Development of a miniaturized mechanoacoustic sensor for continuous, objective cough detection, characterization and physiologic monitoring in children with cystic fibrosis.

Cough is an important symptom in children with acute and chronic respiratory disease. Daily cough is common in Cystic Fibrosis (CF) and increased cough is a symptom of pulmonary exacerbation. To date, cough assessment is primarily subjective in clinical practice and research. Attempts to develop objective, automatic cough counting tools have faced reliability issues in noisy environments and practical barriers limiting long-term use. This single-center pilot study evaluated usability, acceptability and performance of a mechanoacoustic sensor (MAS), previously used for cough classification in adults, in 36 children with CF over brief and multi-day periods in four cohorts. Children whose health was at baseline and who had symptoms of pulmonary exacerbation were included. We trained, validated, and deployed custom deep learning algorithms for accurate cough detection and classification from other vocalization or artifacts with an overall area under the receiver-operator characteristic curve (AUROC) of 0.96 and average precision (AP) of 0.93. Child and parent feedback led to a redesign of the MAS towards a smaller, more discreet device acceptable for daily use in children. Additional improvements optimized power efficiency and data management. The MAS's ability to objectively measure cough and other physiologic signals across clinic, hospital, and home settings is demonstrated, particularly aided by an AUROC of 0.97 and AP of 0.96 for motion artifact rejection. Examples of cough frequency and physiologic parameter correlations with participant-reported outcomes and clinical measurements for individual patients are presented. The MAS is a promising tool in objective longitudinal evaluation of cough in children with CF.

Trimodal wireless intramuscular device detects muscle pressure, flow, and oxygenation changes in porcine model of lower extremity compartment syndrome.

PURPOSE: Compartment syndrome remains difficult to diagnose early in its clinical course. Pressure transducer catheters have been used to directly measure intracompartmental pressure (ICP), but this method is unreliable, with a false positive rate of 35%. We have previously used intramuscular near infrared spectroscopy to detect changes in tissue oxygen saturation (StO2) in response to increasing ICP using a novel implantable probe. However, measuring StO2 may not be sufficient to identify CS in the clinical setting. The pathophysiology of CS consists of increased ICP, leading to decreased tissue perfusion, and resulting in reduced tissue oxygenation. More clinically useful information may come from the integration of multiple data streams to aid in the diagnosis of CS. In this study, we present a novel, intramuscular probe capable of simultaneous measurement of ICP, StO2, and microvascular blood flow in a porcine model of ACS. METHODS: Proof of concept for this device is demonstrated in a porcine lower extremity balloon compression model of ACS. Pressure was maintained for 20 min (short-term) or 3 h (long-term) before the balloon volume was removed. RESULTS: In both short- and long-term experiments, as ICP increased with increasing balloon volume, the novel multimodal sensor simultaneously and reliably detected pressure elevation and corresponding reversible reductions in microvascular flow rate and tissue oxygenation. CONCLUSION: This novel trimodal device simultaneously measured the elevated ICP, decreased perfusion, and tissue ischemia of evolving ACS, substantiating our basic understanding of CS pathophysiology.

A wireless, implantable bioelectronic system for monitoring urinary bladder function following surgical recovery.

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.

A skin-interfaced, miniaturized platform for triggered induction, capture and colorimetric multicomponent analysis of microliter volumes of sweat.

Eccrine sweat can serve as a source of biomarkers for assessing physiological health and nutritional balance, for tracking loss of essential species from the body and for evaluating exposure to hazardous substances. The growing interest in this relatively underexplored class of biofluid arises in part from its non-invasive ability for capture and analysis. The simplest devices, and the only ones that are commercially available, exploit soft microfluidic constructs and colorimetric assays with purely passive modes of operation. The most sophisticated platforms exploit batteries, electronic components and radio hardware for inducing sweat, for electrochemical evaluation of its content and for wireless transmission of this information. The work reported here introduces a technology that combines the advantages of these two different approaches, in the form of a cost-effective, easy-to-use device that supports on-demand evaluation of multiple biomarkers in sweat. This flexible, skin-interfaced, miniaturized system incorporates a hydrogel that contains an approved drug to activate eccrine sweat glands, electrodes and a simple circuit and battery to delivery this drug by iontophoresis through the surface of the skin, microfluidic channels and microreservoirs to capture the induced sweat, and multiple colorimetric assays to evaluate the concentrations of chloride, zinc, and iron. As demonstrated in healthy human participants monitored before and after a meal, such devices yield results that match those of traditional laboratory analysis techniques. Clinical studies that involve cystic fibrosis pediatric patients illustrate the use of this technology as a simple, painless, and reliable alternative to traditional hospital systems for measurements of sweat chloride.

