US6046056A
Expired / Lapsed
US
⏱️ 0.0 years remaining
High throughput screening assay systems in microscale fluidic devices
Assignee: Caliper Life Sciences Inc
•
Filing: 1996-12-06
•
Granted: 2000-04-04
•
Expires: 2016-12-06
Abstract
Abstract The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.
Inventors
- 👤 J. Wallace Parce
- 👤 Anne R. Kopf-Sill
- 👤 Luc J. Bousse
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 02:05
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/5005; G01N33/5091; B; B01; B01J; B01J19/00; B01J19/0093; B01L; B01L3/00; B01L3/50; B01L3/502; B01L3/5025; B01L3/5027; B01L3/50273; B01L3/502753; B01L3/502761; B01L3/502769; B01L3/502784; G01N27/00; G01N27/26; G01N27/416; G01N27/447; G01N27/44756; G01N27/44791; G01N33/5008; G01N33/5011; G01N33/502; G01N33/5044; G01N33/5064; G01N33/5094; G01N33/53; G01N33/5302; G01N33/5304; G01N33/575; G01N33/57515; B01L2200/00; B01L2200/06; B01L2200/0605; B01L2200/0647; B01L2200/0668; B01L2200/0673; B01L2200/0689; B01L2200/12; B01L2300/00; B01L2300/08; B01L2300/0809; B01L2300/0816; B01L2300/0861; B01L2300/0864; B01L2300/0877; B01L2300/0887; B01L2400/00; B01L2400/04; B01L2400/0403; B01L2400/0415; B01L9/00; B01L9/52; B01L9/527; G01N35/00; G01N35/08; Y; Y10; Y10S; Y10S366/00; Y10S366/02; Y10S435/00; Y10S435/81; Y10S435/97; Y10S436/00; Y10S436/805; Y10S436/806; Y10S436/807; Y10S436/809
Claims Analysis
Total Claims: 40
Claim 1
Independent Claim
172 words
An apparatus for screening test compounds for an effect on a flowing biochemical system, comprising: a substrate having at least one surface; at least two intersecting channels fabricated into said surface of said substrate, at least one of said at least two intersecting channels having at least one cross-sectional dimension in the range from about 0.1 to about 500 μm; a source of a plurality of different test compounds fluidly connected to a first of said at least two intersecting channels; a source of at least one component of said biochemical system fluidly connected to a second of said at least two intersecting channels; a fluid direction system for flowing said at least one component within said second of said at least two intersecting channels and for flowing said different test compounds from said first to said second of said at least two intersecting channels; a cover mated with said surface; and a detection zone in said second channel for detecting an effect of said test compound on said flowing biochemical system.
Claim 2
Independent Claim
172 words
An apparatus for screening test compounds for an effect on a flowing biochemical system, comprising: a substrate having at least one surface; at least two intersecting channels fabricated into said surface of said substrate, at least one of said at least two intersecting channels having at least one cross-sectional dimension in the range from about 0.1 to about 500 μm; a source of a plurality of different test compounds fluidly connected to a first of said at least two intersecting channels; a source of at least one component of said biochemical system fluidly connected to a second of said at least two intersecting channels; a fluid direction system for flowing said at least one component within said second of said at least two intersecting channels and for flowing said different test compounds from said first to said second of said at least two intersecting channels; a cover mated with said surface; and a detection zone in said second channel for detecting an effect of said test compound on said flowing biochemical system.
Claim 3
Dependent Claim
44 words
The apparatus of claim 1, wherein said fluid direction system generates a continuous flow of said at least one component along said second of said at least two intersecting channels, and periodically injects a test compound from said first channel into said second channel.
Claim 4
Dependent Claim
51 words
The apparatus of claim 1, further comprising a source of a second component of said biochemical system, and a third channel fabricated into said surface, said third channel fluidly connecting at least one of said at least two intersecting channels with said source of said second component of said biochemical system.
Claim 5
Dependent Claim
51 words
The apparatus of claim 3, wherein said fluid direction system generates a continuous flow of a mixture of said at least one component and said second component along said second of said at least two intersecting channels, and periodically ejects a test compound from said first channel into said second channel.
Claim 6
Dependent Claim
45 words
The apparatus of claim 1, wherein said fluid direction system continuously flows said plurality of different test compounds from said first into said second of said at least two intersecting channels, each of said plurality of different test compounds being separated by a fluid spacer.
