Figure: Focal therapies for prostate and kidney cancer.  (Left) Multi-probe cryosurgery of the prostate.  By improving the overlap between the iceball and injury as proposed in this work, we can more precisely destroy local cancer without morbidity to the whole gland and adjacent structures.  (Right) Improved adjuvants can also be used in kidney cancer during both cryosurgery and other focal therapies

The goal with focal therapies is to ablate neoplastic and/or dysfunctional tissue as an adjuvant or alternative to surgical resection in cases where resection is not feasible. The types of focal therapies differ in both the energy delivery modalities and the physical geometry of the probe. Three types of energy delivery methods for focal therapy which is studied in our lab are 1)Hyperthermic temperatures (>43C) 2)Cryogenic temperratures (<-20C) and 3)Irreversible Electroporation. While the first two methods rely on diffusion of heat and nonequilibirum thermodynamics to destroy targeted tissue, the least one uses pulsed electric fields to disrupt cellular membrane and inhibit cellular function to destroy cells. Our work focuses on both the mechanism of action of the energy modalities as well as animal models which require design and deployment of specific probes. We have collaborations with University of Minnesota Medical School, Mayo Clinic and medical devices companies including Boston Scientific, Medtronic, Covidien.

Publications:

• Hoffmann, N.E. and Bischof, J.C., 2002. The cryobiology of cryosurgical injury. Urology, 60(2), pp.40-49

  • http://www.sciencedirect.com/science/article/pii/S0090429502016837

• Jiang, C., Davalos, R.V. and Bischof, J.C., 2015. A review of basic to clinical studies of irreversible electroporation therapy. IEEE Transactions on Biomedical Engineering, 62(1), pp.4-20.

  • http://ieeexplore.ieee.org/abstract/document/6949110/

• He, X. and Bischof, J.C., 2005. The kinetics of thermal injury in human renal carcinoma cells. Annals of Biomedical Engineering, 33(4), pp.502-510.

  • http://link.springer.com/article/10.1007/s10439-005-2508-1

Figure: Thermal contrast diagnostics to improve carcinogen and blood borne cancer marker detection. By applying laser heating to the test line of common gold nanoparticle based lateral flow assays (LFA), vastly improved sensitivity can be achieved.  This translational approach promises laboratory-based diagnostic sensitivity at POC.

Lateral Flow Assay Sensitivity Improvement

This work is responsive to the need for point of care (POC) testing for cancer diagnosis and prevention and the new federal focus on personalized and precision medicine. In short, having a quick, easy, low cost, and highly sensitive test for environmental carcinogens or blood borne markers of cancer is increasingly important.  Our patented approach entitled:  “Thermal Contrast” is a platform technology initially developed for infectious disease, that addresses this need, having delivered a 4 to 8-fold increase in sensitivity and quantification with common gold nanoparticle based lateral flow assays (LFA). Current LFAs are among the least expensive, easiest, and fastest POC tests in the world, with the notable weaknesses of low sensitivity and inability to quantify antigen burden.  By increasing sensitivity and demonstrating quantification with Thermal Contrast, environmental carcinogens such as alflatoxin, an important environmental biomarker in food linked to hepatocellular carcinoma, can be detected more quickly and quantified (collaborator R-Biopharm.de).  Additionally, Thermal contrast of blood borne markers of liver cancer such as Hepatitis B can be used to diagnose liver cancer more quickly and with higher sensitivity at POC (collaborator Premiermedcorp.com).  Up to a further 100 ~1000 fold improvement in sensitivity of thermal contrast can be envisioned by re-design of the LFA laser interactions with collaborators, showing promise in creating a POC diagnostic platform that is competitive in sensitivity, analytical range and quantitation with the state-of-the-art laboratory based technologies. Existing international partners from University of Toronto (Warren Chan), Xi’an Jiaotong (Feng Xu and T.J. Lu - http://bebc.xjtu.edu.cn) and industrial diagnostic partners (R-Biopharm and Premier Medical Corp. Ltd) will help achieve the goals of this aim. This area is a federal research priority, can reduce cancer risk due to environmental carcinogens, and assist in developing screening for early detection.

Publications:

• Qin, Z., Chan, W. C., Boulware, D. R., Akkin, T., Butler, E. K., & Bischof, J. C. (2012). Significantly improved analytical sensitivity of lateral flow immunoassays by using thermal contrast. Angewandte Chemie International Edition, 51(18), 4358-4361.

• Boulware, D. R., Rolfes, M. A., Rajasingham, R., von Hohenberg, M., Qin, Z., Taseera, K....Meya, D. B. (2014). Multisite Validation of Cryptococcal Antigen Lateral Flow Assay and Quantification by Laser Thermal Contrast. Emerging Infectious Diseases, 20(1), 45-53. https://dx.doi.org/10.3201/eid2001.130906.

• Wang, Y., Qin, Z., Boulware, D.R., Pritt, B.S., Sloan, L.M., González, I.J., Bell, D., Rees-Channer, R.R., Chiodini, P., Chan, W.C. and Bischof, J.C., 2016. Thermal Contrast Amplification Reader Yielding 8-Fold Analytical Improvement for Disease Detection with Lateral Flow Assays. Analytical Chemistry, 88(23), pp.11774-11782.