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WO1998010122A1 - Reseau capillaire hybride a microstructure et ensemble de detection a canaux multiples - Google Patents

Reseau capillaire hybride a microstructure et ensemble de detection a canaux multiples Download PDF

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Publication number
WO1998010122A1
WO1998010122A1 PCT/US1997/015461 US9715461W WO9810122A1 WO 1998010122 A1 WO1998010122 A1 WO 1998010122A1 US 9715461 W US9715461 W US 9715461W WO 9810122 A1 WO9810122 A1 WO 9810122A1
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WO
WIPO (PCT)
Prior art keywords
channels
substrate
microfabricated
capillaries
assembly
Prior art date
Application number
PCT/US1997/015461
Other languages
English (en)
Inventor
Barry L. Karger
Shaorong Liu
Frantisek Foret
Quifeng Xue
Original Assignee
Northeastern University
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 Northeastern University filed Critical Northeastern University
Publication of WO1998010122A1 publication Critical patent/WO1998010122A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44704—Details; Accessories
    • G01N27/44717—Arrangements for investigating the separated zones, e.g. localising zones
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44704—Details; Accessories
    • G01N27/44717—Arrangements for investigating the separated zones, e.g. localising zones
    • G01N27/44721—Arrangements for investigating the separated zones, e.g. localising zones by optical means
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44704—Details; Accessories
    • G01N27/44743—Introducing samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44756—Apparatus specially adapted therefor
    • G01N27/44791—Microapparatus

Definitions

  • the present invention relates in general to chemical and biological analytical systems. BACKGROUND OF THE INVENTION
  • one analytical method used if there are many capillaries in an array has detectors or light sources moving at a sufficient speed that peak signals from all of the capillaries will be observed.
  • sensitivity may be decreased if this method is used because the integration time for each capillary is limited.
  • the limited data acquisition rate and mechanical vibration noise may also cause problems.
  • Proper alignment of the capillaries vis-a-vis the coherent light source, so that each capillary receives the intended light intensity is also very important but is difficult to achieve in practice.
  • multiple capillaries in an array cannot be spaced sufficiently closely to achieve the density required for simultaneous detection of very large numbers of samples.
  • the limited available surface area on a chip furthermore makes it difficult to introduce sample to the chip by conventional means, particularly in a multi-channel mode.
  • sample introduction means are necessary to place a new sample onto the chip for each consecutive analysis.
  • the chips developed for capillary electrophoresis have large inlet ports for pipetting in the sample.
  • a given sample, once loaded onto the chip, can be analyzed repeatedly; however, different new samples can be analyzed only with difficulty.
  • Such a system may be a good design for a cheap, disposable device, but it does not allow the chip to be reused easily.
  • microfabricated device is made of an expensive material, e.g., quartz, or contains complex, difficult to fabricate structures which make the concept of disposability too expensive.
  • an interface would also be desirable when a sample is to be processed through multiple analytical procedures off chip, e.g., when part of the analysis is performed in a standard non-micromachined instrument, followed by consecutive analytical (e.g., detection) steps on a microfabricated device.
  • An additonal advantage of such a configuration would be that only a portion of an analyzed sample need be applied to a microfabricated device. The remaining portion could be used for other purposes.
  • the hybrid microfabricated substrate (e.g., microchip) capillary array assembly of the invention combines the separation power available in capillary electrophoresis with the convenience-of-manipulation capability (e.g., reaction or separation) and detection in the microchip format.
  • the invention is directed to a hybrid microfabricated substrate capillary array assembly that includes one or more capillaries each having a first cross-sectional shape; a microfabricated substrate including one or more channels for conducting a fluid in the substrate, the one or more channels each having a second cross-sectional shape; and a connecting structure formed in the substrate, connecting the one or more capillaries to the one or more channels in the substrate so as to enable fluid communication between the capillaries and the channels.
  • the capillaries and the channels each may be of any convenient cross-sectional shape, e.g., ellipsoidal, trapezoidal or circular.
  • the channels can also be different shapes in different portions of the substrate.
