COVID-19 has increased the demand for easy and rapid medical diagnostic tests for the public. Lab-on-PCB (Figure 1), initiated by Agilent in 2000, has evolved into other materials and applications1.
Lab-on-a-Chip (LoC) and Lab-on-PCB (LoPCB) are devices that integrate one or more lab functions onto a single integrated circuit or board. LoC devices are microelectromechanical systems (MEMS) devices (Figure 1) that function as micrototal analysis systems (micro-TAS) and typically use microfluidics principles to manipulate small volumes of fluids. . In practical terms, microfluidics is about doing chemistry on a small scale and trying to mimic nature. Biomedical MEMS (bioMEMS) has emerged as a subset of his MEMS devices for biomedical research and medical microdevice applications, with an emphasis on mechanical components and microfabrication techniques. Applications include disease detection, chemical monitoring, and drug delivery. The market for bioMEMS technology is growing rapidly, and many bioMEMS devices are already commercially available. A familiar example is a blood sugar sensor. His microfluidic-based LoC and LoPCB technologies have great potential for large-scale commercialization.
Lab-on-PCB Elements
The component devices that make up a typical LoC and LoPCB are:
- Fluid movement by electrophoresis
- Microfluidics: channels, valves, pumps, mixers
- separation column
- Heating: cooling and mixing
- reaction chamber
- Adding reagents
- Chembio detectors and sensors
- UV-VIS/colorimetric sensor
- microfluidic chip
Together, these units form the schematic of a functional lab (Figure 2) provided by Agilent.
material
Over the years, several materials have been developed for use in LoC and LoPCB. It started with silicon in the late 1990s as the microelectronics industry developed various methods of MEMS for accelerometers for airbag sensors. Materials have branched out from silicon wafers to glass to polymers. Recent interest has been in the use of PCBs and various paper materials.
Silicon and glass have several advantages for LoC manufacturing, but are the most expensive. Polymers, and in particular PCBs, have become a new option due to the variety of materials available and the integration of electronics and various printing techniques. Although some research is currently focused on paper, its use is still in its infancy. Table 1 shows some properties of each of these materials.
Operation sequence
It is quite remarkable what can be achieved on a miniaturized scale. Once his MEMS technology was perfected on silicon wafers using photolithography, etching, metallization, and lamination processes, it became possible to miniaturize chemical analysis. However, it has been discovered that certain activities that have no equivalent in the larger real world, such as electrophoresis (the movement of fluids due to surface tension and applied voltage), can be accomplished in the micro- and fluidic fields.
Once the sample is deposited at the inlet port of the LoC or LoPCB, the movement of the electroosmotic fluid takes over and performs various actions. The sample is heated and passed over a fixed bed of reagents, and additional fluid can be added and mixed by an external device. The sample reacts in a reaction chamber and is then sent to various sensors for analysis.
One unique variation is in the Agilent DNA and RNA analyzer, which prepares the sample in a LoC cell (Figure 3e) and then feeds the sample into a nano inkjet cartridge that prints thousands of nanoparticles onto a prepared optical slide. Drops are deposited. Thousands of microspots react to prepared samples. After incubation, a laser scanner records the results and prints the final report (Figure 3f).
Figure 3 shows some of these sequences and sensors that today provide medical diagnosis in minutes. It used to take clinical laboratories weeks to perform this, and new techniques like DNA and RNA analysis were undreamed of just a few years ago.
example
In Figure 4, researchers at the University of Bath started with LoC experiments and then progressed to using PCBs. His LoPCB components such as DNA sensors and heaters on his PCB are now available (Figures 4a-c). This process fabricates the fluidic channel and sensor/activator and glues the biosensor chip before final sealing (Figure 4d). The performance and diagram of the lactose and glucose PCB plated sensor are shown in Figure 4e. Figure 4f shows a polyimide (PI) flexible PCB with copper (Cu) and gold (Au) plated sensors coated with a gel of EDOT on a graphene carrier of AuNPs and GOx (WE).
Figure 5 shows a microfluidic element where fluidics/osmotic fluid movement is of paramount importance. A photosensitive dry film solder mask is used to form the fluidic network, as shown in Figure 5a. Figure 5b shows the CAD design and the actual 3D printed transparent serpentine mixer. Figure 5c is a 3D printed microdevice of a chip with a reaction chamber that can integrate a mixing stage and a photomultiplier tube for bioluminescence detection. Figure 5d shows multilayer microchannels as small as 32 mm utilizing flexible silicone resin and subsequently 3D printed directly onto an unmodified Arduino PCB, resulting in a fully integrated microfluidic-microelectronic interface (Fig. 5e).
Some PCB medical devices are so small that they can be swallowed and guided into the intestine to perform 2D optical coherence tomography (Figure 6) with Portelligent disassembly. The endoscope scanner uses a 2D scanning MEMS mirror with a diameter of only 1 mm to provide doctors with real-time 3D images and videos of his. The device is only 3 mm square. Future devices will have propulsion and steering capabilities.
summary
Advances in μHDI PCBs and additive 3D printing have led to new products in smart microfluidic packaging for medical diagnostics. Therefore, a potential link between microfluidics and multifunctional biosensing is found in the realization of 3D microfluidic manifolds, promoting lab-on-PCB technology to create low-cost and rapid micrototal analysis systems, i.e., micro-TAS. (μTAS).
References
- “Advances in medical diagnostics using lab-on-a-chip and lab-on-PCB technology” by Happy Holden, PCB007 Magazine, April 2020.
- “LoPCB Technology”, Despina Moschou, AltiumLive, Munich 2019.
- “LoPCB: A step closer to achieving µTAS,” BioMicrofluidics, May 2022.
This column originally appeared in the January 2024 issue of the magazine. PCB007 Magazine.
