Martin Goossens, system engineer and concept lead, Benchmark
Lab-on-a-chip (LOC) is a large and growing market, leveraging small samples of fluid on microfluidic chips for a number of promising diagnostic applications. In addition to diagnostics, microfluidic chips are used in other fields, such as drug delivery and personalised drug therapy. For instance, the microfluidic chips can produce microbubbles that enable a drug to be targeted at cancer cells. Microfluidic chips can also act as a chamber that allows a laboratory analyst to decipher the optimal dose for a patient.
While development of microfluidic chips can be time-intensive and expensive, for many applications, core design elements need to be extremely consistent from one chip design to the next. For example, all microfluidic chips need to avoid airborne contamination and must hold a tight seal to the test device. Benchmark, a US-based engineering and manufacturing services provider, is developing a foundational microfluidic cartridge testing platform to support many microfluidics applications at its Medical Device Center of Excellence in Almelo, the Netherlands.
A multipurpose microfluidic cartridge testing platform
The conversion from micro to macro scale, the connection from the microfluidic device to the analysing device, poses a number of conflicting challenges. To conduct tests, the fluid, gas and electrical connections must be formed and maintained between the chip and the device.
Currently, there are no standards for any of these connections, resulting in many different solutions that have varying shapes and dimensions. This means each chip is designed specifically for that application’s device, and each device has unique connector plate dimensions, inlet and outlet positions, and other attributes. This prevents interchangeability and interoperability. The process of adapting the chip consumes time and money. As the tests conducted using LOC technology are very sensitive, the system design must be extensively tested and validated.
Benchmark set out to develop a microfluidic cartridge testing platform that makes analysis tools simpler, faster and cheaper to operate for end users. For microfluidic system developers, using the platform affords several benefits, including:
- a reduction in development costs;
- faster proof of concept;
- faster time to market;
- increased product flexibility;
- greater risk mitigation;
- an adaptable machine interface;
- automated connections; and
- a significant decrease in dead volume.
The platform facilitates multiple fluidic, gas and electric connections between the chip and the device. This means that for each test, all the required connections are available. Platform components can be shared between companies, enhancing cooperation.
Cartridge architecture
The primary purpose of the cartridge is to house any thickness chips, align them and place their inlets and outlets concentric with the hole pattern integrated in the top of the cartridge. The concept is a ratchet-type top that allows multiple positions along the Z-axis from the top of the cartridge, facilitating a range of chips within the same housing using a single component design. When positioned, the cartridge acts as a bridge between the chip and the machine interface, positioning and aligning the connectors with the corresponding ports or connectors. The cartridge is assembled by the user like a Lego platform, placing the corner pieces in the right spot for that particular chip. The four main components of the cartridge are shown in figure 1.
Figure 1: The four main components of the cartridge: top (light grey), seal gasket (green), corner pieces (red) and microfluidic chip (white) and bottom (dark grey).
The ability to have any thickness chips in any position in the cartridge makes this concept very flexible. The cartridge can hold multiple chips so that multiple tests can be run using one system. The port pitch is 3 mm, smaller than most products on the market, allowing it to deliver more functionality in a smaller surface area. There are 31 by 19 connection rows, giving the user 589 possible connection positions.
The cartridge acts as a sandwich surrounding the chip. When closed, the chip is fully surrounded on each side and ready to be loaded in the machine. The chip is placed on the bottom and located using the red corner pieces. Then the top is placed on the bottom, housing the gasket seal and mating with the top of the chip, ready for the connector to make contact. The top and bottom of the cartridge align with the device interface. A side view of the cartridge is shown in figure 2.
Figure 2: A side view of the cartridge.
Sealing from airborne contamination is critical and must be a verifiable portion of the process to ensure accuracy. Making a good seal is critical. Anything under 5 bar or 500 kPa is considered insufficient, and 10 bar is preferred to maximise the applications the platform can address. A gasket seal consisting of 0.8 mm thickness of soft material is applied underneath to enable more compression and thus a tighter fit between the interface and the cartridge. A clear plastic seal is placed on top of the cartridge during shipping to reduce risk of contamination. The seal is pulled off at the last possible moment.
