Arrays for Point-of-Care Early Cancer Detection

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James F. Rusling

Departments of Chemistry & Cell Biology

University of Connecticut and UCHC

Storrs, CT, USA

Detecting cancer through protein biomarkers

• Early cancer detection holds great promise for preventive therapies to avoid cancer.

• Cancer biomarkers are biomolecules (proteins) expressed in cancer and cancer-risk situations.

• Measurement of collections of protein cancer biomarkers provides reliable diagnostics (~99% correct)

• Genetic cancer markers important for full picture

The Grand Challenge• Inexpensive point-of-care biosensor arrays

for cancer biomarker screening• automated, easy to use and interpret• measure several hundred biomarkers in

several drops of patient serum• achieve effective cancer prevention for

millions• lead to new mechanism-based therapies

Example: 4 Prostate Cancer Biomarkers Prostate Specific Antigen (PSA)

glycoprotein MW 33 kD

PSA in serum: clinical method for detecting prostate cancer

4-10 ng/mL up to 5 years before clinical signs of disease

• PF4 – Platelet Factor 4 – Normal conc. in human plasma 2-10 ng/mL, early cancer>10 ng/mL

• MMP-2 – Matrix Metalloproteinase 2– zinc dependant proteinase;3 enhances tumor growth; human plasma

conc. normal < 300 ng/mL; cancer 300-1200 ng/mL• PSMA - Prostate Specific Membrane Antigen

– overexpressed in high grade prostate cancer;– human plasma conc. normal < 250 ng/mL; cancer 250-400 ng/mL

One approach - electrochemical sandwich immunoassays• nanostructured electrodes• multi-label detection; • ultralow NSB

Xin Yu, Bernard Munge, Vyomesh Patel, Gary Jensen, Ashwin Bhirde, Joseph D. Gong, Sang-Nyon Kim, John Gillespie, J. Silvio Gutkind, Fotios Papadimitrakopoulos and James F. Rusling,"Carbon Nanotube Amplification Strategies for Highly Sensitive Immunosensing of CancerBiomarkers in Serum and Tissue", J. Am. Chem. Soc., 2006, 128, 11199-11205.

The Dream

Microfluidic system interfaced to multi-elementChip for sample, reagent,& wash automation.User need only add sample

Interfaced laptop provides dataanalysis, database comparisons,interpreted results, transmittal to physicians.

MultielectrodeChip - many

capture antibodies