Comprehensive Manufacturing of Microfluidic Diagnostic Devices
Author: Christopher Coyne
Historically, the use of microfluidic devices has been confined to the laboratory, in which they have particularly been employed for drug discovery applications or DNA analysis. However, with the advent of more-cost-effective manufacturing techniques, microfluidic devices are being increasingly used as portable diagnostic tools to test blood samples for such electrolytes as sodium and potassium and to create arrays for measuring hematocrit/hemoglobin, blood gases, coagulation, drug screening, and cardiac markers.
Portable microfluidic devices are at the forefront of point-of-care and in-the-field testing applications that allow patients with chronic medical conditions to monitor themselves at home. These innovative devices also enable doctors to test patients and receive immediate results, accelerating the diagnostic process by eliminating the need to use outside labs.
By 2016, the market for microfluidic devices is projected to grow 24% annually to approximately $4 billion. Hence, OEM manufacturers that are interested in producing single-use, disposable, or point-of-care devices must shift from low-volume techniques, such as photolithography on specialized glass, to higher-volume production using commercially available materials.
To produce microfluidic devices, particularly those at lower price points, manufacturers must combine optimized fabrication techniques with medical-grade materials using an automated process. However, for OEMs hoping to bring new products to market for emerging microfluidic applications, developing optimized fabrication techniques could represent a large hurdle, especially if they cannot invest in R&D, engineering teams, or the capital equipment necessary to develop these processes from scratch.
In order to overcome this hurdle, OEMs often turn to medical device contract manufacturers such as Rochester, NY–based Fabrico Medical, which can provide converted materials and advanced assembly for the design to manufacture of high-quality, low-cost microfluidic devices.
Building microfluidic devices and other diagnostic disposables requires that medical device manufacturers employ a repeatable process that can create precise micrometer-size channels with high-tolerance accuracy and without substrate deformation. In addition, they must ensure that their devices meet specified performance characteristics, such as precise flow rates for nanoliter quantities of fluid.
Traditionally, creating microfluidic devices required the use of photolithography; glass etching; specialized molds, castings, and tools; heat curing; and other time-consuming processes. Many of these techniques are challenging to scale to commercial volume or are too costly for producing inexpensive, disposable microfluidic devices.
To manufacture today’s single-use microfluidic devices, the clear choice is laser ablation used alone or in combination with high-speed rotary processes. Advanced laser systems can cut extremely small features and intricate designs in a range of flexible materials. Precision laser cutting can also produce through holes, slots, and diameters that can be significantly smaller and exhibit tighter tolerances than features generated using other converting processes.
Low- to high-wattage CO2 laser cutting machines incorporating computerized control and xy motion systems provide cutting accuracy and repeatability, enabling them to create small and intricate features. For example, most such systems can achieve the following specifications:
• Laser-cut feature tolerances as small as 100 µm
• Fixed-beam etchings focused down to 70 µm
• Position feature tolerances as low as 50 µm
• Microfluidic channels as narrow as 125 µm, positioned within a tolerance of 50 µm
Laser systems can also precisely cut the top layer of a lamination, etching it to expose the layer underneath. Fine control of cut depth allows such systems to create shallow or deep channels and wells, depending on the treatment or the device requirements.
Manufacturing such precision devices should be performed in a quality-controlled environment in which they can be produced, assembled, and packaged without contamination. While sterility may not always be required, a cleanroom environment with HEPA air filtration and tightly controlled environmental conditions—including humidity, temperature, and pressure—ensures a better end product.
The use of laser technology to manufacture microfluidic devices is highly dependent on the type of material chosen for the application. The material must generally feature a high refractive index to achieve smaller feature sizes, be able to absorb laser wavelengths, and exhibit high viscosity to achieve quality manufacturing.1
Usually manufactured from polymers, glass, and silicon, and occasionally from metals and ceramics, microfluidic devices are often constructed from multiple layers of material bonded using nonmigratory, inert adhesives that can aid in the lateral flow of fluids. All of these materials can be used to create nanoscale features, but the speed of the manufacturing process is directly proportional to the processing efficiency or how the material is converted.
Many manufacturers prefer using polymers for point-of-care devices because of their biocompatibility, good performance, lower cost, and simpler manufacturability. Preferred polymer types include silicones, transparent thermoplastics, polystyrene, polycarbonate, polyacrylate, polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), and cyclic olefin copolymer (COC).2,3
The selection of the correct, biocompatible material is highly dependent on the application. For example, if a biological reaction in the device must be observed visually, the material must have high optical transparency.4
Coupled with biocompatibility is adherence to ISO 10993, which FDA considers to be the guide for manufacturers of sterile and nonsterile microfluidic devices. According to FDA, “Medical devices with sub-micron components may require specialized techniques for characterization and biocompatibility tests.”5 Devices made from materials that have been well characterized chemically and physically and that have a long history of safe use may not necessarily have to undergo all of the FDA-mandated tests.
Because choosing the right fabrication techniques and selecting the appropriate materials is a difficult balancing act, some medical device manufacturers may be reluctant to put these decisions into the hands of multiple outside vendors. For this very reason, OEM manufacturers should partner with full-service suppliers that have R&D, design, and process engineering staffs that can work closely with customers to meet all of their performance and design-to-manufacture objectives.
Manufacturers of point-of-care and disposable microfluidic devices must consider different factors than companies that create low-volume, high-cost devices. The pressures inherent in reducing the cost per device must not diminish quality or device performance. Instead, manufacturers should look to contract manufacturers that can provide material selection expertise and advanced assembly capabilities. By tightly coupling these skills, manufacturers can accelerate time-to-market for innovative devices that improve patient health and lower the overall cost of medical services.
1. Shiguang Li et al., “Review of Production of Microfluidic Devices: Material, Manufacturing, and Metrology,” MEMS, MOEMS, and Micromachining III: Proceedings of SPIE 6993 (2008); available from Internet: holylab.wustl.edu/~zxu/Review of production of microfluidic devices_published version.pdf.
2. Shiguang Li et al., “Microfluidic Devices.”
3. Ahmed Alrifaiy et al., “Polymer-Based Microfluidic Devices for Pharmacy, Biology, and Tissue Engineering,”Polymers 4, no. 3 (2012): 1349–1398; available from Internet: www.mdpi.com/2073-4360/4/3/1349
4. Shiguang Li et al., “Microfluidic Devices.”
5. Draft Guidance for Industry and Food and Drug Administration Staff, “Use of International Standard ISO-10993, ‘Biological Evaluation of Medical Devices Part 1: Evaluation and Testing,’ Draft Guidance for Industry and Food and Drug Administration Staff” (Rockville, MD: U.S. Food and Drug Administration, 2013).
About the Author:
Christopher Coyne is the medical market sales and business development manager at Rochester, NY–based Fabrico Medical. He has more than 10 years of experience in the fields of medical device, soft-tissue repair, pharmaceutical, and drug-delivery manufacturing. Before joining the company, he was a business development, sales, and marketing executive at such companies as Adhesives Research, Tapemark, and Nonin Medical. He also served in product management roles at Coloplast Corp. and EISAI Corp., both of which are involved in the implantable medical device market. Coyne received BA and MBA degrees from the University of St. Thomas in Minneapolis
Source from: Medical Device and Diagnostic Industry
Leave a comment