Commercialization of microfluidic devices

Lisa R. Volpatti1 and Ali K. Yetisen2

1 Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK2 Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QT, UK

Science & Society

Microfluidic devices offer automation and high-through-put screening, and operate at low volumes of consum-ables. Although microfluidics has the potential to reduceturnaround times and costs for analytical devices, par-ticularly in medical, veterinary, and environmentalsciences, this enabling technology has had limited diffu-sion into consumer products. This article analyzes themicrofluidics market, identifies issues, and highlightssuccessful commercialization strategies. Addressingniche markets and establishing compatibility with exist-ing workflows will accelerate market penetration.

Microfluidics is an enabling platform technology thatallows automation and multiplexing of laboratory equip-ment, drug screening technologies, and in vitro diagnosticdevices [1]. Over the past two decades, several ventureshave emerged to commercialize microfluidic technologies.Initially, these devices were envisioned to be used inbiological analyses and chemical syntheses so that a rangeof substances could be prepared and analyzed at lowvolumes in order to replace manual processing and bulkybenchtop equipment. Pioneering companies have arguedthat the efficient consumption of reagents, high-through-put analyses, miniaturization of components, and the abil-ity of microfluidic devices to be produced from low-costmaterials will reduce costs as compared to conventionalbenchtop equipment. Although there has been a lot ofpromise in microfluidics, a limited number of productshave been delivered [2]. After purchasing a commercialmicrofluidic device, end users may face difficulties in syn-chronization with associated hardware, such as externalpumps and pneumatic fluid handling systems. Since addi-tional training may also be necessary to operate the device,many end users are not willing to change their convention-al practices and instruments. As a result of these hurdles,many end users are not willing to change their practicesand prefer using conventional instruments. This complica-tion depreciates the value proposition of microfluidicdevices and diminishes the incentive to use them in thelaboratory or the field. There must be a significant opera-tional advantage or cost reduction in order to opt for a newmicrofluidic technology. This advantage has become ap-parent in two key fields of biotechnology: genomics andpoint-of-care (POC) diagnostics.

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Corresponding author: Yetisen, A.K. (ay283@cam.ac.uk).Keywords: commercialization; market entry; microfluidics; lab-on-a-chip.

The marketIn 2013, the microfluidics market was valued at $1.6 billion[3]. With an expected compound annual growth rate(CAGR) of 18–29%, the market is projected to reach$3.6–5.7 billion by 2018 [3,4]. This high growth rate islargely due to recent advances in biotechnology, includinggene sequencing and in vitro diagnostics (Table 1).

Gene sequencing

With the completion of the human genome project in 2003and the advent of next-generation sequencing, microfluidictechnology has been used to increase automation anddecrease turnaround times in genomics. Key companiesin the field of microfluidic genotyping include Illumina Inc.and Fluidigm Corp. In 2013, Illumina acquired AdvancedLiquid Logic Inc. to gain access to their digital microflui-dics platform. Their electrowetting technology manipu-lates discrete droplets in a microfluidic device withoutpumps, valves, or channels; therefore, these devices havethe potential to offer readily scalable solutions [5]. Al-though Illumina expanded their portfolio recently to in-clude microfluidic technologies, Fluidigm was founded tomarket the integrated fluidic circuit (IFC) based on apneumatic rubber valve developed in the laboratory ofStephen Quake, then at Caltech [6]. With this technology,Fluidigm became the first company to commercialize adigital PCR in 2006, and it held its initial public offeringin 2011.

To facilitate sample preparation further for next-gener-ation sequencing, RainDance Technologies Inc. developeda single-molecule picodroplet system for digital PCR. Eachpicodroplet is loaded with a uniform quantity of genomicDNA and primers; therefore, this system enhances repro-ducibility and enables the targeting of specific regions ofthe genome [7]. Another company with single moleculeexpertise is Sphere Fluidics Ltd., whose microfluidic sys-tem can perform high-throughput analyses of single cells toproduce their genetic, proteomic, and transcriptomic pro-files in picoliter volume droplets [8]. These picodroplets arecompatible with PCR machines and next-generationsequencers and can also be used in applications such asdrug discovery and biomarker identification.

Point-of-care diagnostics

A second area of biotechnology that has commerciallybenefited from microfluidic technologies is POC diagnos-tics. Large pharmaceutical companies have expanded theirdiagnostic platforms to include POC lab-on-a-chip devices.For example, Abbott Laboratories markets the i-STATsystem, a handheld device that integrates microfluidicsand electrochemical detection to analyze blood chemistry.