Microfluidic interface
Every fluidic connection must have minimal dead volume and be reusable, making a temporary connection. Dead volume refers to unintended empty pockets in the flow path. It is also important that fluid connections are clean and sterile so no contamination can compromise the test results. When working on the microscale with fragile components that need to be fluid and air-tight, all connections need to be accurate, precise and reliable. The testing procedure needs to be fool-proof for any system operator; the connections must not fail during the test.
A multipurpose system should not include proprietary elements controlled by a single supplier. The connection points should be flexible or configurable to the specific system’s needs. This way, the system can work with chips of different suppliers or the designer can order one to specification.
Many types of microfluidic connectors were considered for the platform using various mechanisms to achieve a sealed connection between the chip and the cartridge, such as:
- magnetic connection;
- epoxy resin;
- threaded connection;
- press fit;
- rubber insert;
- polycaprolactone seal;
- socket-plug;
- ball joint;
- tube insert with needle;
- fixed tube;
- under fill seal; and
- compression connector.
Additionally, a custom tubing was designed to minimise dead volume.
A final concept choice for the connectors was made using a design decision matrix. An example of an important criterion for the fluid connector was defined as creating a seal of at least 5 bars with a stretch goal of 10 bars. The selected design was a custom tubing, which scores points on every aspect of the requirements. It is a simple design with no extraneous components, is easy to produce and decreases dead volume by 28 percent. The design also offers more functionality on a smaller footprint with connectors placed on a 3 mm pitch. Assembly for the user is very easy and simple.
Connector architecture and electrical interface
The connector between the cartridge and device is a vital aspect of overall design. A good connector design should be user-friendly with a simple closing mechanism that intuitively suggests the closing action. The design should be cost-efficient to manufacture but maintain structural integrity through repeated use. Also, given the dynamic nature of the microfluidics market, the platform must take cartridges of different types and materials to extend usable life.
The platform’s connector plate acts as a backbone for assembling the connectors, simplifying development and prototpying. An engineer can prepare the connector plate on their benchtop and be confident that the connectors will be in the correct position. Each connector hole on the grid has a marking—A-Q for the Y-axis and 1-29 for the X-axis, starting from the top left corner. The engineer designs the chip following this grid and marks them. The fluid connectors are pulled through from the underside until they snap in place.
The electrical connectors are mounted on a pre-made printed circuit board assembly (PCBA), as shown in figure 3. The pogo pins stick out under the fluid connector flange so they make contact first, pushing the pin in 2 mm before the fluid flange mates with the cartridge seal gasket.
Figure 3: The electrical connectors mounted on a printed circuit board assembly (PCBA).
On the bottom of the connector plate are beveled edges that locate the cartridge and align it with the connectors. During the upwards movement, the cartridge should already be perfectly aligned. However, any misalignment is rectified by the edges, slowly guiding the cartridge to the centre. The assembly with the cartridge placed against the connector plate is shown in figure 4. This is how the compression of the gasket is achieved. The bottom tray will keep pushing until the top of the cartridge meets the bottom of the connector plate. As the connector flange is thicker than the top of the cartridge, it compresses the seal gasket below, making the connection. The electrical connector diameter is 1 mm, which is smaller than the gasket holes. This way, they can reach the chips’ surface, making contact with the electrical pads.
Figure 4: The cartridge placed against the connector plate.
Co-development partners sought
After initial design elements were selected, significant testing was conducted to evaluate fluid seal integrity, platform endurance and pressure. With these test results, further potential improvements have been identified and will be implemented.
Benchmark is actively looking for partners to take the next steps in further developing the microfluidic cartridge testing platform. The platform will help partners to mitigate risks while reducing time-to-market and development costs. Developed platform components can also be shared with partners to further facilitate collaboration.