  • the substrate is of a light transmissive material
  • both the capillaries and the channels are circular in cross-section where they join, and the channels are substantially parallel to one another and lie substantially in the same plane at a position in the substrate where detection might take place.
  • Either the capillaries or the channels can be configured for transport or manipulation (e.g., separation or reaction) of fluid suspended molecular species conducted therethrough.
  • the channels are spaced very closely together at one end and terminate at a common port, which can be configured, e.g., for fluid washing of the channels or for replacement of fluid media, for example separation matrix.
  • the invention is directed to a multichannel detection assembly that includes a light transmissive microfabricated substrate having a plurality of channels formed therein for conducting a fluid in the substrate, the channels being positioned substantially parallel to each other and defining a plane in the substrate; a light source having an output directed through the substrate at an angle to the plane, wherein the angle is less than the critical reflective angle of the substrate, the light source output travelling through the plurality of channels; and a detector positioned adjacent to the substrate to receive light transmitted through the channels in the substrate.
  • the channels are spaced more closely together at one end than at the other and the light source is positioned so that the light source output travels through the plurality of channels in the plane defined by the channels and at the end of the substrate in which the channels are more closely spaced.
  • the light source and detector may be any combination known to those of skill in the art as likely to detect the molecular species being analyzed.
  • the light source is a laser
  • the detector is a fluorescence detector and sample analysis is by laser fluorescence detection.
  • the light source could be, e.g., UV light
  • the detector could be, e.g., an absorbance detector.
  • the hybrid microfabricated substrate capillary array assembly of the invention is useful, for example, as an injection system for repeated introduction of different samples into a reusable microfabricated device, e.g. a microchip.
  • Sample separation or other analytical procedures such as reaction or derivatization, can be carried out directly on the microchip.
  • the channels in the microchip can conveniently be washed via their common termination port.
  • the interface assembly of the invention can be used simply to provide access to an on-chip detection system following various off-chip analytical procedures, e.g., separation of samples in the individual capillaries of the system capillary array.
  • FIG. 1 is a diagram of an embodiment of a hybrid microchip capillary array assembly of the invention
  • Fig. 2A is a diagram of a first embodiment of a chip-to- capillary array interface
  • Fig. 2B is a diagram of a second embodiment of a chip-to- capillary array interface
  • Fig. 2C is a diagram of a third embodiment of a chip- to- capillary array interface
  • Fig. 3A is a diagram of a section of a microfabricated multichannel detection assembly of the invention in which the output of the excitation light source is directed perpendicular to the side edge of the substrate microchip
  • Fig. 3B is a diagram of a section of a microfabricated multichannel detection assembly of the invention in which the output of the excitation light source is directed at an angle with respect to the side edge of the substrate microchip
  • Figs. 4A and 4B show laser induced fluorescence detection of DNA sequencing reaction products separated on a hybrid microchip capillary array assembly of the invention and a capillary-only instrument, respectively;
  • Fig. 5 shows an image of the fluorescence signal from all channels of the embodiment of Fig. 1 under side illumination
  • Fig. 6 is a diagram showing a microfabricated hybrid capillary array and multichannel detection assembly of the invention in use for analysis of samples in a microtiter well plate .
  • the microfabricated hybrid capillary array and multichannel detection assembly of the invention includes a number of features which are independently useful.
  • a microchip 10 is fabricated to contain a plurality of channels 12, useful, e.g., for simultaneous sample detection, each of which is adapted at one end 14 to receive a flexible capillary 16 from an array of capillaries 18.
  • channels 12 are spaced further apart in region 13 of the microchip, for ease of coupling with capillary array 18, and are spaced more closely together in region 15 of the microchip to facilitate on-chip detection of separated samples, as will be described in more detail below.
  • Channels 12 terminate by merging to a common port 20.
  • This port provides a place for connection to a common buffer reservoir (e.g., anodic) for all channels and serves as a means to wash or replace any matrix material in the channels.
