Department of Mechanical Engineering
University of Maryland, Baltimore County
1000 Hilltop Circle Baltimore, MD 21250
Website: Bioheat Transfer Laboratory
Ph.D., Mechanical Engineering, City University of New York, 1995
B.S., Mechanical Engineering, University of Science and Technology of China, 1988
|2014-present||Professor, Mechanical Engineering|
|2010-present||Director, Mechanical Engineering S-STEM Scholarship Program at UMBC|
|2004-2014||Associate Professor, Mechanical Engineering|
|1998-2004||Assistant Professor, Mechanical Engineering|
Honors and Awards
|2021 – 2022||Fulbright US Fellow|
|2010, 2014, 2018||NSF S-STEM Grants|
|2015||Fellow, American Society of Mechanical Engineers (ASME)|
|2012, 2015||FDA Contract|
|2007, 2008, 2013, 2017||NSF CBET Research Grants, NSF MRI Grant|
|2008||State of Maryland TEDCO Fund|
|2006||UMBC ADVANCE Program Research Assistantship|
|1999||Whitaker Biomedical Research Grant Award|
|1988||Guo Muo-Ruo Prize, University of Science & Technology of China|
Heating Enhanced Nanoparticle Delivery to Tumors — Recent research in our lab is focused on using mild whole body hyperthermia to tumor-bearing mice or local heating to tumors to enhance gold nanoparticle delivery. In vivo experiments were performed to illustrate that local or whole body heating to 40C reduces interstitial fluid pressures (IFPs) and significantly increase local or whole body blood perfusion rate. MicroCT analyses and ICP-MS quantifications demonstrated more than 50% increases in the total amount of gold nanoparticles delivered to PC3 tumors and improves particle delivery to the tumor core. In addition, theoretical simulations of nanoparticle transport in porous tumors suggest that increases in the hydraulic conductivity and recovery of lymphatic functions are possible mechanisms that lead to IFP reductions and enhancement in nanoparticle deposition in PC3 tumors observed in our in vivo experimental studies.
Magnetic Nanoparticle Hyperthermia — One research focuses on theoretical and experimental study of temperature elevations in tumor using magnetic nanoparticle hyperthermia. In this study, we design experiments to understand the nanoparticle distribution after intra-tumoral injection and how nanoparticle spreading is affected by injection strategies such as injection rate and injection amount. In vitro and in vivo experiments have then been performed to evaluate the temperature rises in tumor after the nanoparticles are subject to an alternating magnetic field. We also developed a computer algorithm to inversely determine the injection strategies involving multi-injection site in an irregular shaped tumor to maximize the heating in tumor with minimal collateral damage to the surrounding tissue. Currently we are employing a microCT system to visualize the particle distribution in tumor based on the assumption that the nanoparticles change the local material density and the density change is detectable by x-ray. Recent theoretical simulations are performed to evaluate whether thermal damage induced porosity increase caused nanoparticle migration in tumors.
Development of a Whole Body Heat Transfer Model — The human body has limited ability to maintain a normal, or euthermic, body temperature. In extreme situation such as heavy exercise or harsh thermal environment, the body temperature can shift to a high or low level from the normal range. In addition, active control of body temperature is increasingly employed therapeutically in several clinical scenarios, most commonly to protect the brain from the consequences of either primary (i.e., head trauma, stroke) or secondary injury (i.e., after cardiac arrest with brain hypo-perfusion). In those situation, the Pennes bioheat equation alone is unable to predict how the body/blood temperature changes. Our lab has developed a whole body heat transfer model to address the challenge. Our approach consists of the Pennes equation to simulate the temperature distribution in the body and an energy balance equation to capture the transient changes in the arterial blood/body temperature. The two equations are coupled during the transient process simulations, as the Pennes equation requires the input of the arterial blood temperature, and the change of the arterial blood temperature relies on the overall heat exchange between the tissue and blood in the Pennes equation. This whole body heat transfer model has been used in various physical/clinical scenarios to predict body temperature changes and the results agree well with experimental observations.
Photothermal Therapy Using Gold Nanoshells/Nanorods in Cancer Therapy — Currently we are exploring research field of photothermal therapy using gold nanorods in cancer treatment. Gold nanorods can be tuned to maximally absorb laser energy at certain laser wavelengths. Once the nanorods are injected into a tumor, it will serve as an energy absorber to concentrate the laser energy to the tumor site, therefore, to achieve targeted laser ablation of the tumor, while preserving the surrounding healthy tissue. Similar to our magnetic nanoparticle hyperthermia project, we are interested in quantifying the particle distribution (using the microCT imaging system) and mapping the temperature rise distribution in the tumor during laser photothermal therapy.
