Immunological assay conducted in a microlaboratory array

• US 5,858,804 A
• Filed: 08/20/1997
• Issued: 01/12/1999
• Est. Priority Date: 11/10/1994
• Status: Expired due to Fees

• Current Assignee: Sarnoff Corporation (SRI International, Inc.)
• Original Assignee: Sarnoff Corporation (SRI International, Inc.)
• Inventors: Zanzucchi, Peter John, Cherukuri, Satyam Choudary, McBride, Sterling Edward
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US08/914,941
• Time in Patent Office: 510 Days
• Field of Search: 422/55, 422/57, 422/58, 435/7.92, 435/287.1, 435/287.2, 435/288.2, 435/288.4, 435/288.5, 436/164, 436/165, 436/514, 436/518, 436/527, 436/536, 436/538, 436/541, 436/805, 436/807
• US Class Current: 506/9
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00353 Pumps
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00488 by rotation of the reaction vessels
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 : Covalent
• CPC Class Codes: B01J 2219/00637 : by coating it with another layer
• CPC Class Codes: B01J 2219/00648 : by the use of solid beads
• CPC Class Codes: B01J 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/0068 : Means for controlling the apparatus of the process
• CPC Class Codes: B01J 2219/00686 : Automatic
• CPC Class Codes: B01J 2219/00698 : Measurement and control of process parameters
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01J 2219/00826 : Quartz
• CPC Class Codes: B01J 2219/00828 : Silicon wafers or plates
• CPC Class Codes: B01J 2219/00831 : Glass
• CPC Class Codes: B01J 2219/00891 : Feeding or evacuation
• CPC Class Codes: B01J 2219/00952 : Sensing operations
• CPC Class Codes: B01L 2200/0605 : Metering of fluids
• CPC Class Codes: B01L 2200/12 : Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/147 : Employing temperature sensors
• CPC Class Codes: B01L 2300/0803 : Disc shape
• CPC Class Codes: B01L 2300/0806 : Standardised forms, e.g. compact disc [CD] format
• CPC Class Codes: B01L 2300/0864 : comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 : Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 : Multiple sequential chambers
• CPC Class Codes: B01L 2300/0874 : Three dimensional network
• CPC Class Codes: B01L 2300/1827 : using resistive heater
• CPC Class Codes: B01L 2400/0406 : capillary forces
• CPC Class Codes: B01L 2400/0409 : centrifugal forces
• CPC Class Codes: B01L 2400/0415 : electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0633 : with moving parts
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• CPC Class Codes: B01L 3/502707 : characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C07K 1/042 : characterised by the nature of the carrier
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: Y10S 436/805 : Optical property
• CPC Class Codes: Y10S 436/807 : Apparatus included in process claim, e.g. physical support structures
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis

Abstract

The present invention provides a method of performing an immunological assay separately and in parallel for each of at least a first sample containing or prospectively containing a first binding moiety, which can be an antigen or an antibody, and a second sample containing or prospectively containing the first binding moiety, the method comprising: placing the first sample and the second sample into an array comprising a solid substrate, a plurality of wells and channels, wherein at least one channel is a crossover channel formed in the upper surface of the substrate and is situated above another channel formed in the lower surface of the substrate, thereby forming crossovers comprising crossing but non-intersecting channels; moving said first sample into a first well containing a second binding moiety, which can be an antigen or an antibody, that binds to the first binding moiety, wherein the second binding moiety is bound to the walls of the first well; moving said second sample into a second well containing the second binding moiety bound to the walls thereof; and parallelly pumping one or more fluids through the first and second wells to develop a detectable result that varies depending on the amount of the first binding moiety present in the first or second wells.

