Microfluidics: Potential to Drive the Next Generation of Diagnostics Devices

Author: Caitlin Ho

With the ever-growing demand of cost-friendly, easy-to-use and effective diagnostics test for point of care (POC); microfluidic technology is an attractive road for paving the way to producing a large variety of diagnostic applications, using microfluidic fabrication technology to miniaturise laboratory workflows into lab-on-chip (LOC) or a credit card sized format.

A microfluidic LOC is a pattern of microchannels comprised of various components that can be engineered into a small, low-cost diagnostics tests with high throughput, clinically accepted results. Additional benefits of investing into microfluidic LOC include: faster reaction time (15-20 minutes); enhanced analytical sensitivity and temperature control; required reagent volume are significantly lower; and minimal operator handling through integration of laboratory routines. Opening a gateway of opportunities, microfluidic LOC have remarkable potential to greatly impact the quality of medical care, worldwide. (1)

Here are some descriptions of current activities of applications for microfluidic diagnostics devices.

Cancer
With over 200 different known forms of cancer, an estimated 19.3 million new cases, and almost 10 million cancer-related deaths worldwide in 2020: the call for diagnostic tests that produce fast accurate results in the early stages of cancer is in high demand. (2) Early detection and diagnosis offers better outcomes for cancer treatment.
Currently, microfluidics is mainly being used to detect genetic mutations, including DNA and miRNA mutations, that correspond to breast cancer. Due to the short time required for each test and the high throughput results, it allows for more sample volumes to be analysed in comparison to the traditional methods, in a shorter amount of time. A lot of research into utilising microfluidics in the early detection of cancer via identification of specific biomarkers, such as circulating tumour DNA, microRNAs, protein and serum vesicles has been done. Additionally, research into combining microfluidics with nanoparticles to measure specific biomarkers, more specifically in breast and prostate cancer. (3)

Infectious Disease
Rapid detection of pathogens is critical in early stages of treatment of diseases to help provide timely treatment. The potential for microfluidic-based point of care tests to be user-friendly, fast and effective diagnostics tools, both in the clinic and at home, could help with identifying and controlling the spread of highly infectious diseases. (4)
There are some commercial microfluidic chips (mChip) currently available on the market. Key benefits of using microfluidics for the diagnostics of infectious diseases are that the devices can be miniaturised, and the sample preparations can be incorporated onto the mChip: allowing the device to be used at point of care, especially in areas where expensive diagnostic tests are not as readily available. (5)
One example integrates thermoplastic material, nasopharyngeal swabs and aspirates in the patient to amplify the influenza A virus, see figure 1.

Figure 1: Microfluidic assay flow
A sample from the swab is loaded into the device and stripped of the target materials; then, on-chip cell lysis is performed by the chip. A series of purification, reverse transcription and polymerase chain reactions follow within the device and a reader is then able to determine the final output. (6)

Cardiovascular Diseases (CVDs)

CVDs are the leading cause of death followed by cancer worldwide, estimated to 17.9 million lives lost each year. Current conventional methods for CVD biomarker detection are expensive, involve complicated laboratory procedures and take time to get results (at least a few hours compared to the ~15 minutes taken by a LOC). Additionally, some CVD markers, such as troponin, are notoriously difficult to test due to the fact that only low levels are present in blood, especially in early detection of heart tissue damage. (7) Earlier detection is crucial in preventing mortality due to CVD.
Microfluidics have also been used in cardiovascular drug discovery: through simulating the in vitro environment of vascular models and heart models via microfluidic-based cardiovascular-mimetic organs-on-a-chip. This technology offers great potential in investigating therapeutic mechanisms of drugs and better efficacy for new drug discovery though high-throughput compound screening. (8)

