Ultrasound-assisted electrochemical distinction of normal and cancerous cells

Patent metadata

Field	Value
Publication number	US-11079355-B2
Application number	US-201815960542-A
Country	US
Kind code	B2
Filing date	Apr 23, 2018
Priority date	Apr 24, 2017
Publication date	Aug 3, 2021
Grant date	Aug 3, 2021

Abstract

A method for cancer diagnosis is disclosed. The method includes forming a plurality of cultured cells on an electrochemical biosensor placing the electrochemical biosensor in a medium solution comprising a cell culture solution of a plurality of biological cells, measuring a first electrochemical response from the electrochemical biosensor with the plurality of cultured cells, forming a plurality of stimulated cells on the electrochemical biosensor by ultrasonically stimulating of the plurality of cultured cells, measuring a second electrochemical response from the electrochemical biosensor with the plurality of stimulated cells, and detecting presence of cancer cells responsive to a difference between the first electrochemical response and the second electrochemical response being less than a threshold. Where, the first electrochemical response includes an electrochemical response of the plurality of cultured cells and the second electrochemical response includes an electrochemical response of the plurality of stimulated cells.

First claim

What is claimed is:

1. A method for detecting cancer cells, comprising:
preparing an electrochemical-ultrasonic system, comprising:
fabricating an electrochemical biosensor, the electrochemical biosensor comprising an integrated three-electrodes array patterned on a nanoroughened surface of a substrate, the integrated three-electrodes array comprising a working electrode, a counter electrode, and a reference electrode;
culturing a plurality of biological cells on the electrochemical biosensor comprising attaching the plurality of biological cells onto the working electrode by placing the electrochemical biosensor in a medium solution, the medium solution comprising a cell culture solution of the plurality of biological cells;
connecting the electrochemical biosensor with the plurality of cultured cells to an electrochemical stimulator-analyzer system, the electrochemical stimulator-analyzer system configured to measure electrochemical responses; and
exposing the electrochemical biosensor with the plurality of cultured cells to an ultrasonic system;

generating a plurality of microbubbles on the electrochemical biosensor with the plurality of cultured cells comprising electrolysis of the medium solution by applying an instantaneous electrical potential in the medium solution utilizing a cyclic voltammetry technique using the electrochemical stimulator-analyzer system, applying the instantaneous electrical potential in the medium solution comprising applying a DC signal with a voltage between −2 V and −0.5 V for a time duration less than 1 seconds on the biosensor with the plurality of cultured cells;
measuring a first electrochemical response from the electrochemical biosensor with the plurality of cultured cells using the electrochemical stimulator-analyzer system, the first electrochemical response comprising an electrochemical response of the plurality of cultured cells;
forming a plurality of stimulated cells on the electrochemical biosensor by applying ultrasonic waves to the plurality of cultured cells and the plurality of microbubbles using the ultrasonic system;
measuring a second electrochemical response from the electrochemical biosensor with the plurality of stimulated cells using the electrochemical stimulator-analyzer system, the second electrochemical response comprising an electrochemical response of the plurality of stimulated cells; and
detecting presence of cancer cells responsive to a difference between the first electrochemical response and the second electrochemical response being less than a threshold.

2. A method for detecting cancer cells, comprising:
forming a plurality of cultured cells on an electrochemical biosensor by placing the electrochemical biosensor in a medium solution comprising a cell culture solution of a plurality of biological cells;
measuring a first electrochemical response from the electrochemical biosensor with the plurality of cultured cells, the first electrochemical response comprising a first cyclic voltammetry (CV) pattern comprising a first set of measured electrical currents versus a range of applied electrical potentials comprising a respective first current peak;
generating a plurality of microbubbles on the electrochemical biosensor with the plurality of cultured cells comprising electrolysis of the medium solution by applying an instantaneous electrical potential to the electrochemical biosensor with the plurality of cultured cells via a cyclic voltammetry technique using an electrochemical stimulator-analyzer system;
forming a plurality of stimulated cells on the electrochemical biosensor by applying ultrasonic waves to the plurality of cultured cells and the plurality of microbubbles using an ultrasonic system;
measuring a second electrochemical response from the electrochemical biosensor with the plurality of stimulated cells, the second electrochemical response comprising a second CV pattern comprising a second set of measured electrical currents versus the range of applied electrical potentials comprising a respective second current peak; and
detecting presence of cancer cells responsive to a difference between the first electrochemical response and the second electrochemical response being less than a threshold, the difference between the first electrochemical response and the second electrochemical response comprising a peak to peak

Δ
⁢

⁢
I

I

,

the peak to peak

Δ
⁢

⁢
I

I

being defined by:
peak to peak

Δ
⁢

⁢
I

I

=

I

US
⁢

⁢
off

-

I

US
⁢

⁢
on

I

US
⁢

⁢
off

where I USoff comprises the first current peak and I USon comprises the second current peak.

3. The method of claim 2 , wherein detecting the presence of cancer cells comprises detecting presence of breast cancer cells responsive to the peak to peak

Δ
⁢
I

I

being less than the threshold comprising a value of 0.15.

4. The method of claim 3 , wherein:
the threshold comprises a value of 0.05 for the ultrasonically stimulating of the plurality of cultured cells with an intensity of less than 1 W/cm 2 and a duration of less than 5 seconds, and
the threshold comprises a value of 0.15 for the ultrasonically stimulating of the plurality of cultured cells with an intensity of more than 1 W/cm 2 and a duration of less than 5 seconds.

5. The method of claim 2 , wherein each of the measuring the first electrochemical response from the electrochemical biosensor with the plurality of cultured cells and measuring the second electrochemical response from the electrochemical biosensor with the plurality of stimulated cells comprises measuring an electrochemical response via the cyclic voltammetry technique using the electrochemical stimulator-analyzer system.

6. The method of claim 5 , wherein the electrochemical stimulator-analyzer system comprises a potentiostat.

Assignees

• Abdolahad Mohammad
• Khayamian Mohammad Ali
• Ansaryan Saeid
• Baniassadi Majid
• Nano Hesgarsazan Salamat Arya

Inventors

• Abdolahad Mohammad
• Khayamian Mohammad Ali
• Ansaryan Saeid
• Baniassadi Majid

Classifications

• G01N27/327 Primary

  Biochemical electrodes {, e.g. electrical or mechanical details for in vitro measurements} · CPC title

• C25B11/091

  consisting of at least one catalytic element and at least one catalytic compound; consisting of two or more catalytic elements or catalytic compounds · CPC title

• C23C14/205

  by cathodic sputtering · CPC title

• C25B11/057

  consisting of a single element or compound · CPC title

• C23C14/5846

  Reactive treatment · CPC title