11 Sep Challenges Associated with Integrating Microfabricated Chips in Diagnostic Systems
Smaller devices, desirable for so many practical reasons, enable use at the point of care, and in certain cases, at home with the patient, or out in the field, when used in lab-on-a-chip devices. These devices are growing in demand in the market, as is the incorporation of microfabricated diagnostic chips that enable higher sensitivity and specificity in the measurements they are making.
A microfabricated diagnostic chip is typically fabricated in a foundry from silicon, and functionalized in a specialized manner unique to the assay and measurement, such as an electrochemical or optical measurement. The chip is then integrated into a larger diagnostic cartridge that interfaces with the diagnostic device. It is important to determine what to include where, on the chip or on the device. If you’re making millions of cartridges for a diagnostic test, for example, then you want the cartridge design to be as cheap and as simple as possible. But making cheap and simple cartridges may increase the complexity and cost of the instrument.
More demands for chip based diagnostics can make designing products today tougher than ever.
The most unique challenge to microfabricated diagnostic chips comes from their size. When you are working on such a microscale, the chip is very sensitive to ESD – electrostatic discharge. Even very, very low, non-perceptible voltage levels can cause problems and ruin a chip. These chips require special handling precautions. We recommend using ESD mats and bracelets to ground yourself, even when doing early de-risking testing.
You can’t touch any of the exposed metal. In chips with hundreds of electrode sites for example, with pins that stick out and interact with a durable electrical system, it’s necessary to never make an electrical connection prior to use, otherwise you risk damage. This requires the chips to be packaged in such a way that the chip is insulated from the outside world until it needs to be used. Then the design question becomes when is the protective insulation, which can be a simple plastic covering, removed? And how? Is it a human action – removing the plastic, or is it something in the device that removes it?
Other similar considerations that need to be managed in human interaction or in an automated way could involve temperature or humidity control.
Reducing the number of electrical connections can be important from a quality, risk management and cost reduction standpoint. The lower the number of electrical connections, the lower the potential margin of error. Alignment is often an issue. Usually, the user inserts the disposable, and then the instrument must move the interface connections to engage with the disposable. Putting features in place to guide the alignment helps to reduce error. Another factor to consider is handling the chips with ‘white’ gloves, which is a precaution to prevent extra grease on fingers from changing the impedance of the electrical connection in the testing unit, skewing your results
Fluid handling into and out of the chip. At the bare minimum, this requires an inlet/outlet seal and a way to move fluid. These three features shape the fluid dynamics on the chip’s surface and can vary wildly depending on what the application requires. An O-ring is a simple way to form a seal, but it creates room for hide-outs and forces the inlets and outlets to work around its height and diameter. A gasket could allow for more creative inlet and outlet geometries to more finely control flow but it takes greater upfront investment and could still lose compression over time. Sealing permanently to the chip gives the cleanest connection, but of course cannot be removed for debugging testing.
Moving fluid generally boils down to a pump. Will the pump push or pull, contact fluid directly or only touch the lines like a peristaltic pump setup. Will the pumping system dispense to one chip at a time, or many? What sorts of valves control where the fluid goes at a given moment? Choosing one path depends largely on how sensitive the process is to cross contamination, fluid volume, speed, and flexibility, just to name a few.
Mixing is important as well. If a diagnostic device processes a patient sample, then it is almost guaranteed that the sample will have to be mixed at some point with various reagents required in the assay. Mixing at a micro level is encumbered by surface tensions – Small amounts of fluid like to stay together, and getting two 50 uL drops of fluids to want to join can be tricky. When you get to this scale and the fluids are in a microfluidic chip, they can be pumped back and forth to encourage diffusion and laminar mixing.
Pico amp currents require special design considerations. Microfabricated diagnostic chips typically include very small electrical signals tied to the measurements they are taking, down to the picoamp level. It is important to minimize noise when designing the data acquisition electronics for such a small, sensitive signal.
Consider the cost of these expensive, sometimes rare, microfabricated chips. In the R&D phase, microfabricated chips can cost in the hundreds of dollars per chip, and you can really go through them in your testing, if you don’t carefully consider even simple things like the handling challenges above. It is important to keep the R&D chip costs in mind during your prototyping phase in order to keep costs in control. For example, interfacing materials should be pliant so you minimize the risk of breaking the chip in testing. We develop test fixtures designed to accommodate the chips. The test bed needs to be designed such that you can understand what is happening on the chip – this is typically achieved by developing 2-D test fixtures that include regions to visibly inspect and debug assay steps on the chip.
For microfabricated chips and microfluidic diagnostic devices to be successful, it is imperative for design teams to incorporate experts at all points along the value chain, from concept to design to manufacturing. The assay team has to interface with a foundry making the microfabricated chips, and the cartridge and instrument development teams must understand the intricacies of each assay step and foundry process, to optimally design the right cartridge and instrument. These teams must have excellent communication established to balance and check all the moving parts and considerations involved in developing a product around a microchip. In this way, a team can ensure that every angle has been considered, and usability, accuracy, cost, and integrations have all been maximized.
For more information on how Key Tech works with clients to create an optimized chip and device solution specific to needs, contact us at TalkToUs@keytechinc.com.
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