Microfluidics-based in vivo mimetic systems for the study of cellular biology

The human body is a complex network of molecules, organelles, cells, tissues, and organs: an uncountable number of interactions and transformations interconnect all the system's components. In addition to these biochemical components, biophysical components, such as pressure, flow, and morphology, and the location of all of these interactions play an important role in the human body. Technical difficulties have frequently limited researchers from observing cellular biology as it occurs within the human body, but some state-of-the-art analytical techniques have revealed distinct cellular behaviors that occur only in the context of the interactions. These types of findings have inspired bioanalytical chemists to provide new tools to better understand these cellular behaviors and interactions. What blocks us from understanding critical biological interactions in the human body? Conventional approaches are often too naïve to provide realistic data and in vivo whole animal studies give complex results that may or may not be relevant for humans. Microfluidics offers an opportunity to bridge these two extremes: while these studies will not model the complexity of the in vivo human system, they can control the complexity so researchers can examine critical factors of interest carefully and quantitatively. In addition, the use of human cells, such as cells isolated from donated blood, captures human-relevant data and limits the use of animals in research. In addition, researchers can adapt these systems easily and cost-effectively to a variety of high-end signal transduction mechanisms, facilitating high-throughput studies that are also spatially, temporally, or chemically resolved. These strengths should allow microfluidic platforms to reveal critical parameters in the human body and provide insights that will help with the translation of pharmacological advances to clinical trials. In this Account, we describe selected microfluidic innovations within the last 5 years that focus on modeling both biophysical and biochemical interactions in cellular communication, such as flow and cell-cell networks. We also describe more advanced systems that mimic higher level biological networks, such as organ on-a-chip and animal on-a-chip models. Since the first papers in the early 1990s, interest in the bioanalytical use of microfluidics has grown significantly. Advances in micro-/nanofabrication technology have allowed researchers to produce miniaturized, biocompatible assay platforms suitable for microfluidic studies in biochemistry and chemical biology. Well-designed microfluidic platforms can achieve quick, in vitro analyses on pico- and femtoliter volume samples that are temporally, spatially, and chemically resolved. In addition, controlled cell culture techniques using a microfluidic platform have produced biomimetic systems that allow researchers to replicate and monitor physiological interactions. Pioneering work has successfully created cell-fluid, cell-cell, cell-tissue, tissue-tissue, even organ-like level interfaces. Researchers have monitored cellular behaviors in these biomimetic microfluidic environments, producing validated model systems to understand human pathophysiology and to support the development of new therapeutics.