Electro-chemical analysis device with integrated thermal sensor and method for monitoring a sample using the device

• US 20030113907A1
• Filed: 12/18/2001
• Published: 06/19/2003
• Est. Priority Date: 12/18/2001
• Status: Active Grant

• Current Assignee: Motorola, Inc. (Motorola Solutions, Inc.)
• Original Assignee: Motorola, Inc. (Motorola Solutions, Inc.)
• Inventors: Roberts, Peter C., Sadler, Daniel J., Zenhausern, Frederic, Burdon, Jeremy W.
• Granted Patent: US 6,756,223 B2
• Time in Patent Office: Days
• US Class Current: 435/287.2
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00576 fluorophore
• 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 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 3/508 rigid containers not provided for above
• CPC Class Codes: B01L 7/00 Heating or cooling apparatus autoclaves B01J3/04; Heat insulating devices
• CPC Class Codes: C12Q 1/6834 Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: C12Q 2565/607 being a sensor, e.g. electrode

Abstract

An electrochemical analysis device and method for analyzing biomolecular samples, including a means for holding a sample on a substrate platform, a thermal sensor, a biosensor formed having a specific spatial resolution as related to the thermal sensor, and a means for providing radiation to the biomolecular sample. The means for holding the sample, the thermal sensor, the biosensor, and the means for providing radiation all three-dimensionally integrated with the substrate platform, thereby defining a compact biomolecular analysis device having a volume resolution of less than 50 micro liters. During operation, radiation is provided to the biomolecular sample to provide for a constant temperature at which hybridization of the biomolecules takes place. The temperature of the biomolecular sample is monitored and controlled by the integrated thermal sensor and the integrated heater. Once hybridization takes place, the change in electric condition (e.g. voltage, current and/or power) is recorded and identification of the molecule within biomolecular sample is made by utilizing an exterior reader.

Claims

1. An electro-chemical analysis device, comprising:

a means for holding a sample undergoing analyzation;

at least one thermal sensor for sensing the temperature of the sample during analyzation and providing sensed temperature data;

at least one biosensor, formed proximate the thermal sensor and in thermal contact with the sample;

a means for providing radiation to the sample, wherein the at least one thermal sensor, the at least one biosensor, and the means for providing heat are three-dimensionally integrated in a single substrate platform;

electronics for transforming the sensed temperature data into an output measurement signal, the electronics formed as part of a feedback circuit, thereby providing for the maintenance of a preferred temperature of the sample.

2. An electrochemical analysis device as claimed in claim 1 wherein the at least one thermal sensor and the at least one biosensor are formed having a spatial resolution of less than 10 microns.

3. An electrochemical analysis device as claimed in claim 2 wherein the at least one thermal sensor has a temporal resolution of less than 10 milliseconds.

4. An electrochemical analysis device as claimed in claim 3 wherein the electrochemical analysis device has a volume resolution of less than 50 microliters.

5. An electrochemical analysis device as claimed in claim 4 wherein the means for holding a sample undergoing analyzation is a bioreactor chamber.

6. An electrochemical analysis device as claimed in claim 4 wherein the means for holding a sample undergoing analyzation is interfacial surface tension.

7. An electrochemical analysis device as claimed in claim 4 wherein the sample is a biomolecular sample.

8. A biomolecular sample as claimed in claim 7 wherein the sample is a nucleic acid biomolecule, DNA, RNA or a protein

9. An electrochemical analysis device as claimed in claim 4 wherein the at least one biosensor comprises an array of biological probes each of the biological probes characterized as including an electronically active electrode coated with a specific DNA probe.

10. An electrochemical analysis device as claimed in claim 4 wherein the at least one thermal sensor is formed as one of a p-n junction, a thermistor, or a resistance temperature detector (RTD).

11. An electrochemical analysis device as claimed in claim 4 wherein the means for providing radiation to the biomolecular sample includes generating radiant heat by one of a thermal reaction, a chemical reaction, a fluid, or magnetic induction, proximate the biomolecular sample to heat the sample.