Targeted Brain Cooling Using an Interstitial Cooling Device — This research project focuses on studying temperature distribution in human neck and brain during selective brain cooling (SBC) and developing new cooling devices for patients suffering ischemia or head injury. The computer and software in our lab at UMBC have been used to simulate the temperature distribution in brain tissue. In vivo animal experiments have been performed in the laboratory to study blood flow and temperature responses to various cooling approaches in SBC.
Using Laser or Heating Catheters in Bacterial Disinfection in Endodontics — We also adopted our computation skill to dentistry to simulate temperature distribution in dentin during various thermal procedures including lasers and heating catheters for bacterial disinfection. The microCT system can be used to generate precise physical models for theoretical simulations. Theoretical simulation has been used to design a feasible treatment protocol to maintain sufficient high temperature elevations in deep dentin while preserving the sensitive surrounding periodontal ligament and cementum.
Classes Taught at UMBC
|ENME489H/813||Heat Transfer in Biological Systems|
|ENME489Y/631||Advances in Conduction and Radiation|
Singh, M., Ma, R., and Zhu, L.. (2021) Theoretical Evaluation of Enhanced Gold Nanoparticle Delivery to PC3 Tumors due to Increased Hydraulic Conductivity or Recovered Lymphatic Function after Mild Whole Body Hyperthermia. Medical & Biological Engineering & Computing 59:301–313, 2021. DOI: https://doi.org/10.1007/s11517-020-02308-4
Singh, M., Ma, R., and Zhu, L.. (2021) Quantitative Evaluation of Effects of Coupled Temperature Elevation, Thermal Damage, and Enlarged Porosity on Nanoparticle Migration in Tumors during Magnetic Nanoparticle Hyperthermia. International Communications of Heat and Mass Transfer, 126:105393. https://doi.org/10.1016/j.icheatmasstransfer.2021.105393
Gu, Q., Liu, S., Saha Ray, A., Florinas, S., Christie, R. J., Daniel, M-C., Bieberich, C., Ma, R., and Zhu, L.. (2020) Mild Whole Body Hyperthermia Induced Interstitial Fluid Pressure (IFP) Reduction and Enhanced Nanoparticle Delivery to PC3 Tumors: In Vivo Studies and MicroCT Analyses. ASME Journal of Thermodynamic Sciences and Engineering Applications, 12:061001(1-10), 2020.
Zhu, L., Eggleton, C., Topoleski, L.D.T., Ma, R. and Madan, D.. (2020) Establishing the Need to Broaden Bioengineering Research Exposure and Research Participation in Mechanical Engineering and Its Positive Impacts on Student Recruitment, Diversification, Retention and Graduation: Findings from the UMBC ME S-STEM Scholarship Program. ASME Journal of Biomechanical Engineering, 142:111010(1-7).
Singh, M., Gu, Q., Ma, R., and Zhu, L.. (2020) Heating Protocol Design Affected by Nanoparticles Re-distribution and Thermal Damage Model in Magnetic Nanoparticle Hyperthermia for Cancer Treatment. ASME Journal of Heat Transfer, 142, 072501(1-9).
Gu, Q., Joglekar, T., Bieberich, C., Ma, R., and Zhu, L.. (2019) Nanoparticle Redistribution in PC3 Tumors Induced by Local Heating in Magnetic Nanoparticle Hyperthermia: In Vivo Experimental Study. ASME Journal of Heat Transfer, 141(3), 032402.
Vesnovsky, O., Zhu, L., Grossman,L. W., Casamento, J. P., Chamani, A.,., and Topoleski, L. D. T.. (2019) Identifying Critical Design Parameters for Improved Body Temperature Measurements: A Clinical Study Comparing Transient and Predicted Temperature Measurements. ASME Journal of Medical Devices, 13:011005(1-15).
LeBrun, A., and Zhu, L.. (2018) Magnetic Nanoparticle Hyperthermia in Cancer Treatment: History, Mechanism, Imaging-Assisted Protocol Design, and Challenges. In Theory and Application of Heat Transfer in Cells and Organs, edited by Devashish Shrivastava, Chapter 29, pp. 758-776, John Wiley & Sons Ltd, Hoboken, NJ, 2018, ISBN 9781119127307.
Min Zaw, M., Hedrich, W., Munuhe, T., Wang, H., Gadsden, S. A., Zhu, L., Ma, R.. (2018) Fabrication of a cell culture plate with a 3D printed mold and thermal analysis of PDMS-based casting process. ASME Journal of Thermal Science and Engineering Applications. 10:061002(1-8).