Claims

1. A method of performing an immunological assay separately and in parallel for each of at least a first sample containing or prospectively containing a first binding moiety and a second sample containing or prospectively containing the first binding moiety, the method comprising:

placing the first sample and the second sample into an array comprising a solid substrate having an upper surface and a lower surface, a plurality of reservoirs, a plurality of wells connected to the reservoirs and channels that provide the connections between the wells and the reservoirs, wherein at least one channel is a crossover channel formed in the upper surface of the substrate and is situated above another channel formed in the lower surface of the substrate, thereby forming crossovers comprising crossing but non-intersecting channels;

moving said first sample into a first well containing a second binding moiety that binds to the first binding moiety, wherein the second binding moiety is bound to within the first well;

moving said second sample into a second well within which the second binding moiety is bound;

parallelly pumping from the reservoirs one or more fluids into the first and second wells to develop a detectable result that varies depending on the amount of the first binding moiety present in the first or second wells; and

measuring the detectable result.

2. A method according to claim 1, wherein the first well and the second wells are heated by one or more heaters built into each said well.

3. The method of claim 1, wherein there are light-transmitting pathways from the exterior of the substrate to each of the first and second wells, and wherein the measuring is conducted by optical detection the amount of detectable result developed for the first and second wells.

4. The method according to claim 2, wherein the substrate has a first cover that is sealed onto the top of the substrate to enclose said channel in the upper surface of the substrate and a second cover that is sealed to the bottom of the substrate to enclose said channel in the lower surface of the substrate.

5. The method according to claim 2, further comprising programming a control means to control fluid flow into a channel or well.

6. The method according to claim 1, wherein the reservoirs comprise plastic release containers containing reagents for developing the detectable result.

7. The method according to claim 2, wherein the first sample comprises blood.

8. The method according to claim 1, further comprising parallelly operating the method to process additional samples having the same chemical composition as the first sample to parallelly detect the presence of one or more substances distinct from the first binding moiety, the processing of additional samples comprising:

placing each of the additional samples in the array;

moving each additional sample into an additional well, each additional well containing an additional binding moiety, wherein each of the additional binding moieties bind to substances present or prospectively present in the additional samples;

parallelly, together with the pumping through the first and second wells, pumping from the reservoirs one or more fluids into the additional wells to develop a detectable result that varies depending on the amount of the substance bound by the additional binding moiety found in respective additional well; and

measuring the detectable result for each of the additional wells.

9. A method according to claim 2, wherein the substrate comprises a dielectric substrate.

10. A method according to claim 9, wherein the substrate comprises a high melting temperature glass.

11. A method according to claim 10, wherein the substrate comprises a glass having a flow temperature of about 700 degrees Celsius or more.

12. A method of performing an immunological assay which comprises:

a) providing substrate having formed therein (i) at least a first reservoir and a second reservoir, (ii) a plurality of wells that each have a connection to the first and second reservoirs, and (iii) channels forming the connections, wherein the channels connecting the wells to reservoirs do not intersect to allow mixing of reagents or solvents provided from the reservoirs prior to such reagents or solvents being deposited in wells;

b) providing a binding moiety bound with each said well which binding moieties bind a ligand that is present or prospectively present in a sample with which the well will be contacted, wherein at least two different binding moieties are provided in separate said wells;

c) moving a sample from a reservoir into each of the wells to contact the bound binding ligand;

d) parallelly pumping fluids from the connected first and second reservoirs through the wells to develop a detectable result that varies depending on the amount of the ligand present in the wells that binds to the binding moiety bound to the respective well; and

e) measuring the detectable result.

13. The method of claim 12, wherein there are light-transmitting pathways from the exterior of the substrate to each of the first and second wells, and wherein the measuring is conducted by optical detection the amount of detectable result developed for the first and second wells.

14. The method according to claim 12, further comprising programming a control means to control fluid flow into a channel or well.

15. The method according to claim 12, wherein the substrate comprises a dielectric substrate.

16. The method according to claim 15, wherein the substrate comprises a high melting temperature glass.

17. The method according to claim 16, wherein the substrate comprises a glass having a flow temperature of about 700 degrees Celsius or more.

18. The method according to claim 12, wherein the substrate has at least one hundred said wells.