IP Library Granted Patent US 11,536,722
Granted Patent B2
US 11,536,722 · App. 17/329,090 · Granted Dec 27, 2022

Chemically-sensitive field effect transistors, systems, and methods for manufacturing and using the same

Inventors: Brett R. Goldsmith (San Diego, CA); Mitchell Lerner (San Diego, CA); Paul Hoffman (San Diego, CA)
Assignee: Cardea Bio, Inc.
G01N33/5438G01N27/4146
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Quick Facts
Patent No.
US 11,536,722
App. No.
17/329,090
Granted
Dec 27, 2022
Kind
B2
Abstract

An apparatus includes a biosensor integrated circuit (IC) chip with sensing zones and/or well structures configured to receive a liquid with biological analytes. The chip includes a passivation layer with an opening over a channel layer and an array of graphene field effect transistors (gFETs) individually having a 2D graphene channel disposed on a dielectric oxide layer, a conductive drain, and a conductive source. A liquid gate is formed above the top surface of the graphene channel. The chip further includes reference electrodes formed in a metal layer, configured to contact the liquid, and disposed at a horizontal distance apart from the graphene channels. The individual gFETs are operable to enable a set of measurements to sense parameters of the biological analytes based on changes in a shape of Id-Vgs transconductance curves. A system and a method have similar structures and perform the functions of the apparatus.

Claims (51)

1. An apparatus comprising:

a biosensor integrated circuit (IC) chip comprising

one or more sensing zones within one or more well structures configured to receive a liquid comprising one or more biological analytes;

a passivation layer with an opening over a channel layer and comprising an array of graphene field effect transistors (gFETs), the individual gFETs comprising:

a graphene channel formed in the channel layer and comprising a two-dimensional layer of carbon atoms, the graphene channel disposed on a dielectric oxide layer;

a conductive drain connected at a first end of the graphene channel; and

a conductive source connected at a second end of the graphene channel,

wherein a liquid gate is formed above the top surface of the graphene channel upon receipt of the liquid;

the biosensor IC chip further comprising:

one or more reference electrodes formed in a metal layer of the biosensor IC chip and configured to contact the liquid, the one or more reference electrodes disposed at a horizontal distance apart from the graphene channels of the gFETs in the array, wherein:

at least one of the one or more reference electrodes is configured to apply a liquid gate voltage to the liquid; and

at least one of the one or more reference electrodes is configured to measure a liquid gate voltage of the liquid,

wherein the individual gFETs and the first and second reference electrodes are operable to enable a set of measurements to be made to sense one or more parameters of a biological analyte in the liquid based on changes in a shape of a chemical sensing I d -V gs curve relative to a reference I d -V gs , in response to the presence of the biological analyte in the liquid on or over the channels of the individual gFETs.

2. The apparatus of claim 1 , wherein the changes in the shape of the chemical sensing I d -V gs curve relative to a reference I d -V gs curves include transconductance slope changes.

3. The apparatus of claim 2 , wherein the transconductance slope changes include changes to transconductance slope in both a p-type region and an n-type region of the chemical sensing I d -V gs curve.

4. The apparatus of claim 2 , wherein the individual gFETs are configured to enable sensing of one or more parameters of the one or more biological analytes in the liquid based on shifts of a chemical sensing I d -V gs curve relative to a reference I d -V gs .

5. The apparatus of claim 4 , wherein the shifts of the chemical sensing I d -V gs curve relative to a reference I d -V gs are selected from horizontal shifts, vertical shifts, or combinations thereof.

6. The apparatus of claim 4 , wherein the shifts of the chemical sensing I d -V gs curve relative to a reference I d -V gs include shifts in parameters selected from on current (I on ) in the p-type region, Dirac voltage (V Dirac ), on current (I on ) in the n-type region, and combinations thereof.

