Lab-on-Chip: an Overview

Lab-on-chip (LOC) technology has the potential to provide a robust and portable point-of-care (POC) toolset at a fraction of the size and cost of conventional laboratory sampling methods. However, it is still an emerging technology, and commercial applications of LOCs are presently limited. Several major technical bottlenecks hamper the commercial viability of LOCs, including material quality, commercial-scale fabrication challenges, sample complexity, and many other hindrances.

WHO ASSURED Standard

ASSURED (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable to end-users) is a World Health Organization (WHO) guideline for point-of-care (POC) devices. It lays out a set of ideal qualities that a POC device must possess to be effective in the field. A LOC, being a POC solution, should also satisfy all of the ASSURED criteria:

• Affordable it must be sufficiently cheap to be used in mass-scale operations such as preventive healthcare, disaster response, and disease diagnosis, especially for the developing world, to have a tangible impact on medical services; otherwise, high costs will limit its use and effectiveness.
• Sensitive  a well-designed LOC device must be sufficiently sensitive to reliably and consistently carry out operations on micro-scale biosamples.
• Specific By design, these systems should target specific biomarkers. However, future LOC applications may attempt to target several pathologies on a single chip.
• User-Friendly to be useful to untrained personnel such as police officers, disaster response crews, and the general public, it must require minimal training for use; otherwise, the potential for the device will be squandered by accessibility constraints.
• Rapid and Robust practical applications of LOCs should fulfill their namesake, they are labs on small polymer (or glass, silicon, cellulose, etc.) chips that provide a miniaturized version of a full-scale lab's functionality; however, in addition to offering robust diagnostic and measuring suites, LOCs must be able to produce rapid results much more quickly than a lab can.
• Equipment Free pumping, measuring, and reporting mechanisms for fluid samples should be present on the chip; the need for external interfaces is non-ideal. Additionally, they should be compact, battery-powered, and not require much in the way of sample preparation.
• Deliverable to end-users the fulfillment of this criteria is especially relevant for disaster response situations and the resource-limited environments of developing countries.

State of the Art

At present, very few LOC devices have moved out of the laboratory and into the field. Practical applications of LOCs are beset by a wider range of challenges than their lab-based counterparts (which are commercially available, yet limited). Such challenges include the complexity of fluid samples collected in the field (blood, feces, saliva, etc.) being difficult for LOC devices to handle, the necessity of off-chip equipment in LOC processes, and the lack of standardization and user-friendliness in state-of-the-art chip designs. However, LOCs see use within controlled medical settings, as complements to standard laboratory methods.

Many exploratory and commercially available LOCs are comprised of polymers such as polydimethylsiloxane (PDMS), polycarbonate, and polyolefin. PDMS possesses several qualities that make it especially well-suited for LOC applications such as optical transparency, low toxicity, and high permeability to oxygen and carbon dioxide (meaning PDMS chips can process living mammalian cells). Unfortunately, PDMS is difficult to manufacture on a commercial scale, thereby limiting the use of the most well-researched LOC material to experimental models and niche applications.

Microfluidic Paper-based Analytical Devices (µPADs) are convenient POC platforms that use (photoresist patterned) paper as the principal substrate through which fluids are processed. Cellulose-based paper has a natural porous microstructure that, due to capillary action, promotes lateral flow. This eliminates the need for external or complicating mechanisms like pumps to move fluid along a substrate. However, like their elastomeric counterparts, mass production of µPADs is a bottleneck. At present, there is a conflict between cost and performance considerations during fabrication. Nonetheless, the fact that µPADs are demonstrably useful in diagnosing and monitoring a range of conditions, notably diabetes, suggests that µPADs may be a viable POC device candidate for answering the growing demand for chronic disease monitoring systems.

Conclusion

For more than two decades, lab-on-a-chip devices have promised to one day make healthcare more accessible, convenient, and affordable. Material constraints, manufacturing problems, technical complexities, and a myriad of other issues have prevented the fulfillment of this promise. However, as the potential market for LOCs continues to expand, as the pace of research continues to exponentiate, and as the demand for a LOC healthcare solution continues to grow, it is possible that the emergence of a mass-market LOC device is on the horizon.