LC contact lens sensor for ultrasensitive intraocular pressure monitoring

Glaucoma, a leading cause of irreversible vision loss, affects millions globally. Early detection and management are vital, necessitating continuous IOP monitoring. Current tonometers provide only intermittent measurements, insufficient for understanding IOP fluctuations. Implantable sensors offer high accuracy but carry surgical risks. Contact lens sensors offer a non-invasive alternative, with electrical sensors (specifically LC resonant sensors) showing promise for 24-hour monitoring. However, existing LC sensors often lack sufficient sensitivity or suffer from poor wearing comfort due to rigid components. This research addresses these limitations by introducing a novel LC sensor design with enhanced sensitivity and improved comfort.

Existing technologies for continuous IOP monitoring include implantable and wearable sensors. Implantable sensors, while accurate, involve surgery and potential long-term complications. Wearable sensors, particularly contact lens-based devices, offer a less invasive approach. These contact lenses utilize various sensing principles including microfluidic, optical, and electrical methods. Microfluidic and optical sensors are limited by their dependence on visual or optical signals and cannot function with closed eyelids. Electrical sensors, particularly those based on LC resonant circuits, offer the capability of 24-hour IOP monitoring. However, existing LC sensors, including those using liquid metal for stretchability, have demonstrated slightly insufficient sensitivity. This study aims to overcome this limitation by proposing a novel LC sensor design.

The researchers designed a contact lens sensor employing room temperature liquid metal (GaInSn) integrated within a soft silicone matrix. The liquid metal forms both an inductive coil and a capacitive plate, enabling simultaneous sensing of IOP changes. The device's fabrication involves microchannel liquid metal injection, using soft lithography and surface-modified bonding techniques. The sensing mechanism is modeled analytically, validated by finite element analysis (FEM), investigating the influence of corneal parameters (elastic modulus, thickness), tear film parameters (elastic modulus, thickness), and contact lens parameters (elastic modulus, thickness, diameter, coil radius) on sensitivity. Usability and reliability tests included burst testing for sealing strength, oxygen permeability and light transmittance measurements, in vivo wearability testing in rabbits, and cyclic stretching/folding tests. The sensor's performance was evaluated using biomimetic eyeballs with varying mechanical properties, enucleated porcine eyes (ex vivo), and in vivo pig eyes. Finally, in vivo human eye evaluations assessed wearability and sensor performance during a head-down bed-rest experiment, comparing the sensor's IOP measurements with those obtained using an Icare tonometer.

The developed LC sensor demonstrates several key features: 1. **Enhanced Sensitivity:** The sensor exhibits a threefold increase in sensitivity compared to existing liquid metal inductive sensors, achieving sensitivities of 1665 ppm/mmHg and 2209 ppm/mmHg in biomimetic eyeballs and 1211-1252 ppm/mmHg in enucleated porcine eyes, and 1213 ppm/mmHg and 1595 ppm/mmHg in vivo pig and human eyes respectively. This surpasses the sensitivity of current state-of-the-art wearable tonometers. 2. **Reliability and Biocompatibility:** The device passes rigorous reliability tests, including burst testing (withstanding pressures exceeding 36 psi), demonstrating robust sealing of the liquid metal. The oxygen permeability exceeds commercial contact lens standards, ensuring sufficient oxygen transmission to the cornea. Light transmittance is above 93%, and in vivo rabbit studies show excellent corneal wearability with no abrasion. 3. **In Vivo Performance:** The sensor accurately tracks IOP changes in both biomimetic and biological eyes (pig and human), demonstrating real-time responsiveness to pressure variations. The in vivo tests in pigs and humans show a strong correlation between the sensor’s measurements and those obtained using standard tonometers (Icare). 4. **Modeling Accuracy:** Analytical and FEM models accurately predict the sensor's behavior and show that the sensitivity is influenced by corneal and tear film properties and the contact lens structure. The analytical model provides a valuable tool for optimizing sensor design. 5. **Robust Wireless Signal:** Sensor signal acquisition is wireless and robust to misalignment and small displacements between the sensor and the reader coil.

The results demonstrate the success in developing a highly sensitive and reliable LC contact lens sensor for continuous IOP monitoring. The threefold increase in sensitivity compared to previous liquid metal-based inductive sensors represents a significant advancement. The sensor's biocompatibility and reliable operation in both animal and human studies pave the way for potential clinical applications in glaucoma management. The accurate tracking of IOP fluctuations over time, particularly the ability to detect both diurnal and nocturnal variations, provides valuable insights into disease progression and treatment response that are impossible with current intermittent measurement techniques. The analytical and FEM modeling contribute to a deeper understanding of the sensor’s behavior and can guide further design optimizations.

This study successfully developed a highly sensitive LC contact lens sensor for continuous IOP monitoring. The device shows significant improvements in sensitivity, reliability, and biocompatibility compared to existing technologies. Future work will focus on mass production using printing methods and developing personalized calibration models using corneal biomechanical parameters and deep learning techniques to further enhance accuracy and clinical applicability. This technology holds significant promise for improving glaucoma care.

The study's limitations include the relatively small sample size for in vivo human trials. Further research with larger cohorts is necessary to confirm the sensor's performance and clinical utility. The response of the sensor is dependent on corneal stiffness, which varies among individuals. Therefore, future research will focus on incorporating methods to account for individual variations in corneal biomechanics. Long-term in vivo studies are needed to fully assess the sensor's long-term stability and potential long-term effects on the ocular surface.