Bladder cancer is the ?fth most common cancer in the United States and one key challenge for bladder cancer is the high recurrence rate after initial treatment1-3. Furthermore, a number of medical and environmental conditions are associated with higher incidence of bladder cancer. Therefore, regular surveillance of bladder cancer is critical in subpopulations to detect disease early, prevent relapse and progression and improve overall survival. The current gold standard of bladder cancer detection is cystoscopy, which is invasive and expensive. Existing urine-based testing methods for bladder cancer have not been widely adopted in clinical practices either due to low test sensitivity and speci?city (conventional cytology, ELISA), or technical complexities, long turn-around time and high cost (RT-qPCR, sequencing)2-6. To address these challenges, Accure Health proposes to commercialize a non-invasive, fast, affordable and highly accurate diagnostic platform based on integrated magneto-electronic sensing (iMES) of urine exosomes (or extracellular vesicles, EVs). EVs have emerged as a new class of biomarker for cancer management detectable in urine, circulation and other body ?uids. These secreted vesicles carry molecular information from their originating cells7-12, and capturing this information can provide a representative, real-time window to monitor tumor burden13-15. A variety of EV biomarkers have been investigated to speci?cally detect tumor originating EV16-20. One critical unmet need to harness the translational potential of EV is to develop more integrated, highly sensitive, and easy-to-use clinical systems since puri?cation and conventional analytics are often too complex, time consuming and expensive. In preliminary work we have developed and validated the easy-to-use and sensitive iMES technology, which seems ideally suited for point-of-care diagnostics for bladder cancer. We now propose to further improve the user interface, miniaturize the sensor for commercialization and perform correlative benchmarking measurements against accepted gold-standards. We also plan to develop several smart diagnostic modules, including smart-device communication and cloud- based data management. We believe that, by connecting patients and doctors through smart devices and cloud-based resources, patient care and disease management can be signi?cantly improved. This Phase I proposal will focus on two speci?c Aims: (i) Develop a smart iMES platform for rapid and sensitive urine biomarker analysis; and (ii) apply the new iMES platform to screen urinary EVs for bladder cancer detection. Successful completion of this Phase I project will result in a product prototype ready for direct analyses of urine samples from bladder cancer patients. During a subsequent Phase II, we will perform clinical testing with key partners. The smart features, together with non-invasiveness, high sensitivity and low cost of this system will allow Accure Health to be in a position to ?le for Investigational Device Exemption by the end of Phase II, which will further strengthen our competitive advantages and value proposition.
Public Health Relevance Statement: PROJECT NARRATIVE We will develop a new diagnostic platform based on integrated magneto-electronic sensing (iMES) of urine exosomes (or extracellular vesicles, EVs). By integrating miniaturized biosensor technologies and digital healthcare solutions, this smart iMES platform will enable non-invasive, fast, affordable and highly accurate diagnosis of bladder cancer in point-of-care settings, and facilitate remote patient monitoring and personalized treatment.
Project Terms: accurate diagnosis; Accure; Address; Adopted; Advanced Development; base; Benchmarking; Biological Assay; Biological Markers; Biosensor; Blood Circulation; Body Fluids; cancer biomarkers; Cancer cell line; Cancer Detection; cancer diagnosis; Cancer Patient; Cells; Centrifugation; Cessation of life; circulating biomarkers; Clinical; clinical practice; Clinical Research; cloud based; commercialization; Communication; communication device; Complex; cost; Creatinine; Cystoscopy; Cytology; Data Analyses; Data Base Management; Detection; Devices; Diagnostic; digital; Disease; Disease Management; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor Receptor; ERBB2 gene; exosome; experimental study; extracellular vesicles; FGFR3 gene; Filtration; Goals; Gold; Health; Healthcare; Human; improved; Incidence; Inferior; Investigation; Label; magnetic beads; Magnetism; Malignant neoplasm of urinary bladder; Malignant Neoplasms; Measurement; Measures; Medical; Methods; miniaturize; Molecular; Molecular Profiling; Monitor; Mucin 1 protein; novel diagnostics; Nucleic Acids; Patient Care; Patient Monitoring; Patients; Performance; personalized medicine; Phase; point of care; point-of-care diagnostics; Positioning Attribute; prevent; Procedures; product development; protein biomarkers; Proteins; prototype; Recurrence; Relapse; Reporting; Reproducibility; research clinical testing; Resources; Sampling; Scheme; Sensitivity and Specificity; sensor; Specificity; System; TACSTD1 gene; Technology; Testing; Time; tumor; United States; United States Food and Drug Administration; urinary; Urine; Vesicle; Wireless Technology; Work