7. The apparatus of claim 1 , further comprising one or more capture regions on or over the channel of the one or more gFETs, the individual capture regions configured respectively to accommodate attachment of a selected biomaterial to a top surface of the graphene channel, the biomaterial selected to detect a biological analyte of the one or more biological analytes in the liquid.

8. The apparatus of claim 1 , wherein the biomaterials in the respective capture regions of the one or more capture regions are selected to detect analytes selected from ions associated with biomolecules, nucleic acids, antigens, polysaccharides, proteins, peptides, small molecules, and combinations thereof.

9. The apparatus of claim 1 , wherein at least a portion of the source electrodes and the drain electrodes have interdigitated geometries.

10. The apparatus of claim 1 , wherein the passivation layer provides an insulating layer between liquid and the regions at which the source electrode and the drain electrode connect to the graphene channel of the individual gFETs.

11. The apparatus of claim 10 , wherein the passivation layer comprises silicon nitride.

12. The apparatus of claim 11 , further comprising an ion permeable membrane disposed above the graphene channel and configured to allow selected ions to pass to the sensing region of the graphene channel.

13. The apparatus of claim 1 , further comprising flow channels that bring reagents and/or analytes to the one or more well structures.

14. A system comprising:

a biosensor integrated circuit (IC) chip having one or more well structures configured to receive a liquid comprising one or more biological analytes;

sensing zones within the one or more well structures comprising a passivation layer with an opening over a channel layer and comprising an array of graphene field effect transistors (gFETs), the individual gFETs comprising:

a graphene channel formed in the channel layer and comprising a two-dimensional layer of carbon atoms, the graphene channel disposed on a dielectric oxide layer;

a conductive drain connected to a first end of the graphene channel; and

a conductive source connected to a second end of the graphene channel, wherein the individual gFETs are configured such that the liquid received by the one or more well structures is confined to form a liquid gate above the top surface of the graphene channel;

the biosensor IC chip further comprising:

one or more reference electrodes formed in a metal layer of the biosensor IC chip and configured to contact the liquid, the one or more reference electrodes disposed at a horizontal distance apart from the graphene channels of the gFETs in the array, wherein:

at least one of the one or more reference electrodes is configured to apply a liquid gate voltage to the liquid; and

at least one of the one or more reference electrodes is configured to measure a liquid gate voltage of the liquid,

wherein the individual gFETs and the first and second reference electrodes are operable to enable a set of measurements to be made to sense one or more parameters of a biological analyte in the liquid based on changes in a shape of a chemical sensing Id-Vgs curve relative to a reference Id-Vgs, in response to the presence of the biological analyte in the liquid on or over the channels of the individual gFETs;

the system further comprising a processor configured to read digitized signals from the individual gFETs to respectively determine one or more parameters of the one or more biological analytes in the liquid based on changes in the shape of the chemical sensing I d -V gs curve relative to the reference I d -V gs , in response to the presence of the analyte in the liquid on or over the graphene channel of the individual gFETs.

15. The system of claim 14 , wherein the changes in the shape of the chemical sensing I d -V gs curve relative to a reference I d -V gs include transconductance slope changes.

16. The system of claim 15 , wherein the transconductance slope changes include changes to transconductance slope in both a p-type region and an n-type region of the chemical sensing I d -V gs curve.

17. The system of claim 16 , wherein the individual gFETs are configured to enable sensing of one or more parameters of the one or more biological analytes in the liquid based on shifts of a chemical sensing I d -V gs curve relative to a reference I d -V gs , the shifts selected from horizontal shifts, vertical shifts, or combinations thereof.

18. The system of claim 17 , wherein the shifts of the chemical sensing I d -V gs curve relative to a reference I d -V gs include shifts in parameters selected from on current (I on ) in the p-type region, Dirac voltage (V Dirac ), on current (I on ) in the n-type region, and combinations thereof.

19. The system of claim 14 , further comprising one or more capture regions on or over the channel of the one or more gFETs, the individual capture regions configured respectively to accommodate attachment of a selected biomaterial to a top surface of the graphene channel, the biomaterial selected to detect a biological analyte of the one or more biological analytes in the liquid.

