IVD device representation with reagent blisters

The continuing growth of point-of-care (POC) in vitro diagnostic (IVD) testing is supported by technology improvements and the recognition that rapid test results offer economic and patient outcome benefits. Frangible seal technology offers an elegant and cost-effective solution for dispensing unit-of-use reagents for POC medical diagnostic devices.

Frangible sealed reservoirs use differential weld strengths that are designed to fail under specific pressures, allowing for a unit-of-use measure to be precisely delivered to a target well or reaction zone. By incorporating frangible seal technology into on-board reagent blisters of POC devices, the device manufacturer is able to better control performance variability, reduce overall manufacturing and disposal costs, and simplify the end-user experience.
Incorporating Blister Technology into POC Devices
An increasing number of POC device manufacturers are incorporating burst and frangible seal reagent blister reservoirs into lateral flow and lab-on-a-chip/card formats as they are easily integrated and reliably dispense unit-of-measure volumes of reagent precisely to the targeted area. This is replacing the use of conventional eyedropper and bottled reagents by the technician to deliver an approximate volume to a device capture zone, thereby eliminating the opportunity for sampling errors.

It is important that frangible seal manufacturers consider the specific requirements of every custom blister reservoir and design a blister solution that considers material compatibility, burst characteristics, reagent volume delivered, and long-term storage requirements. There are several different types of materials that can be used for reagent blisters and generally can be described as specialized foils and laminates used for cold- and thermo-formed packaging. These materials have various thicknesses and seal strengths that can be used for pierced or burst/push-through, peelable, and hybrid peel-push barriers.

Depending on the form factor and release requirements, a wide range of materials can be processed to create “frangible” blister seal reservoirs with differential weld strengths designed and engineered to either be permanent or break, distort, or yield on contact actuation or fail under a specific pressure. These weld strengths on the reservoir seals are a function of the material properties and applying unique welding processes that are combinations of pressure, temperature, and time to meet the seal specification.

An understanding of these specialized material properties and processing allows the blister fabricator to “dial-in” the specific burst strength needed for activation – though not fragile enough to rupture prematurely due to routine handling, assembly, or shipping activities. Demonstrating this flexibility, a single blister design was created with a frequently used foil material set and then sealed using different processing parameters. The sealed blisters were then actuated and measured for the force required to release the contents¹ (Chart).

This processing control of the seal strength allows the medical device manufacturer to have confidence that the reservoirs will release their contents under defined and controlled conditions. Additional levels of seal strength (lbf — pounds force) can be developed and optimized using different material sets and processing conditions, thereby expanding the selectivity of the activation range of the blisters.

Cost Considerations
There are tangible reductions in overall manufacturing and end-user costs by incorporating frangible seal reagent blisters into POC devices.

• It reduces the number and cost of separate reagent bottles and applicators, and associated costs of filling, packaging, and labeling (i.e., less inventory management).
• The reagent blister stores and delivers just the right amount of reagent needed for the determination, so excess reagent is not required. The liquid volume for single dose reagents can range from 30 to 5,000 μl.
• The blister form factors are compatible with various reagents, powders, beads, liquids, and solvents, thereby reducing the number of materials needed for the test kit.
• Larger blister cards with multiple reagents (multiplexing) can be used to reduce the number of overall components and assembly steps.
• The reagents can be lot-matched appropriately on the device, removing potential confusion and misuse by the end user.
• Reservoirs are lightweight and disposable components when integrated into the device, reducing waste.
• The materials used have low vapor barrier transmission rates, resulting in greater stability and longer shelf life (>2 years), in some cases eliminating the need and cost of desiccants.

Additionally, blisters are easily customized and integrated into many existing platforms; this helps manufacturers create new offerings without drastic changes in the product line. Burst pressure and pin-point release of the reagent from the blister reservoirs can be designed into the blister shape for either manual or mechanical actuation. Accurate filling and dispensing by design — in single or multiplex formats — allows tests to be consistent and reproducible.

Conclusion
The application of frangible seal technology to reagent blisters enables greater control over unit-of-measure release of testing reagents and provides improved performance characteristics and practical implications when compared to current drop bottle formats.

These features translate into benefits for the POC device manufacturer by lowering manufacturing and packaging costs, increasing reagent stability, and providing a smaller disposable footprint that offers easy, accurate, and precise fluid transfer.

In turn, by integrating frangible seal technology into on-board reagent delivery, POC tests can lower cost, shorten time-to-result, and increase reliability and stability. Frangible sealed reagent blisters show the promise of making POC devices more affordable and reproducible, with improved patient outcomes and high confidence in the test results.

Source: J-Pac Medical