Zhu, L.. (2018) Hypothermia Used in Medical Applications for Brain and Spinal Cord Injury Patients. In Molecular, Cellular, and Tissue Engineering in Vascular System, Editors: Bingmei Fu and Neil Wright, Springer, New York, pp. 295-319, 2018.
LeBrun, A., Joglekar, T., Bieberich, C., Ma, R. and Zhu, L.. (2017) Treatment efficacy for validating microCT based theoretical simulation approach in magnetic nanoparticle hyperthermia for cancer treatment ASME Journal of Heat Transfer, 139:051101(1-7).
Bartgis, C., LeBrun, A., Ma, R., and Zhu, L.. (2016) Determination of Time of Death in Forensic Science via a 3-D Whole Body Heat Transfer Model. Journal of Thermal Biology, 62:109-115.
Manuchehrabadi, N., and Zhu, L.. (2014) Development of a Computational Simulation Paradigm to Design a Protocol for Treating Prostate Tumor Using Transurethral Laser Photothermal Therapy, International Journal of Hyperthermia, 30(6): 349-361.
Chamani, A., Mehta, H. P., McDermott, M. K., Djeffal, M., Nayyar, G., Patwardhan, D. V., Attaluri, A., Topoleski, L. D. T., and Zhu, L.. (2014) Theoretical simulation of temperature elevations in a joint were simulator during rotations. ASME Journal of Biomechanical Engineering, 136: 021027(1-6).
Manuchehrabadi, N. Chen, Y., LeBrun, A., Ma, R., and Zhu, L.. (2013) Computational simulation of temperature elevation in tumors using Monte Carlo method and comparison to experimental measurements in laser photothermal Therapy. ASME Journal of Biomechanical Engineering, 135: 121007 (1-11).
Gill, J., Arola, D., Fouad, A., and Zhu, L.. (2012) Design of Laser Treatment Protocols for Bacterial Disinfection in Root Canals Using Theoretical Modeling and MicroCT Imaging. ASME J. Thermodynamic Sciences and Engineering Applications, 4:031011(1-9).
Attaluri, A., Ma, R., Qiu, Y., Li, W., and Zhu, L.. (2011) Nanoparticle Distribution and Temperature Elevations in Prostatic Tumors in Mice during magnetic nanoparticle hyperthermia. International Journal of Hyperthermia, 27(5):491–502.
Smith, K., & and Zhu, L.. (2010). Theoretical evaluation of a simple cooling pad in inducing hypothermia in spinal cord following traumatic injury. Medical and Biological Engineering & Computing, 48(2), 167-175.
Zhu, L.. (2010) Recent developments in biotransport. ASME Journal of Thermodynamic Sciences and Engineering Applications, 2(4):040801(1-11).
Zhu, L.., Tolba, M., Arola, D., Salloum, M., & Meza, F. (2009). Evaluation of effectiveness of Er,Cr:YSGG laser for root canal disinfection: Theoretical simulation of temperature elevations in root dentin. Journal of Biomechanical Engineering, 131(7), 1-8).
Diller, K., & Zhu, L.. (2009). Hypothermia Therapy for Brain Injury. Annual Review of Bioengineering. 11, 135-162.
Zhu, L., Schappeler, T., Cordero-Tumangday, C., & Rosengart, A. J. (2009). Thermal interactions between blood and tissue: development of a theoretical approach in predicting body temperature during blood cooling/rewarming. Advances in Numerical Heat Transfer, 3, 197-219.
Salloum, M., Ma, R., & Zhu, L.. (2009) Enhancement in treatment planning for magnetic nanoparticle hyperthermia: optimization of the heat absorption pattern. International Journal of Hyperthermia, 25(4), 311-323.
Tang, W., Tasch, U., Neerchal, N. K., Zhu, L., & Yarowsky, P. (2009). Measuring early pre-symptomatic changes in locomotion of SOD1-G93A rats – a rodent model of amyotrophic lateral sclerosis. Journal of Neuroscience Methods, 176(2), 254-262.
Rosengart, A. J., Zhu, L., Schappeler, T., & Goldenberg, F. D. (2009). Fever control in hospitalized stroke patients using simple intravenous fluid regimens – a theoretical evaluation. Journal of Clinical Neuroscience, 16(1), 51-55,.
Salloum, M., Ma, R. Weeks, D., & Zhu, L. (2008). Controlling nanoparticle delivery in magnetic nanoparticle hyperthermia for cancer treatment: experimental study in agarose gel. International Journal of Hyperthermia, 24(4), 337-345.