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Table 1. Selected companies that have commercialized microfluidic technologies, their major products and applications

Company name Major products Applications Founded/

acquired

Country

Roche Diagnostics Genome Sequencer FLX System, LightCycler

Systems, Cedex HiRes

Genotyping, microarray

analysis, cell analysis

1896 Switzerland

and US

Advanced Liquid Logic, Inc.

(acquired by Illumina)

NeoPrep Library Prep System Next-generation

sequencing

1998/2013 US

i-STAT Corp. (acquired by

Abbott Laboratories)

i-STAT Systems POC diagnostics 1983/2004 US

Agilent Technologies 2100 Bioanalyzer Human diseases, genomics 1999 US

Danaher Corporation Original equipment manufacturer Manufacturing for life

sciences and diagnostics

1969 US

Caliper Life Sciences

(acquired by PerkinElmer)

LabChip Systems Diagnostics, molecular testing 1995/2011 US

Life Technologies Corporation

(acquired by Thermo Fisher)

TaqMan Assays Genotyping, diagnostics,

drug discovery

1983/2013 US

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,

ThunderStorm System

Genotyping and

sequencing

2004 US

Claros Diagnostics

(acquired by OPKO)

Prostate-Specific Antigen (Total PSA) Test

4KScore Prostate Cancer Test

POC diagnostics 2005/2011 US

Gyros AB Gyrolab xP Workstation, Gyrolab Bioaffy CDs,

Gyrolab Mixing CD

Immunoassays, biomarker

monitoring, drug analysis

2000 Sweden

Micronit Microfluidics Microreactors, Micromixers, Droplet

Generators, Chip Electrophoresis

Manufacturing custom

microfluidic devices

1999 Netherlands

Dolomite Microfluidics Multiflux Manufacturing custom

microfluidic devices

2005 UK

Sphere Fluidics Ltd. Pico-Gen Picodroplet Formation Chips Human diseases,

drug discovery,

biomarker analyses

2010 UK

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i-STAT can quantify analytes such as electrolytes, metab-olites, and gases, while also having the capability to per-form immunoassays [9]. Similarly, OPKO Inc. acquiredClaros Diagnostics Inc., a spinout from the laboratory ofGeorge Whitesides at Harvard, to complement its in vitrodiagnostics portfolio. Claros has developed a benchtopmicrofluidic analyzer that reads a credit-card-sized dispos-able cassette containing a blood sample and performsmultiple marketed tests for urology and infectious disease[10]. OPKO Health has used this technology in conjunctionwith its proprietary biomarkers, such as antibody-basedassays for the early diagnosis of Alzheimer’s or Parkinson’sdiseases [11].

Rather than technical novelty, practical and marketabledevices are needed to address major clinical problems,particularly in the developing world. To bring high-perfor-mance diagnostic solutions to resource-limited settings,Daktari Diagnostics Inc. has utilized microfluidic technol-ogy to integrate sample preparation and analysis withinone device. This device incorporates a microfluidic differ-ential counter, which is able to quantify CD4+ or CD8+

immune cells in a blood specimen [12]. With an accuracycomparable to conventional flow cytometry, this device hasthe potential to reduce costs in the diagnosis of HIV.Another company that has positioned itself for the devel-oping world markets is Diagnostics for All (DFA). Theirpaper-based microfluidic devices utilize capillary forces todirect the movement of fluidics and enables multiplexedassays with built-in capabilities, which is an improvement

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over lateral-flow assays [13]. DFA aims to deliver low-costmedical diagnostics, veterinary tests, and environmentalmonitoring devices to resource-poor countries. AlthoughDFA serves a non-profit mission, they also generate reve-nue through licensing agreements to supplement fundingfor further research and development.