12. An electrochemical analysis device, comprising:

a substrate platform;

a bioreactor chamber formed integral with the substrate platform, the bioreactor chamber characterized as providing for a chamber to hold a biomolecular sample during analysis;

at least one thermal sensor formed in thermal contact with the bioreactor chamber and the biomolecular sample and integral with the substrate platform, the at least one thermal sensor characterized as providing for the sensing of a temperature of the biomolecular sample and having a temporal resolution of less than 10 milliseconds, the at least one thermal sensor providing sensed temperature data and having a temperature resolution of less than 0.1 degree centigrade;

a plurality of biosensors, formed having a spatial resolution of less than ten microns to the at least one thermal sensor, wherein the plurality of biosensors are formed integral with the substrate platform and in physical contact with the biomolecular sample;

a reference probe formed proximate the at least one biosensor and integral the substrate platform, the reference probe characterized as performing as an electro-chemical reference;

a means for providing radiation to the biomolecular sample formed integral with the substrate platform, and in thermal contact with the biomolecular sample; and

a means for the transforming the sensed temperature data into an output measurement electrical signal, the means for transforming the sensed temperature data formed as part of a feedback circuit with the means for providing heat to the biomolecular sample, thereby providing for the maintenance of a preferred temperature for the biomolecular sample.

13. An electrochemical analysis device as claimed in claim 12 wherein each of the plurality of biological probes includes an electronically active electrode coated with a specific DNA probe.

14. An electrochemical analysis device as claimed in claim 12 wherein the at least one thermal sensor is formed as one of a p-n junction, a thermistor, or a resistance temperature detector (RTD).

15. An electrochemical analysis device as claimed in claim 12 wherein the means for providing radiation to the biomolecular sample includes providing radiant heat, generated by a resistive film formed proximate the bioreactor chamber.

16. An electrochemical analysis device as claimed in claim 12 wherein the means for providing radiation to the biomolecular sample includes providing for a chemical reaction proximate the bioreactor chamber, the chemical reaction generating radiant heat to heat the biomolecular sample.

17. An electrochemical analysis device as claimed in claim 12 wherein the means for providing radiation to the biomolecular sample includes providing for magnetic induction of heat proximate the biocompatible to heat the biomolecular sample.

18. A method for monitoring a sample using an electrochemical analysis device, comprising the steps of:

providing at least one thermal sensor having a temporal resolution of less than 10 milliseconds and at least one biosensor three-dimensionally related on a substrate platform, the at least one thermal sensor and the at least one biosensor positioned having a spatial resolution of less than 10 microns;

providing for a bioreactor chamber integrated with the substrate platform, and formed proximate the at least one biosensor, the bioreactor chamber characterized as holding a biomolecular sample for testing;

providing a means for providing radiation to the biomolecular sample formed integral the substrate platform;

introducing a biomolecular sample into the bioreactor chamber, the biomolecular sample characterized as being in thermal contact with the at least one thermal sensor and in physical contact with the at least one biosensor, the biomolecular sample having a temperature;

probing and detecting the temperature of the biomolecular sample with the thermal sensor;

generating an output measurement electrical signal from the sensed temperature;

processing the output measurement signal to submit a response signal to activate the means for providing radiation.

19. A method for monitoring a biomolecular sample using an electrochemical analysis device as claimed in claim 18 wherein the step of providing at least one thermal sensor includes providing one of a p-n junction, a thermistor, or a resistor temperature detector (RTD).

20. A method for monitoring a biomolecular sample using an electrochemical analysis device as claimed in claim 18 wherein the step of providing at least one biosensor includes providing a plurality of biological probes each of the plurality of biological probes characterized as including an electronically active electrode coated with a specific DNA probe.

21. A method for monitoring a biomolecular sample using an electrochemical analysis device as claimed in claim 18 wherein the step of providing a means for providing radiation to the biomolecular sample includes providing radiant heat generated by one of a resistive film formed proximate the bioreactor chamber, a chemical reaction proximate the bioreactor chamber, or magnetic induction of heat proximate the bioreactor chamber to heat the biomolecular sample.