Science & Society Commercialization of microfluidic devices 1 2 Lisa R. Volpatti and Ali K. Yetisen 1 Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK 2 Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QT, UK Microfluidic devices offer automation and high-through- The market put screening, and operate at low volumes of consum- In 2013, the microfluidics market was valued at $1.6 billion ables. Although microfluidics has the potential to reduce [3]. With an expected compound annual growth rate turnaround times and costs for analytical devices, par- (CAGR) of 18–29%, the market is projected to reach ticularly in medical, veterinary, and environmental $3.6–5.7 billion by 2018 [3,4]. This high growth rate is sciences, this enabling technology has had limited diffu- largely due to recent advances in biotechnology, including sion into consumer products. This article analyzes the gene sequencing and in vitro diagnostics (Table 1). microfluidics market, identifies issues, and highlights successful commercialization strategies. Addressing Gene sequencing niche markets and establishing compatibility with exist- With the completion of the human genome project in 2003 ing workflows will accelerate market penetration. and the advent of next-generation sequencing, microfluidic technology has been used to increase automation and Microfluidics is an enabling platform technology that decrease turnaround times in genomics. Key companies allows automation and multiplexing of laboratory equip- in the field of microfluidic genotyping include Illumina Inc. ment, drug screening technologies, and in vitro diagnostic and Fluidigm Corp. In 2013, Illumina acquired Advanced devices [1]. Over the past two decades, several ventures Liquid Logic Inc. to gain access to their digital microflui- have emerged to commercialize microfluidic technologies. dics platform. Their electrowetting technology manipu- Initially, these devices were envisioned to be used in lates discrete droplets in a microfluidic device without biological analyses and chemical syntheses so that a range pumps, valves, or channels; therefore, these devices have of substances could be prepared and analyzed at low the potential to offer readily scalable solutions [5]. Al- volumes in order to replace manual processing and bulky though Illumina expanded their portfolio recently to in- benchtop equipment. Pioneering companies have argued clude microfluidic technologies, Fluidigm was founded to that the efficient consumption of reagents, high-through- market the integrated fluidic circuit (IFC) based on a put analyses, miniaturization of components, and the abil- pneumatic rubber valve developed in the laboratory of ity of microfluidic devices to be produced from low-cost Stephen Quake, then at Caltech [6]. With this technology, materials will reduce costs as compared to conventional Fluidigm became the first company to commercialize a benchtop equipment. Although there has been a lot of digital PCR in 2006, and it held its initial public offering promise in microfluidics, a limited number of products in 2011. have been delivered [2]. After purchasing a commercial To facilitate sample preparation further for next-gener- microfluidic device, end users may face difficulties in syn- ation sequencing, RainDance Technologies Inc. developed chronization with associated hardware, such as external a single-molecule picodroplet system for digital PCR. Each pumps and pneumatic fluid handling systems. Since addi- picodroplet is loaded with a uniform quantity of genomic tional training may also be necessary to operate the device, DNA and primers; therefore, this system enhances repro- many end users are not willing to change their convention- ducibility and enables the targeting of specific regions of al practices and instruments. As a result of these hurdles, the genome [7]. Another company with single molecule many end users are not willing to change their practices expertise is Sphere Fluidics Ltd., whose microfluidic sys- and prefer using conventional instruments. This complica- tem can perform high-throughput analyses of single cells to tion depreciates the value proposition of microfluidic produce their genetic, proteomic, and transcriptomic pro- devices and diminishes the incentive to use them in the files in picoliter volume droplets [8]. These picodroplets are laboratory or the field. There must be a significant opera- compatible with PCR machines and next-generation tional advantage or cost reduction in order to opt for a new sequencers and can also be used in applications such as microfluidic technology. This advantage has become ap- drug discovery and biomarker identification. parent in two key fields of biotechnology: genomics and point-of-care (POC) diagnostics. Point-of-care diagnostics A second area of biotechnology that has commercially benefited from microfluidic technologies is POC diagnos- Corresponding author: Yetisen, A.K. ([email protected]). tics. Large pharmaceutical companies have expanded their Keywords: commercialization; market entry; microfluidics; lab-on-a-chip. diagnostic platforms to include POC lab-on-a-chip devices. 