Wireless broadband acousto-mechanical sensing system for continuous physiological monitoring.

The human body generates various forms of subtle, broadband acousto-mechanical signals that contain information on cardiorespiratory and gastrointestinal health with potential application for continuous physiological monitoring. Existing device options, ranging from digital stethoscopes to inertial measurement units, offer useful capabilities but have disadvantages such as restricted measurement locations that prevent continuous, longitudinal tracking and that constrain their use to controlled environments. Here we present a wireless, broadband acousto-mechanical sensing network that circumvents these limitations and provides information on processes including slow movements within the body, digestive activity, respiratory sounds and cardiac cycles, all with clinical grade accuracy and independent of artifacts from ambient sounds. This system can also perform spatiotemporal mapping of the dynamics of gastrointestinal processes and airflow into and out of the lungs. To demonstrate the capabilities of this system we used it to monitor constrained respiratory airflow and intestinal motility in neonates in the neonatal intensive care unit (n = 15), and to assess regional lung function in patients undergoing thoracic surgery (n = 55). This broadband acousto-mechanical sensing system holds the potential to help mitigate cardiorespiratory instability and manage disease progression in patients through continuous monitoring of physiological signals, in both the clinical and nonclinical setting.

Synchronized wearables for the detection of haemodynamic states via electrocardiography and multispectral photoplethysmography.

Cardiovascular health is typically monitored by measuring blood pressure. Here we describe a wireless on-skin system consisting of synchronized sensors for chest electrocardiography and peripheral multispectral photoplethysmography for the continuous monitoring of metrics related to vascular resistance, cardiac output and blood-pressure regulation. We used data from the sensors to train a support-vector-machine model for the classification of haemodynamic states (resulting from exposure to heat or cold, physical exercise, breath holding, performing the Valsalva manoeuvre or from vasopressor administration during post-operative hypotension) that independently affect blood pressure, cardiac output and vascular resistance. The model classified the haemodynamic states on the basis of an unseen subset of sensor data for 10 healthy individuals, 20 patients with hypertension undergoing haemodynamic stimuli and 15 patients recovering from cardiac surgery, with an average precision of 0.878 and an overall area under the receiver operating characteristic curve of 0.958. The multinodal sensor system may provide clinically actionable insights into haemodynamic states for use in the management of cardiovascular disease.

Implantable, Bioresorbable Radio Frequency Resonant Circuits for Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is widely used in clinical care and medical research. The signal-to-noise ratio (SNR) in the measurement affects parameters that determine the diagnostic value of the image, such as the spatial resolution, contrast, and scan time. Surgically implanted radiofrequency coils can increase SNR of subsequent MRI studies of adjacent tissues. The resulting benefits in SNR are, however, balanced by significant risks associated with surgically removing these coils or with leaving them in place permanently. As an alternative, here the authors report classes of implantable inductor-capacitor circuits made entirely of bioresorbable organic and inorganic materials. Engineering choices for the designs of an inductor and a capacitor provide the ability to select the resonant frequency of the devices to meet MRI specifications (e.g., 200 MHz at 4.7 T MRI). Such devices enhance the SNR and improve the associated imaging capabilities. These simple, small bioelectronic systems function over clinically relevant time frames (up to 1 month) at physiological conditions and then disappear completely by natural mechanisms of bioresorption, thereby eliminating the need for surgical extraction. Imaging demonstrations in a nerve phantom and a human cadaver suggest that this technology has broad potential for post-surgical monitoring/evaluation of recovery processes.

Soft skin-interfaced mechano-acoustic sensors for real-time monitoring and patient feedback on respiratory and swallowing biomechanics.

Swallowing is a complex neuromuscular activity regulated by the autonomic nervous system. Millions of adults suffer from dysphagia (impaired or difficulty swallowing), including patients with neurological disorders, head and neck cancer, gastrointestinal diseases, and respiratory disorders. Therapeutic treatments for dysphagia include interventions by speech-language pathologists designed to improve the physiology of the swallowing mechanism by training patients to initiate swallows with sufficient frequency and during the expiratory phase of the breathing cycle. These therapeutic treatments require bulky, expensive equipment to synchronously record swallows and respirations, confined to use in clinical settings. This paper introduces a wireless, wearable technology that enables continuous, mechanoacoustic tracking of respiratory activities and swallows through movements and vibratory processes monitored at the skin surface. Validation studies in healthy adults (n = 67) and patients with dysphagia (n = 4) establish measurement equivalency to existing clinical standard equipment. Additional studies using a differential mode of operation reveal similar performance even during routine daily activities and vigorous exercise. A graphical user interface with real-time data analytics and a separate, optional wireless module support both visual and haptic forms of feedback to facilitate the treatment of patients with dysphagia.

