Continuous Monitoring of CRP, IL-6, and Calprotectin in Inflammatory Bowel Disease Using a Perspiration-Based Wearable Device.

BACKGROUND: Wearable sensor devices represent a noninvasive technology to continuously track biomarkers linked to inflammatory bowel disease (IBD). We assessed the inflammatory markers associated with IBD in human perspiration. METHODS: Participants with IBD were monitored for 40 to 130 minutes with a proprietary wearable sensor device used to measure C-reactive protein, interleukin-6, and calprotectin. Sensor response using electrochemical impedance spectroscopy and serum samples were measured on the same day. The Mann-Whitney test was used to analyze the relationship between active and remission IBD in serum and perspiration, classified according to endoscopic reports and serum biomarker levels. Asynchronously collected fecal calprotectin from a subset of the population was similarly analyzed. RESULTS: A total of 33 subjects were enrolled. Expression of calprotectin was significantly elevated in the active cohort compared with the remission cohort in perspiration (P < .05; median = 906.69 ng/mL; active 95% confidence interval [CI], 466.0-1833 ng/mL; remission 95% CI, 328.4-950.8 ng/mL), serum (median = 1860.82 ng/mL; active 95% CI, 1705-2985 ng/mL; remission 95% CI, 870.2-1786 ng/mL), and stool (P < .05; median = 126.74 µg/g; active 95% CI, 77.08-347.1 µg/g; remission 95% CI, 5.038-190.4 µg/g). Expression of CRP in perspiration and serum was comparable between the active and remission cohorts (perspiration: P > .05; median = 970.83 pg/mL; active 95% CI, 908.7-992 pg/mL; remission 95% CI, 903.3-991.9 pg/mL; serum: median = 2.34 µg/mL; active 95% CI, 1.267-4.492 µg/mL; remission 95% CI, 1.648-4.287 µg/mL). Expression of interleukin-6 in perspiration was nonsignificant in the active cohort compared with the remission cohort and was significantly elevated in serum (perspiration: P < .05; median = 2.13 pg/mL; active 95% CI, 2.124-2.44 pg/mL; remission 95% CI, 1.661-2.451 pg/mL; serum: median = 1.15 pg/mL; active 95% CI, 1.549-3.964 pg/mL; remission 95% CI, 0.4301-1.257 pg/mL). Analysis of the linear relationship between perspiration and serum calprotectin (R2 = 0.7195), C-reactive protein (R2 = 0.615), and interleukin-6 (R2 = 0.5411) demonstrated a strong to moderate relationship across mediums. CONCLUSIONS: We demonstrate the clinical utility of perspiration as a noninvasive medium for continuous measurement of inflammatory markers in IBD and find that the measures correlate with serum and stool markers across a range of disease activity.

This work establishes the clinical utility of perspiration as a noninvasive, continuous marker for gut inflammation and demonstrates the ability to distinguish between active and inactive inflammatory bowel disease across perspiration, serum, and stool.

Longitudinal assessment of sweat-based TNF-alpha in inflammatory bowel disease using a wearable device.

Wearable devices can non-invasively monitor patients with chronic diseases. Sweat is an easily accessible biofluid for continuous sampling of analytes, including inflammatory markers and cytokines. We evaluated a sweat sensing wearable device in subjects with and without inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract. Participants with an IBD related hospital admission and a C-reactive protein level above 5 mg/L wore a sweat sensing wearable device for up to 5 days. Tumor necrosis factor-alpha (TNF-α) levels were continually assessed in the sweat via the sensor, and daily in the blood. A second cohort of healthy subjects without chronic diseases wore the device for up to 48 h. Twenty-eight subjects were enrolled. In the 16 subjects with IBD, a moderate linear relationship between serum and sweat TNF-α levels was observed (R2 = 0.72). Subjects with IBD were found to have a mean sweat TNF-α level of 2.11 pg/mL, compared to a mean value of 0.19 pg/mL in 12 healthy controls (p < 0.0001). Sweat TNF-α measurements differentiated subjects with active IBD from healthy subjects with an AUC of 0.962 (95% CI 0.894-1.000). A sweat sensing wearable device can longitudinally measure key sweat-based markers of IBD. TNF-α levels in the sweat of subjects with IBD correlate with serum values, suggesting feasibility in non-invasive disease monitoring.

Longitudinal monitoring of IL-6 and CRP in inflammatory bowel disease using IBD-AWARE.

