Multi-array impedimetric biosensors for the detection of concussion and traumatic brain injuries

Patent metadata

Field	Value
Publication number	US-2019317089-A1
Application number	US-201716467116-A
Country	US
Kind code	A1
Filing date	Dec 11, 2017
Priority date	Dec 9, 2016
Publication date	Oct 17, 2019
Grant date	—

Abstract

The invention relates to ex-situ biosensors that impedimetrically detect one or more target biomarkers of interest in bodily fluid sample derived from a patient. The biosensors include a multi-array of conducting material, such as platinum wires, having immobilized thereon antibody and/or aptamer that is selected to specifically and selectively bind to the one or more target biomarkers of interest. The biosensors are contacted with a portion of the bodily fluid sample, and the antibody and/or aptamer binds to the target biomarker(s) of interest in the bodily fluid sample. As a result, an electrochemical impedance signal is generated and therefore, a change in the electrochemical impedance is indicative of the presence of the target biomarker(s) of interest in the bodily fluid sample. The biosensors are point-of-care, on-demand devices that can be used in a medical environment, as well as in domestic and health emergency settings.

First claim

1 . A portable, ex-situ system to impedimetrically detect one or more target biomarkers related to brain injury or disease in a bodily fluid sample of a patient, comprising:
a conducting material interface having a surface; a biological sensor agent applied to the surface of the conducting material interface, the biological sensor agent comprising:
an immobilization agent; and
at least one antibody and/or aptamer selected to interact with the immobilization agent and selected to bind with the one or more target biomarkers related to brain injury or disease;
a signaling agent comprising an electrochemical impedance signal generated by binding of the antibody and/or aptamer with the one or more target biomarkers related to brain injury or disease; and the bodily fluid sample derived from the patient having a presence or an absence of the one or more target biomarkers related to brain injury or disease, and in contact with the antibody and/or aptamer, wherein a change in electrochemical impedance is indicative of the presence of the one or more target biomarkers related to brain injury or disease in the bodily fluid sample, and wherein no change in electrochemical impedance is indicative of the absence of the one or more target biomarkers related to brain injury or disease in the bodily fluid sample.

2 . The system of claim 1 , wherein the conducting material interface, comprises:
an epoxy; and a multi-array of vertically aligned conducting material wires cast in the epoxy substrate.

3 . The system of claim 1 , wherein the conducting material interface comprises an element selected from the group consisting of platinum, gold, iridium, ruthenium, palladium, osmium, and alloys thereof.

4 . The system of claim 1 , wherein the bodily fluid sample is a blood sample.

5 . The system of claim 1 , wherein the one or more target biomarkers related to brain injury or disease are selected from Tau proteins, Glial Fibrilar Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase L1 (UCH-L1).

6 . The system of claim 1 , wherein the antibody and/or aptamer is conjugated with biotin.

7 . The system of claim 1 , wherein the immobilization agent is selected from the group consisting of avidin, streptavidin, neutravidin and mixtures thereof.

8 . The system of claim 1 , wherein the immobilization agent is applied to a treating agent, and the treating agent is applied to the surface of the conducting material interface comprising the multi-array of vertically aligned conducting material wires.

9 . The system of claim 1 , wherein the antibody and/or aptamer is effective to impedimetrically detect simultaneously a plurality of target biomarkers related to brain injury or disease in the bodily fluid sample.

10 . The system of claim 2 , wherein the multi-array of vertically aligned conducting material wires are arranged in a concentric configuration.

11 . A method of detecting one or more target biomarkers related to brain injury or disease in a bodily fluid sample of a patient, comprising:
obtaining from a patient the bodily fluid sample having a presence or an absence of the one or more target biomarkers related to brain injury or disease; forming a detection device, comprising:
forming a conducting material interface having a surface; and
forming a biological sensor agent, comprising:
applying an immobilization agent to the surface of the conducting material interface;
selecting an antibody and/or aptamer to selectively bind with the one or more target biomarkers related to brain injury or disease; and
interacting the antibody and/or aptamer with the immobilization agent;

contacting the antibody and/or aptamer with the bodily fluid sample; generating an electrochemical impedance signal as a result of the antibody and/or aptamer binding with the one or more target biomarkers related to brain injury or disease; assessing a presence or an absence of a change in electrochemical impedance; determining the presence of the one or more target biomarkers related to brain injury or disease in the bodily fluid sample due to the change in electrochemical impedance; and determining the absence of the one or more target biomarkers related to brain injury or disease in the bodily fluid sample due to no change in electrochemical impedance.

12 . The method of claim 11 , wherein the electrochemical impedance signal is transduced to a read-out value.

13 . The method of claim 12 , wherein the electrochemical impedance signal is connected to a portable device such as a hand-held device that is effective to display the read-out value.

14 . The method of claim 11 , wherein the detection device is in the form of a test strip and the method, comprises:
contacting the bodily fluid sample with the test strip; assessing a visual change to the test strip; correlating the visual change with a chart or key; and based on said correlating, determining if the visual change is indicative of the presence of a change in electrochemical impedance, and the presence of the one or more target biomarkers related to brain injury or disease in the bodily fluid sample.

15 . The method of claim 11 , wherein the forming a conducting material interface, comprises:
providing an epoxy substrate; vertically aligning a multi-array of conducting material wires; and casting the multi-array of vertically aligned conducting material wires in the epoxy substrate.

Assignees

• Univ Pittsburgh Commonwealth Sys Higher Education

Inventors

• Kumta Prashant
• Patil Mitali
• Okonkwo David
• Kormos Robert

Classifications

• G01N33/6893

  related to diseases not provided for elsewhere · CPC title

• A61B5/4064

  Evaluating the brain (for intracranial pressure A61B5/031; for cerebral blood gases A61B5/14553; using EEG A61B5/369) · CPC title

• A61B2562/0285

  Nanoscale sensors · CPC title

• G01N33/54373 Primary

  involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings · CPC title

• C07K16/18 Primary

  against material from animals or humans · CPC title