Abstract
Gradients of chemical and physical parameters such as oxygen, nutrients, pH, temperature, and shear stress are fundamental regulators of cellular function and tissue homeostasis in the human body. These physiochemical gradients are inherently dynamic, shaped by diffusion, convection, organ architecture, and metabolic activity and they evolve continuously in response to changing biological conditions. The dynamic nature of chemical and thermal gradients are caused and controlled by transport phenomena related to heat and species diffusion and convection. During pathological events such as ischemia, inflammation, infection, fibrosis, and cancer metastasis, these gradients are often disrupted, leading to altered cell signalling, phenotype, and viability. Clinical interventions, including surgery, drug administration, or implant insertion, can further modify these gradients by imposing abrupt or sustained microenvironmental changes. Understanding how cells respond to such dynamic and heterogeneous gradients is critical for modelling physiology, disease progression, and therapeutic outcomes. Organ-on-a-Chip platforms offer a powerful microfluidic framework to engineer, impose, and control these gradients with high spatial and temporal resolution. Unlike conventional static cultures, these systems allow the application of well-defined imposed gradients (whether stepwise, linear, or dynamic) of oxygen tension, metabolite/drug concentration, shear, or thermal stress. Through vascular-like perfusion, tissue-specific interfaces, and micro-compartmentalization, Organ-on-a-Chip models can mimic complex physiological gradients across critical organ barriers such as the intestinal wall, renal nephrons, or cardiac tissue. This keynote explores the role of imposed gradients in intestine, cardiac and kidney functions using organ-on-a-chip models to decode transport phenomena and cellular behaviour under both healthy and disease-mimicking conditions. In intestine models, both individual and interplay of chemical and thermal gradients are used to investigate bacterial taxis, offering insights into microbiome and infection dynamics. In cardiac-on-a-chip models, gradients of oxygen are engineered to simulate ischemia and reperfusion, enabling analysis of calcium signalling, and mitochondrial stress. Similarly, Kidney-on-a-Chip platforms use hydrostatic pressure, tissue stiffness and solute gradients to replicate nephron-level functions and assess filtration, reabsorption, and drug-induced nephrotoxicity. Shear stress gradients are also investigated to understand their influence on cancer cell proliferation under drug exposure where metastasis paradoxically increases post-chemotherapy. Overall, this talk will provide a cross-disciplinary perspective, rooted in heat and mass transfer principles on how advanced microfluidic engineering can be leveraged to replicate the complexity of gut, inter organ cancer metastasis, cardiac and renal physiology on-chip. We envision these platforms as testbeds to unravel organ-specific thermo-chemical phenomena that will drive the next generation of in vitro diagnostics, therapeutics, and treatment strategies.
Keywords: Gradients, Organ-on-a-Chip, Heart, Kidney, Intestine, Chemical, Thermal, Shear Stress
Short Bio
Professor Sarit K. Das is an Institute Professor at the Indian Institute of Technology Madras, Chennai. He is the first occupant of the V. Balakrishnan Chair Professorship. He is the former Director (President) of the Indian Institute of Technology Ropar. He is also the former Dean (Academic Research) of IIT Madras.
Prof. Das studied at the Jadavpur University, NIT Rourkela and the Helmut Schmidt University of Hamburg, Germany. His research group works on various aspects of thermo -fluids sciences like heat and mass transfer in industrial equipment such as heat exchangers and fuel cells, multiphase flow and energy conversion. Water management in PEM fuel cells and thermal management of battery stack are the two active areas in this direction. He also works on cooling technology for electronic material processing using novel eutectic binary mixture of organic fluids. The group also works on thermal desalination techniques such as HDH (Humidification and Dehumidification) technique. The group is known for works on Micro-Nano scale processes and is known to be one of the leading groups on fundamentals and applications of Nanofluids in the world. Another area of major focus of the group is bio-microfluidics, which are specifically conceptualized to mimic human physiological conditions through novel organ-on-chip platforms. The focus is to use this for medical diagnostics, effective drug delivery and understanding the role of chemical and thermal gradients on physiological and pathological states related to cardiovascular diseases, renal failures and cancer metastasis.
Prof. Das is a Fellow of the National Academy of Sciences India (NASI) and the Indian National Academy of Engineering (INAE). Recently, he has been selected a fellow of the Asian Union of Thermal Sciences and Engineering (AUTSE). He was a Peabody Visiting Professor at MIT, Cambridge and a visiting Professor – Lund University, Sweden. He was conferred the prestigious India Citation Awards 2012 by Thomson Reuters. He is the first recipient of the KNS research award given by the Indian Society for Heat and Mass Transfer (ISHMT). He was a fellow of the Alexander von Humdoldt foundation in 2000-01. He has published more than 350 research articles and six books.
Prof. Das is a member of the editorial boards of Heat Transfer Engineering, Taylor & Francis Publishers, former Editor in Chief of International Journal of Micro-Nano Scale Transport and Former Member of the Editorial Board for the International Journal of Heat Exchangers. Visit https://home.iitm.ac.in/skdas/index.html for more information.