Ultralow concentration sensing of bio-matter with perovskite nickelate devices and arrays

Patent metadata

Field	Value
Publication number	US-2022025425-A1
Application number	US-201917311707-A
Country	US
Kind code	A1
Filing date	Dec 10, 2019
Priority date	Dec 19, 2018
Publication date	Jan 27, 2022
Grant date	—

Abstract

Disclosed herein is an ultralow concentration sensor of biomarkers, and the use thereof to help heath industry, medical centers and food industry to sense biomarkers by catalyst assisted charge transfer from the biomarkers to the sensor device, resulting increased electrical resistance of the sensor. Specifically, perovskite nickelate RNiO 3 is used to sense biological material facilitated by specific enzymatic activity in the proximity.

First claim

1 . An ultrasensitive device for detecting low concentration of biomarker in a biological fluid, comprising:
a perovskite nickelate film comprising RNiO3 or strongly correlated transition metal oxide (eg. NiO, FeOx), wherein said perovskite nickelate film is configured as a lattice or with micro-fluidic channels, wherein R is selected from the group consisting of Sm, Nd, Eu, Gd, Dy, Y, Lu, Pr, and La; and an enzyme or other catalyst conjugated to a conductive material, wherein said conductive material is associated with said perovskite nickelate film or in close proximity to said perovskite nickelate film, wherein said enzyme or other catalyst facilitates hydrogen transfer from said biomarker to said perovskite nickelate film and reduces conductivity at the interface between the perovskite nickelate film and said biomarker.

2 . The ultrasensitive device according to claim 1 further comprising an electrode, wherein said electrode captures increased resistivity in said perovskite nickelate film.

3 . The ultrasensitive device according to claim 1 wherein said conductive material is Au electrode.

4 . The ultrasensitive device according to claim 1 , wherein said enzyme is glucose oxidase and the biomarker is glucose in body fluid.

5 . The ultrasensitive device according to claim 4 , wherein the body fluid is blood, sweat or urine.

6 . The ultrasensitive device according to claim 1 , wherein said enzyme is horseradish peroxidase (HRP) and the biomarker is dopamine in cerebrospinal fluid.

7 . The ultrasensitive device according to claim 3 wherein said enzyme is conjugated to Au electrode surface via cystamine.

8 . The ultrasensitive device according to claim 1 is configured as arrays with large scale circuits on a single chip, wherein various enzymes or other catalysts are conjugated to said arrays rendering specificity to different biomarkers simultaneously in said single chip.

9 . A method of detecting ultra-low concentration of biomarker in biological fluid, comprising:
Providing a device comprising following components:
a perovskite nickelate film comprising RNiO3 or strongly correlated oxides with similar transition metal oxide (eg. NiO, FeOx), wherein said perovskite nickelate film is configured as a lattice or with micro-fluidic channels, wherein R is selected from the group consisting of Sm, Nd, Eu, Gd, Dy, Y, Lu, Pr, and La; and
an enzyme or other catalyst conjugated to a conductive material, wherein said conductive material is associated with said perovskite nickelate film or in close proximity to said perovskite nickelate film, wherein said enzyme or other catalyst facilitates hydrogen transfer from said biomarker to said perovskite nickelate film and reduces conductivity at the interface between the perovskite nickelate film and said biomarker;
Measuring the resistance reading R 0 between the device and the conductive material; Immersing the device to a biological fluid; Measuring the resistance reading R between the device and the conductive material after the immersing step; and Identifying the biological fluid with ratio of R/R 0 greater than 1 as the sample comprising said enzyme targeted biomarker.

10 . The method according to claim 9 is used to detect glucose in said biological fluid.

11 . The method according to claim 9 is used to detect dopamine in cerebrospinal fluid.

12 . The method according to claim 9 is conducted at room temperature or body temperature.

13 . The method according to claim 9 is to detect concentrations of biomarker between the ranges of about 10 −16 M to about 10 −17 M.

14 . The method according to claim 9 wherein the device comprising Au as the conductive material.

15 . The method according to claim 9 wherein the device comprising an enzyme selected from the group consisting of glucose oxidase and Horseradish peroxidase (HRP).

16 . The method according to claim 9 wherein the device is configured as arrays with large scale circuits on a single chip to simultaneously sense various biomarkers that corresponding enzymes or other catalysts specifically recognize and facilitate hydrogen transfer.

17 . The method according to claim 10 further comprising integrating said device into a wearable electronic platform for personal healthcare monitoring.

18 . The method according to claim 10 is conducted in room temperature or body temperature.

19 . The method according to claim 10 is conducted spontaneously with biological fluid immersion of the device and free of external energy input.

20 . A method for detecting ultra-low concentration of biomarker in a sample, comprising:
Providing a perovskite nickelate film having strongly correlated oxides from rare-earth or related transition metal oxides; Providing a catalyst that may act on said biomarker in said sample and alter the physical property of said film, wherein said catalyst is in close proximity to said film; Contacting said film with said sample; and Measuring said film's optical, magnetic or thermal properties before and after said contact to determine the existence of said biomarker and use as detection mechanism.

Assignees

• Purdue Research Foundation

Inventors

• Zhang Haitian
• Zuo Fan
• Li Feiran
• Choi Jong Hyun
• Ramanathan Shriram

Classifications

• G01N33/48707 Primary

  by electrical means (G01N33/49, G01N33/493 take precedence) · CPC title

• C12Q1/005 Primary

  involving specific analytes or enzymes (including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence) · CPC title

• A61B5/14546

  for measuring analytes not otherwise provided for, e.g. ions, cytochromes · CPC title

• G01N33/553

  Metal or metal coated · CPC title

• A61B5/1486

  using enzyme electrodes, e.g. with immobilised oxidase · CPC title