Wearable materials with embedded synthetic biology sensors for biomolecule detection.

Integrating synthetic biology into wearables could expand opportunities for noninvasive monitoring of physiological status, disease states and exposure to pathogens or toxins. However, the operation of synthetic circuits generally requires the presence of living, engineered bacteria, which has limited their application in wearables. Here we report lightweight, flexible substrates and textiles functionalized with freeze-dried, cell-free synthetic circuits, including CRISPR-based tools, that detect metabolites, chemicals and pathogen nucleic acid signatures. The wearable devices are activated upon rehydration from aqueous exposure events and report the presence of specific molecular targets by colorimetric changes or via an optical fiber network that detects fluorescent and luminescent outputs. The detection limits for nucleic acids rival current laboratory methods such as quantitative PCR. We demonstrate the development of a face mask with a lyophilized CRISPR sensor for wearable, noninvasive detection of SARS-CoV-2 at room temperature within 90 min, requiring no user intervention other than the press of a button.

Baseline-dependent effect of noise-enhanced insoles on gait variability in healthy elderly walkers.

The purpose of this study was to determine whether providing subsensory stochastic-resonance mechanical vibration to the foot soles of elderly walkers could decrease gait variability. In a randomized double-blind controlled trial, 29 subjects engaged in treadmill walking while wearing sandals customized with three actuators capable of producing stochastic-resonance mechanical vibration embedded in each sole. For each subject, we determined a subsensory level of vibration stimulation. After a 5-min acclimation period of walking with the footwear, subjects were asked to walk on the treadmill for six trials, each 30s long. Trials were pair-wise random: in three trials, actuators provided subsensory vibration; in the other trials, they did not. Subjects wore reflective markers to track body motion. Stochastic-resonance mechanical stimulation exhibited baseline-dependent effects on spatial stride-to-stride variability in gait, slightly increasing variability in subjects with least baseline variability and providing greater reductions in variability for subjects with greater baseline variability (p<.001). Thus, applying stochastic-resonance mechanical vibrations on the plantar surface of the foot reduces gait variability for subjects with more variable gait. Stochastic-resonance mechanical vibrations may provide an effective intervention for preventing falls in healthy elderly walkers.

Prolonged mechanical noise restores tactile sense in diabetic neuropathic patients.

Acute application of stochastic resonance (SR), defined as a subsensory level of mechanical noise presented directly to sensory neurons, improves the vibration and tactile perception in diabetic patients with mild to moderate neuropathy. This study examined the effect of 1 hour of continuous SR stimulation on sensory nerve function. Twenty diabetic patients were studied. The effect of stimulation was measured at 2 time points, at the beginning and after 60 minutes of continual SR stimulation. This effect was measured using the vibration perception threshold (VPT) at the big toe under 2 conditions: a null (no SR) condition and active SR, defined as mechanical noise below the subject's own threshold of perception. The measurements under null and active conditions were done randomly and the examiner was blinded regarding the type of condition. Immediately after SR application, the VPT with SR in null condition was similar to baseline (32.2 +/- 13.1, P = nonsignificant) but was significantly lower during active SR (27.4 +/- 11.9) compared with both baseline (P = .018) and off position (P = .045). The 60 minutes VPT with active SR (28.7 +/- 11.1) reached significance comparing the baseline when one outlier was removed from the analysis (P = .031). It may be concluded that SR for a continuous 60-minute period can sustain the VPT improvement in diabetic patients with moderate to severe neuropathy. These results permit the conclusion that there is no short-term adaptation to the stimulation signal. Long-term application of this technique, perhaps in the form of a continually vibrating shoe insert, or insole, may result in sustained improvement of nerve function.

Noise-enhanced balance control in patients with diabetes and patients with stroke.

OBJECTIVE: Somatosensory function declines with diabetic neuropathy and often with stroke, resulting in diminished motor performance. Recently, it has been shown that input noise can enhance human sensorimotor function. The goal of this study was to investigate whether subsensory mechanical noise applied to the soles of the feet via vibrating insoles can be used to improve quiet-standing balance control in 15 patients with diabetic neuropathy and 15 patients with stroke. Sway data of 12 healthy elderly subjects from a previous study on vibrating insoles were added for comparison. METHODS: Five traditional sway parameters and three sway parameters from random-walk analysis were computed for each trial (no noise or noise). RESULTS: Application of noise resulted in a statistically significant reduction in each of the eight sway parameters in the subjects with diabetic neuropathy, the subjects with stroke, and the elderly subjects. We also found that higher levels of baseline postural sway in sensory-impaired individuals was correlated with greater improvements in balance control with input noise. INTERPRETATION: This work indicates that noise-based devices could ameliorate diabetic and stroke impairments in balance control.

