Microfluidics is a key technology enabling the development of rapid in-vitro diagnostics (IVD). With applications including COVID-19 testing, cardiac arrest assessment and STD screening, decentralised rapid diagnostics are shaping up to be a major part of the future of healthcare and wellness monitoring.
As the name suggests, microfluidics is about the movement and manipulation of very small volumes of liquids to automate test protocols or assays. Currently these assays are (most commonly) centrally processed in hospitals or labs by either large, expensive machines or human beings armed with a selection of pipettes and other gadgets. These current practices are costly, difficult to control and susceptible to human error, which is why the case is strong for microfluidic solutions.
The manufacture of microfluidic devices is anything but straightforward. Having been involved in several in-vitro diagnostic product developments from a mechanical design perspective we appreciate the challenges that come from the scale of the features; they’re not called micro-fluidics for nothing. What we’re exploring here is not only the challenge of making very small things but making them on a big scale.
One way that many IVD providers have attempted to avoid microfluidic features is through development of novel sample processing consumables that can be manufactured using common mass-production processes. Although several have experienced commercial success it is arguable that the compromise is typically oversized consumables, overly complex analysers, and inefficiency in the use of both patient sample and reagents. Once the microfluidic puzzle is solved these ‘macro-fluidic’ products are likely to become niche, if not a thing of the past.
Here are some the engineering challenges typically faced with microfluidics:
Manufacturing tolerances: +/-0.1mm on a specified dimension for case-moulding of a handheld or bench top product is common and generally achievable. In microfluidics 0.1mm is often the size of the feature itself so we need to start talking about tolerances in microns. For the engineers reading – ISO fine doesn’t cut it here!
Uncertainty: The ambiguity of evolving chemistry and/or detection technology typically requires many iterations of a device being developed and tested before settling on the design of the end-product. Designing a platform to perform complex protocols with the requirement for parallelisation of several biomarkers into a single test can best be described as like trying to solve a maze with moving walls.
Liquid interface: At such a small scale the influence of the interface between the fluid and the materials that make up the containing surfaces is significant. The surface energy of polymers is variable not only between different polymer types but by different surface finishes within the same polymer. Whether the face is rough or smooth can be the difference between hydrophobic or hydrophilic behaviour.
Repeatability: Data is King in the world of in-vitro diagnostic development as the foundational science is based on the ability to accurately repeat fluid handling processes and precisely replicate quantitative results. Each design iteration has a significant lifecycle to support the production of a sufficient number of prototypes to allow for data to be gathered. Additionally, it requires a sizeable investment in quality control as inconsistency in production will produce inconsistent results.
Methods for manufacture. The methods that can scale often involve specialist materials and processes which are expensive, have long lead times and are uncommon. Academics have developed several techniques for making single or small batches of devices containing microfluidic channels, however these are labour intensive and cannot scale to production volume. This has led to a monopolistic or arguably non-existent market for capable contract manufacturing organisations. Often these restrictions lead to the use of prototyping methods that do not reflect the end production process.
(1) It requires a significant number of consumables to complete each iteration of assay testing.
(2) It takes time to validate the production of each consumable design iteration such that the results can be trusted.
(3) The production of the consumables for testing tends not to be aligned with mass-production intent.
The limitations of (3) feed into the effort required for (2); variability from (2) into the results for (1); requirements for (1) into the decision making for (3): a continuous circle of complexity and unavoidable compromise into which several start-ups have spiralled and struggled to surface.
Let’s say you manage to navigate this and now have an assay, detection method and consumable design that has proven to be a winning combination. Just one final and significant hurdle to jump: transferring the design to production — how to ensure what you’ve proven to work at a small scale can be made at production quantities (+1million units per annum)?
It’s a challenge but here are some of the areas we recommend focussing on to maximise development efficiency and your chances of technical success:
Quality. Regulatory approval should fall out as the result of a well-considered and proactively documented development strategy. Don’t fall into the trap of thinking that quality management is just a case of ticking the regulatory boxes.
Foresight. Developing a manufacturing plan early and understanding the limitations of production material/process/surface finish up front helps predict the variation (using the modelling method outlined below) and it is often possible to build in compensation to the prototype design where necessary (increasing the resistance of a channel as compensation for increased hydrophobicity in production, for example).
Theorise. It is possible to model and iterate microfluidic designs theoretically before making anything. As with any model, ‘garbage in = garbage out’ so it pays to have past-experience to inform your initial design such that you can have faith in the results. Some modular, bench-level testing must be expected for anything new or novel, but it is possible to save 2–3 development iterations by taking the time to construct and iterate a simulation of the proposed system before diving into the prototyping spiral described above.
Communicate. It is important your team can communicate effectively across disciplines. Engineers, designers, biochemists, and lab-techs need to find a common language such that can work together and stay informed by past efforts & intentions and stay aligned with the bigger picture. Microfluidic developments take on average 10 years to reach the market which means the people who start the project are likely to differ from those who finish. Without documentation of prior work and considered on-boarding of new people it’s easy for a team to lose sight of the reasoning behind their current objectives.
[This article was originally published in September 2021 in the Med-Tech Innovation News magazine and online]