WO1998000231A1 - High-throughput screening assay systems in microscale fluidic devices - Google Patents

High-throughput screening assay systems in microscale fluidic devices Download PDF

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Publication number
WO1998000231A1
WO1998000231A1 PCT/US1997/010894 US9710894W WO9800231A1 WO 1998000231 A1 WO1998000231 A1 WO 1998000231A1 US 9710894 W US9710894 W US 9710894W WO 9800231 A1 WO9800231 A1 WO 9800231A1
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WO
WIPO (PCT)
Prior art keywords
channels
channel
component
biochemical system
substrate
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US1997/010894
Other languages
English (en)
French (fr)
Other versions
WO1998000231A9 (en
Inventor
John Wallace Parce
Anne R. Kopf-Sill
Luc J. Bousse
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Caliper Life Sciences Inc
Original Assignee
Caliper Technologies Corp
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
Priority claimed from US08/671,987 external-priority patent/US5942443A/en
Priority to DE69738941T priority Critical patent/DE69738941D1/de
Priority to NZ333346A priority patent/NZ333346A/xx
Priority to BR9710054-4A priority patent/BR9710054A/pt
Priority to EP97931337A priority patent/EP0907412B1/en
Priority to US09/214,035 priority patent/US6429025B1/en
Application filed by Caliper Technologies Corp filed Critical Caliper Technologies Corp
Priority to AU34990/97A priority patent/AU729537B2/en
Priority to CA002258489A priority patent/CA2258489C/en
Priority to JP50423798A priority patent/JP3788519B2/ja
Publication of WO1998000231A1 publication Critical patent/WO1998000231A1/en
Publication of WO1998000231A9 publication Critical patent/WO1998000231A9/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
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    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • G—PHYSICS
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    • G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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    • Y10S366/02—Micromixers: segmented laminar flow with boundary mixing orthogonal to the direction of fluid propagation with or without geometry influences from the pathway
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation

Definitions

  • test compound refers to the collection of compounds that are to be screened for their ability to affect a particular biochemical system.
  • Test compounds may include a wide variety of different compounds, including chemical compounds, mixtures of chemical compounds, e.g., polysaccharides, small organic or inorganic molecules, biological macromolecules, e.g., peptides, proteins, nucleic acids, or an extract made from biological materials such as bacteria, plants, fungi, or animal cells or tissues, naturally occurring or synthetic compositions.
  • the test compounds are provided, e.g., injected, free in solution, or are optionally attached to a carrier, or a solid support, e.g., beads.
  • electroosmotic fluid direction systems examples include, e.g., those described in International Patent Application No. WO 96/04547 to Ramsey et al. , which is inco ⁇ orated herein by reference in its entirety for all pu ⁇ oses.
  • Inco ⁇ orating this electroosmotic fluid direction system into the device shown in Figure 1 involves inco ⁇ oration of an electrode within each of the reservoirs 104, 106 and 108, and at the terminus of sample channel 112 or at the terminus of any fluid channels connected thereto, whereby the electrode is in electrical contact with the fluid disposed in the respective reservoir or channel.
  • Action of the enzyme upon the substrate will produce an increasing level of the fluorescent or chromatic signal. This increasing signal is indicated by the increasing shading within the main channel as it approaches the detection window. This signal trend will also occur within those test compound or subject material regions which have no effect on the enzyme/substrate interaction, e.g., test compound 126. Where a test compound does have an effect on the interaction of the enzyme and the substrate, a variation will appear in the signal produced.
  • microfluidic system containing at least a first substrate having a first channel and a second channel intersecting said first channel, at least one of said channels having at least one cross-sectional dimension in a range from
  • Apparatus as hereinbefore described having at least two transverse channels fabricated into the surface, wherein each of the plurality of reaction channels is fluidly connected to a first of the at least two transverse channels at a first point in each of the reaction channels, and fluidly connected to a second transverse channel at a second point in each of the reaction channels and an assay apparatus including an apparatus as hereinbefore described are also provided. Examples
  • Enzyme and substrate were continually pumped irough the main channel from their respective ports under both voltage states. Inhibitor or Buffer were delivered into the main channel alternately from their respective wells by alternating between voltage state 1 and voltage state 2. When no inhibitor was present at the detection end of the main channel, a base line level of fluorescent product was produced. Upon introduction of inhibitor, the fluorescent signal was greatly reduced, indicating inhibition of the enzyme/substrate interaction. Fluorescent data obtained from the alternating delivery of inhibitor and buffer into the main channel is shown in Figure 9A.
  • Figure 9B a supe ⁇ osition of the two data segments from Figure 9A, directly comparing the inhibitor data widi control (buffer) data. The control shows only a minor fluctuation in the fluorescent signal that apparently resulted from a dilution of the enzyme substrate mixture, whereas the inhibitor screen shows a substantial reduction in the fluorescent signal, indicating clear inhibition.
  • FIG. 11 A schematic of timing for subject material region spacer region loading is shown in Figure 11.
  • the top panel shows the subject material/first spacer region/second spacer region distribution widiin a channel, whereas the lower panel shows the timing required for loading the channel.
  • the schematic includes die loading (sipping) of high salt (HS) first spacer fluid ("A"), moving die pipettor to the sample or subject material ("B"), sipping the sample or subject material ("C"), moving the pipettor to the high salt first spacer fluid ("D”) sipping the first spacer fluid ("E"), moving the pipettor to the low salt (LS) or second spacer fluid (“F”), sipping the second spacer fluid ("G”) and returning to the first spacer fluid (“H”).
  • HS high salt
  • B moving die pipettor to the sample or subject material
  • C sipping the sample or subject material
  • D moving the pipettor to the high salt first spacer fluid
  • E sipping the first spacer fluid
  • LS low salt
  • F

