LABEL-FREE HIGH THROUGHPUT BIOMOLECULAR SCREENING SYSTEM AND METHOD

• US 20090247427A1
• Filed: 06/09/2009
• Published: 10/01/2009
• Est. Priority Date: 07/20/2005
• Status: Active Grant

• Current Assignee: Anthony G. Frutos, David A. Pastel, Gordon M. Shedd, Mark F. Krol, Stephen J. Caracci, Thomas C. Moore, Volker H.O. Eckelt
• Original Assignee: Anthony G. Frutos, David A. Pastel, Gordon M. Shedd, Mark F. Krol, Stephen J. Caracci, Thomas C. Moore, Volker H.O. Eckelt
• Inventors: Eckelt, Volker H.O., Frutos, Anthony G., Moore, Thomas C., Krol, Mark F., Shedd, Gordon M., Pastel, David A., Caracci, Stephen J.
• Granted Patent: US 8,114,348 B2
• Time in Patent Office: Days
• US Class Current: 506/39
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/00356 Holding samples at elevated temperature (incubation)
• CPC Class Codes: G01N 2035/0097 monitoring reactions as a function of time
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates

Abstract

A screening system and method are described herein which provide a unique and practical solution for enabling label-free high throughput screening (HTS) to aid in the discovery of new drugs. In one embodiment, the screening system enables direct binding assays to be performed in which a biomolecular interaction of a chemical compound (drug candidate) with a biomolecule (therapeutic target) can be detected using assay volumes and concentrations that are compatible with the current practices of HTS in the pharmaceutical industry. The screening system also enables the detection of bio-chemical interactions that occur in the wells of a microplate which incorporates biosensors and surface chemistry to immobilize the therapeutic target at the surface of the biosensors. The screening system also includes fluid handling and plate handling devices to help perform automated HTS assays.

Claims

1. A screening system comprising:

a microplate;

an interface device; and

a measurement chamber into which the microplate is moved by the interface device, the measurement chamber having located therein at least the following;

a plate transport subsystem which receives the microplate from the interface device;

an optical subsystem;

a plate alignment subsystem including a microplate mounting mechanism onto which the microplate is positioned by the plate transport subsystem so that biosensors located in wells of the microplate are interrogated by the optical subsystem, wherein the microplate has at least one angled fiducial marking located outside of the wells where the at least one angled fiducial marking is used to properly position/reposition the microplate relative to the optical interrogation subsystem.

2. The screening system of claim 1, further comprising a computer operatively connected to the interface device, the plate transport subsystem, the optical subsystem, and the plate alignment subsystem.

3. The screening system of claim 1, wherein said interface device includes:

a rotating arm;

a drawer;

a lifter;

a gripper;

a carriage;

a rail;

or

a conveyor.

4. The screening system of claim 1, wherein each biosensor is a resonant waveguide grating (RWG) biosensor.

5. The screening system of claim 1, wherein said plate transport subsystem includes:

a rotating arm;

a plate carriage;

a gripper;

a lifter; and

/or

a conveyor system.

6. The screening system of claim 1, wherein said plate alignment subsystem further includes an X-Y support stage.

7. The screening system of claim 1, further comprising a fluid handling subsystem which is located within the measurement chamber.

8. The screening system of claim 1, wherein the optical subsystem obtains a scanned rate of 40,000 wells in 8 hours.

9. The screening system of claim 1, wherein the optical subsystem scans a 384 well microplate in about 240 seconds.

10. The screening system of claim 1, wherein the measurement chamber further having located therein a measurement nest, an environmental control subsystem, and a fluid handling subsystem.

11. The screening system of claim 1, further comprising an athermalization buffer.

12. The screening system of claim 11, wherein the measurement chamber has located therein the athermalization buffer.

13. The screening system of claim 1, wherein the microplate mounting mechanism includes a base having at least one surface defining a nesting receptacle for the microplate, and at least three supports projecting from the base, the at least three supports support said microplate, said nesting receptacle has at least two side walls and at least two end walls, the nesting receptacle having walls further defining a detection aperture thereby allowing optical access to a bottom surface of the microplate through the detection aperture.

14. The screening system of claim 13, wherein the microplate mounting mechanism further includes at least two X-directional contacts located on the end walls and at least one Y-directional contact located on one of the side walls, and at least one spring-loaded contact on the end wall opposite the X-directional contacts and at least one spring-loaded contact on the side wall opposite the Y-directional contact.

15. The screening system of claim 14, wherein the microplate mounting mechanism further includes one or more adjustment/s to position the microplate which include:

one or more X-directional contact adjustment/s, one or more Y-directional contact adjustment/s, one or more spring-loaded adjustment/s, and/or at least one adjustment for the at least three supports.

16. A screening system for using a label-free detection technique to interrogate biosensors which are located in wells of a microplate, said screening system comprising:

an interface device;

a measurement chamber into which the microplate is moved by the interface device, the measurement chamber having located therein at least the following;

a plate transport subsystem which receives the microplate from the interface device;

an optical subsystem;

a plate alignment subsystem including a microplate mounting mechanism onto which the microplate is positioned by the plate transport subsystem to be interrogated by the optical subsystem, where the microplate mounting mechanism includes a base having at least one surface defining a nesting receptacle for the microplate, and at least three supports projecting from the base, the at least three supports support said microplate, said nesting receptacle has at least two side walls and at least two end walls, the nesting receptacle having walls further defining a detection aperture thereby allowing optical access to a bottom surface of the microplate through the detection aperture.

17. The screening system of claim 16, wherein the measurement chamber further having located therein a measurement nest, an environmental control subsystem, and a fluid handling subsystem.

18. The screening system of claim 16, further comprising an athermalization buffer.

19. The screening system of claim 18, wherein the measurement chamber has located therein the athermalization buffer.

20. The screening system of claim 16, wherein the microplate mounting mechanism further comprising at least two X-directional contacts located on the end walls and at least one Y-directional contact located on one of the side walls, and at least one spring-loaded contact on the end wall opposite the X-directional contacts and at least one spring-loaded contact on the side wall opposite the Y-directional contact.

21. The screening system of claim 20, wherein the microplate mounting mechanism further comprising one or more adjustment/s to position the microplate which include:

one or more X-directional contact adjustment/s, one or more Y-directional contact adjustment/s, one or more spring-loaded adjustment/s, and/or at least one adjustment for the at least three supports.

22. A screening system for using a label-free detection technique to interrogate biosensors which are located in wells of a microplate, said screening system comprising:

an interface device;

a measurement chamber into which the microplate is moved by the interface device, the measurement chamber having located therein at least the following;

a plate transport subsystem which receives the microplate from the interface device;

an optical subsystem;

a plate alignment subsystem including a microplate mounting mechanism onto which the microplate is positioned by the plate transport subsystem to be interrogated by the optical subsystem; and

a computer operatively connected to the interface device, the plate transport subsystem, the optical subsystem, and the plate alignment subsystem, where the computer further includes an assay data storage, an assay binding signal unit, a peak detection algorithm unit, and a raw spectra sorting and binding unit, where the assay data storage is connected to the assay binding signal unit which is connected to the peak detection algorithm unit which is connected to the raw spectra sorting and binding unit which is connected to the optical subsystem.

23. The screening system of claim 22, wherein the measurement chamber further having located therein a measurement nest, an environmental control subsystem, and a fluid handling subsystem.

24. The screening system of claim 22, further comprising an athermalization buffer.

25. The screening system of claim 24, wherein the measurement chamber has located therein the athermalization buffer.