PEER-REVIEWED PUBLICATION

2026

Tissue-adhesive hydrogel–MXene biosensor for in situ intraoral TNF-α detection

Wong TH, Liu W, et al.

Science Advances

Michigan State University, Texas A&M University

RESEARCH SUMMARY
This study reports a clinically oriented, in situ oral biosensing platform for real-time detection of the inflammatory cytokine TNF-α using a tissue-adhesive hydrogel–MXene (TAHM) device architecture. The sensor integrates (i) a graphene/MXene field-effect transistor (FET) sensing probe functionalized with a TNF-α aptamer, (ii) a selectively permeable hydrogel (SPH) membrane that acts as a molecular sieve to reduce biofouling and microbial interference while allowing TNF-α diffusion, and (iii) a tissue-adhesive hydrogel (TAH) patch that covalently bonds to wet tissue and the sensor substrate to maintain attachment and strain insensitivity in the dynamic oral environment. The TAHM biosensor demonstrated ultrasensitive TNF-α detection with a reported limit of detection of 18.2 fg/mL in heterogeneous conditions (with SPH), strong selectivity (interference coefficient <7%), and high mechanical signal stability with resistance variation <0.5% under changing stretch ratios, loading rates, and repeated cycling. Performance was validated across in vitro calibration in multiple artificial biofluids, ex vivo porcine gingiva sensing after local TNF-α injection, and in vivo guinea pig oral testing using a portable readout module, supporting translation of robust point-of-care oral inflammation diagnostics.

CELLSCALE INSTRUMENT USED

UStretch

Mechanical and interfacial characterization of the tissue-adhesive hydrogel (TAH) patch and the assembled TAHM sensor system was performed using a CellScale UStretch device (legacy CellScale platform; now superseded by UniVert. Using the UStretch, the authors quantified tissue adhesion via 90° peel testing following ASTM D6862: porcine skin (and separately porcine gingiva) was adhered to a glass substrate coated with a dried TAH patch, a gentle compressive preload (~5 kPa) was applied for ~5 s to ensure conformal contact, and the assembly was peeled at a constant rate of 1 mm/s while simultaneously translating the stage to maintain a constant 90° peeling geometry; steady-state peel force per unit width was used to compute interfacial toughness, and adhesion time and hydrogel thickness were systematically varied to map adhesion performance. The same UStretch platform was also used to characterize the bulk mechanics of the TAH patch via pure-shear tensile testing on unnotched and notched specimens after controlled rehydration (hydration-time-dependent modulus/stress–stretch behavior and fracture toughness), and to evaluate strain-insensitivity of the biosensor by mounting a sensor on a TAH patch, rehydrating the hydrogel, applying controlled uniaxial stretch magnitudes/frequencies and up to 500 cycles, and recording real-time resistance changes with a DAQ system—demonstrating minimal deformation-induced signal drift (<0.5%) while preserving TNF-α sensing response under strain.
AUTHORS

Wong T.H., Liu W., Li J., Ma J., Cheng Y., Lu R., Koster K.J., Cirillo J.D., Liu X., Sasaki H., Wu C., Lin S..

PUBLICATION DETAILS
JOURNAL

Science Advances

YEAR

2026

INSTITUTIONS

Michigan State University, Texas A&M University

COUNTRIES

United States

INSTRUMENT USED

UStretch

TESTING METHODS

Hydrated and Temperature Controlled TestingPeel TestingTensile Testing

RESEARCH APPLICATIONS

Dental & Oral Tissue BiomechanicsHydrogel Mechanical TestingWearable Bioelectronics

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