Claim 7
Dependent Claim
80 words
The apparatus of claim 1, wherein said fluid direction system comprises: at least tree electrodes, each electrode being in electrical contact with said at least two intersecting channels on a different side of an intersection formed by said at least two intersecting channels; and a control system for concomitantly applying a variable voltage at each of said electrodes, whereby movement of said test compounds or said at least one component in said at least two intersecting channels may be controlled.
Claim 8
Dependent Claim
17 words
The apparatus of claim 1, wherein said detection system includes a detection window in said second channel.
Claim 9
Dependent Claim
14 words
The apparatus of claim 7, wherein said detection system is a fluorescent detection system.
Claim 10
Dependent Claim
10 words
The apparatus of claim 1, wherein said substrate is planar.
Claim 11
Dependent Claim
11 words
The apparatus of claim 1, wherein said substrate comprises etched glass.
Claim 12
Dependent Claim
11 words
The apparatus of claim 1, wherein said substrate comprises etched silicon.
Claim 13
Dependent Claim
16 words
The apparatus of claim 1, further comprising an insulating layer disposed over said etched silicon substrate.
Claim 14
Dependent Claim
12 words
The apparatus of claim 1, wherein said substrate is a molded polymer.
Claim 15
Dependent Claim
32 words
The apparatus of claim 1, wherein said at least one component of a biochemical system comprises an enzyme, and an enzyme substrate which produces a detectable signal when reacted with said enzyme.
Claim 16
Dependent Claim
21 words
The apparatus of claim 14, wherein said enzyme substrate is selected from the group consisting of chromogenic and fluorogenic enzyme substrates.
Claim 17
Dependent Claim
35 words
The apparatus of claim 1, wherein said at least one component of a biochemical system comprises a receptor/ligand binding pair, wherein at least one of said receptor or ligand has a detectable signal associated therewith.
Claim 18
Dependent Claim
32 words
The apparatus of claim 1, wherein said at least one component of a biochemical system comprises a receptor/ligand binding pair, wherein binding of said receptor to said ligand produces a detectable signal.
Claim 19
Independent Claim
222 words
An apparatus for detecting an effect of a test compound on a flowing biochemical system, comprising: a substrate having at least one surface; a plurality of reaction channels fabricated into said surface; at least two transverse channels fabricated into said surface, each of said plurality of reaction channels being fluidly connected to a first of said at least two transverse channels at a first point in said reaction channels, and fluidly connected to a second of said at least two transverse channels at a second point in said reaction channels, said at least two transverse channels and said plurality of reaction channels each having at least one cross-sectional dimension in the range from about 0.1 to about 500 μm; a source of at least one component of said biochemical system, said source of at least one component of said biochemical system being fluidly connected to each of said plurality of reaction channels; a source of test compounds fluidly connected to said first of said at least two transverse channels; a fluid direction system for controlling movement of said test compound and said at least one component within said at least two transverse channels and said plurality of reaction channels; a cover mated with said surface; and a detection system for detecting an effect of said test compound on said flowing biochemical system.
Claim 20
Independent Claim
222 words
An apparatus for detecting an effect of a test compound on a flowing biochemical system, comprising: a substrate having at least one surface; a plurality of reaction channels fabricated into said surface; at least two transverse channels fabricated into said surface, each of said plurality of reaction channels being fluidly connected to a first of said at least two transverse channels at a first point in said reaction channels, and fluidly connected to a second of said at least two transverse channels at a second point in said reaction channels, said at least two transverse channels and said plurality of reaction channels each having at least one cross-sectional dimension in the range from about 0.1 to about 500 μm; a source of at least one component of said biochemical system, said source of at least one component of said biochemical system being fluidly connected to each of said plurality of reaction channels; a source of test compounds fluidly connected to said first of said at least two transverse channels; a fluid direction system for controlling movement of said test compound and said at least one component within said at least two transverse channels and said plurality of reaction channels; a cover mated with said surface; and a detection system for detecting an effect of said test compound on said flowing biochemical system.
Claim 21
Dependent Claim
73 words
The apparatus of claim 18, wherein said fluid control system comprises: a plurality of individual electrodes, each in electrical contact with each terminus of said at least two transverse channels; and a control system for concomitantly applying a variable voltage at each of said electrodes, whereby movement of said test compounds or said at least first component in said at least two transverse channels and said plurality of reaction channels may be controlled.
Claim 22
Dependent Claim
28 words
The apparatus of claim 18, wherein each of said plurality of reaction channels comprises a bead resting well at said first point in said plurality of reaction channels.
