Electrochemical detection of proteases using AC voltammetry on nanoelectrode arrays
Patent Number: US20150011421
Executive Summary:
General Description:
Numerous proteases are overexpressed in cancer cells and secreted into the circulation. The goal of this invention is to develop an electrochemical method based on novel nanoelectrode arrays, for non-invasive diagnosis. The technique has the potential to measure the activity of cancer-associated proteases in various bio specimen, including blood and urine. The authors claim that this innovation provides numerous potential advantages over the existing fluorescence detection commonly used today.
Scientific Progress:
The technique has been applied to lysates of normal breast cancer tissue, as well as breast cancer cells to try to detect and compare protease activities in normal and breast cancer cells. Protease activity positively correlates with the degree of malignancy
Future Directions:
Strengths:
Weaknesses:
Patent Status:
Legal Status: Pending
Publications PMIDs: 23814632, 24480132, 25959927
Publications:
Swisher LZ, Syed LU, Prior AM, Carlson KR, Nguyen TA, Hua DH, Li J. Electrochemical Protease Biosensor Based on Enhanced AC Voltammetry Using Carbon Nanofiber Nanoelectrode Arrays. J Phys Chem C Nanomater Interfaces. 2013 Feb 28;117(8):4268-4277.
Swisher LZ, Prior AM, Shishido S, Nguyen TA, Hua DH, Li J. Quantitative electrochemical detection of cathepsin B in complex tissue lysate using enhanced AC voltammetry at carbon nanofiber nanoelectrode arrays. Biosens Bioelectron. 2014 Jun 15;56:129-36. doi: 10.1016/j.bios.2014.01.002. Epub 2014 Jan 10.
Swisher LZ, Prior AM, Gunaratna MJ, Shishido S, Madiyar FR, Nguyen TA, Hua DH, Li J. Quantitative electrochemical detection of cathepsin B activity in breast cancer cell lysates using carbon nanofiber nanoelectrode arrays towards identification of cancer formation. Nanomedicine. 2015 Oct;11(7):1695-704. doi: 10.1016/j.nano.2015.04.014. Epub 2015 May 8.
Inventor Bio: Jun Li
http://www.k-state.edu/chem/people/grad-faculty/jli/
Executive Summary:
- Invention Type: Diagnostic
- Patent Status: US Grant
- Patent Link: https://patents.google.com/patent/US20150011421A1/
- Research Institute: Kansas State University
- Disease Focus: Cancer, including breast cancer
- Basis of Invention: Electrochemical method for measuring the activity of cancer-related proteases in biological samples
- How it works: Various peptides are covalently attached to carbon nanofibers on a nanoelectrode array. The addition of a biological sample that contains proteases capable of cleaving specific peptides causes a change in voltage across array that can be measured
- Lead Challenge Inventor: Jun Li
- Inventors: Duy Hua, Lateef Uddin Syed, Allan Prior, Luxi Swisher, Jun Li
- Development Stage: Has been tested with lysates from breast cancer cells and tissues.
- Novelty:
- Novel in vitro diagnostic method based on protease activity profiling using nanoelectrode arrays
- Can simultaneously measure the activity of multiple cancer-related proteases
- Clinical Applications:
- In vitro diagnostic (data for breast cancer available)
- Treatment monitoring
General Description:
Numerous proteases are overexpressed in cancer cells and secreted into the circulation. The goal of this invention is to develop an electrochemical method based on novel nanoelectrode arrays, for non-invasive diagnosis. The technique has the potential to measure the activity of cancer-associated proteases in various bio specimen, including blood and urine. The authors claim that this innovation provides numerous potential advantages over the existing fluorescence detection commonly used today.
Scientific Progress:
The technique has been applied to lysates of normal breast cancer tissue, as well as breast cancer cells to try to detect and compare protease activities in normal and breast cancer cells. Protease activity positively correlates with the degree of malignancy
Future Directions:
- Clinical trials
Strengths:
- In vitro diagnostic and treatment monitoring
- Increased portability: The technique can be developed into a disposable chip in a portable electronic system for point-of-care or clinical applications, eliminating the need for a centralized lab
- Multiplicity: The activity of up to 9 (potentially to 16) proteases can be simultaneously detected
- Very small sample size: A single drop of blood, serum, urine or saliva is needed to detect multiple proteases
- Increased accuracy: The accuracy of the detection is significantly increased because the analysis is based on multiple proteases as disease biomarkers.
- Lower cost: The cost of using mass produced chips would be lower than the existing fluorescence technique
Weaknesses:
- Competition possible with other type of assays measuring protease activity (fluorescence assay)
- No commercial test using protease activity: enough specificity for cancer diagnostic?
Patent Status:
Legal Status: Pending
- Priority date: 2013-07-03
- Filing date: 2014-06-30
- Publication date: 2015-01-08
Publications PMIDs: 23814632, 24480132, 25959927
Publications:
Swisher LZ, Syed LU, Prior AM, Carlson KR, Nguyen TA, Hua DH, Li J. Electrochemical Protease Biosensor Based on Enhanced AC Voltammetry Using Carbon Nanofiber Nanoelectrode Arrays. J Phys Chem C Nanomater Interfaces. 2013 Feb 28;117(8):4268-4277.
Swisher LZ, Prior AM, Shishido S, Nguyen TA, Hua DH, Li J. Quantitative electrochemical detection of cathepsin B in complex tissue lysate using enhanced AC voltammetry at carbon nanofiber nanoelectrode arrays. Biosens Bioelectron. 2014 Jun 15;56:129-36. doi: 10.1016/j.bios.2014.01.002. Epub 2014 Jan 10.
Swisher LZ, Prior AM, Gunaratna MJ, Shishido S, Madiyar FR, Nguyen TA, Hua DH, Li J. Quantitative electrochemical detection of cathepsin B activity in breast cancer cell lysates using carbon nanofiber nanoelectrode arrays towards identification of cancer formation. Nanomedicine. 2015 Oct;11(7):1695-704. doi: 10.1016/j.nano.2015.04.014. Epub 2015 May 8.
Inventor Bio: Jun Li
http://www.k-state.edu/chem/people/grad-faculty/jli/