Autoimmune Disease
It is estimated around 4% of the world’s population is affected by autoimmune disease. This number is expected to continue to rise and the need for better, more accurate diagnostics test, especially at POC, is crucial for effective healthcare.
In autoimmune diseases, our body mistakes our body cells and tissue as foreign materials and attack. Autoantibodies are immune cells which cannot distinguish between ‘self’ and ‘non-self’. This can lead to diseases, such as rheumatoid arthritis and lupus, and can affect connective tissues, such as the skin, joints, and blood vessels. Like other diseases, early detection is key for reducing mortality and microfluidic technology is promising in delivering POC devices that can detect autoantibodies, such as rheumatoid factor (RF) found frequently in rheumatoid arthritis, and anti-nuclear antibodies (ANAs) in systemic lupus erythematosus.
Microfluidics has been widely used in single cell analysis of autoimmunity by facilitating the identification of several novel functional immune cell types, quantifying signalling molecules and helping to understand cellular communications and signalling pathways. Microfluidics has been key in developing novel therapies, drug and toxicity screening through aiding in the creation of in vitro cellular microenvironmental models, and POC diagnostics. (9)

As discussed above, microfluidics has huge potential to change the game in POC diagnostics testing. Although not all applications have been covered above, a lot of interest and research has been inputted in utilising microfluidics to its full potential in driving the next generation of POC diagnostics. (10)

Here at Integrated Graphene, we work closely with industry leaders to develop LOC systems from concept to commercialisation. Our engineers utilise their microfluidic expertise to support development from sample-in to readout, always with design for manufacture at the core of what we do. 

If you want to take lead in the next generation of diagnostics, contact us today.

References:

1. Del Rio JA, Ferrer I. Potential of Microfluidics and Lab-on-Chip Platforms to Improve Understanding of "prion-like" Protein Assembly and Behavior. Front Bioeng Biotechnol. 2020;8:570692. Published 2020 Sep 8. doi:10.3389/fbioe.2020.570692

2. Sung, H, Ferlay, J, Siegel, RL, Laversanne, M, Soerjomataram, I, Jemal, A, Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021: 71: 209- 249. https://doi.org/10.3322/caac.21660

3. Zhang Z, Nagrath S. Microfluidics and cancer: are we there yet?. Biomed Microdevices. 2013;15(4):595-609. doi:10.1007/s10544-012-9734-8

4. Chin, C., Laksanasopin, T., Cheung, Y. et al. Microfluidics-based diagnostics of infectious diseases in the developing world. Nat Med 17, 1015–1019 (2011). https://doi.org/10.1038/nm.2408

5. Nasseri B, Soleimani N, Rabiee N, Kalbasi A, Karimi M, Hamblin MR. Point-of-care microfluidic devices for pathogen detection. Biosens Bioelectron. 2018;117:112-128. doi:10.1016/j.bios.2018.05.050

6. Cao Q, Fan A, Klapperich C. Microfluidic chip fabrication and method to detect influenza. J Vis Exp. 2013;(73):50325. Published 2013 Mar 26. doi:10.3791/50325

7. Hoff J, Wehner W, Nambi V. Troponin in Cardiovascular Disease Prevention: Updates and Future Direction. Curr Atheroscler Rep. 2016 Mar;18(3):12. doi: 10.1007/s11883-016-0566-5. PMID: 26879078.

8. Ma, Q., Ma, H., Xu, F. et al. Microfluidics in cardiovascular disease research: state of the art and future outlook. Microsyst Nanoeng 7, 19 (2021). https://doi.org/10.1038/s41378-021-00245-2

9. Jammes, F.C., Maerkl, S.J. How single-cell immunology is benefiting from microfluidic technologies. Microsyst Nanoeng 6, 45 (2020). https://doi.org/10.1038/s41378-020-0140-8

10. Sachdeva S, Davis RW and Saha AK (2021) Microfluidic Point-of-Care Testing: Commercial Landscape and Future Directions. Front. Bioeng. Biotechnol. 8:602659. doi: 10.3389/fbioe.2020.602659