Biological Analysis Arrangement and Approach Therefor

• US 20090075838A1
• Filed: 11/26/2008
• Published: 03/19/2009
• Est. Priority Date: 09/16/2002
• Status: Active Grant

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Eltoukhy, Helmy, El Gamal, Abbas, Salama, Khaled
• Granted Patent: US 8,313,904 B2
• Time in Patent Office: Days
• US Class Current: 506/12
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: C12Q 1/66 involving luciferase
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/6454 using an integrated detector array

Abstract

Characteristics of a chemical or biological sample are detected using an approach involving light detection. According to an example embodiment of the present invention, an assaying arrangement including a light detector is adapted to detect light from a sample, such as a biological material. A signal corresponding to the detected light is used to characterize the sample, for example, by detecting a light-related property thereof. In one implementation, the assaying arrangement includes integrated circuitry having a light detector and a programmable processor, with the light detector generating a signal corresponding to the light and sending the signal to the processor. The processor provides an output corresponding to the signal and indicative of a characteristic of the sample.

Claims

1. An apparatus for analyzing light from a biological sample comprising:

a substrate comprising;

an integrated circuit chip having an array of optical sensors and circuitry for both analog and digital signal processing; and

a plurality of microwells configured to contain a biological sample, wherein the optical sensors are configured to detect light emitted from the microwells; and

a fluid delivery system adapted to deliver reagents to the microwells.

2. The apparatus of claim 1, wherein the optical sensors accumulate charge proportional to the intensity of the light and the circuitry is configured to convert the charge to a digital signal.

3. The apparatus of claim 1, wherein the integrated circuit chip comprises a light detection circuit adapted to generate a signal representing the light emitted from the microwells.

4. The apparatus of claim 3, wherein the light detection circuit comprises analog circuitry, further comprising a digital-to-analog converter (DAC) adapted to convert a digital control signal to an analog signal for operating the light detection circuit.

5. The apparatus of claim 3, wherein the substrate further comprises a processor adapted to process the signal to provide an indication of a characteristic of the biological sample.

6. The apparatus of claim 5, wherein the characteristic comprises a nucleic acid sequence.

7. The apparatus of claim 5, wherein the substrate further comprises a data storage circuit, coupled to the processor and adapted to store data, the processor being adapted to retrieve data from the data storage circuit for processing the signal and providing the indication.

8. The apparatus of claim 3, further comprising a control circuit coupled to an external input indicative of the stimulation of the biological sample and adapted to control the light detection circuit to detect light at a selected time in response to the external input for coordinating the light detection with the stimulation.

9. The apparatus of claim 1, further comprising noise reduction circuitry.

10. The apparatus of claim 1, further comprising an analog-to-digital converter (ADC) on the substrate and adapted to convert an analog signal to a digital signal for generating a digital signal as a function of the detected light emitted from the microwells.

11. A method for determining a DNA sequence comprising:

delivering a dNTP to a substrate comprising;

(i) an integrated circuit chip having an array of optical sensors and circuitry for both analog and digital signal processing; and

(ii) an array of microwells, each microwell comprising a primed DNA template;

whereby the incorporation of a dNTP into the primed DNA template results in the release of PPi;

enzymatically generating light from the released PPi; and

detecting the light at the array of optical sensors to determine the amount of dNTP incorporated at each test site.

12. The method of claim 11, wherein the integrated circuit chip generates a signal representing the light emitted from the microwells.

13. The method of claim 12, wherein the integrated circuit chip processes the signal to provide an indication of a nucleic acid sequence of the primed DNA template.

14. The method of claim 13, wherein the substrate comprises a processor that processes the signal to provide the indication of the nucleic acid sequence of the primed DNA template.

15. The method of claim 14, wherein the substrate comprises a data storage circuit, coupled to the processor and adapted to store data, wherein the processor retrieves data from the data storage circuit to process the signal and provide the indication of a nucleic acid sequence of the primed DNA template.

16. The method of claim 12, wherein the substrate comprises a control circuit that synchronizes detection of the light by the optical sensors with delivery of the dNTP.

17. The method of claim 12, wherein the substrate further comprises a memory arrangement that stores the signals for subsequent analysis.

18. The method of claim 12, wherein the substrate comprises noise reduction circuitry that reduces noise in the digital signal.

19. The method of claim 11, further comprising repeating steps (a) through (c) for an additional dNTP.

20. The method of claim 11, wherein reagents used in the method are mixed by electrical methods.