Future prospects of biosensor devices.

Challenges of Current Methods and Devices: 

The use of boronic acid-based detection of glucose has been fundamental in developing colorimetric and fluorescent glucose detecting contact lens sensors that respond well to millimolar concentrations of glucose. However, the sensitivity of these has been found to decrease after incorporation into contact lenses.

An issue with fluorescence-based detection systems is the choice of the fluorophore as photochemical stability is important for long periods of time in continuous monitoring cases, and many fluorophores display limited solubility in aqueous media. Additionally, lactate and other saccharides can be major interfering species in boronic acid sensors as concentrations for lactate range from 1 to 5 mm in the tear fluid. These issues affect both fluorescent and holographic sensors that utilize the boronic acid-binding to glucose for detection. Hence, further investigation into increasing the sensitivity and selectivity of boronic acid-based sensors is required before use in clinical settings.

Biosensors that utilize enzymatic reactions, such as GOD and LOD, to produce electrochemical signals usually face issues with sensing stability. Although enzyme-based sensors show high sensitivity, selectivity, efficiency, and low cost, their downfall is the short lifespan enzymes have due to degradation. This drawback limits enzymatic biosensors to be used within their short effective periods to ensure accuracy. Operating conditions, such as temperature, humidity, and pH can limit the general use of these enzymatic biosensors as well. Also, contact lenses need to be sterilized, via autoclave according to regulations. Unfortunately, the sterilization process is likely to denature the essential enzymes. There are also issues related to effective immobilization of the enzymes, and the unwanted reaction of H₂O₂ and redox-active species, such as ascorbic acid that can interfere with the signal. Moreover, electrochemical sensors require external power to drive the reactions, which is problematic in developing contact lenses for long observation periods.

One major challenge to using contact lens biosensors is repeatability/stability. Obviously, this ability heavily depends on a well-established calibration for each device. The tedious procedure is potentially necessary for clinical environments due to background interferences. Big data acquired from clinical trials can certainly provide valuable information for such calibration purposes. However, a large number of patients needed for the database and expected years of work can also pose a challenging task to interested researchers. Other considerations of the adverse effects raise from continuously wearing contact lens, which would be necessary for long-term observation. In this regard, discomfort, irritation, microbial infection, and inflammatory issues that exist for the general wearing of contact lenses will also occur in contact lens biosensors.

Last but not least is clinical perspectives. Although these concerns are rarely discussed to date, they can be key to the prevalence of contact lens biosensors. An important aspect of which is the management of continuous monitoring of diseases and drug administration. The good coupling between both actions is critical to some diseases, such as diabetes. Another consideration is the comfort of wear. This demand becomes more difficult to achieve after integrating too many components with the contact lens platform. Nevertheless, this factor will determine the actual length of time to be accepted by wearers. Also, an underlying concern is a potentially high cost due to the sophisticated fabrication of the device. This concern may form a barrier to prevent the contact lens sensors from being disposable. Clinical acceptance can also be an issue since data measured from tears is non-standard as compared to blood. How to bridge the gap between blood and other body fluids and convince clinicians their feasibility needs time and tremendous effort.

Conclusion:

The development of contact lens sensor technology has gained traction in the past decade largely due to advances in the miniaturization of electrical circuits and the identification of relevant biomarkers in the tear fluid. This sensor platform has several advantages, including minimally invasive, continuously monitoring of biomarkers. Additionally, smart contact lenses appeal more to patients because of the familiarity of the product and ease of use. However, great improvements are still under work for such types of platforms, such as specificity, sensitivity, biocompatibility, integration with readout circuitry, and reproducibility to achieve practicality. With these issues resolved, it is expected that the use of contact lens biosensors will lead to better personalized medical treatment.

As an emerging technology, contact lens biosensors still face challenges as they move from theory to practice. However, numerous studies up to date have demonstrated the potential of this platform. To this end, other advanced technologies and fabrication techniques have been incorporated into this platform, such as graphene coatings, nanoparticles, and quantum dots to provide readouts compatible with existing electronic devices (smartphones, laptops, and tablets). The pairing of sensors and mobile technology can facilitate real-time data acquisition and transfer to physicians for efficient diagnosis. Notably, this platform will be able to assist future drug therapies and treatments as well. Additionally, a greater understanding of the link between disease and ocular biomarker concentrations is required to enable the practicability of multifunctional contact lens biosensors.