aminomethane and boric acid, 0.2 mM in ethylenediaminetetraacetic acid; prepared from a solid TBE mixture (Fluka, Buchs, Switzerland)) with de-ionized water and filtered through 0.2 mm filters (Millisart ® ).
  • the use of a TBE buffer solution has been found to almost completely eliminate both particle aggregation and adhesion of the particles to the channel walls.
  • a 150 ⁇ M fluoroscein in O.lx TBE solution was prepared by dissolving an appropriate amount of sodium fluoroscein (salt, Fluka) in the O.lx TBE solution.
  • a cleaning solution of 0.5 M sodium hydroxide was prepared from de-ionized water and sodium hydroxide (BDH, Poole, UK).
  • a 0.002 % (-3.6 x 10 6 microspheres/mL) fluorescent microspheres sample solution was prepared by diluting the stock fluorescent polystyrene microspheres sample (2 %) by 1000-fold with the O.lx TBE solution.
  • the particle migration unit 1 was prepared by first drawing an amount of the cleaning solution and then the TBE buffer solution thereinto.
  • the cleaning solution and the TBE buffer solution were drawn into the particle migration unit 1 by applying a vacuum to one of the reservoirs 7, 9, 11, 13 and supplying first the cleaning solution and then the TBE buffer solution to the other of the reservoirs 7, 9, 11, 13.
  • the sample reservoir 7 was then filled with fluoroscein solution, and this solution was then drawn into the migration channel 5 by applying a vacuum to the buffer waste reservoir 13, with the TBE buffer solution being supplied to the other reservoirs.
  • the sample reservoir 7 was then emptied of the remaining fluoroscein solution and filled with sample solution, and the buffer waste reservoir 13 was filled with the TBE buffer solution.
  • the migration channel 5, now loaded with fluorescein solution, was then aligned with the light beam, such that the linear light beam irradiated the detection region of the migration channel 5 through the windows 17 in the slit array 15.
  • a high- voltage protocol as given in Table 1, was then run.
  • the fluorescein solution was purged from the migration channel 5 into the buffer waste reservoir 13.
  • the fluorescent microspheres in the sample reservoir 7 were drawn into and through the migration channel 5.
  • the time-domain signal as detected by the optical detector 27 was then recorded for a period of 120 s; the data points being stored as text files in the data acquisition unit 29 and processed using Igor Pro 3 in the processing unit 35.
  • Figure 5 illustrates part of the time-domain signal.
  • analysis of the data is by way of a Fourier transform (FT) or a wavelet transform (WT). Analysis of the data using both of these techniques will be described hereinbelow.
  • FT Fourier transform
  • WT wavelet transform
  • Figure 6(a) illustrates the resulting magnitude plot in the frequency domain, with a fundamental peak having a center frequency of 7.1 Hz and an S/N ratio of 16 being determined.
  • the velocity of the particles u is given by equation (2) below, where /is the frequency of the fundamental peak and d is the center-to-center spacing between adjacent detection windows 17.
  • a fundamental peak frequency of 7.1 Hz translates to a velocity of 497 ⁇ ms "1 (7.1 Hz x 70 ⁇ m).
  • the number of particles detected is represented by the amplitude of the fundamental peak.
  • the frequency-domain signal also provides for measurement of numbers of particles.
  • Figure 6(b) illustrates in enlarged scale the section of the magnitude plot of Figure 6(a) encompassing the fundamental peak at 7.1 Hz.
  • the fundamental peak comprises a plurality of narrow peaks centred about a frequency of 7.1 Hz, each peak representing a particular velocity.
  • a plurality of peaks are observed as a plurality of particles having different velocities passed the detection region during the sampling period. This distribution in velocities arises as a result of a distribution in the charge-to- size ratios of the particles.
  • WT is performed by moving a short piece of a waveform ('wavelet') along the time axis of the signal and expressing the goodness of fit at every location in a coefficient C(l,t).
  • the wavelet is subsequently scaled with a scaling factor a and the process repeated providing coefficients C( ⁇ ,t).
  • This scaling is then repeated with further, higher scaling factors a to achieve a higher compression.
  • Typical representations of a wavelet transform present the goodness of fit (the values of C(a,t)) in a two-dimensional plot, with the time on the x-axis and the scaling factor a on the y axis. Scaling factor a is thereby proportional to the frequency.
  • the scaling can be done with factors of two (discrete wavelet transform) or in a continuous fashion (continuous wavelet transform).
  • WT decreases the size of the analysis window with increasing frequency, yielding a higher time resolution.
  • the wavelet was designed to give an optimal balance between time and frequency resolution for the acquired data.
  • the high power of x was chosen such as to cause the envelope of the wavelet to have steep boundaries and thereby provide a sharper resolution of the particles on the time scale.
  • the coefficient in the cosine function was adjusted to produce a wavelet of about 50 periods, fitting exactly on the 50 emission peaks generated by a moving particle. The selection of 50 oscillations maximises the frequency information and provides a time separation between successive particles.
  • Figures 7(a) and (b) illustrate respectively the time-domain signal and a plot of the fit coefficients of a continuous WT with the wavelet of equation (3) for frequencies around 7 Hz. Maxima can be clearly distinguished, indicating particles travelling with particular velocities at different times. The range of frequencies observed is between 6.8 and 7.3 Hz which is in accordance with the results of the FT transform.
  • the velocity of the particles is derived from a multiplication of the frequency /with the center-to-center spacing d of adjacent windows 17, in this embodiment 70 ⁇ m, as given above in equation (2).
  • the number of particles detected is determined from a determination of the number of maxima.
  • the number of maxima is estimated at between 60 and 70 particles, which is in accordance with the number calculated from the particle concentration.
  • the slit array 15 could be formed such that the windows 17 have a width which is half the center-to-center spacing of adjacent windows 17, for example, windows 17 having a width of 35 ⁇ m and a center-to-center spacing of 70 ⁇ m. In this way, the first harmonics could be removed from the frequency-domain plots.
  • particles are electrophoretically driven tlirough a fluid medium.
  • this transport mechanism is exemplary and that many transport mechanisms could be employed.
  • particles could be transported in a fluid flow through the migration channel or driven through a fluid medium in the migration channel.
  • particles could be pressure driven through the migration channel, driven through the migration channel by hydrodynamic chromatography, driven through the migration channel by flow-field fractionation, driven through the migration channel by electrophoresis, in particular dielectrophoresis, and driven through the migration channel by hydrodynamic pumping, in particular electrohydrodynamic pumping and magnetohydrodynamic pumping.
  • the detection of particles is by the fluorescent emission of the particles. It should be appreciated that this particular kind of optical detection is exemplary and that many detection techniques could be utilized. Other techniques include detection of the light scattering from the particles and the optical absorption by the particles.
  • the Shah detection function is achieved by utilising a slit array 15 to illuminate a plurality of spaced sections in the detection region of the migration channel 5.
  • this illumination technique is exemplary and that the Shah detection function could be otherwise achieved.
  • a plurality of spaced light elements could be utilized to illuminate the plurality of spaced sections in the detection region of the migration channel 5.
  • the measurement system could comprise at least one light source and a plurality of light-transmitting elements, such as holographic lenses, waveguides and optical fibers, coupled to the at least one light source and disposed in spaced relation to the detection region in the migration channel 5 such as to illuminate respective ones of the plurality of spaced sections in the detection region of the migration channel 5.
  • the Shah detection function could be realized through the detection technique instead of the illumination technique.
  • the measurement system could comprise a single light source 19 for illuminating the detection region of the migration channel 5, and, as illustrated in Figure 8, an optical detector 27 which comprises a plurality of spaced detector elements 37, such as photodetectors, for detecting optical emission from a plurality of spaced sections in the detection region of the migration channel 5.
  • an optical detector 27 could be provided by a continuous array of detector elements 37, ones 37a of which are operative to detect optical emission and others 37b of which are inoperative.
  • One advantage of such a detector 27 would be to enable the center-to- center spacing of the spaced sections in the detection region which are to be detected to be readily altered according to a required detection regime.
  • the operation of the described embodiment has been described in relation to detecting fluorescent microspheres. It should be appreciated that the detection of microspheres is purely exemplary, and that the measurement technique of the present invention extends to the detection of any particles. In this regard, the measurement technique of the present invention finds particular application in the detection of single molecules, particles of particle-based assays, in particular an immunoassays, and biological cells, such as red and white blood cells, viruses and bacteria.