Integrated, Transparent Silicon Carbide Electronics and Sensors for Radio Frequency Biomedical Therapy.

The integration of micro- and nanoelectronics into or onto biomedical devices can facilitate advanced diagnostics and treatments of digestive disorders, cardiovascular diseases, and cancers. Recent developments in gastrointestinal endoscopy and balloon catheter technologies introduce promising paths for minimally invasive surgeries to treat these diseases. However, current therapeutic endoscopy systems fail to meet requirements in multifunctionality, biocompatibility, and safety, particularly when integrated with bioelectronic devices. Here, we report materials, device designs, and assembly schemes for transparent and stable cubic silicon carbide (3C-SiC)-based bioelectronic systems that facilitate tissue ablation, with the capability for integration onto the tips of endoscopes. The excellent optical transparency of SiC-on-glass (SoG) allows for direct observation of areas of interest, with superior electronic functionalities that enable multiple biological sensing and stimulation capabilities to assist in electrical-based ablation procedures. Experimental studies on phantom, vegetable, and animal tissues demonstrated relatively short treatment times and low electric field required for effective lesion removal using our SoG bioelectronic system. In vivo experiments on an animal model were conducted to explore the versatility of SoG electrodes for peripheral nerve stimulation, showing an exciting possibility for the therapy of neural disorders through electrical excitation. The multifunctional features of SoG integrated devices indicate their high potential for minimally invasive, cost-effective, and outcome-enhanced surgical tools, across a wide range of biomedical applications.

Thermally switchable, crystallizable oil and silicone composite adhesives for skin-interfaced wearable devices.

Continuous health monitoring is essential for clinical care, especially for patients in neonatal and pediatric intensive care units. Monitoring currently requires wired biosensors affixed to the skin with strong adhesives that can cause irritation and iatrogenic injuries during removal. Emerging wireless alternatives are attractive, but requirements for skin adhesives remain. Here, we present a materials strategy enabling wirelessly triggered reductions in adhesive strength to eliminate the possibility for injury during removal. The materials involve silicone composites loaded with crystallizable oils with melting temperatures close to, but above, surface body temperature. This solid/liquid phase transition occurs upon heating, reducing the adhesion at the skin interface by more than 75%. Experimental and computational studies reveal insights into effects of oil mixed randomly and patterned deterministically into the composite. Demonstrations in skin-integrated sensors that include wirelessly controlled heating and adhesion reduction illustrate the broad utility of these ideas in clinical-grade health monitoring.

Intramuscular Near-Infrared Spectroscopy for Muscle Flap Monitoring in a Porcine Model.

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are limited to flaps which carry a cutaneous paddle. As such, this useful and reliable technology has not previously been applicable to muscle-only free flaps where other modalities with substantial limitations continue to be utilized. METHODS: We present the first NIRS probe which allows continuous monitoring of local tissue oxygen saturation (StO2) directly within the substance of muscle tissue. This probe is flexible, subcentimeter in scale, waterproof, biocompatible, and is fitted with resorbable barbs which facilitate temporary autostabilization followed by easy atraumatic removal. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. During these experiments, the T.Ox device was affixed to the skin paddle, while the novel probe was within the muscle component of the same flap. RESULTS: The intramuscular NIRS device and skin-mounted ViOptix T.Ox devices produced very similar StO2 tracings throughout the vascular clamping events, with obvious and parallel changes occurring upon vascular clamping and release. The normalized cross-correlation at zero lag describing correspondence between the novel intramuscular NIRS and T.Ox devices was >0.99. CONCLUSION: This novel intramuscular NIRS probe offers continuous monitoring of oxygen saturation within muscle flaps. This experiment demonstrates the potential suitability of this intramuscular NIRS probe for the task of muscle-only free flap monitoring, where NIRS has not previously been applicable. Testing in the clinical environment is necessary to assess durability and reliability.

Compliant 3D frameworks instrumented with strain sensors for characterization of millimeter-scale engineered muscle tissues.