0167-7799/ For example, Abbott Laboratories markets the i-STAT ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tib- system, a handheld device that integrates microfluidics tech.2014.04.010 and electrochemical detection to analyze blood chemistry. Trends in Biotechnology, July 2014, Vol. 32, No. 7 347 Science & Society Trends in Biotechnology July 2014, Vol. 32, No. 7 Table 1. Selected companies that have commercialized microfluidic technologies, their major products and applications Company name Major products Applications Founded/ Country acquired Roche Diagnostics Genome Sequencer FLX System, LightCycler Genotyping, microarray 1896 Switzerland Systems, Cedex HiRes analysis, cell analysis and US Advanced Liquid Logic, Inc. NeoPrep Library Prep System Next-generation 1998/2013 US (acquired by Illumina) sequencing i-STAT Corp. (acquired by i-STAT Systems POC diagnostics 1983/2004 US Abbott Laboratories) Agilent Technologies 2100 Bioanalyzer Human diseases, genomics 1999 US Danaher Corporation Original equipment manufacturer Manufacturing for life 1969 US sciences and diagnostics Caliper Life Sciences LabChip Systems Diagnostics, molecular testing 1995/2011 US (acquired by PerkinElmer) Life Technologies Corporation TaqMan Assays Genotyping, diagnostics, 1983/2013 US (acquired by Thermo Fisher) drug discovery Cepheid Xpert and GeneXpert Systems Diagnostics 1996 US Fluidigm Corporation BioMark HD System, C1 System, EP1 System Genotyping and sequencing 1999 US RainDance Technologies RainDrop System, Genotyping and 2004 US ThunderStorm System sequencing Claros Diagnostics Prostate-Specific Antigen (Total PSA) Test POC diagnostics 2005/2011 US (acquired by OPKO) 4KScore Prostate Cancer Test Gyros AB Gyrolab xP Workstation, Gyrolab Bioaffy CDs, Immunoassays, biomarker 2000 Sweden Gyrolab Mixing CD monitoring, drug analysis Micronit Microfluidics Microreactors, Micromixers, Droplet Manufacturing custom 1999 Netherlands Generators, Chip Electrophoresis microfluidic devices Dolomite Microfluidics Multiflux Manufacturing custom 2005 UK microfluidic devices Sphere Fluidics Ltd. Pico-Gen Picodroplet Formation Chips Human diseases, 2010 UK drug discovery, biomarker analyses i-STAT can quantify analytes such as electrolytes, metab- over lateral-flow assays [13]. DFA aims to deliver low-cost olites, and gases, while also having the capability to per- medical diagnostics, veterinary tests, and environmental form immunoassays [9]. Similarly, OPKO Inc. acquired monitoring devices to resource-poor countries. Although Claros Diagnostics Inc., a spinout from the laboratory of DFA serves a non-profit mission, they also generate reve- George Whitesides at Harvard, to complement its in vitro nue through licensing agreements to supplement funding diagnostics portfolio. Claros has developed a benchtop for further research and development. microfluidic analyzer that reads a credit-card-sized dispos- able cassette containing a blood sample and performs Overcoming challenges to commercialization multiple marketed tests for urology and infectious disease Major challenges in commercializing a product involve [10]. OPKO Health has used this technology in conjunction customer acceptance and market adoption. By specifically with its proprietary biomarkers, such as antibody-based focusing on market entry routes, many successful startups assays for the early diagnosis of Alzheimer’s or Parkinson’s have been able to use product development and customer diseases [11]. development methodology in parallel. In microfluidics, Rather than technical novelty, practical and marketable academic publications of proof-of-concept devices are abun- devices are needed to address major clinical problems, dant, but the diffusion of this technology to consumer particularly in the developing world. To bring high-perfor- products has been limited over the past two decades due mance diagnostic solutions to resource-limited settings, to the absence of customer development and validation of Daktari Diagnostics Inc. has utilized microfluidic technol- market need. Although microfluidics is a promising labo- ogy to integrate sample preparation and analysis within ratory tool, the technology is still seeking the best applica- one device. This device incorporates a microfluidic differ- tions. Because of the lack of a ‘killer application’ + + ential