20. A method comprising:

providing a biosensor integrated circuit (IC) chip having a plurality of well structures configured to receive a liquid comprising one or more biological analytes, the chip comprising a passivation layer with an opening over one or more graphene field effect transistors (gFETs), the individual gFETs comprising:

a graphene channel comprising a two-dimensional layer of carbon atoms;

a capture region on or over the graphene channel and configured to selectively capture a first analyte or a second analyte of the one or more biological analytes;

a conductive drain connected to a first end of the graphene channel; and

a conductive source connected to a second end of the graphene channel,

the biosensor IC chip further having one or more reference electrodes formed in corresponding metal layer portions of the biosensor IC chip and disposed at a horizontal distance apart from the graphene channels of the one or more gFETs and configured to apply and/or measure a liquid gate voltage to a liquid confined above a top surface of the graphene channels;

sensing one or more parameters of the one or more analytes in the liquid based on changes in a shape of a chemical sensing I d -V gs curve relative to a reference I d -V gs , in response to the presence of the first analyte or the second analyte in the liquid gate being captured on or over the graphene; and

determining differences between the first analyte and the second analyte based on transconductance slope differences of the respective chemical sensing I d -V gs curves.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 3, 2023
From: SENSOREM TECHNOLOGIES INC.
To: NANOMEDICAL DIAGNOSTICS, INC.
Reel/Frame 062877/0962 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 3, 2023
From: AGILOME, INC.
To: SENSOREM TECHNOLOGIES INC.
Reel/Frame 062878/0195 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 16, 2023
From: HOFFMAN, PAUL
To: AGILOME, INC.
Reel/Frame 062722/0966 →
CHANGE OF NAME Recorded Jan 9, 2023
From: NANOMEDICAL DIAGNOSTICS, INC.
To: CARDEA BIO, INC.
Reel/Frame 062326/0064 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 15, 2021
From: GOLDSMITH, BRETT R.; LERNER, MITCHELL
To: CARDEA BIO, INC.
Reel/Frame 057487/0274 →
Continuity (33)
Continuation 16586964 · Sep 28, 2019
Continuation 16014838 · Jun 21, 2018
Continuation 15256493 · Sep 2, 2016
Continuation In Part 15239800 · Aug 17, 2016
Continuation In Part 15225764 · Aug 1, 2016
Continuation In Part 15182533 · Jun 14, 2016
Continuation In Part 15065744 · Mar 9, 2016
Continuation In Part 14963253 · Dec 9, 2015
Continuation In Part 62130594 · Mar 9, 2015
Provisional Application 62215018 · Sep 6, 2015
Provisional Application 62214910 · Sep 4, 2015
Provisional Application 62214912 · Sep 5, 2015
Provisional Application 62214901 · Sep 4, 2015
Provisional Application 62214892 · Sep 4, 2015
Provisional Application 62214850 · Sep 4, 2015
Provisional Application 62213151 · Sep 2, 2015
Provisional Application 62213117 · Sep 2, 2015
Provisional Application 62213112 · Sep 2, 2015
Provisional Application 62206814 · Aug 18, 2015
Provisional Application 62206372 · Aug 18, 2015
Provisional Application 62206166 · Aug 17, 2015
Provisional Application 62205808 · Aug 17, 2015
Provisional Application 62205803 · Aug 17, 2015
Provisional Application 62206224 · Aug 17, 2015
Provisional Application 62206228 · Aug 17, 2015
Provisional Application 62199956 · Jul 31, 2015
Provisional Application 62130621 · Mar 10, 2015
Provisional Application 62130601 · Mar 9, 2015
Provisional Application 62130598 · Mar 9, 2015
Provisional Application 62175351 · Jun 14, 2015
Provisional Application 62199987 · Aug 1, 2015
Provisional Application 62094016 · Dec 18, 2014
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