Methods and devices for detection and acquisition of biomarkers

Patent metadata

Field	Value
Publication number	US-2017145489-A1
Application number	US-201615367015-A
Country	US
Kind code	A1
Filing date	Dec 1, 2016
Priority date	Dec 14, 2012
Publication date	May 25, 2017
Grant date	—

Abstract

The present invention provides devices and methods for detecting and capturing molecular biomarkers from a subject in situ. Specifically, the devices contain an array of microneedles to which are attached probes specific for one or more biomarkers of interest. The devices can be used directly on a subject (e.g., via skin piercing) in detecting the biomarkers in the body of the subject (e.g., tissues, blood stream).

First claim

What is claimed is:

1 . A device for detecting or extracting one or more biomarkers from an in situ tissue or biological sample of a subject, comprising one or more microneedles, and one or more probes specific for the biomarkers, wherein the probes are attached to the microneedles, via covalent or non-covalent linkage.

2 . The device of claim 1 , comprising a plurality of probes specific for a plurality of different biomarkers, wherein each probe is attached to a different microneedle.

3 . The device of claim 1 , comprising one probe for a specific biomarker, wherein the probe is attached to two or more microneedles.

4 . The device of claim 1 , wherein the microneedles are made of a polymer, a metal or a ceramic.

5 . The device of claim 1 , wherein the biomarkers are polynucleotides, and the probes are polynucleotides complementary to the biomarkers.

6 . The device of claim 5 , wherein the microneedles are polycarbonate, and the probes are attached to the microneedles via a thiol/amino bifunctional linker.

7 . The device of claim 1 , wherein the biomarkers are peptides or polypeptides, and the probes are antibodies specific for the biomarkers.

8 . The device of claim 1 , wherein the probes the attached to the microneedles via a linker such as poly(ethylene glycol) or another linker as a spacer or to stabilize the orientation of the probes.

9 . The device of claim 1 , wherein the array of microneedles is formed on a substrate.

10 . The device of claim 1 , further comprising a means for amplifying and identifying the biomarkers captured by the probes.

11 . A method for detecting one or more biomarkers from an in situ tissue or biological sample in a subject, comprising (a) preparing a device comprising one or more microneedles to which one or more probes specific for the biomarkers are covalently attached; (b) contacting the microneedle device with the tissue or biological sample of the subject; and (c) detecting biomarkers that are bound to the probes on the microneedle array.

12 . The method of claim 11 , wherein the device comprises a plurality of probes specific for a plurality of different biomarkers, and wherein each probe is attached to a different microneedle.

13 . The method of claim 11 , wherein the device comprises one probe specific for a biomarker, and wherein the probe is attached to two or more microneedles.

14 . The method of claim 11 , wherein the microneedles are made of a polymer, a metal or a ceramic.

15 . The method of claim 11 , wherein the biomarkers are polynucleotides, and the probes are polynucleotides complementary to the biomarkers.

16 . The method of claim 15 , wherein the biomarkers bound to the probes on the microneedles are detected by PCR.

17 . The method of claim 15 , wherein the microneedles are polycarbonate, and the probes are attached to the microneedles via a thiol/amino bifunctional linker.

18 . The method of claim 11 , wherein the biomarkers are peptides or polypeptides, and the probes are antibodies specific for the biomarkers.

19 . The method of claim 18 , wherein the biomarkers bound to the probes on the microneedles are detected by an oligonucleotide-tagged secondary antibody and PCR amplification of the conjugated tag.

20 . The method of claim 11 , wherein the array of microneedles is formed on a substrate.

21 . The method of claim 11 , wherein the tissue is the subject's blood stream, and the microneedle device is contacted with the blood stream by piercing the skin of the subject.

22 . The device of claim 1 , wherein the biomarkers are small molecules or metabolites, and the probes are ligands that are specific for the biomarkers.

Assignees

• Mindera Corp
• Scripps Research Inst

Inventors

• Mahmood Tahir A
• Dickerson Tobin J
• Mahmood Nadir A
• Capek Petr

Classifications

• A61B10/0045

  Devices for taking samples of body liquids · CPC title

• A61B5/1468

  using chemical or electrochemical methods, e.g. by polarographic means · CPC title

• A61B5/150015

  Source of blood · CPC title

• C12Q1/6837

  using probe arrays or probe chips (C12Q1/6874 takes precedence) · CPC title

• A61B2562/046

  in a matrix array · CPC title