One of the main challenges for implantable biomedical sensing schemes is obtaining a reliable signal while maintaining biocompatibility. In this work, we demonstrate that a combination of medical ultrasound imaging and smart hydrogel micromechanical resonators can be employed for continuous monitoring of analyte concentrations. The sensing principle is based on the shift of the mechanical resonance frequencies of smart hydrogel structures induced by their volume-phase transition in response to changing analyte levels. This shift can then be measured as a contrast change in the ultrasound images due to resonance absorption of ultrasound waves. This concept eliminates the need for implanting complex electronics or employing transcutaneous connections for sensing biomedical analytes in vivo. Here, we present proof-of-principle experiments that monitor in vitro changes in ionic strength and glucose concentrations to demonstrate the capabilities and potential of this versatile sensing platform technology.

A novel glucose sensor is presented using smart hydrogels as biocompatible implantable sensing elements, which eliminates the need for implanted electronics and uses an external medical-grade ultrasound transducer for readout. The readout mechanism uses resonance absorption of ultrasound waves in glucose-sensitive hydrogels. In vivo glucose concentration changes in the interstitial fluid lead to swelling or deswelling of the gels, which changes the resonance behavior. The hydrogels are designed and shaped such as to exhibit specific mechanical resonance frequencies while remaining sonolucent to other frequencies. Thus, they allow conventional and continued ultrasound imaging, while yielding a sensing signal at specific frequencies that correlate with glucose concentration. The resonance frequencies can be tuned by changing the shape and mechanical properties of the gel structures, such as to allow for multiple, colocated implanted hydrogels with different sensing characteristics or targets to be employed and read out, without interference using the same ultrasound transducer, by simply toggling frequencies. The fact that there is no need for any implantable electronics, also opens up the path toward future use of biodegradable hydrogels, thus creating a platform that allows injection of sensors that do not need to be retrieved when they reach the end of their useful lifespan.

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There is a strong commercial need for inexpensive point-of-use sensors for monitoring disease biomarkers or environmental contaminants in drinking water. Point-of-use sensors that employ smart polymer hydrogels as recognition elements can be tailored to detect almost any target analyte, but often suffer from long response times. Hence, we describe here a fabrication process that can be used to manufacture low-cost point-of-use hydrogel-based microfluidics sensors with short response times. In this process, mask-templated UV photopolymerization is used to produce arrays of smart hydrogel pillars inside sub-millimeter channels located upon microfluidics devices. When these pillars contact aqueous solutions containing a target analyte, they swell or shrink, thereby changing the resistance of the microfluidic channel to ionic current flow when a small bias voltage is applied to the system. Hence resistance measurements can be used to transduce hydrogel swelling changes into electrical signals. The only instrumentation required is a simple portable potentiostat that can be operated using a smartphone or a laptop, thus making the system suitable for point of use. Rapid hydrogel response rate is achieved by fabricating arrays of smart hydrogels that have large surface area-to-volume ratios.

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