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Abstract

L'invention concerne un procédé et un système de mesure permettant de caractériser des particules d'un échantillon de fluide. Ledit système comporte : une puce microfluidique comportant un canal de migration à travers lequel des particules d'un échantillon de fluide sont conduites dans un milieu fluide ; une unité d'éclairage permettant d'éclairer au moins une pluralité de sections espacées dans une zone de détection du canal de migration ; un détecteur optique permettant de détecter une émission optique d'au moins la pluralité de sections espacées dans la zone de détection du canal de migration ; une unité d'acquisition permettant de générer un signal en domaine temporel de l'émission optique détectée ; et une unité de traitement couplée de manière fonctionnelle à l'unité d'acquisition, afin de recevoir le signal en domaine temporel et de transformer le signal en domaine temporel en un signal en domaine fréquentiel, ledit signal en domaine fréquentiel caractérisant les particules.
PCT/GB2001/004552 2001-10-12 2001-10-12 Systeme de mesure de particules utilisant un transformateur temps-frequence WO2003034041A1 (fr)

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US8308926B2 (en) 2007-08-20 2012-11-13 Purdue Research Foundation Microfluidic pumping based on dielectrophoresis
CN106092865A (zh) * 2016-08-12 2016-11-09 南京理工大学 一种基于数字微流控的荧光液滴分选系统及其分选方法
CN107615041A (zh) * 2015-10-07 2018-01-19 Afi技术公司 检查装置、检查系统以及检查方法
EP2593771A4 (fr) * 2010-07-16 2018-02-21 Luminex Corporation Procédés, supports de stockage et systèmes pour analyser une quantité et une distribution de particules dans une région d'imagerie d'un système d'analyse de dosage et pour évaluer les performances d'un routage concentrant effectué sur un système d'analyse de dosage

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Cited By (7)

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US8308926B2 (en) 2007-08-20 2012-11-13 Purdue Research Foundation Microfluidic pumping based on dielectrophoresis
US8470151B2 (en) 2007-08-20 2013-06-25 Purdue Research Foundation Microfluidic pumping based on dielectrophoresis
EP2593771A4 (fr) * 2010-07-16 2018-02-21 Luminex Corporation Procédés, supports de stockage et systèmes pour analyser une quantité et une distribution de particules dans une région d'imagerie d'un système d'analyse de dosage et pour évaluer les performances d'un routage concentrant effectué sur un système d'analyse de dosage
CN102759621A (zh) * 2011-04-26 2012-10-31 复旦大学 基于微流控芯片的高通量快速检测疟疾血清的方法
CN107615041A (zh) * 2015-10-07 2018-01-19 Afi技术公司 检查装置、检查系统以及检查方法
CN106092865A (zh) * 2016-08-12 2016-11-09 南京理工大学 一种基于数字微流控的荧光液滴分选系统及其分选方法
CN106092865B (zh) * 2016-08-12 2018-10-02 南京理工大学 一种基于数字微流控的荧光液滴分选系统及其分选方法

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