LC contact lens sensor for ultrasensitive intraocular pressure monitoring

Glaucoma is a leading cause of irreversible blindness and affects tens of millions worldwide. IOP fluctuates with circadian rhythms and daily activities, with higher nighttime values, necessitating continuous, 24-hour monitoring to optimize treatment. Conventional tonometers provide intermittent measurements and miss critical fluctuations. Emerging implantable and wearable sensors offer continuous monitoring; implantables are accurate but limited by surgical risks and long-term safety concerns. Wearable contact-lens sensors provide a non-invasive, detachable alternative. Existing modalities include microfluidic, optical, and electrical approaches; only electrical sensors (RFIC-based and LC resonant) can measure around the clock, including with eyelids closed. RFIC-based lenses add thickness and rigidity, compromising comfort and safety. LC-based sensors are simpler and more comfortable, but stretchable inductive LC lenses built with liquid metal have had limited sensitivity. This work proposes an LC contact lens sensor in which both the inductive coil and the facing double-layer segments form a stretchable inductor and capacitor, enabling simultaneous inductive and capacitive responses to corneal deformation from IOP and thereby enhancing sensitivity.

Wearable IOP sensors include microfluidic channels that transduce corneal curvature/strain to fluid displacement, and optical methods (e.g., photonic crystals), but both are limited under closed eyelids or low-light conditions. Electrical systems comprise RFIC-based platforms (e.g., TriggerFish) that enable system-level functionalities but increase lens thickness and stiffness, risking abrasion and discomfort, especially at night. LC resonant sensors fabricated from Cu/Au, silver composites, or room-temperature liquid metals integrated in hydrogels, silicones, or polyimide enable passive wireless readout. Prior LC lenses typically sense IOP via inductive or compressible capacitive elements alone, limiting responsivity. State-of-the-art sensitivities reported include ~37–1121 ppm/mmHg for various LC and RFIC sensors, with comfort and transparency trade-offs. A previous liquid-metal stretchable inductive LC lens showed sensitivity ~37 ppm/mmHg, motivating designs that leverage both L and C changes to amplify frequency shifts under IOP.