Enhancing sensation in diabetic neuropathic foot with mechanical noise.

OBJECTIVE: Localized low-level mechanical or electrical noise can significantly enhance tactile sensitivity in healthy young subjects and older adults. This phenomenon is termed stochastic resonance (SR). In this study, we examined the effect of SR on vibratory and tactile sensation in patients with moderate to severe diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS: A total of 20 subjects were included in the study. The vibration perception threshold (VPT) test and the Semmes-Weinstein filament (SWF) threshold at the plantar surface of the left foot and the big toe were determined under two mechanical noise stimulus conditions: null (no noise) condition and at 10% lower than each subject's mechanical noise threshold of perception. RESULTS: The baseline values (mean +/- SD) were as follows: Neuropathy Symptom Score (NSS) 5.2 +/- 2.5, Neuropathy Disability Score (NDS) 5.0 +/- 2.1, VPT 24 +/- 11 V, and SWF threshold 5.6 +/- 0.8 at the plantar surface of the foot and 5.3 +/- 0.9 at the big toe. The VPT improved significantly from 24 +/- 11 under null condition to 19 +/- 10 V with mechanical noise (P < 0.0001). Mechanical noise also significantly increased the number of detections of the SWF at the plantar surface of the foot (detection rate 66 +/- 11 vs. 59 +/- 15%, P < 0.02) but not at the big toe (63 +/- 10 vs. 61 +/- 16%, P = NS). CONCLUSIONS: Mechanical noise stimulation improves vibration and tactile perception in diabetic patients with moderate to severe neuropathy. Additional studies are required to examine the effect of long-term noise stimulation on parameters of nerve function.

Vibrating insoles and balance control in elderly people.

Somatosensory function declines with age, and such changes have been associated with diminished motor performance. Input noise can enhance sensory and motor function. We asked young and elderly participants to stand quietly on vibrating gel-based insoles, and calculated sway parameters and random-walk variables. In our 27 participants, application of noise resulted in a reduction in seven of eight sway parameters in young participants and all of the sway variables in elderly participants. Elderly participants showed greater improvement than young people in two variables, mediolateral range (p=0.008), and critical mean square displacement (p=0.012). Noise-based devices, such as randomly vibrating insoles, could ameliorate age-related impairments in balance control.

Noise-enhanced balance control in older adults.

Somatosensory information is critical to balance control and fall prevention in older adults. Recently, it has been shown that low-level input noise (electrical or mechanical) can enhance the sensitivity of the human somatosensory system. In this study, we tested the effect of low-level electrical noise, applied at the knee, on balance control in 13 healthy elderly volunteers. Subjects performed multiple single-legged stance trials with imperceptible electrical noise applied at the knee during half of the trials. Balance performance was characterized using a force platform to measure the displacement of the center of pressure (COP) under the subject's stance foot. Seven sway parameters were extracted from the COP time series. Improved balance was defined as a reduction in postural sway as indicated by decreases in the COP measures. Six of the seven sway parameters decreased with electrical noise. Three of these parameters decreased significantly ( < 0.05), and a fourth parameter was borderline significant. Averaged across subjects, the application of electrical noise resulted in a 3.8% reduction in mediolateral COP standard deviation ( = 0.04), a 5.4% decrease in the maximum anteroposterior COP excursion ( = 0.03), a 3.1% reduction in the COP path length ( = 0.04), and a 7.8% decrease in swept area ( = 0.05). The results suggest that imperceptible electrical noise, when applied to the knee, can enhance the balance performance of healthy older adults. These findings suggest that electrical noise-based devices may be effective in improving balance control in elderly people.

Enhancing tactile sensation in older adults with electrical noise stimulation.

Older adults often suffer from diminished somatosensation stemming from age-related neuropathy. Recently, localized low-level electrical noise stimulation was shown to enhance tactile sensitivity in healthy young subjects. Here, we hypothesized that fine-touch sensitivity in older adults can be similarly improved. Semmes-Weinstein monofilaments were used to evaluate fine-touch sensitivity on the first metatarsal phalangeal joint with four electrical stimulus conditions and a null (no-noise) condition in nine healthy elderly subjects. Electrical noise stimulation resulted in a statistically significant increase in the number of detections below the null-condition detection threshold, for five of the nine subjects, as well as across the entire population. This work suggests that electrical noise-based techniques may enable people to overcome functional difficulties due to age-related sensory loss.