There are limitations to monitoring modalities for chronic inflammatory conditions, including inflammatory bowel disease (IBD). Wearable devices are scalable mobile health technology that present an opportunity to monitor markers that have been linked to worsening, chronic inflammatory conditions and enable remote monitoring. In this research article, we evaluate and demonstrate a proof-of-concept wearable device to longitudinally monitor inflammatory and immune markers linked to IBD disease activity in sweat compared to expression in serum. Sixteen participants with an IBD-related hospital admission and a C-reactive protein (CRP) > 5 µg/mL were followed for up to 5 days. The sweat sensing device also known as IBD AWARE was worn to continuously measure CRP and interleukin-6 (IL-6) in the sweat of participants via electrochemical impedance spectroscopy. Serum samples were collected daily. A linear relationship between serum and sweat readings for CRP and IL-6 was demonstrated based on individual linear correlation coefficients. Pooled CRP and IL-6 serum-to-sweat ratios demonstrated improving correlation coefficients as serum cutoffs decreased. Between the first and last day of observation, significant and non-significant trends in serum CRP and IL-6 were observed in the sweat. Comparison of sweat measurements between the subjects with active IBD and 10 healthy subjects distinguished an inflamed and uninflamed state with an AUC of 0.85 (95% CI: 0.68-1.00) and a sensitivity and specificity of 82% and 70% at a CRP cutoff of 938.9 pg/mL. IBD AWARE wearable device holds promise in longitudinally monitoring individuals with IBD and other inflammatory diseases.

A Proof-of-Concept Electrochemical Skin Sensor for Simultaneous Measurement of Glial Fibrillary Acidic Protein (GFAP) and Interleukin-6 (IL-6) for Management of Traumatic Brain Injuries.

This work demonstrates the use of a noninvasive, sweat-based dual biomarker electrochemical sensor for continuous, prognostic monitoring of a Traumatic Brain Injury (TBI) with the aim of enhancing patient outcomes and reducing the time to treatment after injury. A multiplexed SWEATSENSER was used for noninvasive continuous monitoring of glial fibrillary acidic protein (GFAP) and Interleukin-6 (IL-6) in a human sweat analog and in human sweat. Electrochemical impedance spectroscopy (EIS) and chronoamperometry (CA) were used to measure the sensor response. The assay chemistry was characterized using Fourier Transform Infrared Spectroscopy (FTIR). The SWEATSENSER was able to detect GFAP and IL-6 in sweat over a dynamic range of 3 log orders for GFAP and 2 log orders for IL-6. The limit of detection (LOD) for GFAP detection in the sweat analog was estimated to be 14 pg/mL using EIS and the LOD for IL-6 was estimated to be 10 pg/mL using EIS. An interference study was performed where the specific signal was significantly higher than the non-specific signal. Finally, the SWEATSENSER was able to distinguish between GFAP and IL-6 in simulated conditions of a TBI in human sweat. This work demonstrates the first proof-of-feasibility of a multiplexed TBI marker combined with cytokine and inflammatory marker detection in passively expressed sweat in a wearable form-factor that can be utilized toward better management of TBIs. This is the first step toward demonstrating a noninvasive enabling technology that can enable baseline tracking of an inflammatory response.

Renal biopsy under augmented reality guidance.

Kidney biopsies are currently performed using preoperative imaging to identify the lesion of interest and intraoperative imaging used to guide the biopsy needle to the tissue of interest. Often, these are not the same modalities forcing the physician to perform a mental cross-modality fusion of the preoperative and intraoperative scans. This limits the accuracy and reproducibility of the biopsy procedure. In this study, we developed an augmented reality system to display holographic representations of lesions superimposed on a phantom. This system allows the integration of preoperative CT scans with intraoperative ultrasound scans to better determine the lesion's real-time location. An automated deformable registration algorithm was used to increase the accuracy of the holographic lesion locations, and a magnetic tracking system was developed to provide guidance for the biopsy procedure. Our method achieved a targeting accuracy of 2.9 ± 1.5 mm in a renal phantom study.

A complex dual-modality kidney phantom for renal biopsy studies.

We developed a reliable and repeatable process to create hyper-realistic, kidney phantoms with tunable image visibility under ultrasound (US) and CT imaging modalities. A methodology was defined to create phantoms that could be produced for renal biopsy evaluation. The final complex kidney phantom was devised containing critical structures of a kidney: kidney cortex, medulla, and ureter. Simultaneously, some lesions were integrated into the phantom to mimic the presence of tumors during biopsy. The phantoms were created and scanned by ultrasound and CT scanners to verify the visibility of the complex internal structures and to observe the interactions between material properties. The result was a successful advancement in knowledge of materials with ideal acoustic and impedance properties to replicate human organs for the field of image-guided interventions.