Principle and modeling: The lens integrates room-temperature liquid metal microchannels encapsulated in silicone, forming an upper single-turn inductive coil and a lower return path aligned beneath it. Overlapping upper/lower segments form a parallel-plate capacitor with the silicone dielectric. Thus, the LC resonance depends on both inductance and capacitance, each changing with corneal-driven lens stretch under IOP. Resonant frequency and quality factor follow fr = 1/(2π√(LC)) and Q = (1/R)√(L/C). A mechanics-based analytical model combining thin-shell corneal deformation and shear-lag transfer across the tear film was developed to relate IOP to lens strain and LC parameter changes; assumptions include thin-shell cornea and linear elasticity for cornea and tear film. A 3D FEM (COMSOL) was built for validation. Sensitivity dependencies on cornea (modulus, thickness), tear film (modulus, thickness), and lens structural parameters (modulus, thickness, diameter, coil radius) were analyzed; analytical and FEM results agreed within ~17% error. Design and fabrication: Soft silicone rubber (MED-4286; E ≈ 0.08 ± 0.01 MPa) was used to reduce stiffness, with a lens thickness profile of 0.2 mm center and 0.45 mm periphery to preserve vision and house the coil. Lens diameter was 14.0 mm, with coil distribution diameters 12 and 10 mm to avoid the pupil. Microchannels (≈300 μm width × 100 μm height) were formed by soft lithography and bonded via corona treatment and thermal curing to create sealed channels. Liquid metal GaInSn (Ga68.5%/In21.5%/Sn10%) was injected through punched ports and sealed. The circular device was integrated into a contact lens mold for final curing. Fabrication steps included: casting/cure patterned and flat silicone films; surface activation and irreversible bonding; port punching; liquid metal injection; sealing; die-cutting (10.4 and 12.6 mm cutters); molding into the final lens. Device characterization: - Microchannel cross-sections were imaged by SEM. - Mechanical properties assessed by uniaxial tensile tests (ISO 37-2005). - Bonding/sealing strength by burst tests using a syringe pump and pressure transducer. - Oxygen permeability (Coulomb method, GB/T11417.7-2012) and optical transmittance (U-2910 spectrophotometer, 380–780 nm, GB/T11417.5-2012). - Surface wettability via contact angle after corona treatment. Usability, reliability, and safety: - Rabbit wear test (>16 h) with slit-lamp fluorescein staining to assess corneal integrity. - Mechanical reliability: 4000 cycles of 25% and 50% tensile strain and folding; frequency shifts monitored by handheld VNA (36211) via PCB reader coil. - Maintenance reliability: 10 vibration-cleaning cycles (20 min each) and 30-day storage in care solution, with periodic resonance checks. Wireless readout: Signals acquired from an external reader coil (integrated in glasses/eye mask or fixed via dressing) coupled to the lens; impedance real part spectra from a VNA were used as the primary readout for resonance tracking, robust to misalignment effects that mainly affect amplitude, not peak frequency. Performance testing: - Biomimetic eyeballs: Silicone corneas (PDMS 25:1 and 35:1; E ≈ 0.49 and 0.34 MPa) mounted on a pressurizable fixture with syringe pump and pressure gauge; lens conformally applied without additional tear film. Pressure cycled across 3–48 mmHg or 3–40 mmHg; spectra collected at up to 5 fps via a 2-turn PCB reader coil positioned within 8 mm. Analytical and FEM sensitivities computed with ttear=0 to match test configuration; compared with experiments. - Ex vivo porcine eyes (n=3): Needle-saline setup to control IOP (9–27 mmHg, 3 mmHg steps). Lens adhered via native mucus; reader coil within 8 mm; resonance measured at each step. - In vivo pig: One anesthetized miniature pig; one eye for LC sensing, contralateral for IOP by animal tonometer (Tonovet Plus). Six-hour session with half-hourly acquisitions; a bio-shock event induced IOP changes for calibration. - Human volunteers (n=2, prior contact lens users): Safety/comfort assessed after surface corona treatment. Wireless acquisition via goggles with integrated reader coil. Head-down tilt bed-rest (0° to −30° and back) induced IOP changes for calibration, with contralateral eye measured by Icare ic100. Longer-term tracking for 5–6 h with periodic acquisitions; noise mitigated by sliding evaluation algorithm. Thermal assessment: 12-h ex vivo porcine monitoring with infrared thermography to confirm negligible heating.

• Sensitivity enhancement by simultaneous L and C modulation: Analytical and FEM models predict near 3× sensitivity compared with inductance-only liquid-metal LC sensors; model–FEM agreement within ~17%. - Biomimetic eyeballs: Linear calibrations (R² > 0.99). Responsivity: 0.733 MHz/mmHg (1665 ppm/mmHg) for higher-modulus PDMS and 0.972 MHz/mmHg (2209 ppm/mmHg) for lower-modulus PDMS, consistent with theory (softer cornea → higher sensitivity). Experimental vs. model/FEM sensitivities within ~22% error. - Ex vivo porcine eyes (n=3): Linear fits in 9–30 mmHg range yield responsivities of −0.533, −0.484, and −0.551 MHz/mmHg (R² = 0.981, 0.976, 0.982), corresponding to sensitivities 1211, 1100, and 1252 ppm/mmHg. Nonlinear tissue mechanics caused larger responses at low IOPs. - In vivo pig (6 h): Responsivity −0.529 MHz/mmHg (R² = 0.993), sensitivity 1213 ppm/mmHg; resonance trends tracked IOP including a large drop after induced thoracic shock. - Human head-down tilt: Responsivity −0.702 MHz/mmHg (R² = 0.896), sensitivity 1595 ppm/mmHg; dynamic trends match Icare measurements. Five-hour follow-up showed close agreement between lens-derived IOP and Icare with consistent trends. - Misalignment tolerance: Increasing reader distance (4–12 mm) or angular deflection (0–45°) reduces peak amplitude but not peak frequency, preserving readout accuracy. - Usability and safety: Rabbit wear >16 h showed no corneal abrasion on fluorescein staining. Volunteers reported thickness greater than commercial lenses but acceptable; no overheating during continuous (25 min) or intermittent (5 h) acquisitions. Thermal imaging during 12-h ex vivo run showed no appreciable heating. - Reliability and robustness: • Burst pressure averaged 36.7 psi (>30 psi standard), indicating strong sealing. • Oxygen permeability >300×10^-11 (cm²/s)[mL O2/(mL·hPa)] (>>~50×10^-11 standard). • Visible transmittance >93%. • Surface contact angle 49° (hydrophilic after corona). • Mechanical cycling (4000 cycles at 25% and 50% strain; folding): resonance shift <0.3 MHz. • Vibration cleaning (10×): frequency shift ≤0.10 MHz. • 30 days storage: frequency shift within ±0.1 MHz. • Lens stretchability at least 120% tensile without failure. - Comparative performance: Table 1 indicates this work’s sensitivity (about −0.69 to −0.70 MHz/mmHg, ~−1560 to −1595 ppm/mmHg) achieves approximately threefold improvement over prior stretchable inductive LC lenses and exceeds sensitivities of other state-of-the-art wearable electrical tonometers.

