Prostate cancer is the most common malignancy among men in developed countries with current annual mortality of more than 27,000 in the United States and 570 in Ireland. Current practice in prostate cancer detection and staging leads to inaccurate assessments often resulting in many unnecessary treatments that impact negatively patient quality of life. This proposal comprises a US-Ireland R&D Partnership grant application from the Univ. of CT, University College Dublin (UCD) Medical School, National University of Ireland at Galway, and University of Ulster. The long term goal is to provide multi-biomarker diagnostics to enable accurate grading and staging of prostate cancer. Our hypothesis is that detection of a small panel of cancer biomarker proteins in patient serum can be used to accurately detect and establish stage and grade of prostate cancers. We will develop an optimized, validated biomarker panel and appropriate measurement devices to establish grade and stage of prostate cancer as well as to identify cancer-free patients. The biomarker panel will be optimized by evaluating a protein set combining general accepted biomarkers for prostate cancer with newly identified biomarker proteins for aggressive cancer identified by research from UCD and others. Development of assays and validation of the biomarker panel will be done with a rapid, ultrasensitive, versatile, microfluidic immunoassay already developed at Univ. of CT. Simultaneously, a simplified, low cost, disposable, label-free device for clinical use will be designed and fabricated by University of Ulster, and tested by the entire team. Validation will be done on samples obtained by UCD School of Medicine and George Washington University Hospital from prostate cancer patients and controls. Excellent patient follow-up from related ongoing studies in these institutions will facilitate additional information for validation of the panel in later years.
Specific aims i n brief include: (1) Develop immunoassays using an existing microfluidic array for an initial panel of proteins;(2) Investigate redox polymer mediation to simplify assay protocols and enhance sensitivity;(3) Validate analytical accuracy of array for initial protein panel by comparing to commercial bead based assays for a limited set of serum samples;(4) Analyze >600 serum samples from patient cohorts (Irish and USA) to establish disease prediction and staging characteristics using statistical analyses;use these data to optimize panel composition. (5) Design and fabricate a pump-free, label-free microfluidic array suitable for clinical measurements of the validated protein panel in a single drop of whole blood. This research strategy is specifically designed to translate to the clinic for prostate cancer diagnostics and personalized therapy. !

Public Health Relevance

Current diagnostic practice for prostate cancer leads to many unnecessary treatments. This project will develop new reliable tools based on biomarker panels for reliable early diagnosis and treatment guidance for prostate cancer. It will also develop a rapid, low cost test device to test single drops of blood for prostate cancer diagnostics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB016707-01A1
Application #
8629949
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Lash, Tiffani Bailey
Project Start
2014-02-01
Project End
2018-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Storrs-Mansfield
State
CT
Country
United States
Zip Code
06269
Mosa, Islam M; Pattammattel, Ajith; Kadimisetty, Karteek et al. (2017) Ultrathin Graphene-Protein Supercapacitors for Miniaturized Bioelectronics. Adv Energy Mater 7:
Bhakta, Snehasis; Dixit, Chandra K; Bist, Itti et al. (2017) Albumin removal from human serum using surface nanopockets on silica-coated magnetic nanoparticles. Chem Commun (Camb) 53:9254-9257
Shen, Min; Rusling, James; Dixit, Chandra K (2017) Site-selective orientated immobilization of antibodies and conjugates for immunodiagnostics development. Methods 116:95-111
Sharafeldin, Mohamed; Bishop, Gregory W; Bhakta, Snehasis et al. (2017) Fe3O4 nanoparticles on graphene oxide sheets for isolation and ultrasensitive amperometric detection of cancer biomarker proteins. Biosens Bioelectron 91:359-366
Kadimisetty, Karteek; Malla, Spundana; Rusling, James F (2017) Automated 3-D Printed Arrays to Evaluate Genotoxic Chemistry: E-Cigarettes and Water Samples. ACS Sens 2:670-678
Tang, C K; Vaze, A; Rusling, J F (2017) Automated 3D-printed unibody immunoarray for chemiluminescence detection of cancer biomarker proteins. Lab Chip 17:484-489
Dixit, Chandra K; Bhakta, Snehasis; Kumar, Ajeet et al. (2016) Fast nucleation for silica nanoparticle synthesis using a sol-gel method. Nanoscale 8:19662-19667
Otieno, Brunah A; Krause, Colleen E; Jones, Abby L et al. (2016) Cancer Diagnostics via Ultrasensitive Multiplexed Detection of Parathyroid Hormone-Related Peptides with a Microfluidic Immunoarray. Anal Chem 88:9269-75
Dixit, Chandra K; Kadimisetty, Karteek; Otieno, Brunah A et al. (2016) Electrochemistry-based approaches to low cost, high sensitivity, automated, multiplexed protein immunoassays for cancer diagnostics. Analyst 141:536-47
Otieno, B A; Krause, C E; Rusling, J F (2016) Bioconjugation of Antibodies and Enzyme Labels onto Magnetic Beads. Methods Enzymol 571:135-50

Showing the most recent 10 out of 18 publications