An implantable sensor developed to measure synovial fluid pH for noninvasive early detection and monitoring of hip infections using standard‐of‐care plain radiography is described. The sensor is made of a pH responsive polyacrylic acid‐based hydrogel, which expands at high pH and contracts at low pH. A radiodense tantalum bead and a tungsten wire are embedded in the two ends of the hydrogel to monitor the change in length of the hydrogel sensor in response to pH via plain radiography. The effective acid dissociation constant (pKa) of the hydrogel‐based pH sensor is 5.6 with a sensitivity of 3 mm/pH unit between pH 4 and 8. The sensor shows a linear response and reversibility in the physiologically relevant pH range of pH 6.5 and 7.5 in both buffer and bovine synovial fluid solutions with a 30‐minute time constant. The sensor is attached to an explanted prosthetic hip, and the pH response is determined from the X‐ray images by measuring the length between the tantalum bead and the radiopaque wire. Therefore, the developed sensor will enable noninvasive detection and studying of implant hip infection using plain radiography.
The advent of implanted medical devices has greatly improved the quality of life and increased longevity. However, infection remains a significant risk because bacteria can colonize device surfaces and form biofilms that are resistant to antibiotics and the host’s immune system. Several factors contribute to this resistance, including heterogeneous biochemical and pH microenvironments that can affect bacterial growth and interfere with antibiotic biochemistry; dormant regions in the biofilm with low oxygen, pH, and metabolites; slow bacterial growth and division; and poor antibody penetration through the biofilm, which may also be regions with poor acid product clearance. Measuring pH in biofilms is thus key to understanding their biochemistry and offers potential routes to detect and treat latent infections. This review covers the causes of biofilm pH changes and simulations, general findings of metabolite-dependent pH gradients, methods for measuring pH in biofilms, effects of pH on biofilms, and pH-targeted antimicrobial-based approaches.
Peritonitis is a common complication for patients with end-stage renal disease undergoing peritoneal dialysis (PD) and is a direct cause or contributor in >15% deaths in PD patients. Since early detection is key to treatment, patients and their care teams need rapid, on-site diagnostics. A hydrogelbased peritoneal fluid pH sensor attached to a peritoneal dialysis catheter is developed to measure local acidosis indicative of peritoneal infections for early detection and monitoring of infections using X-ray imaging. The sensor comprises a polyacrylic acid hydrogel with embedded radiopaque markers enclosed in a polymer casing; contraction of the hydrogel in response to acidic pH is evident from the radiographically measured marker position. The sensor has a pH 4-8 response range; between pH 6.5 and 7.5 it responds linearly with a slope of 14% pH 7 length per pH unit, and about 1% length precision. The sensor is attached to a catheter and implanted in a rat peritoneum. Results in awake rats show a rapid pH drop during infection not observed in systemic C-reactive proteins (CRP) levels nor in the uninfected control animal, with negligible drift over 2 weeks. To our knowledge, this is the first report of an in vivo chemically responsive hydrogel sensor.
A radiographically visualized implantable dissolved carbon dioxide (CO2) sensor is developed to non‐invasively detect and monitor hip infections. The sensor is based on a pH‐responsive hydrogel as the sensing material, immersed in a carbonate buffer contained in a capsule with a CO2‐permeable membrane. Dissolved CO2 decreases the buffer pH causing the polyacrylic acid‐based hydrogel to shrink. The hydrogel length is determined using plain radiography by measuring the movement of a radiodense tantalum bead embedded in the hydrogel with respect to a metal wire in the casing. The sensor shows a clear response in the range of 15–115 mm Hg CO2, with a 4.3 mm Hg precision at 15 mm Hg CO2 level and a 6.4‐hour response time. The hydrophobic CO2‐permeable membrane is impermeable to aqueous molecules rendering the CO2 measurement independent of the external solution pH, which can be measured with a separate X‐ray visualized sensor. Separating the sensor from the aqueous environment is also expected to reduce the potential for biofouling and increase longevity. In summary, the first dissolved gas sensor that can be visualized radiographically is described; it has potential applications in detecting and studying implant infection and local carbon tissue CO2 levels.
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