Overcoming challenges to commercializationMajor challenges in commercializing a product involvecustomer acceptance and market adoption. By specificallyfocusing on market entry routes, many successful startupshave been able to use product development and customerdevelopment methodology in parallel. In microfluidics,academic publications of proof-of-concept devices are abun-dant, but the diffusion of this technology to consumerproducts has been limited over the past two decades dueto the absence of customer development and validation ofmarket need. Although microfluidics is a promising labo-ratory tool, the technology is still seeking the best applica-tions. Because of the lack of a ‘killer application’(revenues > $100 million) in microfluidics, many investorshave opted for other emerging technologies with well-defined market routes [14]. Typically, the venture capitalindustry expects a return on investment of 5–10 times formicrofluidic technologies. Furthermore, funding agenciesare increasingly interested in a tangible return on theirinvestments. It is in this competitive context that research-ers may choose to shift their focus from innovative demon-strations to marketable products to maintain current

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levels of funding. In order to surmount the barriers tocommercialization, innovators of microfluidic devices needto focus on two areas that currently lack sufficient atten-tion: standardization and integration.

Standardization

Academics in microfluidic research often fail to cite repro-ducibility statistics and quantify chip-to-chip (batch-to-batch) variability within a given prototyping or fabricationmethod. As a result of this lack of standardization acrossthe field, novel microfluidic assays for a specific applica-tion, including the protocols, equipment and materials areoften not compatible with existing technologies in themarket. For example, poly(dimethylsiloxane) (PDMS) isthe dominant material of choice for use in fabricatingmicrofluidic devices in the laboratory [15]. However, mostcompanies in the microfluidic sector with the exception ofFluidigm refrain from using PDMS due to issues withscaling up and manufacturability. PDMS is a relativelyhigh-cost material in comparison to industry-standardcost-effective polymers such as poly (methyl methacrylate)(PMMA) and polycarbonate. These accessible materialshave established high-throughput manufacturing andshaping methods such as injection molding, rolling,embossing, laser-induced cutting and computer numericalcontrol (CNC) milling. However, most microfluidic capa-bilities (e.g., displacement valves and pumps) achievedwith highly elastic polymers such as PDMS are not readilytransferable to other cost-effective rigid polymers [16].Therefore, research efforts either need to focus on thescalable manufacture of PDMS-based devices or the fabri-cation of microfluidic devices from other ideally low-costpolymers.

Integration

Past research has focused on the invention of individuallab-on-a-chip (LOC) components, leaving the integrationof these components as an afterthought. However, issueswith standardization preclude the possibility of easilystitching together these innovative components to formfunctional, fully integrated devices. In order to realizethe potential of LOC devices, researchers must considerthe final commercial application from the early designstages and ensure that each component is mutuallycompatible. For example, many devices require pumpsor a voltage supply to operate the device and specificcomputer software that the user must learn to analyzeand interpret the results. Furthermore, many biologicalassays require sample pretreatment. If sample prepara-tion is the rate-limiting step and must be done off-chip,then customers would be unlikely to use the device.Therefore, successful performance of technically complexanalyses on-chip requires the procedures to be run si-multaneously, seamlessly moving from one step to thenext. Moreover, the integrated product should be self-contained, ideally not requiring prior sample treatment,preparation, or amplification. It should be fully automat-ed to reduce errors and facilitate use for operators with-out microfluidics expertise. The results should be clearlydisplayed to minimize the need for subjective user inter-pretation.

Concluding remarks and future perspectivesTo aid in the development of microfluidics as a widespreadtechnology, industrial maturation should be synchronizedwith academic efforts. Industrial partners with marketingexpertise should take an active role in discussing thepotential for a product to succeed in a given market andproviding feedback on end-user requirements and expec-tations. Academic researchers, in turn, may focus on deliv-ering a fully integrated product with a specific application.Such an effort will also require striking a balance betweenacademic publishing, consulting to commercial partners,and pursuing patent protection to increase social impact[17].

To market the technology at scale, the microfluidicproduct must far surpass the existing technology in per-formance and capability or offer the results at a signifi-cantly lower cost. Many current microfluidic devices,however, only provide incremental improvements overexisting technologies and do not offer solutions to problemsthat are otherwise insoluble. The microfluidic communityshould, therefore, move forward with the current pressingneeds where microfluidics is the only solution to overcomea challenge. This requires developers to embrace micro-fluidic technologies as a component of a large commercialtechnology that is compatible with existing workflows.Rather than waiting for a killer application, targetingre-segmented niche markets, where existing technologiesdo not address specific customer needs, will reduce marketentry barriers and facilitate the commercialization ofmicrofluidic technologies. The combination of developingtechnologies to solve practical problems that can be pro-duced at scale and easily integrated into any laboratorywill thus allow microfluidics to reach its full commercialpotential.

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