Advances in Medical Diagnostics Using LoC and LoPCB Technologies

Figure 9: A three-layer PCB design that includes a microfluidic on one layer, implemented in a dry-film photoresist (Riston^TM), with integrated AgCl and gold electrochemical sensors ^[5].

This LoPCB proved to be very successful. The optical and electrochemical electrodes (sensors) provided data equal to those measured in laboratory test and in some cases, even more sensitivity—plus, there were no fluidic leaking.

Figure 11 shows the three layers of this cartridge before and after lamination. Also shown is the cartridge prepared to accept the medical fluids and human test sample. Other researchers on LoPCB have performed similar experiments and designed similar modules.

Figure 11: The three layers of the ELISA LoPCB cartridge before lamination, the finished PCB multilayer, and the LoPCB prepared for testing with biofluids and the human serum ^[1].

Figure 12 illustrates a portable microfluidic diluter with a variable and actively controlled dilution ratio suitable for PoC implementations. It is fabricated entirely using the developed LoPCB manufacturing technology by the same PCB manufacturers. A standard microfluidic network (Figure 12a) comprising two inlets and two outlets was designed and fabricated (Figure 12b, c, & e), where the resulting dilution ratio is thermally regulated using a power MOSFET as a heating element (Figure 12c) ^[6].

The manufacturing process has been developed to produce a three-layer printed circuit utilizing FR-4 laminate. The stackup utilizes a top, middle, and bottom layer. The top layer is silver plated, with the vias as pseudo reference electrodes, if pre-chlorinated. The middle layer is gold plated; thus, vias can be used as sensing electrodes since enzymes, antibodies, cells, and microorganisms can be immobilized onto the gold electrode surface, making them effective biosensors. The bottom layer serves as the microfluidic network, interconnecting the inlet and outlet vias of the PCB. The microchannels are formed in dry photoresist (Figure 13).

Figure 13: The PCB-based active control diluter stackup of the developed LoPCB; (a) exploded view; (b) cross-sectional view along the microfluidic channel ^[6].

Conclusion

As this technology evolves, more materials are introduced to see if the overall cost of these devices could be brought down. As seen in Table 1, paper was introduced as well as ceramics, polymers, and then PCBs. Today, 3D printing, printed electronics (PE), and various inkjet technologies are being investigated to make LoPCB cost less and more accurate for more applications.

In fact, during the month of March 2020, the U.S. Food and Drug Administration (FDA) issued emergency use authorization (EUA) to six firms to allow them to use their SARS-CoV-2 EUA test for the fastest available molecular point-of-care (PoC) test for the detection of COVID-19. These six firms are:

1. Roche Holding AG (March 13) ^[7]: The test uses Roche's fully automated Cobas 6800 and Cobas 8800 systems. With this authorization it will have millions of tests available each month for use on the two Cobas systems.
2. Thermo Fisher Scientific (March 14) ^[8]: The test can be run on and is optimized for use on the Applied Biosystems 7500 Fast Dx Real-Time PCR instrument. 150,000 test kits are available today, and TFS expects to ramp up to 5 million a month by April.
3. Hologic Laboratories (March 16) ^[9]: Tests run on the automated, high-throughput molecular diagnostic platform, the Panther Fusion, which can provide results in less than three hours and process up to 1,150 coronavirus tests in 24 hours.
4. Quidel (March 17) ^[10]: Noted that its Lyra product (Lyra SARS-CoV-2 assay for the detection of the coronavirus that causes COVID-19) line offers PCR reagent kits that can be used by laboratories equipped with molecular testing instrumentation, such as the Applied Biosystems 7500 Fast DX platforms from Thermo Fisher Scientific.
5. Laboratory Corporation of America (March 23) ^[11]: Can perform on-site serological and molecular tests for COVID-19, using Cepheid’s recently announced GeneXpert System “Xpress SARS-CoV-2 Molecular Test” for up to 20,000 tests per day.
6. Abbott Laboratories (March 27) ^[12]: The test runs on the m2000 RealTime Molecular System for centralized lab environments combined with ID NOW controller. It can provide positive results in five minutes and negative results in 13 minutes. Abbott is prepared to produce 50,000 test devices per day.

Other molecular PoC testing platforms from Agilent Technologies, Alere Toxicology, Acelis Health, and Sony Micronics may not be far behind.

References

1. D. Moschou, “The Challenges of Redesign for Lab-on-PCB,” AltiumLive Conference, Munich, Germany, October 2018
2. Agilent 2100 Bioanalyzer Product brochure.
3. D. Moschou, “Commercial PCB Technology Is Advancing Point-Of-Care Medical Diagnostics,” Electronics World, June 2019.
4. J. Pawan, J. Rainbow, A. Reqoutz, P. Estrela, & D. Moschou, “A PNA-based Lab-on-PCB diagnostic platform for rapid and high sensitivity DNA quantification,” Centre for Biosensors, Bioelectronics, and Biodevices, Department of Electronics and Electrical Engineering, University of Bath, U.K.
5. D. Moschou & A. Tserepi, “The Lab-on-PCB approach: Tackling the uTAS commercial upscaling bottleneck,” Journal of the Royal Society of Chemistry, Vol. 17, 2017, pp. 1,388–1,405.
6. N. Vasilakis, K.I. Papadimitriou, D. Evans, H. Morgan, & T. Prodromakis, “A Commercially Available Lab-on-PCB Technology for Affordable, Electronic-Based Point-of-Care Diagnostics,” Nanofabrication Centre, School of Electronics and Computer Science, University of Southampton, U.K.
7. Roche, “Roche’s cobas SARS-CoV-2 Test to detect novel coronavirus receives FDA Emergency Use Authorization and is available in markets accepting the CE mark,” March 13, 2020.
8. 360DX, “Thermo Fisher Coronavirus Test Gets FDA Emergency Use Authorization,” March 14, 2020.
9. 360X, “FDA Grants Emergency Use Authorization for Coronavirus Assays From Hologic, LabCorp,” March 16, 2020.
10. Genomeweb, “Quidel Nabs FDA Emergency Use Authorization for Coronavirus Assay,” March 17, 2020.
11. Laboratory Corporation of America, “LabCorp Developing Options to Prioritize COVID-19 Testing for Inpatient Population in Support of Guidance from the White House Coronavirus Task Force,” March 23, 2020.
12. Abbott, “Detect COVID-19 in as Little as 5 Minutes,” March 27, 2020.

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