Past, Current & Future: Marrying Microfluidics, Synthetic Biology, and Growing Defense and Applications

As we embark on a journey to explore the intersection of microfluidics, synthetic biology, and defence applications, it is essential to begin by tracing the historical trajectory of microfluidics. By doing so, we can gain a deeper understanding of the evolution of lab-on-a-chip systems and situate ourselves within the broader context of the scientific community, enabling us to form informed opinions on the current state of the field and its potential future directions. The history of microfluidics dates back to the 1950s and 1960s, when pioneering scientists first began to investigate the behaviour of fluids at the microscale. However, it was not until the 1980s that microfluidics started to take shape as a distinct field, with researchers such as Andreas Manz and D. Jed Harrison developing the first microfluidic devices, which were essentially miniaturized versions of traditional laboratory equipment.

The 1990s witnessed a significant surge in the growth of microfluidics, driven by advances in microfabrication techniques and the development of new materials, for instance polydimethylsiloxane (PDMS) [1]. This led to the creation of more complex microfluidic devices, including microchips and lab- on-achip systems, which integrated multiple functions, namely pumping, mixing, and sensing [2]. The early 2000s saw the emergence of microfluidics as a powerful tool for biological research, with applications in fields spanning across genomics, proteomics, and cell biology. Researchers like George Whitesides and Stephen Quake developed innovative microfluidic devices for tasks including DNA sequencing, protein analysis, and cell sorting [3,4].

Today, microfluidics is a vibrant and interdisciplinary field, with applications in areas encompassing point- of-care diagnostics, synthetic biology, and tissue engineering. The development of new materials, fabrication techniques, and sensing technologies has enabled the creation of increasingly sophisticated microfluidic devices, including organ-on-a-chip systems and wearable sensors. Throughout its history, microfluidics has been driven by the convergence of advances in materials science, engineering, and biology. As the field continues to evolve, we can expect to see new breakthroughs and innovations that transform our understanding of biological systems and improve human health. The application of microfluidics for defence purposes has a relatively recent history, dating back to the early 2000s. Initially, researchers explored the use of microfluidics for detecting biological and chemical agents, with the goal of developing portable and rapid detection systems for military and homeland security applications.

The United States Defense Advanced Research Projects Agency (DARPA) played a significant role in driving microfluidics research for defence purposes, launching several programs aimed at developing microfluidic-based systems for detecting and analysing biological and chemical threats. The Biofluidic Chips program was established to demonstrate technologies for self-calibrating, reconfigurable, totally integrated “bio-fluidic” chips with local feedback control of physical/chemical parameters and on- chip, direct interface to sample collection. Through this program, the first set of prototypes were identified and tested by U.S. Army Soldier and Biological Chemical Command (Edgewood, MD), for improving automation, reducing reagent consumption, and increasing sample throughput rates for pathogen detection and consumption. These programs led to the development of innovative microfluidic devices, including lab-on-a-chip systems and micro total analysis systems (μTAS), which could detect and identify biothreat agents (e.g. anthrax and ricin) [5].

In the mid-2000s, researchers began to explore the use of microfluidics for other defence-related applications, water purification and explosives detection. Microfluidic devices were developed to remove contaminants from water, making it safe for drinking, and to detect explosives like TNT and RDX [6,7]. Today, microfluidics plays a more significant role in defence research and development, with applications in areas covering chemical and biological defence, explosives detection, and medical countermeasures. Microfluidic devices are being used to develop portable and rapid detection systems for chemical and biological agents, as well as to create miniaturized systems for medical diagnosis and treatment. The use of microfluidics for defence purposes has also led to the development of new technologies, such as microfluidic-based sensors and assays, which have the potential to revolutionize the field of defence research [8]. As the field continues to evolve, we can expect to see new innovations and applications of microfluidics for defence purposes, from detecting emerging threats to developing new medical countermeasures and even into novel material synthesis.

As seen already in several commercial sectors, the impacts of microfluidics will be delivered not only in the form of microfluidic consumables as a tool, but also as microfluidic platforms to generate and synthesize cells and materials with enhanced capability. Overall, the history of microfluidics for defence purposes is a story of rapid innovation and advancement, driven by the need for rapid and effective detection and response to emerging threats. Given the rich history and broad utility of microfluidics in the life sciences, it is natural to ask where microfluidics can continue to drive impact within the synthetic biology defence community. One way to approach this question is through the lens of technology development in general. When developing novel technologies, simple solutions are often preferred over complex ones because they tend to be more reliable, easier to maintain, and less prone to errors. Complex solutions, on the other hand, can introduce unnecessary variables and dependencies that can increase the risk of system failures and make troubleshooting more challenging.

Additionally, simple solutions can be more scalable and adaptable to changing requirements, allowing developers to iterate and refine their designs more quickly. By embracing simplicity, developers can create more efficient, user-friendly, and costeffective technologies that meet the needs of their users without introducing unnecessary complexity. Therefore, for microfluidics to continue to drive impact, the field must return to developing simple fluidic solutions to complex problems. Historically, microfluidics has added value to established fields by providing simple solutions to complex problems, and we can expect to find new opportunities for broader adoption in the future. At its core, microfluidics is an enabling tool. It is simply the hardware behind the biological, chemical, or physiological “software”. A clear direction is needed for building new tools and applications.

To end, I will quote George Whitesides (the father of microfluidics) in a seminal microfluidic work regarding the prospects of the field, “That fact—that there is a wide range of opportunities, and a wide range of opinions on what is more important and what is less important—gives a measure of the health of the field. So long as there are lots of opportunities, and lots of differences in opinion, the broad area encompassing LoC [Lab-on-a-Chip] and microfluidic technology is in good shape [9].”

1. Whitesides GM (2006) The origins and the future of microfluidics. Nature 442(7101): 368- 373.
2. Folch A (2022) Hidden in Plain Sight: The History, Science, and Engineering of Microfluidic Technology. The MIT Press.
3. Convery N, Gadegaard N (2019) 30 years of microfluidics. Micro and Nano Engineering 2(1): 76-91.
4. Huebner A, Sharma S, Sirsa-Art M, Hollfelder F, Edel JB, et al. (2008) Microdroplets: A sea of applications?. Lab on a chip 8(8): 1244-1254.
5. Meagher RJ, Hatch AV, Renzi RF, Singh AK (2008) An integrated microfluidic platform for sensitive and rapid detection of biological toxins, Lab on a chip 8(12): 2046-2053.
6. Charles PT, Adams AA, Howell PB, Deschamps JR, Kuster beck AW, et al. (2010) Fluorescence- based sensing of 2,4,6-trinitrotoluene (TNT) using a multi-channeled poly (methyl methacrylate) (PMMA) micro immunosensor. Sensors (Basel) 10(1): 876-889.
7. Yousefian J, Alizadeh N (2019) Photothermal lens microfluidic sensor for femtomole detection of 2,4,6- trinitrotoluene based on Meisenheimer complexation. Sensors and Actuators B: Chemical 298(2): 126882-126890.
8. Wang Zh, Liu W, Dai Y, Liu Zp, Ma Md, et al. (2024) On-site trace detection of explosives: From ultra-sensitive SERS to integrated detection technology, Energetic Materials Frontiers 12(8): 1-5.
9. Whitesides GM (2011) What Comes Next? Lab on a chip 11(2): 191-193.