Biosensing system and methods using electron-ionic mechanisms at fluid-sensor interfaces

• US 10,006,882 B2
• Filed: 11/20/2015
• Issued: 06/26/2018
• Est. Priority Date: 11/21/2014
• Status: Active Grant

• Current Assignee: EnLiSense, LLC
• Original Assignee: EnLiSense, LLC
• Inventors: Prasad, Shalini, Muthukumar, Sriram, Selvam, Anjan Panneer
• Primary Examiner(s): Dinh, Bach T
• Application Number:
  US14/946,899
• Publication Number:
  US 20160146754A1
• Time in Patent Office: 949 Days
• Field of Search: 204450-470, 204546-550, 204600-621, 204643-645, 20440301-40315, 2057775-778, 205792
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 5/1468 using chemical or electrochemical methods, e.g. by polarographic means A61B5/1486 takes precedence
• CPC Class Codes: A61B 5/1477 non-invasive
• CPC Class Codes: G01N 27/447 using electrophoresis
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

An example biosensor is provided and includes a semiconductor sensing element, a first electrode and a second electrode located on a first plane of the sensing element with a first electric field being applied thereacross, a third electrode located on a second plane of the sensing element parallel to and removed from the first plane with a second electric field being applied across the first electrode and the third electrode perpendicular to the first electric field, and a dielectric substrate having a first portion that constrains a fluid including an analyte on a surface of the sensing element, and a second portion that facilitates dielectric separation of the fluid from the electrodes. The mutually perpendicular electric fields facilitate adjusting a height of a fluid-sensor interface comprising an electrical double layer in the fluid enabling detection and characterization of the analyte.

Claims

1. A biosensor, comprising:

a semiconductor sensing element;

a first conducting electrode and a second conducting electrode located on a first plane of the sensing element, wherein a first electric field is applied across the first electrode and the second electrode;

a third conducting electrode located on a second plane of the sensing element parallel to and removed from the first plane, wherein a second electric field is applied across the first electrode and the third electrode perpendicular to the first electric field; and

a dielectric substrate having a first portion adjacent a second portion, the first portion adjacent the sensing element and comprising pores, the first portion facilitating reception and containment of a fluid comprising an analyte on a surface of the sensing element distal from the third electrode, the surface defining an interface between the first portion and the sensing element, and the second portion facilitating dielectric separation of the fluid from the first electrode, the second electrode and the third electrode, wherein the mutually perpendicular first electric field and the second electric field facilitate adjusting a height of a fluid-sensor interface comprising an electrical double layer (EDL) in the fluid enabling detection and characterization of the analyte;

wherein the first portion of the substrate facilitates reception and containment of the fluid in the pores.

2. The biosensor of claim 1, wherein the first electric field is generated from direct current (DC) voltage applied across the first electrode and the second electrode, wherein the second electric field is generated from alternating current (AC) voltage applied across the first electrode and the third electrode.

3. The biosensor of claim 1, wherein the fluid-sensor interface further comprises a surface of the sensing element.

4. The biosensor of claim 3, wherein the fluid-sensor interface further comprises a layer of linker molecules bound to the surface of the sensing element.

5. The biosensor of claim 4, wherein the fluid-sensor interface further comprises a layer of capture probes bound to the layer of linker molecules.

6. The biosensor of claim 5, wherein the fluid-sensor interface further comprises blocking molecules bound to some of the linker molecules.

7. The biosensor of claim 1, wherein a first electrical response is measured across the first electrode and the third electrode, wherein a second electrical response is measured across the first electrode and the third electrode, wherein a comparison between the first electrical response and the second electrical response provides a measure of a signal-to-noise ratio (SNR) of the biosensor.

8. The biosensor of claim 7, wherein the first electric field is adjusted to change a Debye length of the EDL generated in the fluid, wherein the Debye length affects the SNR of the biosensor.

9. The biosensor of claim 7, wherein a concentration of the analyte is estimated from the second electrical response based on a calibration chart.

10. The biosensor of claim 1, wherein the first portion of the substrate comprises a porous, hydrophilic, biocompatible material, wherein the second portion of the substrate comprises a hydrophobic biocompatible material.

11. The biosensor of claim 1, wherein sensing element comprises a thin-film semiconductor, wherein the first electrode, the second electrode and the third electrode comprise nanostructures patterned on the thin-film sensing element.

12. The biosensor of claim 1, wherein the first electric field produces a gradient electric field facilitating electrokinetic focusing of the analyte on the sensing element.

13. The biosensor of claim 1, wherein the mutually perpendicular electric fields facilitate size and charge based detection and characterization of low concentrations of the analyte in a small volume of the fluid.

14. The biosensor of claim 1, wherein the biosensor is configured to be wearable, wherein the analyte is generated by the wearer, wherein the biosensor tests the analyte in-situ.

15. The biosensor of claim 1, wherein the analyte comprises a plurality of different target species in the fluid, wherein the biosensor enables separately detecting and characterizing each target species.

16. The biosensor of claim 1, further comprising a plurality of linker molecules residing on the surface within each of the pores.