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  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
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  • Cell Biology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Food Science & Technology (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Physiology (AREA)
  • Organic Chemistry (AREA)
  • Botany (AREA)
  • Fluid Mechanics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
PCT/US1997/010894 1996-06-28 1997-06-24 High-throughput screening assay systems in microscale fluidic devices Ceased WO1998000231A1 (en)

Priority Applications (8)

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JP50423798A JP3788519B2 (ja) 1996-06-28 1997-06-24 微小スケール流体装置の高処理能力スクリーニングアッセイシステム
NZ333346A NZ333346A (en) 1996-06-28 1997-06-24 High-throughput screening assay systems in microscale fluidic devices
BR9710054-4A BR9710054A (pt) 1996-06-28 1997-06-24 Aparelhos para separar compostos de teste para um efeito sobre um sistema bioquìmico e para detectar ummefeito de um composto de teste sobre um sistema bioquìmico, processos de determinação de se uma amostra contém um composto capaz de afetar um sistema bioquìmico, de separação de uma pluralidade de compostos de teste para um efeito sobre um sistema bioquìmico e usos de um sistema microfluido e de um substrato de ensaio.
EP97931337A EP0907412B1 (en) 1996-06-28 1997-06-24 High-throughput screening assay systems in microscale fluidic devices
US09/214,035 US6429025B1 (en) 1996-06-28 1997-06-24 High-throughput screening assay systems in microscale fluidic devices
DE69738941T DE69738941D1 (de) 1996-06-28 1997-06-24 Hochdurchsatz-screening-testsystem mittels mikrofluidischer vorrichtungen
AU34990/97A AU729537B2 (en) 1996-06-28 1997-06-24 High throughput screening assay systems in microscale fluidic devices
CA002258489A CA2258489C (en) 1996-06-28 1997-06-24 High-throughput screening assay systems in microscale fluidic devices

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US08/671,987 US5942443A (en) 1996-06-28 1996-06-28 High throughput screening assay systems in microscale fluidic devices
US08/671,987 1996-06-28
US08/761,575 US6046056A (en) 1996-06-28 1996-12-06 High throughput screening assay systems in microscale fluidic devices
US08/761,575 1996-12-06

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