Smart Hydrogel Micromechanical Resonators with Ultrasound Readout for Biomedical Sensing

Abstract

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.

In vivo Monitoring of Glucose using Ultrasound-induced Resonance in Implantable Smart Hydrogel Microstructures

“…The response time of the hydrogel structures was also compared by calculating their T90 value using an exponential fit [36] when transitioning from an external environment containing no glucose to 2 mM glucose. The transition to higher glucose levels results in a negative correlation with MGV, as reported before [26] . The T90 response time was 2.2 h (R 2 =98.8%) for autoclaved, and 5.1 h (R 2 =98.9%) and 3.5 h (R 2 =99.9%) for non-autoclaved samples.…”

“…Nevertheless, the mean grayscale value (MGV) of the box always contains the information on the absorption of ultrasound waves by the hydrogel structure(s) as long as the position of the box is kept constant throughout all the images. With respect to the in vivo experiments, the disruptions resulted from the natural reflexes, movements, and relaxation of the body were observed in the MGV signal as a step change of the overall level of the signal, which was not observed in our in vitro experiments [26,36] . These disruptions were corrected using a baseline correction technique in addition to the previously applied stabilization technique.…”

“…Fabrication of the implants The stimuli-responsive hydrogels used in this study contain boronic acid moieties incorporated into the polymer network, enabling them to have a reversible volume response to glucose. It is shown that pH and ionic strength also create a volume response in these types of hydrogels [26,27] . The fabrication process for the hydrogel structures was previously described in detail [26] .…”

“…Two-dimensional pulse-echo (B-Mode) images were acquired at 4 MHz on the ultrasound probe (9L4, Siemens Medical Solutions USA, Inc.) and were saved in an 8-bit grayscale format. The imaging plane for the ultrasound array was adjusted to create a cross-sectional ultrasound image of the implants similar to our previous report [26] . The focal length was adjusted to the minimum possible value (3 cm).…”

A Hydrogel-Based Ultrasonic Backscattering Wireless Biochemical Sensing

“…In contrast, ultrasound can be coupled with the hydrogel's volume response to infer the target stimuli. The ultrasound can offer unique advantages including a long interrogation depth and small sensor dimensions, and simplicity as demonstrated by some of the previous works (Troïani et al, 2011;Park et al, 2018;Farhoudi et al, 2020). In order to achieve the high accuracy, however, the ultrasound interrogation scheme should account for the scattering in biological tissues, which are often unpredictable in its nature (Shung and Thieme, 1992).…”