Sep 22, 2011
The field of microfluidics has transformed the way researchers investigate chemical and biological phenomenon by miniaturizing the scale of reagent manipulation and sample analysis. Over the past two decades, an extensive body of literature and a collection of commercial ventures have arisen to explore and exploit the unique properties exhibited by fluids confined to microscopic channels. Originating from fabrication methods designed for the semiconductor industry, the field was driven in its early days by academic labs constructing a variety of proof-of-concept devices for diverse and often specialized applications in chemical synthesis and biological analysis. The initial adopters of the technology envisioned tiny devices that could rapidly process and analyze a range of substances using only small volumes of valuable reagents and samples. As academics demonstrated the feasibility of miniaturizing and combining the necessary unit processes, the emerging concept of the “lab-on-a-chip” – a self-contained, low-cost, and high-throughput research platform that could replace bulky bench-top instruments – captivated a scientific community in the midst of the genomic revolution and searching for innovative technologies that could capitalize on the new wealth of biological data available.
During the late 1990s a number of companies such as Caliper Life Sciences, Micronit, and Fluidigm were founded to translate breakthroughs into consumer products that promised results using workflows that were faster, cheaper, and more reproducible than standard methods. The explosion in the number of academic groups exploring the field, as well as the progress made in adapting the field’s toolbox to life science applications indicated to many observers that a “killer application” was inevitable and would fulfill the potential that had been identified years before. It seemed just a matter of time before a start-up or an established industry player fit together the pieces that had been scattered across the academic journals and produced a blockbuster device that could generate significant annual revenue (>$100M). As years passed and a high-value application did not materialize, people began to grumble about the technology being overhyped, and many investors moved onto other opportunities with more well-traveled routes to commercialization. Although the field continues to attract large numbers of graduate students and healthy amounts of funding, its industrial maturation has not kept pace with academic development, leading to an uncomfortable asymmetry that has led many to conclude that microfluidics is a discipline best suited for isolated displays of applied technical mastery and not amenable to mass commercialization. But what are the underlying factors that have led to this? Was this simply a case of unrealistic expectations? Is widespread commercial success still on the horizon, and if so, how long will it be until it is reached?
A common criticism is that microfluidic devices generate elegant solutions to problems that nobody is desperate to solve. Successful commercial deployment requires both a functional product and a receptive market eager to adopt it for an identifiable cost- or performance-related reason. Early ventures in the field touted their chips’ efficient consumption of reagents and ability to be produced from cheap materials in an effort to convince investors and potential end-users that shrinking the length scale of the instruments would lead to a similar reduction in cost. However, issues with production scale-up and other challenges that were not encountered in the single-chip experiments of academic settings often eroded this value proposition and thereby greatly diminished the incentive to adopt the emerging technologies. In addition, while the intricacy and complexity of the devices served as proof of technical mastery in journals and at conferences, they meant very little in the marketplace and in many cases were detrimental to the technology’s commercial profile. The microscopic handling of fluids was far more difficult than the electron manipulation that had given rise to the semiconductor and computing industries, and the mazes of tiny passages and delicate functional units often brought to mind Murphy’s Law. Without significant operational advantages or a marquee application, the switch to microfluidic technologies was deemed too risky by many end-users who were content with using their more conventional instruments and techniques.
The disconnect between supply and demand was in large part the product of a similar gulf between the methodologies required for success in academia and industry. Just as fluids behave differently in micro- and macroscale environments, researchers in academia and industry operate within distinct paradigms, working towards outcomes that differ radically in scope and purpose. The proof-of-concept focus of academic researchers produced a working knowledge best described as a mile wide and an inch deep, forcing small ventures to tackle a range of nontrivial commercialization issues related to quality control, mass production, and optimization. Academic pilot studies rarely addressed significant questions regarding chip-to-chip variability, process integration, and standardization of components. Within the academic community, novelty (not consistency) in device design and application became the best way to generate attention in an increasingly crowded research space. This approach led to the development of a wide variety of protocols, tools, and materials that were frequently incompatible with one another, preventing the adoption of a dominant paradigm in the emerging microfluidics industry and producing significant lag times between technological discovery and commercial availability. And even when trends were established, they did not always align with commercial needs. For instance, the widespread use of poly(dimethylsiloxane) (PDMS) for device creation in academic labs led to a range of well-publicized technological breakthroughs in biological applications, but as Holger Becker, co-founder and chief scientific officer of ChipShop GmbH, has pointed out, this material is ill-suited for the mass production processes that are required to realize economies of scale for the industry (1).
In the case of microfluidic technology, normal growing pains have been exacerbated by inflated expectations, an inability to displace entrenched conventional methods, and significant challenges in translating basic research into consumer products. However, despite a history of numerous false-starts and disappointments, there is reason to believe that the commercial prospects of the field are on the rise due to a realignment of technical capacity and consumer need. As Becker has noted in a series of perspective pieces in the journal Lab on a Chip, microfluidic technology has transformed in recent years from a killer-application platform into a classic enabling tool. Current developments such as Fluidigm’s February IPO suggest that the industry is steadily climbing the Gartner Hype Cycle’s so-called “slope of enlightenment” (2) towards a period of market growth and sustained productivity predicated on the creation of devices and microfluidic-enabled solutions targeted at large groups of private consumers, rather than the existing business-to-business model.
A renewed focus on marketable applications rather than technical novelty has led to a new wave of tools that address major clinical needs such as the isolation of circulating tumor cells from blood and the rapid assay of biomolecules in readily-obtainable body fluids for non-invasive diagnostic tests for personalized medicine. These applications leverage the power of small-volume analysis (rapid target capture, low reagent consumption, small instrument footprint) to provide considerable enhancements in performance that cannot be achieved with conventional macroscale platforms while still maintaining simple, user-friendly designs. The miniature scale of microfluidics has also proven to be a tremendous asset in the recent development of systems for high-throughput single-cell analysis, a growing application space that offers unique insights into disease state and the molecular profiles of rare or valuable cell populations. Further opportunities exist in developing countries, where microfluidic cartridges interfaced with smartphones are being explored for “sample in, answer out” point-of-care (POC) diagnostics. In addition to traditional lab-on-a-chip instruments, an increasingly diverse range of microfluidic-enabled products such as specialty chemicals and encoded microparticles are now being developed by entrepreneurs seeking to penetrate new markets.
Scaling the slope of enlightenment will require an entrepreneurial community that is cognizant of the past shortcomings of the industry and prepared to adapt its strategy to meet future demands. Market expansion will occur only if developers embrace microfluidics as a component of a larger commercial package that can easily be inserted into existing workflows. The degree to which the new wave of microfluidic technologies can be integrated into transformative products designed for private consumers will dictate commercial uptake. The maturation of the field has been long and tortuous, but the potential for developing products with significant market impact remains as great as ever.
(1) H. Becker, Lab on a Chip, vol. 10, pp. 271-273 (2010)
(2) H. Becker, Lab on a Chip, vol. 9, pp. 2119-2122 (2009)x