When people go through surgeries in a hospital, they undergo coagulation testing to see whether their blood clotting will be normal during the operation. The testing is so standardized that the procedure has become an insignificant component among other testings in hospitals. These tests are defined by the U.S. Food and Drug Administration (FDA) as in-vitro diagnostics. In-vitro diagnostics are done on samples such as blood or tissue that have been taken from the human body (FDA 2021). The devices that can carry these diagnostics vary, but they can be categorized based on sample usage. In the past, most of these diagnostics, such as coagulation testing, were done through a larger centrifugal device. This device has the capacity for hundreds of samples and typically takes more than thirty minutes to complete. The design reflects IVD’s high-end market as large hospitals treat thousands of patients and administer hundreds of daily operations. However, the emergence of centrifugal microfluidic chips, or Lab-on-a-Chip devices, can revolutionize the industry.

Microfluidic lab-on-a-chip (LOAC) devices are miniaturized devices that perform analysis done in a lab. Such analysis techniques include biomedical diagnostics, DNA analysis, or, the aforementioned coagulation testing. Scientists take a biomedical lab and the diagnostic equipment that would be there and shrink it down into a tiny chip that can process and measure as a full-sized lab would (Rollins 2021). The technology, in theory, has been in development since the late 1980s. However, only recently have we seen a significant improvement in cost efficiency, speed, and, most importantly, sensitivity and consistency of biochemical detection in LOACs. Researchers have indicated that the device can also reduce human error with automated tech, allowing more controlled testing and minimal fluid samples. So, what is the technology that facilitated this advancement?

LOAC devices may vary in their structural design, but it is the sub-group of centrifugal microfluidic disks that makes history. Similar to large centrifugal machines, the tiny chip follows the practice of using centrifugal force to separate the blood sample into plasma and blood cells. More vividly, the device functions as a DVD player, and the microfluidic disk rotates to complete the separation. The brilliant application of a microfluidic chip into a disk-shaped design takes advantage of the rotational force and completes a diagnosis without the assistance of an operator. Also, compared to other LOAC structures, disks are easy to replace, like disposable DVDs. Jens Ducrée, a leading German scholar in microfluidic systems, has published extensive research in microfluidic technology. Ducrée has argued that the centrifugal approach offers a unique way to integrate liquid handling for sample preparation and subsequent detection. The integration on a single substrate eliminates the need for an off-chip liquid handled by costly and error-prone pipetting robotics (Ducrée 2007). The introduction of microfluidic centrifugal disks in the commercial world is because of the advances in microchip manufacturing.

Looking deeper into the chips, every cell in the disk has a set of chambers allowing different sediments and gas to mix with the blood sample. The disk rotates at different speeds during the diagnostic, and the centrifugal force opens and closes vessels with air pumps. In the end, the blood is separated into blood cells and plasma. The sample will reach the outer ring of the disk, and the mixture of the blood cells with chemicals would produce the desired test results. Its brilliance is the use of making microfluidic chips into a lower-cost device. MDPI’s review elaborated on the multi-application of this “biomedical centrifugal microfluidic platform” in many areas of IVD such as nucleic acid analysis, Polymerase Chain Reaction (PCR), DNA hybridization, and more (Tang, Minghui, Guanghui Wang, Siu-Kai Kong, and Ho-Pui Ho 2016). The potential application throughout the IVD industry and its high-efficiency design make microfluidic chips one of the revolutionary technologies in this century.

The technology is promising, but there are still challenges ahead, mainly in its commercialization process. One of the biggest challenges with lab-on-a-chip devices is that they are generally fabricated in clean rooms, a lab that's free from dust and other contaminants. Ensuring the appropriate level of cleanliness can take up to three or four days. This causes production and distribution to the market to become expensive, slow, and difficult (Rollins 2021). An interdisciplinary team of researchers at Brigham Young University, led by BYU engineering professor Greg Nordin, has researched microfluidic chips. Nordin and his team have encountered an obstacle when mass printing these devices. As industry specialists comment, the commercial 3D printers are not advanced enough to make the microchannels and minuscule tech for the chip. Because of this, Nordin and his team of researchers say they have built their own 3D printers for around $100,000 each. These special printers have allowed the fabrication of the smallest lab-on-a-chip devices. This LOAC is made out of a type of plastic created by photo-polymerized liquid turned into a high-resistant, solid material layer by layer in a matter of five to seven minutes without the multimillion-dollar expense of setting up and using a cleanroom. After the initial cost of building the printer, the low cost of development would mean that these devices could be produced at a low cost, improving availability to underserved communities.

