Common Material Challenges in Miniaturizing In Vitro Diagnostics

The miniaturization of diagnostic tests comes with several unique challenges. The aim is to transform the fast turnaround time and specificity of Lab on a Chip (LOC) diagnostics into a mass-produced product that delivers the same result to consumers in the real world. For researchers, overcoming these challenges means designing specifications and meeting investors' requirements in order to manufacture a product that meets customers' needs to a high degree of accuracy.

There is significant potential for point-of-care (POC) diagnostics to vastly improve disease detection and treatment in developing countries, adding to the need for miniaturized diagnostics to meet cost and durability requirements in order to be produced and transported on a large scale. In this article we touch on some of the challenges that come with miniaturizing in-vitro diagnostics for POC use.

Materials

Cost

Common LOC diagnostics include those that make use of arrays and beads, manufactured on glass or silicone, which poses a problem for POC manufacture; these can be high-cost materials. Particularly when considering the potential for POC diagnostics to revolutionize healthcare in developing nations, cost-effective materials, such as paper or plastic, are a necessary component.

Properties

Additionally, the materials used in a POC diagnostic test should be flexible and able to withstand the stresses of an unpredictable environment. Laboratories are well-controlled in several aspects; humidity, temperature, introduction of foreign materials, and the manner of operation of the tests themselves.

Lateral flow tests that utilize capillary action to draw samples up a sample and conjugate pad and onto a membrane have been applied with great success to POC diagnostics, as in the case of pregnancy tests and detection strips for numerous pathogens. There are several considerations involved in transferring lateral flow assays from the lab to the public. The chosen materials for the sample and conjugate pads have implications for the design of the device's housing and the accuracy of the test. For example, the thickness, porosity, and tensile strength affect the volume and rate at which the sample travels to the membrane. Additionally, the smaller samples associated with POC diagnostics require materials that can compensate with greater capillary action. 

The challenges associated with the materials used in a POC diagnostic test extend to the rest of the challenges outlined below. The functional issues associated with designing and launching a durable, easy-to-use POC diagnostic test hinge on the qualities of the chosen materials.

Detecting Low Concentrations

For devices like a blood glucose monitor, the concentrations are in a range that surpasses that needed to detect and measure them. A normal blood glucose level ranges from 70-130 mg/dL. Other targets are present at far lower concentrations, adding complexity to the issue. For example, some cancer markers are present at concentrations of 10^-14g/mL. A LOC device detecting low concentrations of a target requires that either the target is amplified prior to testing, or the sensitivity of the device is increased. This poses challenges to the user who does not possess training to complete extra steps in order to operate the device.

Quantifying

Miniaturized in vitro diagnostics are often limited to a binary output; a yes or no test is much simpler to design, manufacture, and apply to public use than a test with the capability to quantify. Quantitation is quite possible on LOC diagnostic tests performed by trained technicians. Methods include everything from mass spectrometry to ELISA. Attempts to miniaturize diagnostic quantitation, however, have proven to be complex.

Facing Complexity

POC devices need to be able to take the user from sample collection all the way through to presenting a result. This makes the complexity of the device a significant challenge. The number of steps involved in a diagnostic test, such as that involving blood, varies depending on the test, but may include complex sample collection, pre-processing of the sample to eliminate unwanted components, and may even require input or management by the user. To introduce such complex processes into the market as a single, user-friendly product is a significant challenge to overcome. 

Conclusion

Miniaturizing in vitro diagnostics is a challenging goal, but one that has the potential to bring great change to healthcare. The challenges outlined above do not form an exhaustive list of the issues facing the design and production of POC diagnostic devices. However, none of these challenges are insurmountable.