The study addresses the unmet need for comfortable, continuous 24-h IOP monitoring by creating a passive LC contact lens in which both inductance and capacitance vary with corneal deformations transmitted through the tear film. By leveraging stretchable liquid-metal microchannels in a double-layer geometry, the device translates IOP-induced corneal expansion into larger resonance frequency shifts than inductance-only designs. Analytical and FEM models clarify parameter dependencies: increased corneal modulus or thickness reduces sensitivity; an optimal tear film modulus maximizes transfer; softer, thinner lenses and larger coil distribution radius on a smaller diameter lens enhance sensitivity. Experiments on biomimetic and biological eyes validate linear calibrations, real-time responsiveness, and insensitivity of peak frequency to coil misalignment, facilitating practical deployment. Safety and comfort metrics (oxygen permeability, transparency, hydrophilicity) meet or exceed commercial benchmarks, and reliability tests confirm mechanical and chemical robustness. In vivo pig and human tests demonstrate that lens resonance tracks physiological IOP changes and agrees with reference tonometry. Collectively, results confirm that simultaneous L and C sensing significantly enhances sensitivity while maintaining wearability and signal quality, advancing non-invasive glaucoma monitoring.

This work introduces a liquid-metal LC contact lens in which both the inductor and capacitor respond to IOP-driven corneal strain, yielding substantially increased resonance frequency shifts and approximately threefold sensitivity improvement over prior stretchable inductive LC lenses. Through modeling-guided design, microchannel-based fabrication, and extensive bench, ex vivo, and in vivo tests (porcine and human), the device demonstrates high signal quality, robustness, safety, and comfort, with linear calibration and tolerance to readout misalignment. Future directions include: (1) transitioning to scalable printing-based manufacturing for mass production; (2) developing individualized calibration models that integrate measured corneal biomechanics (e.g., via ocular response analyzer) with deep learning to account for intersubject variability and improve accuracy across diverse populations.

• Inter-subject variability: Sensitivity depends on corneal stiffness and thickness, causing variation between individuals; personalized calibration is required. - Modeling assumptions: Analytical model assumes thin-shell cornea and linear elastic behavior; comparative errors up to ~17% (analytical vs. FEM) and ~22% (models vs. biomimetic experiments) indicate simplifications. - Biomimetic tests lacked an explicit tear film layer, potentially overestimating strain transfer relative to in vivo conditions. - Human testing was limited to two volunteers and short durations (head-down tilt and ~5–6 h monitoring), without overnight or long-term clinical trials. - Device form factor: Volunteers perceived the lens as thicker than commercial hydrogel lenses (though acceptable), suggesting a need for further thinning/comfort optimization. - Current readout used a VNA and external reader coil; miniaturized, user-friendly consumer hardware and integrated wearers (e.g., masks/glasses) require further development for routine daily use.