With Nordin’s new printing technology for microfluidic chips, the IVD industry could face an upcoming opportunity to expand diagnostic coverages to smaller-scale hospitals, local clinics, and pet hospitals. The overall IVD industry has two dimensions: the type of diagnostic and the sample usage at the end market. In-vitro testing has a range of diagnostic methods, such as clinical chemistry, immunochemistry, hematology, coagulation and hemostasis, microbiology, and molecular diagnostics (Furion analytics Research & Consulting 2021). Alternatively, the other factor is the end market daily sample usage. Although the sample usage of individual clinics varies depending on the type of diagnostic, the general top-to-bottom order is from the larger state/regional hospitals with laboratories to smaller local hospitals to clinics to patient self-testing, and finally, pet hospitals. In the case of coagulation testing, the central cluster of demand for coagulation testing devices is in large hospitals with daily surgeries. The large diagnostic devices could administer over a hundred samplings through each round of testing. Because of the large sample scale and the high correlation between coagulation testing and surgery, more than two thirds of the coagulation diagnostic market are in these large hospitals. Consequently, the introduction of microfluidic chips could fulfill the vacuum of lower end markets. The low cost, similar diagnostic sensitivity, and small sample scale are attractive to smaller hospitals with lower budget and lower patient volumes. 

Another reason to look forward to the application of microfluidic devices is their small size allows for easier handling and could be administered by a nurse, not to mention easy to distribute. It also makes developing different technologies and functions within the chip easier because prototypes are cheaper and easier to build, and each chip will be able to perform multiple tests and serve multiple functions.

The supply chain crisis attracted attention to the shortage of chips in smartphones and vehicles, but semiconductors in electronic devices should not be the only chip people talk about. Microfluidic chips have progressed in recent decades. With the recent breakthrough of printing technology, microfluidic chips can revolutionize the in-vitro diagnostic industry in healthcare. The miniaturization of lab testing would lower costs and increase diagnostic coverage to communities that otherwise would not be able to afford the larger and more expensive preceding devices. While the challenge of commercialization remains, developers and entrepreneurs already have the technology and available testing resources to bring microfluidic devices into the market. Whether investment in this field is worthwhile is still unclear. Further research on the potential market size for microfluidic devices is needed to complete the analysis. But microfluidic technology and lab-on-a-chip devices have advanced dramatically in the past five years. Such breakthroughs would change the landscape of in-vitro diagnostics allowing greater exposure to diagnostics in the future.

References

Center for Devices and Radiological Health. 2021. “In Vitro Diagnostics.” U.S. Food and Drug Administration. https://www.fda.gov/medical-devices/products-and-medical-procedures/in-vitro-diagnostics 

Rollins, Jenny. 2021. “Could BYU-Developed Lab-on-a-Chip Devices Help Save Lives?” KSL.com. October 3, 2021. https://www.ksl.com/article/50251870/could-byu-developed-lab-on-a-chip-devices-help-save-lives. 

Tang, Minghui, Guanghui Wang, Siu-Kai Kong, and Ho-Pui Ho. 2016. “A Review of Biomedical Centrifugal Microfluidic Platforms.” Micromachines 7, no. 2 (2016): 26. https://doi.org/10.3390/mi7020026.  

Ducrée, Jens, Stefan Haeberle, Sascha Lutz, Sarah Pausch, Felix von Stetten, and Roland Zengerle. 2007. “The Centrifugal Microfluidic Bio-Disk Platform.” Journal of Micromechanics and Microengineering 17, no. 7 (2007). https://doi.org/10.1088/0960-1317/17/7/s07.  

Furion Analytics Research & Consulting. 2021. “Cancer IVD Market Share, Size and Industry Growth Analysis 2021-2026.” IndustryARC. https://www.industryarc.com/Research/Cancer-IVD-Market-Research-507107.