  • a common buffer reservoir e.g., anodic
  • grooves which are semicircular in cross-section are formed by isotropic etching in mirror image on the surface of two substrates, e.g., glass wafers. The substrates are then bonded together to mate the channel halves and form circular channels in the body of the substrate microchip, to which flexible capillaries, which are similarly circular in cross-section, may be mated.
  • Common photolithographic technology enables fabrication of tightly packed channels on such a chip; for example, in an area as small as 5 cm wide on a glass or fused-silica wafer, it is possible to fabricate 500 channels 50 ⁇ m wide, spaced 50 ⁇ m apart.
  • the completed assembly, microchip plus attached capillary array, can be supported in a chip holder.
  • the diameters 22 of the channels 12 are fabricated so they are the same dimension as the outer diameter of the capillaries 16 in the array.
  • the capillaries are inserted directly into the chip channels and glued in place.
  • this fabrication process is simple, a junction 24 is created in which the size of the resulting passage diameter changes sharply from capillary to channel, which may result in some degradation in resolution of separated samples.
  • a multi-step fabrication process may be used to create channels of different diameters for different segments of the chip.
  • the individual capillaries 16 of the capillary array 18 are inserted into the chip segment with the larger diameter portions 32 of the channels.
  • the capillaries extend no further than the beginning of the chip segment with smaller diameter 34 channel portions (which match the inner diameters of the capillaries) .
  • the advantage of this embodiment over a two-chip combination is that there is no need to align and seal the separately constructed chips .
  • a further embodiment as shown in Fig. 2C, comprises two chips 52, 54 of differing channel sizes mated together.
  • first chip 54 which can function as a disposable capillary array holder
  • channel diameters 56 are the same as, or slightly larger than, the outer diameters of the capillaries in the array.
  • Capillaries 16 are inserted into the channels in the first chip 54, and they are then sealed and blunt cut at the point where they exit the channels.
  • the channels in the second chip 52 are constructed to match the inner diameters 58 of the capillaries. Since the channels of both chips 52, 54 are measured precisely, it is possible to achieve perfect or near perfect alignment of the capillary array and the channels on the chip.
  • the finished device thus provides a uniform capillary-to-channel inner diameter and the capability for simple replacement of the capillary array.
  • An important aspect of this embodiment is that two chips of different materials can be combined.
  • the first chip 54 can be made of an inexpensive material (such as glass, plastic or polymer) so that it is disposable, since it serves only as a framework or holder for the capillaries.
  • the second chip 52 which can be employed for detection, can be made of a more expensive material, e.g., quartz.
  • the flexible capillaries of the array can be used, e.g., for sample injections or for cleaning of the channels on the chip.
  • This structure allows sample injection conduits to be omitted from the chip, leaving more space for channel fabrication.
  • the attached array of capillaries effectively extends the lengths of the channels on the chip.
  • the capillaries of the array can be used for analyte separation, which eliminates the need for inconvenient and time-consuming preparation of the microchip channels themselves before runs, a shortcoming previously associated with microfabricated chips.
  • the presented embodiments for introducing samples and supporting fluids to a microchip have the advantage of being easy to fabricate, since no drilling of holes and/or preparation of wells is required. When the chip is fully machined, the size and position of channels are precise; therefore, the manufacture of the device can be automated. Since microfabrication enables design of complex conduits on a chip, once samples and supporting fluids are introduced, it is possible to conduct most types of chemical operations (reagent addition, separation/mixing, concentration, dilution, etc.) on the chip itself .
  • the closely spaced channels on the microfabricated chip provide an excellent environment for detection of samples travelling in the channels. For example, detection may be performed by introducing a laser perpendicular to the side edge of the device (i.e., side illumination as shown in Fig. 3A) such that the laser traverses the entire array of channels or by introducing the laser at an angle to the side of the chip. Since the chip is surrounded by air, which has a lower index of refraction than the chip material, the microfabricated device acts as an optical wave guide for the laser light. Multiple reflections occur within the chip to illuminate the solutions in all the channels uniformly.
