Factors pushing IVD device fabrication limits

The desire to reduce sample size and reagent consumption, increase speed of analysis, and decrease cost, contribute to the factors pushing IVD device fabrication limits while increasing the device functional integration and complexity. Post-fabrication modifications, such as biological recognition molecules, coatings, and other steps, also influence device production workflow and cost.

A microfluidic flow cell approach allows for the automation of the analysis of volumes smaller than a drop of blood. However, the dimensions and complexity of microfluidic flow cells for IVDs present significant challenges to IVD device design, fabrication, and production scale-up.

Overcoming obstacles for IVD devices

Choosing the right material for a microfluidic flow cell for IVD devices can be the first step in guaranteeing IVD performance within budget and schedule.

Each material has its strengths. Silicon is most useful for the arbitrary aspect ratios that can be etched using anisotropic chemical etch or reactive ion etch. However, with the advent of advanced laser microfabrication, glass is becoming more and more feasible.

Both glass and silicon are easy to modify with additive methods such as standard processes from the MEMS and the optical industry e.g. chemical vapor deposition in order to add other materials, metals and dielectric coatings, for additional functionality such as electrodes or waveguides. The patterning of Indium Tin Oxide (ITO), the best material for electrowetting and spectroelectrochemical applications for digital microfluidics, on glass is robust and well understood [1].

Silicon oxide layers can be created on silicon, introducing regions that have some glass like properties. The ability to create three dimensional structures, for example to create a scaffold for cells, is attribute of silicon that makes it a strong candidate for organ-on-a-chip applications. However, soft lithography materials such as PDMS, and 3D printed materials such as hydrogels, biopolymers, and cells, are even more attractive because of their biocompatibility and likelihood of maintaining cell viability.

Hybrid materials – glass on silicon, silicon on glass, and plastic on glass, can also be constructed to enhance surface properties that are more favorable to the health and functionality of the bioassay and its biological components. Post-fabrication modification using silanization chemistry to create hydrophilic, hydrophobic, or chemically reactive surfaces is best understood for glass.

Nonetheless, polymers have their sweet spots. Many applications, such as immunoassay, have well understood methodologies for dealing with polymer surfaces, and the cost for millions of disposables is hard to beat using glass or silicon. Additionally, the cyclic polyolefins can give a “good enough” optical transparency and auto-fluorescence for many applications. The cost of consumable reagents is also driving IVD developers to explore label-free approaches, reducing the need for optical transparence and low auto-fluorescence in those cases.

For applications such as PCR, the physical properties of glass (thermal expansion coefficient and low auto-fluorescence) are hard to beat, though silicon-glass devices and other hybrid devices, are very commonly employed. Where electrokinetic forces are required, glass is often the best choice due to its high impedance and the ability to control its surface charge.

The desire to reduce sample size and reagent consumption, increase speed of analysis, and decrease cost, is pushing IVD device fabrication to new limits while increasing the device functional integration and complexity. Post-fabrication modifications, such as biological recognition molecules, coatings, and other steps, also influence device production workflow and cost.

A microfluidic flow cell approach allows for the automation of the analysis of volumes smaller than a drop of blood. However, the dimensions and complexity of microfluidic flow cells for IVDs present significant challenges to IVD device design, fabrication, and production scale-up.