Digital biosensors and method of using same

• US 5,074,977 A
• Filed: 10/23/1990
• Issued: 12/24/1991
• Est. Priority Date: 05/05/1987
• Status: Expired due to Term

• Current Assignee: Washington Technology Center
• Original Assignee: Washington Technology Center
• Inventors: Furlong, Clement E. Jr., Wieler, Edward B., Cheung, Peter W.
• Primary Examiner(s): Tung, T.
• Application Number:
  US07/601,940
• Time in Patent Office: 427 Days
• Field of Search: 204/153.1, 204/153.12, 204/400, 204/403, 204/416, 204/418, 435/4, 435/7, 435/817, 436/518, 436/806
• US Class Current: 205/775
• CPC Class Codes: G01N 27/4148 Integrated circuits therefor, e.g. fabricated by CMOS processing CMOS processing per se H01L21/82
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode
• CPC Class Codes: Y10S 436/806 Electrical property or magnetic property

Abstract

A mearsuring instrument is disclosed having a reversibly selective binding protein immobilized upon the insulated-gate region of a field-effect transistor located on a sensor. With the sensor immersed in solution, the protein binds a select component of the solution to the gate producing an effect on a current flowing through the IGFET. A plurality of such binding protein-IGFET arrangements can be provided on the same sensor, including the same binding proteins having different binding coefficients K_D or an array of proteins with different ligand specificity and/or affinity. Analysis of the IGFET'"'"'s response to binding by a microprocessor allows, for example, the concentration of the component in solution to be determined. With a plurality of different binding proteins employed, the concentration of different components can be determined. Similarly, with binding proteins employed having different binding coefficients K_D, the output of the sensor can be analyzed in either a digital or analog manner, or some combination of the two. To release the component from the protein, heat can be applied to the sensor through a resistive bank integrated into the sensor chip. Alternatively, the application of a reverse bias to the gate can be used to enhance release.

Claims

1. A sensor for detecting a characteristic of a component of a medium comprising:

a plurality of field-effect transistors for responding electronically when exposed to said component; and

organic ligand binders for binding said component to said field-effect transistors, a separate said organic ligand binder being coupled to each said field-effect transistor, each said separate organic ligand binder having a different binding coefficient with respect to said component of said solution.

2. A system for detecting a characteristic of a component of a medium, said system comprising:

a sensor including detection means for responding electronically when exposed to said component and a plurality of binding means for binding said component to said detection means, said detection means including a plurality of detection elements, upon which said binding means are immobilized, said binding means being immobilized on at least two separate said detection elements binding the same component of said medium but having different binding coefficients, each said detection element producing an electronic response to the binding of said component to said detection element by said binding means immobilized thereon; and

processing means, coupled to said sensor, for producing an output indicative of said characteristic of said component of said medium.

3. The system of claim 2, wherein said binding means reversibly bind said component to said detection means.

4. The system of claim 2, wherein said electronic response produced by each said detection element is an analog signal, said processing means producing a separate digital detection element signal when each said analog signal has exceeded some threshold.

5. The system of claim 4, wherein said processing means uses said digital detection element signals to produce said output indicative of said characteristic of said component.

6. The system of claim 5, wherein said processing means determines whether said digital detection element signals are in error and does not use said digital detection element signals that are determined to be in error to produce said output.

7. The system of claim 5, wherein said processing means further uses one analog signal to produce said output indicative of said characteristic of said component.

8. The system of claim 7, wherein said processing means uses the analog signal having the highest magnitude that is still less than the threshold at which said processing means produces a digital detection element signal.

9. A method of detecting a characteristic of a component of a medium, said method comprising the steps of:

binding said component to a plurality of detection elements that respond electronically to said component, said component being bound to different said detection elements in different degrees;

monitoring the electronic response of said detection elements to said component; and

producing an output indicative of said characteristic of interest, said output being a function of the electronic response monitored.

10. The method of claim 9, wherein said step of binding said component to said detection elements comprises the step of reversibly binding said component to said detection elements.

11. The method of claim 10, wherein said step of producing an output indicative of said characteristic of said component further comprises the step of producing a digital output for each said detection element as a function of the electronic response of said detection element to the binding of said component.

12. The method of claim 11, further comprising the steps of determining whether any of said digital outputs are in error and rejecting said digital outputs determined to be in error.

13. A system for detecting a characteristic of a component of a medium, said system comprising:

a sensor including a plurality of detection elements for responding electronically when exposed to said component and a plurality of binding means for binding said component to said detection elements, each said binding means being selectively responsive to a specific range of said component characteristic and being immobilized on separate said detection elements, each said detection element responding electronically to the binding of said component to said detection element; and

processing means coupled to said sensor, for producing a digital output corresponding to the electronic response of each said detection element and analyzing said digital outputs to determine said characteristic of said component without reference to an external calibration standard.