  • a laser perpendicular to the side edge of the device i.e., side illumination as shown in Fig. 3A
  • the microfabricated device acts as an optical wave guide for the laser light. Multiple reflections occur within the chip to illuminate the solutions in all the channels uniformly.
  • Laser-induced fluorescence (LIF) detection is often a method of choice for sensitive detection on microfabricated chips.
  • a laser beam or other excitation light source 60 is introduced at one side, or edge, 62 of the chip 64, parallel to the plane defined by the separation channel (s) 66 and directed through all the channels. It is most convenient to position the laser beam at the region of the chip where the channels are most closely spaced, as depicted in Fig. 1.
  • Emitted fluorescence from molecular species travelling in the channels under the influence of an electric field is detected via a detection system 68, placed adjacent to the body of the microchip on one side or the other of the plane defined by the channels.
  • the refractive index of a buffer solution present in the channels can be adjusted (e.g., by addition of sucrose) to match the refractive index of the device material.
  • the excitation light travels from the first channel to the last, traversing the entire group. In some cases the refractive index of the separation matrix may not match that of the material of the chip, and the excitation laser light may be scattered from the walls between the channels.
  • the walls between the channels could be removed at the cross-section at which detection is carried out, to form gaps in the channels, and thus eliminate any laser scatter. Since the gap can be very short (0.1-2 mm), the electric field would not be severely distorted, preventing any channel cross-contamination.
  • the laser beam may be shaped into a line to illuminate all the channels from a side of the chip above or below the plane of the channels, or an array of beams for individual illumination of each channel can be used. In an alternative detection scheme, as shown in Fig.
  • the solutions in the individual channels can be illuminated by introducing the laser beam at an angle 68 less than the critical angle of the substrate material, so that inner multireflection occurs.
  • the device body also functions as a wave guide for the excitation light.
  • the reflected laser beam then illuminates the solution in every channel . Fluorescence detection is again carried out above and/or beneath the device .
  • Example I Capillary electrophoresis of a single terminator DNA sequencing reaction, which produces fragments having single stranded DNA base lengths ranging from 77 to 503, was carried out in a capillary of 30 cm effective length using 2% w/v liquid polyacrylamide (Fig. 4B) and on a hybrid chip of the invention having a capillary of the same length (Fig. 4A) .
  • the time based peak widths do not vary significantly between runs of the different capillary configurations, and therefore, no significant resolution degradation was found for DNA sequencing when a capillary and a channel on a chip were joined (Fig. 4A) compared to the single capillary setup (Fig. 4B) .
  • Example II The side illumination detection system of the invention was also tested.
  • a fluorescent solution of 2 X 10 ⁇ 7 M fluorescein was injected into channels of a microfabricated chip.
  • An excitation laser beam was introduced from the edge of the chip, parallel to the plane of the channels in the chip. As the beam was reflected within the chip, it illuminated all the channels.
  • the upper panel of Fig. 5 shows the fluorescence signals from all channels of the chip, which were recorded by a CCD camera.
  • the lower panel of Fig. 5 was generated from the upper panel data, by measuring the intensity profiles of the fluorescent spots, and shows that the fluorescence intensity of each channel is relatively uniform. This example illustrates that multiple channels can be illuminated from the side of the chip with relatively even fluorescence emission.
  • Example III Fig. 6 is a simplified depiction of a multichannel detection assembly 70 in accordance with the invention in use to screen samples from a microtiter well plate.
  • Detection assembly 70 features a microfabricated chip 71 containing a plurality of channels 72 of a circular cross-section, which have been filled with a separation matrix.
  • the channels 72 are mated to external capillaries 73 via connecting structures 74, constructed substantially as described above, and the capillaries are glued in place.
  • the array of external capillaries 73 serves as an injection apparatus to transfer samples to microchip 71 for analysis, in the following manner.
  • the ends of capillaries 73, distant from the microchip, are inserted in open wells 75 of microtiter plate 76, which contain the samples to be analyzed.
  • Electrodes 77 which are also inserted in microtiter plate wells 75, are electrically connected to high voltage power supply 78.
