At its inception, the term “molecular diagnostics” was narrowly applied to DNA- and RNA-based test and methods. The meaning of molecular diagnostics, however, has since expanded to include other molecules such as proteins and metabolites.
Rapid incorporation of scientific discoveries into diagnostics kits has led to a proliferation of complex analyses, often with multiple different analytes. Regardless of the term, an impressive amount of research is now focused on developing diagnostic applications that can help medical practitioners achieve faster and more accurate diagnosis, reliably assess disease prognosis, and monitor treatment.
Multiple opposing forces are shaping technology trends in molecular diagnostics. Significant advances in sample preparation and signal amplification have made diagnostic assays based on a single-copy or low concentration targets possible. As the technical complexity of assays increases, the diagnostic frontier is shifting from specialized labs and company-based CLIA labs to physician offices and even further into the field, to those dealing with major public health threats, military operations, or to patients’ homes.
Users are demanding fully integrated assay platforms that require minimal training to use and provide easy interpretation of results. Field applications demand low-cost solutions, which are contrary to the increasing costs of obtaining sufficient clinical evidence and traditionally low rates of reimbursement. The high clinical value offered by modern diagnostic systems underscores the long-overdue need for the overhaul of the reimbursement system.
In the interim, the quest for cost savings is further pushing the limits of technology to miniaturize the reactions, to increase multiplexing, and to improve signal amplification. The companies described in this article, all of whom will present at Select Biosciences’ upcoming “Molecular Diagnostics World Congress,” are capitalizing on these trends by offering unique solutions to the challenges of clinical in vitro diagnostics.
Polymer Laminate Technology
Microfluidics is a framework of micro- or nano-size channels enabling fluid flow for separation and analysis of macromolecules. The test cartridges within the device enable various functions such as automatic sampling, sample transport, any necessary chemical reactions, and detection on a single, miniaturized platform.
The advantages of microfluidics clearly support the needs of modern diagnostics by offering faster separations, shorter transport time, lower sample and reagent consumption, and the possibility of multicomponent testing under the same conditions.
To truly serve diagnostic needs, however, microfluidic platforms need to deliver fully integrated micrometer-scale systems, while maintaining biological compatibility, biomolecule stability, and extremely sensitive detection.
Material properties impact not just mechanical performance but also fluid behavior. The surface energy and geometry of the channel features also influence the fluid flow. Therefore, the choice of material and design of the cartridge and device are of paramount importance. But the huge amount of materials available for microstructure fabrication makes the selection difficult, especially for those not intimately familiar with polymer chemistry.
“Innovations are required from microfluidics manufacturers to reduce the price per cartridge from a typical $20 to a more sustainable price of $5 at launch, and further to $1.00 or less at high volumes,” comments Leanne Levine, founder of ALine.
“Such innovations come not only from novel materials, but also from integrated design-build-supply capabilities. This has necessitated a paradigm shift from silos of expertise in microfabrication to a wholly integrated manufacturing infrastructure.”
ALine’s mission is to innovate microfluidic platform enginering by vertically integrating a full suite of necessary functions, including novel material technology (polymer laminate; PLT), rapid prototyping, manufacturing, and the supply chain network.
The PLT process begins with a 2-D CAD design “split” into necessary layers, 12.5 micron to 3 mm thick. The layers are designed to incorporate necessary microfluidics features such as channels, valves, pumps, and filters. Different stock polymer materials can be used for each layer. The layers are cut with CO2 gas lasers and stacked and bonded using pressure-sensitive adhesives.
ALine’s fabrication approach simplifies connection to the valves, membranes, sensors, and other interfaces. “The eSENSOR® Genotyping cartridge for warfarin sensitivity testing developed by ALine and GenMark Diagnostics combines polymer laminate layers containing complex fluid channels with the injection molded part for sample loading and the electrical sensor circuit,” Dr. Levine continues.
“This product required numerous design iterations to empirically optimize pumping functions and material selection. But now we have the capacity to produce 25,000 parts per month in our current facility.”