Tissue-on-chip systems represent promising platforms for monitoring and controlling tissue functions in vitro for various purposes in biomedical research. The two-dimensional (2D) layouts of these constructs constrain the types of interactions that can be studied and limit their relevance to three-dimensional (3D) tissues. The development of 3D electronic scaffolds and microphysiological devices with geometries and functions tailored to realistic 3D tissues has the potential to create important possibilities in advanced sensing and control. This study presents classes of compliant 3D frameworks that incorporate microscale strain sensors for high-sensitivity measurements of contractile forces of engineered optogenetic muscle tissue rings, supported by quantitative simulations. Compared with traditional approaches based on optical microscopy, these 3D mechanical frameworks and sensing systems can measure not only motions but also contractile forces with high accuracy and high temporal resolution. Results of active tension force measurements of engineered muscle rings under different stimulation conditions in long-term monitoring settings for over 5 wk and in response to various chemical and drug doses demonstrate the utility of such platforms in sensing and modulation of muscle and other tissues. Possibilities for applications range from drug screening and disease modeling to biohybrid robotic engineering.

Real-Time UV Measurement With a Sun Protection System for Warning Young Adults About Sunburn: Prospective Cohort Study.

BACKGROUND: Melanoma is attributable to predisposing phenotypical factors, such as skin that easily sunburns and unprotected exposure to carcinogenic UV radiation. Reducing the proportion of young adults who get sunburned may reduce the incidence of melanoma, a deadly form of skin cancer. Advances in technology have enabled the delivery of real-time UV light exposure and content-relevant health interventions. OBJECTIVE: This study aims to examine the feasibility of young adults performing the following tasks daily: wearing a UV dosimeter, receiving text messages and real-time UV-B doses on their smartphone, and responding to daily web-based surveys about sunburn and sun protection. METHODS: Young adults aged 18-39 years (n=42) were recruited in the United States in June 2020 via social media. Participants received the UV Guard sun protection system, which consisted of a UV dosimeter and a smartphone app. During 3 consecutive periods, intervention intensity increased as follows: real-time UV-B dose; UV-B dose and daily behavioral facilitation text messages; and UV-B dose, goal setting, and daily text messages to support self-efficacy and self-regulation. Data were self-reported through daily web-based surveys for 28 days, and UV-B doses were transmitted to cloud-based storage. RESULTS: Patients' median age was 22 years (IQR 20, 29), and all patients had sun-sensitive skin. Sunburns were experienced during the study by fewer subjects (n=18) than those in the preceding 28 days (n=30). In July and August, the face was the most commonly sunburned area among 13 body locations; 52% (22/42) of sunburns occurred before the study and 45% (19/42) occurred during the study. The mean daily UV-B dose decreased during the 3 periods; however, this was not statistically significant. Young adults were most often exercising outdoors from 2 to 6 PM, walking from 10 AM to 6 PM, and relaxing from noon to 2 PM. Sunburn was most often experienced during exercise (odds ratio [OR] 5.65, 95% CI 1.60-6.10) and relaxation (OR 3.69, 95% CI 1.03-4.67) relative to those that did not exercise or relax in each category. The self-reported exit survey indicated that participants felt that they spent less time outdoors this summer compared to the last summer because of the COVID-19 pandemic and work. In addition, 38% (16/42) of the participants changed their use of sun protection based on their app-reported UV exposure, and 48% (20/42) shifted the time they went outside to periods with less-intense UV exposure. A total of 79% (33/42) of the participants were willing to continue using the UV Guard system outside of a research setting. CONCLUSIONS: In this proof-of-concept research, young adults demonstrated that they used the UV Guard system; however, optimization was needed. Although some sun protection behaviors changed, sunburn was not prevented in all participants, especially during outdoor exercise. TRIAL REGISTRATION: ClinicalTrials.gov NCT03344796; http://clinicaltrials.gov/ct2/show/NCT03344796.

Surgical implantation of wireless, battery-free optoelectronic epidural implants for optogenetic manipulation of spinal cord circuits in mice.

The use of optogenetics to regulate neuronal activity has revolutionized the study of the neural circuitry underlying a number of complex behaviors in rodents. Advances have been particularly evident in the study of brain circuitry and related behaviors, while advances in the study of spinal circuitry have been less striking because of technical hurdles. We have developed and characterized a wireless and fully implantable optoelectronic device that enables optical manipulation of spinal cord circuitry in mice via a microscale light-emitting diode (µLED) placed in the epidural space (NeuroLux spinal optogenetic device). This protocol describes how to surgically implant the device into the epidural space and then analyze light-induced behavior upon µLED activation. We detail optimized optical parameters for in vivo stimulation and demonstrate typical behavioral effects of optogenetic activation of nociceptive spinal afferents using this device. This fully wireless spinal µLED system provides considerable versatility for behavioral assays compared with optogenetic approaches that require tethering of animals, and superior temporal and spatial resolution when compared with other methods used for circuit manipulation such as chemogenetics. The detailed surgical approach and improved functionality of these spinal optoelectronic devices substantially expand the utility of this approach for the study of spinal circuitry and behaviors related to mechanical and thermal sensation, pruriception and nociception. The surgical implantation procedure takes ~1 h. The time required for the study of behaviors that are modulated by the light-activated circuit is variable and will depend upon the nature of the study.

