Stage and platform for building a biochip and biochip

• US 20040005697A1
• Filed: 01/17/2003
• Published: 01/08/2004
• Est. Priority Date: 12/12/2000
• Status: Active Grant

• Current Assignee: Autogenomics
• Original Assignee: Autogenomics
• Inventors: Mahant, Vijay K., Kureshy, Fareed
• Granted Patent: US 7,736,888 B2
• Time in Patent Office: Days
• US Class Current: 435/287.2
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00731 Saccharides
• 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 40/12 Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: G01N 33/542 with steric inhibition or signal modification, e.g. fluorescent quenching
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing

Abstract

A biochip, a platform which composes the biochip, and a stage which composes the platform. The biochip is for detecting analytes in a test sample. The platform comprises a stage. The stage of the invention includes a carrier.

Claims

1. A biochip comprising:

a carrier with a hydrophilic surface;

at least one light-blocking matrix layer comprising a light-blocking agent, wherein the at least one light-blocking matrix layer is coupled to the hydrophilic surface and is effective to render the carrier optically inactive;

a coupling matrix layer coupled to the light-blocking matrix layer, and a cross-linking agent physically suspended in the coupling matrix layer, wherein the cross-linking agent is optionally covalently coupled to the coupling matrix layer;

a plurality of sensing elements, each of the plurality of sensing elements having a capture portion that binds to the cross-linking agent, and wherein the sensing elements are bound to the cross-linking agent in the coupling matrix layer in predetermined positions; and

a modification matrix layer coupled to the coupling matrix layer, wherein the modification matrix layer provides at least one of a chromatographic function, a light absorbing function, a penetration delay function, and an assay function.

2. The biochip of claim 1 wherein at least one of the light-blocking matrix layer, the coupling matrix layer, and the modification matrix layer comprises agarose at a concentration of about 1% by weight to about 5% by weight.

3. The biochip of claim 2 wherein the chromatographic function is selected from the group consisting of size exclusion chromatography, affinity chromatography, and ion exchange chromatography.

4. The biochip of claim 2 wherein the light absorbing function is selected from the group consisting of filtering of an incident light and filtering of an emitted light.

5. The biochip of claim 2 wherein the assay function is selected from the group consisting of providing a substrate for an enzymatic assay, providing a co-substrate for an enzymatic assay, providing an enzyme for an enzymatic assay, and providing a chromogenic or luminogenic substrate for an enzymatic assay.

6. The biochip of claim 2 further comprising a base matrix layer that is disposed between the hydrophilic surface and the light-blocking matrix layer.

7. The biochip of claim 2 wherein the light blocking agent is iron oxide and wherein the cross-linking agent is avidin or streptavidin.

8. A biochip comprising:

a carrier with a first and second surface, wherein at least one of the first and second surfaces is hydrophilic or wherein the first surface has a hydrophilic coating;

a base matrix layer coupled to the hydrophilic coating or hydrophilic surface;

a light-blocking matrix layer coupled to the base matrix layer and comprising a light-blocking agent, wherein the light-blocking matrix layer is coupled to the base matrix layer and is effective to render the carrier optically inactive;

a coupling matrix layer coupled to the light-blocking matrix layer, and a cross-linking agent physically suspended in the coupling matrix layer, wherein the cross-linking agent is optionally covalently coupled to the coupling matrix layer;

a plurality of sensing elements, each of the plurality of sensing elements having a capture portion that binds to the cross-linking agent, and wherein the sensing elements are bound to the cross-linking agent in the coupling matrix layer in predetermined positions;

wherein at least one of the base layer, the light-blocking matrix layer, and the coupling matrix layer comprises an additive selected from the group consisting of a buffer, a detergent, a humectant, and a light-blocking agent; and

wherein the plurality of sensing elements are coupled to the coupling matrix layer via droplet deposition of liquid droplets having a diameter of between 20 and 1000 micrometer to form a corresponding plurality of sensing element spots.

9. The biochip of claim 8 wherein at least one of the base matrix layer, the light-blocking matrix layer, and the coupling matrix layer comprise agarose at a concentration of about 1% by weight to about 5% by weight.

10. The biochip of claim 9 wherein buffer is an amphoteric buffer, and wherein the light blocking agent is an iron oxide.

11. The biochip of claim 9 wherein the coupling matrix layer comprises aldehyde-activated agarose at a concentration of about 1% by weight to about 5% by weight.

12. The biochip of claim 11 wherein the cross-linking agent is avidin, streptavidin, or an antibody, and wherein the cross-linking agent is covalently coupled to the coupling matrix layer.

13. The biochip of claim 12 wherein the capture portion comprises a biotin.

14. The biochip of claim 9 wherein the carrier is a flexible and optically pure polymer film with a thickness of about 100 micrometers and further includes a gelatin coating as the hydrophilic coating.

15. The biochip of claim 9 wherein the additive controls surface irregularity of the coupling matrix layer, thereby allowing optical detection using a confocal microscope of a plurality of signals from a plurality of analytes bound to the plurality of sensing elements without recalibration of the confocal microscope.

16. The biochip of claim 9 wherein the light-blocking agent is present at a concentration to increase a signal-to-noise ratio when an optical detection of a signal from the biochip is employed.

17. A biochip comprising:

a carrier with a first and second surface, and a hydrophilic coating coupled to the first surface of the carrier;

at least one light-blocking matrix layer comprising a light-blocking agent, wherein the at least one light-blocking matrix layer is coupled to the hydrophilic coating and is effective to render the carrier optically inactive;

a coupling matrix layer coupled to the light-blocking matrix layer, and a cross-linking agent physically suspended in and on the coupling matrix layer, wherein the cross-linking agent is optionally covalently coupled to the coupling matrix layer;

a plurality of sensing elements, each of the plurality of sensing elements having a capture portion that binds to the cross-linking agent, and wherein the sensing elements are bound to the cross-linking agent in the coupling matrix layer in predetermined positions; and

wherein the plurality of sensing elements are coupled to the coupling matrix layer via droplet deposition of liquid droplets having a diameter of between 20 and 1000 micrometer to form a corresponding plurality of sensing element spots.

18. The biochip of claim 17 wherein at least one of the light-blocking matrix layer and the coupling matrix layer comprise agarose at a concentration of about 1% by weight to about 5% by weight, and wherein the light-blocking agent is present at a concentration to increase a signal-to-noise ratio when an optical detection of a signal from the biochip is employed.

19. The biochip of claim 18 wherein the carrier is a flexible and optically pure polymer film with a thickness of about 100 micrometers and further includes a gelatin, a polyvinyl alcohol, or a polyvinyl pyrrolidone coating as the hydrophilic coating.

20. The biochip of claim 18 further comprising a base matrix layer that is disposed between the hydrophilic coating and the light-blocking matrix layer.