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FOCAL ABLATION & NANOPARTICLE PRE-CONDITIONING IN CANCER TREATMENT
FOCAL ABLATION & NANOPARTICLE PRE-CONDITIONING IN CANCER TREATMENT
Collaborations with University of Minnesota Medical School, Mayo Clinic and medical devices companies including Boston Scientific, Medtronic, Covidien.
Figure: Focal therapies for prostate and kidney cancer. (Left) Multi-probe cryosurgery of the prostate. By improving the overlap between the ice-ball 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 research aimed to evaluate focal therapies for ablating neoplastic or dysfunctional tissue as an alternative or supplement to surgical resection, especially in cases where resection was not feasible. The lab investigated three focal therapy energy delivery methods: 1) hyperthermic temperatures (>43°C), 2) cryogenic temperatures (<-20°C), and 3) irreversible electroporation. While the first two methods used heat diffusion and nonequilibrium thermodynamics to ablate tissue, the third utilized pulsed electric fields to disrupt cell membranes. The work centered on both understanding the mechanisms of these energy modalities and developing animal models with tailored probe designs.
Hoffmann, N.E. and Bischof, J.C., 2002. The cryobiology of cryosurgical injury. Urology, 60(2), pp.40-49.
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.
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.
THERMAL CONTRAST AND LATERAL FLOW ASSAY IMPROVEMENT
THERMAL CONTRAST AND LATERAL FLOW ASSAY IMPROVEMENT
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.
Thermal Contrast Amplification Reader
Lateral Flow Assay Sensitivity Improvement
This work addressed the need for point-of-care (POC) cancer diagnostics and aligned with the federal shift towards personalized and precision medicine. It focused on creating a fast, affordable, and sensitive test for environmental carcinogens or blood-borne cancer markers. The patented "Thermal Contrast" platform, initially developed for infectious diseases, achieved a 4-8 fold sensitivity increase with gold nanoparticle-based lateral flow assays (LFAs). By enhancing sensitivity and enabling quantification, this technology allowed quicker detection of carcinogens like aflatoxin, linked to liver cancer, and blood markers of liver cancer, such as Hepatitis B. Collaborations with institutions, including the University of Toronto and diagnostic industry partners, aimed to improve sensitivity further, moving toward a competitive POC diagnostic platform for cancer screening and early detection.
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.
MULTI-SCALE BIOPHYSICAL PROPERTY MEASUREMENT
MULTI-SCALE BIOPHYSICAL PROPERTY MEASUREMENT
We collaborated with Prof. Chris Dames (experts on 3ω technology) at University of California, Berkeley and Prof. John Rogers (experts on microfabricating sensors on flexible substrates) at Northwestern University, Evanston for this project.
This work focused on improving monitoring for focal treatments of atrial fibrillation (AF), a condition that affects millions and can lead to cardiovascular disease, stroke, and death if untreated. While cryoablation for pulmonary vein (PV) isolation has been used for over a decade, variations in probe contact, tissue thickness, and freeze completion affect its efficacy, potentially causing collateral damage. Under-freezing may result in insufficient treatment, while over-freezing risks complications like phrenic nerve palsy and esophageal injury. Conventional imaging methods (US, MRI, CT) lack the resolution to monitor PV cryoablation accurately. To address this, the team developed a 3ω-based micro-thermal sensor array designed to monitor tissue contact, thickness, and freeze progress around the PV with sub-millimeter precision, marking an advancement in AF treatment monitoring.
Figure: 3ω method: Use of micro-thermal 3ω sensors for monitoring balloon cryoablation in pulmonary vein (PV). (a) Sensors integrated onto a balloon (Rogers group); (b) Cryoballoon approaching PV (Arctic Front MedtronicTM ); (c) A sensor array can be microfabricated around the balloon circumference (future goal). Each sensor has 4 wires attached allowing an individual or group of sensors to be activated. (d) Each sensor produces a thermal wave, and corresponding 3ω response, from penetration into the PV and surrounding tissue. The sensor array can help position and seat the balloon in contact with the PV. Further, it is designed to measure PV thickness, adjacent tissue contact, and freeze initiation and completion (Courtesy – John Rogers, Medtronic, Andy Grams Artwork).
Figure: Thermal properties of biomaterials: pig liver (with or without glycerol, a cryoprotective additive) using traditional measurement methods of pulsed heating and step power input with a thermistor probe: (a) subzero thermal conductivity (b) subzero specific heat; Thermal conductivity of cardiac tissues: (c) Pulmonary vein (d) Phrenic nerve (e) Esophagus
This research examined thermal transport measurement and modeling in biological tissues, critical for bioheat transfer applications. In regenerative medicine, cryopreserved heart valves and blood vessels are transplanted for cardiovascular repairs, while in cardiac interventions, thermal probes are used to heat or cool vessels to treat conditions like atrial fibrillation and renal hypertension. Accurate and controlled thermal processes are essential to preserve or ablate tissues at millimeter scales, yet precise data on heat transfer properties in thin tissues at varied temperatures remains limited. The lab employed the 3ω technique for thermal conductivity measurements and differential scanning calorimetry for specific heat capacity of biological tissues, contributing to an NSF/NIH-supported biotransport research roadmap.
Natesan, H., Hodges, W., Choi, J., Lubner, S., Dames, C. and Bischof, J., 2016. A Micro-Thermal Sensor for Focal Therapy Applications. Scientific Reports, 6, p.21395.
Natesan, H., & Bischof, J. C. (2016). Multi-Scale Thermal Property Measurements for Biomedical Applications. ACS Biomaterials Science & Engineering.
Choi, Jeunghwan, Michael Morrissey, and John C. Bischof. "Thermal processing of biological tissue at high temperatures: impact of protein denaturation and water loss on the thermal properties of human and porcine liver in the range 25–80 C." Journal of Heat Transfer 135.6 (2013): 061302.
Choi, Jeunghwan, and John C. Bischof. "Review of biomaterial thermal property measurements in the cryogenic regime and their use for prediction of equilibrium and non-equilibrium freezing applications in cryobiology." Cryobiology 60.1 (2010): 52-70.
Choi, Jeung Hwan, and John C. Bischof. "A quantitative analysis of the thermal properties of porcine liver with glycerol at subzero and cryogenic temperatures." Cryobiology 57.2 (2008): 79-83.
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