  • Power supply 78 provides the electromotive force necessary to move sample analytes and fluid through the capillaries 73 to the channels of microchip 71.
  • High voltage power supply 78 is further connected via power line 79 to buffer reservoir and pump 80, which is in fluid communication with microchip channels 72 via conduit 81 inserted in common channel termination port 82, to complete the electrical circuit.
  • charged analytes from sample wells 75 are transferred via capillaries 73 to channels 72 in the microchip, where they are separated in the separation matrix contained in the channels.
  • Laser 83 which is aligned to direct the laser output across all of channels 72, is used to excite the separated analytes of a given sample in channels 72 as they pass by the laser position. Fluorescence emission from sample analytes is detected by multichannel fluorescence detector 84 and presented in any conventional manner to give the results of the specific separation.
  • Laser 83 may be positioned at the portion of the microchip where channels 72 are very closely spaced, as shown in Fig. 6.
  • analyte separation is carried out in capillaries 73 instead of in the channels 72 of the microchip, it may be preferable to position the laser just beyond connecting structures 74 so that detection can be carried out before the bands of separated analytes can disperse.
  • the electrical circuit can be disconnected, capillaries 73 can be removed from the sample wells, and pump 80 can be used to pump washing fluid through the matrix in channels 72 or to replace the matrix completely, in preparation for analysis of additional samples.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Electrochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Dispersion Chemistry (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Optical Measuring Cells (AREA)

Abstract

L'invention concerne un ensemble réseau capillaire à substrat à microstructure hybride, servant d'interface entre les canaux intégrés (12) sur un substrat (10) à microstructure, comme par exemple une micropuce, et des capillaires flexibles (18). Le dispositif hybride permet, par exemple, une injection apropriée d'échantillons provenant d'un réseau capillaire (18) dans des canaux (12) situés sur une micropuce (10) et permet également, par exemple, une détection appropriée sur le dispositif par fluorescence induite par laser. Grâce à l'utilisation d'un tel ensemble, on peut traiter simultanément une grande quantité d'échantillons, ce qui permet d'effectuer des analyses à grande vitesse et à haut rendement.
PCT/US1997/015461 1996-09-03 1997-09-03 Reseau capillaire hybride a microstructure et ensemble de detection a canaux multiples WO1998010122A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US2509896P 1996-09-03 1996-09-03
US60/025,098 1996-09-03
US92167197A 1997-09-02 1997-09-02
US08/921,671 1997-09-02

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WO1998010122A1 true WO1998010122A1 (fr) 1998-03-12

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Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999046590A1 (fr) * 1998-03-12 1999-09-16 Imperial College Of Science, Technology & Medicine Dispositif d'electrophorese capillaire
WO2000008451A1 (fr) * 1998-08-07 2000-02-17 The Regents Of The University Of California Systeme et procede de localisation optique des positions de microcanaux
WO2000005435A3 (fr) * 1998-07-24 2000-04-27 Ce Resources Pte Ltd Appareil d'electrophorese en reseau
WO2001020309A1 (fr) * 1999-09-13 2001-03-22 Aclara Biosciences, Inc. Canaux de microfluides activites par une lumiere laterale
