A look at best practices in the design and development of microfluidic devices for point-of-care diagnostics.
Dave Franta, Global Business Manager, 3M Medical Materials and Technologies
Jake Eldridge, Senior Manufacturing Technology Engineer, 3M Medical Materials and Technologies
Microfluidic devices are used to enable rapid results at the diagnostic point-of-care around the world. The results give healthcare providers and patients the ability to get answers and explore treatment options outside the physical setting of a hospital or clinic. As demand for point-of-care tests (such as infectious disease or blood glucose tests) increases, stakes are higher to consistently design and manufacture reliable devices in large volumes.
A challenge, however, is how to scale production while ensuring test accuracy and effectiveness is balanced with overall cost. Many considerations and decisions need to come together to make the device.
The following best practices can help when designing and producing microfluidic point-of-care devices without compromising reliability.
Ask detailed questions to understand the end-user and their environment
Before starting to design and prototype, it’s important to see the big picture. Posing questions about the end-user and their environment helps construct proper requirements that will serve as guard rails. Iterative feedback will also aid during design.
Below are some examples.
–Who will administer the test using the device – a healthcare professional or patient?
–How will the sample need to be handled, protected and processed before analysis?
–Will the system be robust, intuitive and safe to use by a non-professional in a home environment?
–What design choices can be made (e.g., self-checks, automations, information displays, etc.) that will make it easier for the end-user to operate?
–What controls or features does the device need to incorporate, such as different reagent types, deposit locations and reaction mixing requirements?
In terms of understanding the environment, temperature may play a key role, requiring specific resilient and versatile materials. Thus, it will be important to determine how the device and consumable will be stored.
When looking to understand the application, consider questions about microfluidic functionality, such as:
–What fluids does the device need to move? How can it move them? Are there specific speeds or dwell time requirements for reactions?
–What level of sensitivity is required and how does this impact design parameters?
–To enable good stability and a reliable, scalable deposition process, how do reagents need to be deposited on the device? With what precision?
–How can we seal the device without affecting sensitive device reagents or components?
Almost every bioanalytical application introduces specific technical demands that play into material and manufacturing process selection and scalability.
Knowing these requirements early in the development cycle should decrease the number of design iterations and revisions. Such research will deliver data on what functions, characteristics and nuances the device requires, as well as the end-user expectations.
Material selection and formats, such as sizing, can have a huge impact on scalability. Material attributes, roll sizing, splicing options and traceability requirements are all considerations.
In early development, two challenges are accurate functioning and selecting the right materials. Ideally, select similar or the same materials, if available, for product prototypes of devices when practicing the first miniaturized tests. Prototypes may be constructed from various materials such as glass, polycarbonate, polystyrene and others. There are obvious trade-offs for some design choices. For example, glass has the best chemical resistance and can perform effectively as a prototype. However, it may not be the best material choice for mass-production or use at the point-of-care due to its fragility. As you select materials, think beyond the prototype you’re building. Consider material compatibility and resilience, temperature resistance, the manufacturing process and budget.
–Material compatibility: The surface-to-volume ratio in miniaturized tests is higher than conventional laboratory equipment, potentially creating stronger interactions between sample, material and reagents with the substrate materials used in the device. Material compatibility, therefore, is important because it can affect both the device’s integrity and assay performance.
–Temperature resistance: Consider the thermal properties of materials such as thermal expansion, thermal conductivity, heat capacity and modulus changes. The device may need to withstand extreme temperatures or large temperature gradients either during storage or required for assay performance or reaction speed.
–Manufacturing processes: Consider materials that are compatible to desired manufacturing process. Materials may need to withstand friction or abrasion associated with the chosen manufacturing process. Certain materials will cut better or offer better precision in rotary, laser or die presses during transformation processes.
–Budget: Specialized materials and manufacturing technologies can be expensive and often can’t be justified beyond prototyping. Select materials that are versatile and provide good value and performance characteristics so that you achieve and maintain a competitive price point.
The pros and cons of various manufacturing processes
There are multiple techniques to produce microfluidic devices. A common element of all manufacturing processes is that each can greatly affect material properties.
Roll-to-roll laminate processing
Each layer of a laminate microfluidic device is combined using this method in one or a series of unwind, lamination, cutting and rewind steps. The process typically starts with designing the finished device using CAD software. From there, strategies are selected to bring the required materials together in the proper device geometry. Additional steps can include inspection, steering, alignment or registration techniques. The process accuracy depends on the chosen processing methods, device tolerances and the material properties, such as thickness or adhesion properties if using tapes.
Laminate methods are compatible with a range of materials. They are also scalable in volume and offer benefits in alignment, registration and material tracking. This is because the parts are controlled in a web format until such time as they are singulated later in the process.
As a relatively easy process to tool-up for and execute, hot embossing is a popular one. It can also achieve excellent replication with high-aspect-ratio microstructures. Special consideration should be taken when using this process during scaling to large volumes as feed rates may impact process performance.
Injection molding is highly developed for macro-replication and is increasingly available for the microscale. With multiple cavities and fast cycle times, it caters well to producing large volumes. Be aware, though, that it requires more costly and complex tooling investments.
Powder blasting or jet cutting or lasering techniques
These processes fall within the planar processing category. They are used to create fluidic channels and interconnections and involve a particle jet to remove material. They are viable for small to large volumes, but it is critical to manage potential contamination and keep the finished parts clean.
Similar to injection molding, casting requires a mold to serve as the template for your microfluidic device. To create the actual device, PDMS is poured – or casted – into the mold and then cured. Unlike injection molding, it’s best for small volumes, and it typically does not scale well.
Critical material properties include:
–Optical properties, such as fluorescence, transmission and refraction
–Mechanical properties, such as modulus, density and thermal or electrical conductivity
–Thermal properties and stability
–Surface energies and requirements, such as hydrophilicity
–Surface properties, such as roughness or chemical modifications
–Bio and assay compatibility
–Stability and overall chemical inertness
Designing and bringing a microfluidic device to market may include several iterative cycles. Performance must be confirmed every step of the way, making every decision critical. The most effective way to ensure your device will perform as intended is to partner with a knowledgeable materials supplier with technical abilities to support you from design through manufacturing and beyond.
3M Medical Materials and Technologies
Filed Under: Molding • injection molding components, Medical-device manufacture