Integrated circuit biochip microsystem containing lens

• US 6,197,503 B1
• Filed: 11/26/1997
• Issued: 03/06/2001
• Est. Priority Date: 11/26/1997
• Status: Expired due to Term

• Current Assignee: Lockheed Martin Energy Research Corporation (Martin Marietta Corporation)
• Original Assignee: UT-Battelle LLC
• Inventors: Vo-Dinh, Tuan, Ericson, Milton N., Wintenberg, Alan
• Primary Examiner(s): Horlick, Kenneth R.
• Assistant Examiner(s): Siew, Jeffrey
• Application Number:
  US08/979,672
• Time in Patent Office: 1,196 Days
• Field of Search: 435/6, 435/91.1, 435/91.2, 435/183, 435/287.2, 436/94, 536/23.1, 536/24.3, 536/24.31, 536/24.33, 536/25.3
• US Class Current: 435/6.11
• 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 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2565/632 being a surface enhanced, e.g. resonance, Raman spectrometer
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/6482 Sample cells, cuvettes
• CPC Class Codes: G01N 2021/651 Cuvettes therefore
• CPC Class Codes: G01N 21/64 Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/6454 : using an integrated detector array
• CPC Class Codes: G01N 21/6458 : Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G01N 21/65 : Raman scattering
• CPC Class Codes: G01N 21/658 : enhancement Raman, e.g. surface plasmons

Abstract

The present invention discloses a self-contained miniature DNA biosensor designed to detect specific molecular targets, particularly suitable for detection of nucleic acids. For example, hybridized DNA may be detected without external monitoring or signal transmission. The miniaturized biosensor is a biochip comprising multiple biological sensing elements such as DNA probes, excitation microlasers, a sampling waveguide equipped with optical detectors (fluorescence and Raman), integrated electrooptics, and a biotelemetric radio frequency signal generator. The novel integrated circuit biochip microsystem (ICBM) is suitable for gene analysis and will allow rapid, large-scale, and cost-effective production of gene biochips.

Claims

1. An integrated circuit microchip sensor that detects a target biomolecule, the integrated circuit microchip sensor comprising:

a probe that specifically binds to the target biomolecule;

a solid support to which the probe is secured;

at least one sensor connected to the probe, wherein the probe generates a detection signal, existing at a signal level related to a level of electromagnetic radiation detected by the sensor;

a membrane positioned between the probe and the sensor, the membrane being capable of filtering the electromagnetic radiation;

a lens secured to the solid support and positioned between the probe and the sensor; and

detection circuitry connected to at least one sensor for processing the detection signal, and for generating an output signal proportional to the detection signal, wherein the signal indicates the presence of the biomolecule in the sample.

2. The integrated circuit microchip sensor of claim 1, wherein the membrane is positioned between the lens and the probe.

3. The integrated circuit microchip sensor of claim 1, wherein the probe binds to a nucleic acid, an antibody, an enzyme, a polypeptide, or a peptide.

4. The integrated circuit microchip sensor of claim 1, wherein the probe includes a source of electromagnetic radiation.

5. The integrated circuit microchip sensor of claim 4, wherein the source of electromagnetic radiation includes a light emitting diode or a semiconductor laser.

6. The integrated circuit microchip sensor of claim 1, wherein the target molecule comprises a source of electromagnetic radiation.

7. The integrated circuit microchip sensor of claim 1, wherein the electromagnetic radiation detected by the sensor is radiated in the visible, ultraviolet, infrared, near-infrared, x-ray, or radio frequency spectrum.

8. The integrated circuit microchip sensor of claim 1, wherein the sensor includes a discrete detector.

9. The integrated circuit microchip sensor of claim 8, wherein the discrete detector comprises a phototransistor, an avalanche diode, or a photodiode.

10. The integrated circuit microchip sensor of claim 1, wherein the sensor includes a photodetector.

11. The integrated circuit microchip senior of claim 10, wherein the photodetector comprises a phototransistor, an avalanche diode, or a photodiode.

12. The integrated circuit microchip of claim 1, wherein the detection circuitry includes a transimpedance amplifier converting the generated signal from a current signal to a voltage signal.

13. The integrated circuit microchip of claim 12, wherein the detection circuitry further includes at least one of an amplifier amplifying the converted voltage signal, a low-pass filter and adjustable gain combination, and an adjustable gain.

14. The integrated circuit microchip sensor of claim 1, further comprising a two-dimensional array of probes including the probe.

15. The integrated circuit microchip sensor of claim 14, further comprising a two-dimensional array of sensors including the sensor, the two-dimensional array of sensors corresponding to the two-dimensional array of probes.

16. The integrated circuit microchip sensor of claim 14, wherein the two-dimensional array is one 4 probes×

4 probes or 10 probes by 10 probes.

17. A method of detecting a biomolecule comprising:

contacting a sample suspected of containing the biomolecule with the integrated circuit microchip sensor of claim 1; and

detecting the presence of an output signal from the sensor, wherein the presence of the output signal is indicative of the presence of the biomolecule in the sample.