WO2001036667A1 (fr) * 1999-11-16 2001-05-25 Medical Laboratory Center Of South Western Hospital Third Military Medical University Procede de detection automatique d'un gene cible et applications d'un detecteur utilise dans ce procede
KR100320752B1 (ko) * 1999-08-06 2002-01-17 박한오 자동 시료 미세배열 장치
WO2001068898A3 (fr) * 2000-03-14 2002-03-07 Molecular Dynamics Inc Puce d'electrophorese pseudoradiale
WO2001038844A3 (fr) * 1999-11-12 2002-06-20 Motorola Inc Dispositifs d"electrophorese capillaire comportant des guides d"ondes optiques
WO2002059592A3 (fr) * 2001-01-26 2002-12-19 Biocal Technology Inc Detection optique dans un systeme bioseparateur a canaux multiples
EP1089073A3 (fr) * 1999-09-29 2003-05-21 Hitachi, Ltd. Appareil d'électrophorèse capillaire et réseau de capillaires
US6605472B1 (en) * 1998-10-09 2003-08-12 The Governors Of The University Of Alberta Microfluidic devices connected to glass capillaries with minimal dead volume
EP1340543A1 (fr) * 2002-02-28 2003-09-03 ibidi GmbH Système microfluidique
WO2003072251A3 (fr) * 2002-02-28 2004-02-19 Ibidi Gmbh Systeme microfluidique
KR100456213B1 (ko) * 2002-05-02 2004-11-09 주식회사 가이아모 시료배열장치용 초미세 인쇄용 펜
US6870165B2 (en) 2001-10-19 2005-03-22 Biocal Technology, Inc. Multi-color multiplexed analysis in a bio-separation system
US7208072B2 (en) 2002-01-18 2007-04-24 Biocal Technology, Inc. Multi-segment cartridge for bio-separation with multiplexed fluorescence detection
US7309409B2 (en) 2001-01-26 2007-12-18 Biocal Technology, Inc. Multi-channel bio-separation cartridge
EP1560021A3 (fr) * 2004-01-28 2007-12-19 Shimadzu Corporation Procédé et dispositif de traitement de micro-plaquettes
EP1459052A4 (fr) * 2001-12-19 2008-12-10 3M Innovative Properties Co Dispositif analytique a illumination de reseaux capillaires et de micro-rainures par guide de lumiere
EP2148193A4 (fr) * 2007-04-27 2010-08-18 Nat Inst Of Advanced Ind Scien Puce d'electrophorese, dispositif d'electrophorese et procede d'analyse d'echantillon par un procede d'electrophorese capillaire
CN106885836A (zh) * 2017-04-19 2017-06-23 冯超 书写字迹色痕检测仪
CN107850542A (zh) * 2015-08-21 2018-03-27 株式会社日立制作所 光检测装置

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4908112A (en) * 1988-06-16 1990-03-13 E. I. Du Pont De Nemours & Co. Silicon semiconductor wafer for analyzing micronic biological samples
US5366608A (en) * 1991-09-13 1994-11-22 Hitachi, Ltd. Electrophoresis gel migration apparatus
US5674743A (en) * 1993-02-01 1997-10-07 Seq, Ltd. Methods and apparatus for DNA sequencing

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4908112A (en) * 1988-06-16 1990-03-13 E. I. Du Pont De Nemours & Co. Silicon semiconductor wafer for analyzing micronic biological samples
US5366608A (en) * 1991-09-13 1994-11-22 Hitachi, Ltd. Electrophoresis gel migration apparatus
US5674743A (en) * 1993-02-01 1997-10-07 Seq, Ltd. Methods and apparatus for DNA sequencing

Cited By (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999046590A1 (fr) * 1998-03-12 1999-09-16 Imperial College Of Science, Technology & Medicine Dispositif d'electrophorese capillaire
WO2000005435A3 (fr) * 1998-07-24 2000-04-27 Ce Resources Pte Ltd Appareil d'electrophorese en reseau
WO2000008451A1 (fr) * 1998-08-07 2000-02-17 The Regents Of The University Of California Systeme et procede de localisation optique des positions de microcanaux
US6225635B1 (en) 1998-08-07 2001-05-01 The Regents Of The University Of California System and method for optically locating microchannel positions
US6605472B1 (en) * 1998-10-09 2003-08-12 The Governors Of The University Of Alberta Microfluidic devices connected to glass capillaries with minimal dead volume
