Advances in Medical Diagnostics Using LoC and LoPCB Technologies

Estimated reading time: 14 minutes

LoC Materials

Over the years, several materials have been developed for use with LoC. It started in the late 1990s with silicon, as the microelectronics industry developed various methods of micromachining silicon (MEMS) for accelerometers for airbag sensors. From silicon wafers, the materials branched out to glass and then polymers. The most recent interest has been in PCBs and the use of various paper materials.

Silicon and glass have several advantages for fabricating an LoC, while being the most expensive. Polymers and especially PCBs are a new choice because of various materials available and the integration of electronics and various printing technologies. While paper is coming into focus for research, its use is only just beginning. Table 1 lists several characteristics of each of these materials.

Table 1: Base materials for LoC formations.

1. Silicon-based

Silicon started the LoC point-of-care (PoC) diagnostic uses. Figure 6 shows one of the first on the market—the Agilent 2100 Bioanalyzer System—for DNA, RNA, serum protein, and infectious disease analysis.

Figure 6: Agilent Technology has been involved in the life sciences since 1995. Their “nanolab chips” are used to analyze DNA, RNA, SARS, and other infectious disease proteins ^[2].

2. Glass-based

Glass is a lower cost material if electrical components and circuitry are not required. Glass can be fabricated into microchannels and deposited with many substances such as gels and coating. The glass device seen in Figure 7 is an Agilent 3100 Bioanalyzer Automated LC/MS that comes in numerous forms to separate chemicals and biological samples into microspray streams for use with liquid chromatography/mass spectrometry (LC/MS).

3. Polymer/PCB-based

Many polymers are also optically transparent and can be integrated into systems that use optical detection techniques such as fluorescence, UV/Vis absorbance, or Raman method. Moreover, many polymers are biologically compatible, chemically inert to solvents, and electrical insulating for applications where strong electrical voltages are necessary, such as electrophoretic separation and the surface chemistry of polymers. This can also be modified for specific applications. The most common polymers used in bio-MEMS include PMMA, PDMS, OSTEmer, and SU-8.

So, what could be achieved using PCB technology? Of recent years a lab-on-printed circuit board (LoPCB) approach has been suggested. The PCB industry is mature, well-established worldwide, and has standardized fabrication processes, materials, and production equipment currently dedicated to electronics applications, but with the potential to become a natural partner for LoC development and the scope to be straightforwardly up-scaled.

Enter Dr. Despina Moschou, a researcher at the Centre for Advanced Sensor Technologies, Department of Electronic and Electrical Engineering at the University of Bath in the U.K. Dr. Moschou is a frequent speaker at printed circuit events like AltiumLive ^[1], EIPC Conferences, and the ICT Conferences. Fortunately, for us, she has taken the time to prepare summaries of her, and the many others in this field, work on LoC and LoPCB µTAS approaches.

Early experimentation was focused on bio-electrodes for PCBs and on the microfluidics compatible with PCB fabrication. Figure 8 shows a test vehicle. This was a two-sided FR-4 PCB with gold plated copper traces and sensor electrodes. Two different golds were tested. One was a soft gold—the Metalor R MetGold Pure ATF process, plated 2.57 µm layer of 90 HV hardness. For the hard gold, the Metalor R EnGold 2015CVR process was followed, providing 2.41 µm of gold on top of 3.41 µm of nickel with a final hardness of 140–180 HV.

To handle the delicate microfluidics, the properties of dry film photoresist (like DuPont Riston^TM, or DFR) was employed. This photosensitve material, with proper curing, can be stabilized for long life, and—in some applications—can be used as a photosensitive adhesive. Too bad that the dry-film solder mask (DFSM), like DuPont Vacrel^TM, was no longer available. A thin FR-4 layer (200 µm) was laminated with a 50 µm DFR, that was patterned using standard PCB photolithography, developed and cured for two hours to drive off any solvents. Then, adhesive-based flexible cover coating of PMMA film was laser micromachined to provide for larger fluidic supply channels (~5 mm), and the stackup laminated to the FR-4 sensing layer.Page 3 of 5

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