Bioluminescent bioreporter integrated circuit detection methods

• US 6,905,834 B1
• Filed: 09/12/2000
• Issued: 06/14/2005
• Est. Priority Date: 11/25/1997
• Status: Expired due to Fees

• Current Assignee: UT-Battelle LLC
• Original Assignee: UT-Battelle LLC
• Inventors: Sayler, Gary S., Applegate, Bruce M., Simpson, Michael L., Paulus, Michael J., Ripp, Steven A.
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US09/660,581
• Time in Patent Office: 1,736 Days
• Field of Search: 422/55, 422/57, 422/58, 422/82.01, 422/82.05, 422/82.06, 422/82.07, 422/82.08, 435/7.32, 435/287.1, 435/287.2, 435/288.7, 435/808, 436/805
• US Class Current: 435/7.32
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: C12Q 1/02 involving viable microorganisms
• CPC Class Codes: C12Q 1/66 involving luciferase
• CPC Class Codes: G01N 21/763 Bioluminescence
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
• CPC Class Codes: G01N 33/84 involving inorganic compounds or pH
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 435/849 Escherichia coli
• CPC Class Codes: Y10S 435/879 Salmonella
• CPC Class Codes: Y10S 435/909 Vibrio
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

Disclosed are monolithic bioelectronic devices comprising a bioreporter and an OASIC. These bioluminescent bioreporter integrated circuit are useful in detecting substances such as pollutants, explosives, and heavy-metals residing in inhospitable areas such as groundwater, industrial process vessels, and battlefields. Also disclosed are methods and apparatus for detection of particular analytes, including ammonia and estrogen compounds.

Claims

1. An apparatus for detecting analytes, comprising:

(a) a substrate;

(b) an integrated circuit including a light detection system formed using said substrate;

(c) a selectively permeable container attached to said substrate located on said integrated circuit;

(d) a microorganism housed within said container wherein the microorganism metabolizes a selected analyte to emit light in response to a metabolite of said analyte;

(e) a layer of bioresistant/biocompatible material disposed between the substrate and the container; and

(f) a fluid nutrient reservoir equipped with a microfluidic pump on said substrate.

2. The apparatus of claim 1 wherein the integrated circuit is a CMOS integrated circuit.

3. The apparatus of claim 2 wherein the CMOS integrated circuit includes a photodiode, a current to frequency converter, a digital counter, and a wireless transmitter.

4. The apparatus of claim 3 further comprising a central data collection station to receive transmissions from said transmitter.

5. The apparatus of claim 1 wherein the microorganism is Pseudomonas fluorescens HK44.