KR100320752B1 (ko) * 1999-08-06 2002-01-17 박한오 자동 시료 미세배열 장치
WO2001020309A1 (fr) * 1999-09-13 2001-03-22 Aclara Biosciences, Inc. Canaux de microfluides activites par une lumiere laterale
US7014746B2 (en) 1999-09-29 2006-03-21 Hitachi, Ltd. Capillary electrophoretic instrument and capillary array assembly
EP1089073A3 (fr) * 1999-09-29 2003-05-21 Hitachi, Ltd. Appareil d'électrophorèse capillaire et réseau de capillaires
US7662269B2 (en) 1999-09-29 2010-02-16 Hitachi, Ltd. Capillary electrophoretic instrument and capillary array assembly
WO2001038844A3 (fr) * 1999-11-12 2002-06-20 Motorola Inc Dispositifs d"electrophorese capillaire comportant des guides d"ondes optiques
US6592733B1 (en) 1999-11-12 2003-07-15 Motorola, Inc. Capillary electrophoresis devices incorporating optical waveguides
WO2001036667A1 (fr) * 1999-11-16 2001-05-25 Medical Laboratory Center Of South Western Hospital Third Military Medical University Procede de detection automatique d'un gene cible et applications d'un detecteur utilise dans ce procede
WO2001068898A3 (fr) * 2000-03-14 2002-03-07 Molecular Dynamics Inc Puce d'electrophorese pseudoradiale
WO2002059592A3 (fr) * 2001-01-26 2002-12-19 Biocal Technology Inc Detection optique dans un systeme bioseparateur a canaux multiples
US6828567B2 (en) 2001-01-26 2004-12-07 Biocal Technology, Inc. Optical detection in a multi-channel bio-separation system
US7309409B2 (en) 2001-01-26 2007-12-18 Biocal Technology, Inc. Multi-channel bio-separation cartridge
US6870165B2 (en) 2001-10-19 2005-03-22 Biocal Technology, Inc. Multi-color multiplexed analysis in a bio-separation system
US8268249B2 (en) 2001-12-19 2012-09-18 3M Innovative Properties Company Analytical device with lightguide illumination of capillary and microgroove arrays
EP1459052A4 (fr) * 2001-12-19 2008-12-10 3M Innovative Properties Co Dispositif analytique a illumination de reseaux capillaires et de micro-rainures par guide de lumiere
US7208072B2 (en) 2002-01-18 2007-04-24 Biocal Technology, Inc. Multi-segment cartridge for bio-separation with multiplexed fluorescence detection
US8162357B2 (en) 2002-02-28 2012-04-24 Ibidi Gmbh Microfluid system connection
WO2003072251A3 (fr) * 2002-02-28 2004-02-19 Ibidi Gmbh Systeme microfluidique
EP1880765A3 (fr) * 2002-02-28 2008-01-30 ibidi GmbH Système microliquide
EP1340543A1 (fr) * 2002-02-28 2003-09-03 ibidi GmbH Système microfluidique
KR100456213B1 (ko) * 2002-05-02 2004-11-09 주식회사 가이아모 시료배열장치용 초미세 인쇄용 펜
US7678254B2 (en) 2004-01-28 2010-03-16 Shimadzu Corporation Microchip processing method and apparatus
US8187442B2 (en) 2004-01-28 2012-05-29 Shimadzu Corporation Microchip processing method and apparatus
EP1560021A3 (fr) * 2004-01-28 2007-12-19 Shimadzu Corporation Procédé et dispositif de traitement de micro-plaquettes
EP2148193A4 (fr) * 2007-04-27 2010-08-18 Nat Inst Of Advanced Ind Scien Puce d'electrophorese, dispositif d'electrophorese et procede d'analyse d'echantillon par un procede d'electrophorese capillaire
US9494553B2 (en) 2007-04-27 2016-11-15 National Institute Of Advanced Industrial Science And Technology Electrophoresis chip, electrophoresis apparatus, and method for analyzing sample by capillary electrophoresis
CN107850542A (zh) * 2015-08-21 2018-03-27 株式会社日立制作所 光检测装置
EP3339841A4 (fr) * 2015-08-21 2019-04-10 Hitachi, Ltd. Dispositif de détection de lumière
US10955342B2 (en) 2015-08-21 2021-03-23 Hitachi, Ltd. Light detection device
CN107850542B (zh) * 2015-08-21 2023-10-24 株式会社日立制作所 光检测装置
CN106885836A (zh) * 2017-04-19 2017-06-23 冯超 书写字迹色痕检测仪

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