Label free analyte detection by electronic desalting and field effect transistors
Inventors
Bashir, Rashid • VILASUR SWAMINATHAN, Vikhram • Reddy, JR., Bobby • SALM, Eric M. • DUARTE-GUEVARA, Carlos
Assignees
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Abstract
Provided are methods and devices for the label free detection of analytes in solution, including analytes suspended in a biological fluid. A field effect transistor (FET) is positioned in close proximity to a paired set of reference electrodes and the reference electrodes electrically biased to provide desalting and a stable gate voltage to the FET. In this manner, charged ions are depleted in the sensing region of the sensor and device sensitivity to analyte detection improved by the removal of charge that otherwise interferes with measurement. Also provided are methods and systems providing increased in reference electrode surface area and/or decrease in droplet volume to further improve label-free detection of analytes.
Core Innovation
The invention relates to detecting an analyte in a droplet of a sample solution using a field effect transistor (FET) supported by a substrate, where the droplet is an aqueous droplet disposed on a plurality of reference electrodes in close proximity to the FET. The plurality of reference electrodes comprises paired reference electrodes having a first reference electrode and a second reference electrode opposably facing each other, with the FET positioned between the paired reference electrodes so that the FET and the paired reference electrodes are in a planar configuration relative to the substrate.
A desalting bias is applied between the paired reference electrodes by an electrical controller configured to electrically bias at least one reference electrode relative to the FET or to another reference electrode. The electrical bias generates a stable FET gate bias, electronically removes at least a portion of charged ions in the droplet from a sensor area, and generates a charged ion depletion region in the sensor area, so that the change in an electrical parameter monitored by an electrical sensor corresponds to presence of the analyte in the droplet.
The device is configured with specific droplet and electrode contact constraints, including a droplet volume of 50 nL or less, an electrode contact surface area AED in contact with the droplet of at least 10000 μm^2, and a ratio Vdroplet/AED of less than or equal to 1 when a desalting bias of 1 V is applied. The paired reference electrodes comprise thin patterned metals having a high contact surface area for contacting and supporting the droplet, and the electrode contact surface area comprises a hydrophilic surface treatment, further supporting sensor operation with aqueous droplets and electrically generated ion depletion.
Claims Coverage
The partial content provides one independent claim, which includes multiple structural and operational limitations defining the device architecture and electronic desalting to generate a stable FET gate bias. The independent claim also includes quantitative constraints on paired-electrode separation, droplet volume, electrode contact surface area, and the Vdroplet/AED ratio under a specified desalting bias.
Paired reference electrodes positioned for planar FET configuration in a droplet
A device for detecting an analyte in a droplet of a sample solution includes a FET supported by a substrate and a plurality of reference electrodes positioned in close proximity to the FET and a droplet disposed on the plurality of reference electrodes, where the plurality of reference electrodes comprises paired reference electrodes with a first and second reference electrode opposably facing each other separated by a separation distance, and the FET is positioned between the paired reference electrodes so that the FET and the paired reference electrodes are in a planar configuration relative to the substrate.
High contact surface area thin patterned metal reference electrodes with droplet volume and AED constraints
The plurality of reference electrodes comprise thin patterned metals having a high contact surface area for contacting and supporting the droplet of the sample solution, with separation distance between paired reference electrodes less than or equal to 30 μm, droplet volume Vdroplet of 50 nL or less, and electrode contact surface area AED in contact with the droplet of at least 10000 μm^2.
Hydrophilic wetted aqueous droplet enabling Vdroplet/AED ratio limitation under desalting bias
The droplet is an aqueous droplet and the electrode contact surface area comprises a hydrophilic surface treatment, and wherein a ratio Vdroplet/AED expressed as cm^3/cm^2 is less than or equal to 1 when a desalting bias of 1 V is applied between the paired set of reference electrodes.
Electrical bias generates stable FET gate bias and charged ion depletion region
An electrical controller configured to electrically bias at least one reference electrode relative to the FET or to another reference electrode and generate a stable FET gate bias, further configured to electronically remove at least a portion of charged ions in the droplet from a sensor area and generate a charged ion depletion region in the sensor area.
Monitor FET electrical parameter corresponding to analyte presence
An electrical sensor configured to monitor a FET electrical parameter, wherein a change in the electrical parameter corresponds to presence of the analyte in the droplet of the sample solution.
Across the independent claim, the core claim coverage centers on a planar FET positioned between paired reference electrodes in close proximity to a small aqueous droplet, where thin patterned high-contact-area reference electrodes and a hydrophilic surface treatment satisfy quantitative droplet and electrode-area constraints. A controller applies a desalting bias to generate a stable FET gate bias that electronically removes charged ions and forms a charged ion depletion region, and an electrical sensor monitors a FET electrical parameter that changes when the analyte is present.
Stated Advantages
Reduced ionic shielding by electronically removing charged ions from a sensor area while generating a stable FET gate bias.
Improved sensitivity for detecting an analyte in a droplet by generating a charged ion depletion region in the sensor area so that a monitored FET electrical parameter corresponds to analyte presence.
Enables operation with aqueous droplets having a droplet volume of 50 nL or less and electrode contact constraints defined by AED and the Vdroplet/AED ratio under a desalting bias of 1 V.
Supports label-free analyte detection by correlating changes in a monitored FET electrical parameter to analyte presence.
Documented Applications
Detecting an analyte in a droplet of a sample solution using the described device architecture that electronically removes charged ions and generates a charged ion depletion region so that a change in a monitored FET electrical parameter corresponds to analyte presence.
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