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Implanted sensors to measure pH and other analytes with x-ray readout (Conference Presentation)

X-ray imaging is well-suited for deep tissue analysis, and is routinely used in medical diagnosis, but is normally blind to local biochemical signals. Here we describe simple passive implantable sensors that can report local chemical concentrations (e.g. pH), which are important for detecting and studying infection and other diseases or conditions. The sensors contain hydrogels with chemically-responsive swelling; the chemical concentration is determined using an X-ray to measure the position of radio-opaque markers in embedded in the hydrogel. For example, to measure local pH near the surface of an orthopedic plate, a sensor containing a polyacrylic acid hydrogel was attached to the plate. The hydrogel displayed a pH-dependent swelling, expanding approximately and moving an embedded radio-opaque tungsten marker. The sensor was calibrated in standard pH buffers and tested during bacterial growth in culture. Its response was negligibly affected by changes in temperature and sodium chloride concentration within the normal physiological range. Radiographic measurements were also performed in cadaveric tissue with the sensor attached to an implanted orthopedic plate fixed to a tibia. Pin position readings varied by 100 µm between observers surveying the same radiographs, corresponding to 0.065 pH unit precision in the range pH 4-8 (1.5 mm/pH unit). We are expanding the approach to other analytes (infection markers and mechanical strain sensors to track bone heaing), miniaturized injectable sensors, and imaging at multiple locations. 
Acknowledgement: This research was supported by the following grants: NSF CHE1255535, NIH NIGMS 5P20GM103444-07, NIH 1R21EB019709-01A1, and NIH NIAMS R01 AR070305-01.