Claim 23
Dependent Claim
71 words
The apparatus of claim 18, wherein said source of at least one component of a biochemical system is fluidly connected to said plurality of reaction channels by a third transverse channel, said third transverse channel having at least one cross sectional dimension in a range of from 0.1 to 500 μm and being fluidly connected to each of said plurality of reaction channels at a third point in said reaction channels.
Claim 24
Dependent Claim
25 words
The apparatus of claim 21, wherein said third point in said reaction channels is intermediate to said first and second points in said reaction channels.
Claim 25
Dependent Claim
32 words
The apparatus of claim 22, further comprising a particle retention zone in each of said plurality of reaction channels, between said third and said second points in said plurality of reaction channels.
Claim 26
Dependent Claim
15 words
The apparatus of claim 23, wherein said particle retention zone comprises a particle retention matrix.
Claim 27
Dependent Claim
14 words
The apparatus of claim 23, wherein said particle retention zone comprises a microstructural filter.
Claim 28
Dependent Claim
44 words
The apparatus of claim 18, wherein said plurality of reaction channels comprises a plurality of parallel reaction channels fabricated into said surface of said substrate and said at least two transverse channels are connected at opposite ends of each of said parallel reaction channels.
Claim 29
Dependent Claim
45 words
The apparatus of claim 18, wherein said at least two transverse channels are fabricated on said surface of said substrate in inner and outer concentric channels, respectively, and said plurality of reaction channels extend radially from said inner concentric channel to said outer concentric channel.
Claim 30
Dependent Claim
17 words
The apparatus of claim 27, wherein said detection system comprises a detection window in said second channel.
Claim 31
Dependent Claim
14 words
The apparatus of claim 28, wherein said detection system is a fluorescent detection system.
Claim 32
Dependent Claim
10 words
The apparatus of claim 18, wherein said substrate is planar.
Claim 33
Dependent Claim
11 words
The apparatus of claim 18, wherein said substrate comprises etched glass.
Claim 34
Dependent Claim
11 words
The apparatus of claim 18, wherein said substrate comprises etched silicon.
Claim 35
Dependent Claim
16 words
The apparatus of claim 18, further comprising an insulating layer disposed over said etched silicon substrate.
Claim 36
Dependent Claim
12 words
The apparatus of claim 18, wherein said substrate is a molded polymer.
Claim 37
Dependent Claim
32 words
The apparatus of claim 18, wherein said at least one component of a biochemical system comprises an enzyme, and an enzyme substrate which produces a detectable signal when reacted with said enzyme.
Claim 38
Dependent Claim
20 words
The apparatus of claim 35, wherein said enzyme substrate is selected from the group consisting of chromogenic and fluorogenic substrates.
Claim 39
Dependent Claim
35 words
The apparatus of claim 18, wherein said at least one component of a biochemical system comprises a receptor/ligand binding pair, wherein at least one of said receptor or ligand has a detectable signal associated therewith.
Claim 40
Dependent Claim
32 words
The apparatus of claim 18, wherein said at least one component of a biochemical system comprises a receptor/ligand binding pair, wherein binding of said receptor to said ligand produces a detectable signal.
References Cited (Backward Citations)
US5171534A
Cited
US4978503A
Cited
US5140161A
Cited
US4963498A
Cited
US5144139A
Cited
US5164598A
Cited
US4675300A
Cited
US4908112A
Cited
US5188963A
Cited
US5171132A
Cited
US5126022A
Cited
US5277556A
Cited
US5271724A
Cited
GB2248891A
Cited
US5192405A
Cited
US5296375A
Cited
US5304487A
Cited
EP0637998A1
Cited
EP0639223A1
Cited
US5486335A
Cited
US5427946A
Cited
US5637469A
Cited
US5498392A
Cited
EP0568902A2
Cited
US5375979A
Cited
WO1994005414A1
Cited
US5605662A
Cited
WO1995012608A1
Cited
US5780754A
Cited
US5773298A
Cited
WO1995027210A1
Cited
WO1995027211A1
Cited
WO1995033846A1
Cited
WO1996004547A1
Cited
US5571410A
Cited
US5585069A
Cited
US5593838A
Cited
WO1996015576A1
Cited
WO1996015450A1
Cited
WO1996014933A1
Cited
WO1996015269A2
Cited
WO1996014934A1
Cited
WO1997002357A1
Cited
WO1997022000A1
Cited
WO1998005959A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2003-04-04 | 2003-10-04 | 2004-04-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2007-04-04 | 2007-10-04 | 2008-04-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2011-04-04 | 2011-10-04 | 2012-04-04 | $7700.00 | Window Closed / Lapsed |