Electromechanical approach for cancer detection

Patent metadata

Field	Value
Publication number	US-12085530-B2
Application number	US-202017016435-A
Country	US
Kind code	B2
Filing date	Sep 10, 2020
Priority date	Dec 5, 2015
Publication date	Sep 10, 2024
Grant date	Sep 10, 2024

Abstract

An electromechanical system for detecting cancerous state of a single cell. The electromechanical system includes an aspirating mechanism, an electrical measurement mechanism, and a processing mechanism. The aspirating mechanism is configured to extract a single cell from a suspension of a plurality of suspended biological cells, hold the extracted single cell, and apply a mechanical aspiration to the held single cell by applying a suction force to the held single cell. The electrical measurement mechanism is configured to apply a set of electrical signals to the single cell before and after applying the mechanical aspiration and measure two sets of electrical responses from the held single cell corresponding to the applied set of electrical signals before and after applying the mechanical aspiration The processing mechanism, including a data processor, configured to detect cancerous state of the single cell based on a difference between the two sets of electrical responses.

First claim

What is claimed is:

1. An electromechanical system for detecting cancerous state of a single cell, comprising:
an aspirating mechanism configured to:
extract a single cell from a suspension of a plurality of suspended biological cells;
hold the extracted single cell; and
apply a mechanical aspiration to the held single cell by applying a suction force to the held single cell;

an electrical measurement mechanism, the electrical measurement mechanism configured to:
apply a set of electrical signals to the single cell before and after applying the mechanical aspiration;
measure a first set of electrical responses from the held single cell corresponding to the applied set of electrical signals before the mechanical aspiration; and
measure a second set of electrical responses from the mechanically aspirated single cell corresponding to the applied set of electrical signals after the mechanical aspiration; and

a processing mechanism comprising a data processor, the processing mechanism configured to detect cancerous state of the single cell based on a difference between the first set of electrical responses and the second set of electrical responses.

2. The electromechanical system of claim 1 , wherein the set of electrical signals comprises a set of electrical voltages of 40 mV at a set of frequency values in a range between 100 Hz and 100 KHz.

3. The electromechanical system of claim 1 , wherein each of the first set of electrical responses and the second set of electrical responses comprises a set of at least one of electrical impedance values, electrical phase values, and combinations thereof.

4. The electromechanical system of claim 3 , wherein the data processor is configured to:
receive the first set of electrical responses and the second set of electrical responses from the electrical measurement mechanism;
calculate the difference between the first set of electrical responses and the second set of electrical responses by calculating a set of difference values between each two respective values of the first set of electrical responses and the second set of electrical responses; and
detect the single cell to be cancerous responsive to the calculated difference between the first set of electrical responses and the second set of electrical responses being near zero.

5. The electromechanical system of claim 1 , wherein the aspirating mechanism comprises:
an electrically activated micropipette, comprising a nozzle at a first end of the electrically activated micropipette, configured to transfer the mechanical aspiration to the held single cell, the electrically activated micropipette configured to:
extract the single cell from the suspension of the plurality of suspended biological cells;
hold the extracted single cell; and
act as an electrical ground potential for the electrical measurement mechanism; and

a liquid reservoir connected to a second end of the electrically activated micropipette, the liquid reservoir configured to function a pressure source for the mechanical aspiration.

6. The electromechanical system of claim 5 , wherein the electrically activated micropipette comprises:
a micropipette; and
an electrical conductive layer coated on outer surface of the nozzle, the electrical conductive layer comprising at least one of gold (Au), titanium (Ti), platinum (Pt), and combinations thereof.

7. The electromechanical system of claim 6 , wherein the micropipette is made of at least one of glass, quartz, plastic, and combinations thereof.

8. The electromechanical system of claim 5 , wherein:
the electrically activated glass micropipette is assembled on a microinjection microscope, and
the liquid reservoir comprises a movable water reservoir of the microinjection microscope, the movable water reservoir configured to move downward to supply a suction pressure for the mechanical aspiration.

9. The electromechanical system of claim 1 , wherein the electrical measurement mechanism comprises:
an electrical probe, configured to connect to the held single cell; and
a signal controlling system connected to the electrical probe, the signal controlling system configured to:
apply an electrical signal to the held single cell via the electrical probe; and
acquire an electrical response corresponding to the applied electrical signal from the held single cell via the electrical probe.

10. The electromechanical system of claim 9 , wherein the electrical probe comprises:
a tungsten microwire with a diameter less than 500 μm with a sharpened tip section, the sharpened tip section with a sharp pointed tip with a diameter of 200 nm or less;
a catalyst layer formed on the sharpened tip section of the tungsten microwire;
an array of nanotube electrodes vertically aligned on the catalyst layer, the nanotube electrodes comprising a plurality of doped silicon nanotubes (SiNTs) comprising a long free-end silicon nanotube located on the sharp pointed tip being longer than remaining SiNTs of the plurality of doped SiNTs; and
a gold layer coated over the plurality of doped SiNTs,
wherein the long free-end silicon nanotube is configured to connect with and penetrate into the held single cell.

11. The electromechanical system of claim 10 , wherein the catalyst layer comprises a catalyst bilayer comprising a nickel layer over a gold layer.

12. The electromechanical system of claim 11 , wherein the catalyst layer comprises the nickel layer with a thickness in a range between 10 nm and 40 nm over the gold layer with a thickness in a range between 1 nm and 4 nm.

13. The electromechanical system of claim 10 , wherein the gold layer coated over the plurality of doped SiNTs has a thickness of 5 nm or less.

14. The electromechanical system of claim 10 , wherein the plurality of doped SiNTs comprises a plurality of doped SiNTs with phosphorus.

15. The electromechanical system of claim 9 , wherein the electrical probe is assembled on a microinjection microscope.

16. The electromechanical system of claim 9 , wherein the signal controlling system comprises:
an AC signal source, configured to apply the electrical signal to the electrical probe; and
a data acquisition module, configured to:
acquire the electrical response corresponding to the applied electrical signal from the electrical probe; and
send the electrical response to the data processor.

17. The signal controlling system of claim 16 , wherein the AC signal source is configured to apply a voltage of 40 mV in a frequency range between 100 Hz and 100 KHz to the electrical probe.

18. The electromechanical system of claim 1 , wherein the biological cells comprise a plurality of cells with elastic cell membranes, the cells comprising at least one of epithelial cells, endothelial cells, mesenchymal cells, and combinations thereof.

Assignees

• Abdolahad Mohammad
• Saeidi Ali
• Nano Hesgarsazan Salamat Arya Ncubation Center For Medical Equipment And Devices

Inventors

• Abdolahad Mohammad
• Saeidi Ali

Classifications

• G01N27/028

  Circuits therefor (measuring impedance per se G01R27/02) · CPC title

• G01N33/4833

  of solid biological material, e.g. tissue samples, cell cultures (tissue in vivo A61B5/00; cell suspensions G01N33/48735) · CPC title

• G01N27/283

  Means for supporting or introducing electrochemical probes · CPC title

• C23C14/16 Primary

  on metallic substrates or on substrates of boron or silicon · CPC title

• C23C16/4418

  Methods for making free-standing articles (C23C16/01 takes precedence) · CPC title