Editorial: Frontiers Research Topic: Celebrating 1 Year of Lab on a Chip The Widening Scope of Microfluidics: Two Mainstreams

Michael Mauk^*

• University of Pennsylvania, Philadelphia, United States

Almost 20 years ago, NATHAN BLOW published an article in Nature Biotechnology entitled 'Microfluidics: In Search of the Killer App" [1], surveying efforts to develop integrated, automated microfluidic systems for nucleic acid, protein, and cell-based assays to facilitate customized platforms for high throughput analysis, that would initiate wider adoption of microfluidics technology by life science researchers. At that time, the future appeared to be foundries providing made-to-order systems fabricated by soft lithography in PDMS (polydimethylsiloxane) silicon polymer. The search for a lab-on-a-chip "killer-app" has been a lively topic of discussion. CALCEDO and BRADY [2] surmised the challenge for microfluidics was instead bridging technical gaps so that adoption of microfluidics yields significant operational advantages and/or substantial cost reductions, rather than finding a killer app.Concurrent to development of these specialized microfluidic systems as research tools are decades-long efforts to develop microfluidic lab-on-a-chip devices for point-of-care (POC) diagnostics. The lateral flow strip for immunoassays, such as the home-pregnancy test, COVID antigen tests, and drugs-of-abuse tests, are premier examples of widely-used, commercialized POC devices. The challenge is to implement more complicated 'molecular' diagnostics (nucleic acid amplification tests) that integrate sample processing, enzymatic amplification, and realtime detection in a low-cost, streamlined, minimally instrumented device. Some comparisons of microfluidics with microelectronics, the most consequential technology of the last half century is instructive. Microelectronics has largely converged into a consolidated technology base: transistor devices are made in silicon with a handful of other materials, fabricated by made by-well established, industry-wide methods, to realize implementations of a standard set of functions (e.g., logic, data storage, signal processing). Microfluidics systems, on the other hand, are still made from a wide variety of materials and and diverse fabrication methods, with no standard device building block component similar to a transistor, and are applied to an expanding scope of functions ranging from immunoassays, sample processing, to tissue and cell culture.Four articles in the Frontiers Research Topic "Celebrating 1 Year Frontiers in Lab on a Chip Technologies underscore the diverse range of applications and characteristics of microfluidics technology, in ways and areas perhaps not anticipated in the first decades of the field. Khan et al. "Point-of-care testing: a critical analysis of the market and future trends" which surveys wearable sensors (e.g., patches, wristbands, bandages, and contact lenses) in addition to microfluidic technology. The authors offer several avenues for expanding microfluidics in the point-of-care diagnostics realm, including integrating artificial intelligence and machine learning with point-of-care technology (microfluidic lab-on-a-chip devices and sensors). With improvements in sensitivity and meeting more stringent clinical standards, the authors are optimistic about sig While POC diagnostics is focused on infectious diseases, wider use for non-communicable diseases and continuous patient monitoring offers opportunities for dramatic changes in healthcare delivery.A second article, KAMAT et al. "An economical self-coalescing microfluidic device with an observable readout", is an illustrative example of exploiting the features of fluid flow phenomena at the microscale for implementing a minimally-instrumented multiplexed assay. Dried reagents are spotted in the channel of the chip for multiple assays, and reconstituted by infusion of a liquid. By controlling device geometry, self-coalescence phenomena maintain reagent separation, allowing multiple simultaneous colorimetric tests. Further, a simple fabrication technology using laser-cut silicone tape over a coverslip with spotted reagents is used.Tissue chips are microfluidic systems used as experimental platforms that simulate physiological conditions and where, for example, the response of cells immobilized in channels to microgravity, radiation, drug stimulation, toxins, and blood infusions. In a third article, TAYLOR, MODI, and BAILEY ("An analysis of trends in the use of animal and non-animal methods in biomedical research and toxicology publications") survey the use of Non-Animal Models (NAMs) in biomedical research as the intersection of microfluidics or lab on a chip and in vitro studies that replace in vivo animal models. The motivation for NAMs in research is to avoid the use of animals, shorten study times, and lower costs. Typically, the NAMs are the first phase of projects whereby findings are then confirmed with in vivo studies. Research areas included lung disease, heart disease, breast cancer, blood cancer, diabetes, toxicology, and neurodegenerative diseases.Continuing with the use of microfluidic platforms for culturing tissues, in a fourth article, JOGDAND, LANDOLINA and CHEN ("Organs in orbit: how tissue chip technology benefits from microgravity, a perspective") review the use of tissue chips (also referred to as 'organ on a chip') in space. These systems have the specific objective of predicting health risks to astronauts, and wider interest because microgravity may simulate accelerated aging and other disease processes. Moreover, low-gravity can increase the permeability of the blood-brain barrier, allowing passage of chemotherapeutics. The authors provide a perspective on microgravity tissue chip technology for muscoloskeletal, cardiovascular and nervous systems. This research area provides an example of how microfluidics enables and facilitates the simulation and probing of model systems to investigate disease mechanisms and assess therapies. The world of microfluidics may well further split into a POC sector focused on minimally instrumented, multiplexed molecular assays made in high-volume manufacturing processes ('lab on a chip'), and customized analytical systems sector ('chip in a lab') with ever-more sophisticated designs and ambitious performance aims, including organ-on-a-chip and high-throughput, highly-instrumented analysis platforms [3,4].