Systems and methods for high throughput analysis of conformation in biological entities

• US 10,451,630 B2
• Filed: 04/27/2018
• Issued: 10/22/2019
• Est. Priority Date: 06/30/2014
• Status: Active Grant

• Current Assignee: Quanta Therapeutics, Inc.
• Original Assignee: Biodesy, Inc.
• Inventors: Salafsky, Joshua, Dietz, Louis J., Hebert, Ray, Bahatt, Dar
• Primary Examiner(s): Crawford, Erik B
• Application Number:
  US15/965,577
• Publication Number:
  US 20180340940A1
• Time in Patent Office: 543 Days
• Field of Search: None
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: G01N 21/552 Attenuated total reflection
• CPC Class Codes: G01N 21/636 using an arrangement of pump beam and probe beam; using the measurement of optical non-linear properties; non-linear optics per se G02F1/35
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/6845 Methods of identifying protein-protein interactions in protein mixtures
• CPC Class Codes: G02B 5/04 Prisms
• CPC Class Codes: G02B 5/045 Prism arrays

Abstract

Methods, devices, and systems are disclosed for performing high throughput analysis of conformational change in biological molecules or other biological entities using surface-selective nonlinear optical detection techniques.

Claims

1. A device comprising:

a) a substrate, the substrate comprising;

i) an M×

N array of discrete regions on a surface of the substrate, wherein M is the number of rows of discrete regions and N is the number of columns of discrete regions in the array, and

ii) an R×

S array of prisms integrated with the substrate and optically coupled to the discrete regions, wherein R is the number of rows of prisms and S is the number of columns of prisms in the array;

wherein each discrete region is located directly above a single prism of the array of prisms integrated with the substrate, and wherein R[≠

]M and S=N, or R=M and S [≠

]N.

2. The device of claim 1, wherein each of the discrete regions is optically coupled with at least one input prism and at least one output prism, and wherein the input prism and the output prism are spatially distinct.

3. The device of claim 1, wherein M=8 and N=12.

4. The device of claim 1, wherein M=16 and N=24.

5. The device of claim 1, wherein M=32 and N=48.

6. The device of claim 1, wherein M is greater than 4 and N is greater than 4.

7. The device of claim 1, wherein each discrete region comprises a supported lipid bilayer or is configured to facilitate the formation of a supported lipid bilayer.

8. The device of claim 1, further comprising a well-forming component bonded to a top surface of the substrate in order to isolate each discrete region in a separate well.

9. The device of claim 1, wherein each of the discrete regions comprises an area of up to about 100 mm².

10. The device of claim 1, wherein the substrate is composed of glass, fused-silica, or plastic.

11. A device comprising:

a) a substrate, the substrate comprising;

i) an M×

N array of discrete regions on a surface of the substrate, wherein M is the number of rows of discrete regions and N is the number of columns of discrete regions in the array, and

ii) an R×

S array of prisms integrated with the substrate and optically coupled to the discrete regions, wherein R is the number of rows of prisms and S is the number of columns of prisms in the array;

wherein each discrete region is located directly above a single prism of the array of prisms integrated with the substrate, and wherein each of the discrete regions is optically coupled with at least one input prism and at least one output prism that are not located directly beneath the discrete region.

12. The device of claim 11, wherein M=8 and N=12.

13. The device of claim 11, wherein M=16 and N=24.

14. The device of claim 11, wherein M=32 and N=48.

15. The device of claim 11, wherein M is greater than 4 and N is greater than 4.

16. The device of claim 11, wherein each discrete region comprises a supported lipid bilayer or is configured to facilitate the formation of a supported lipid bilayer.

17. The device of claim 11, further comprising a well-forming component bonded to a top surface of the substrate in order to isolate each discrete region in a separate well.

18. The device of claim 11, wherein the substrate is composed of glass, fused-silica, or plastic.