Soft, skin-interfaced sweat stickers for cystic fibrosis diagnosis and management.

The concentration of chloride in sweat remains the most robust biomarker for confirmatory diagnosis of cystic fibrosis (CF), a common life-shortening genetic disorder. Early diagnosis via quantitative assessment of sweat chloride allows prompt initiation of care and is critically important to extend life expectancy and improve quality of life. The collection and analysis of sweat using conventional wrist-strapped devices and iontophoresis can be cumbersome, particularly for infants with fragile skin, who often have insufficient sweat production. Here, we introduce a soft, epidermal microfluidic device ("sweat sticker") designed for the simple and rapid collection and analysis of sweat. Intimate, conformal coupling with the skin supports nearly perfect efficiency in sweat collection without leakage. Real-time image analysis of chloride reagents allows for quantitative assessment of chloride concentrations using a smartphone camera, without requiring extraction of sweat or external analysis. Clinical validation studies involving patients with CF and healthy subjects, across a spectrum of age groups, support clinical equivalence compared to existing device platforms in terms of accuracy and demonstrate meaningful reductions in rates of leakage. The wearable microfluidic technologies and smartphone-based analytics reported here establish the foundation for diagnosis of CF outside of clinical settings.

Wireless, implantable catheter-type oximeter designed for cardiac oxygen saturation.

Accurate, real-time monitoring of intravascular oxygen levels is important in tracking the cardiopulmonary health of patients after cardiothoracic surgery. Existing technologies use intravascular placement of glass fiber-optic catheters that pose risks of blood vessel damage, thrombosis, and infection. In addition, physical tethers to power supply systems and data acquisition hardware limit freedom of movement and add clutter to the intensive care unit. This report introduces a wireless, miniaturized, implantable optoelectronic catheter system incorporating optical components on the probe, encapsulated by soft biocompatible materials, as alternative technology that avoids these disadvantages. The absence of physical tethers and the flexible, biocompatible construction of the probe represent key defining features, resulting in a high-performance, patient-friendly implantable oximeter that can monitor localized tissue oxygenation, heart rate, and respiratory activity with wireless, real-time, continuous operation. In vitro and in vivo testing shows that this platform offers measurement accuracy and precision equivalent to those of existing clinical standards.

Skin-Interfaced Microfluidic Systems that Combine Hard and Soft Materials for Demanding Applications in Sweat Capture and Analysis.

Eccrine sweat contains a rich blend of electrolytes, metabolites, proteins, metal ions, and other biomarkers. Changes in the concentrations of these chemical species can indicate alterations in hydration status and they can also reflect health conditions such as cystic fibrosis, schizophrenia, and depression. Recent advances in soft, skin-interfaced microfluidic systems enable real-time measurement of local sweat loss and sweat biomarker concentrations, with a wide range of applications in healthcare. Uses in certain contexts involve, however, physical impacts on the body that can dynamically deform these platforms, with adverse effects on measurement reliability. The work presented here overcomes this limitation through the use of microfluidic structures constructed in relatively high modulus polymers, and designed in geometries that offer soft, system level mechanics when embedded low modulus elastomers. Analytical models and finite element analysis quantitatively define the relevant mechanics of these systems, and serve as the basis for layouts optimized to allow robust operation in demanding, rugged scenarios such as those encountered in football, while preserving mechanical stretchability for comfortable, water-tight bonding to the skin. Benchtop testing and on-body field studies of measurements of sweat loss and chloride concentration under imposed mechanical stresses and impacts demonstrate the key features of these platforms.

Sun exposure reduction by melanoma survivors with wearable sensor providing real-time UV exposure and daily text messages with structured goal setting.

Despite knowledge of subsequent melanoma risk and the benefit of sun protection in risk reduction, melanoma survivors often do not engage in adequate sun protection and continue to sunburn at rates similar to individuals without a history of skin cancer. This novel intensive intervention provided a wearable UV sensor delivering real-time UV exposure with a smartphone and daily text messages. On days 1-10 (period 1), behavioral facilitation and outcome expectancies messages were provided. On day 10, participants reviewed and reflected on their daily UV exposure on the previous 10 days and set goals for improving sun protection. Then on days 11-21 (period 2) self-efficacy and self-regulation messages were provided. Sixty melanoma survivors were randomized (1:1) to receive structured or unstructured goal setting queries on day 10. Controlling for cloudy/rain conditions with less UV due to weather, there was a time effect with a significant decrease in UV exposure from periods 1-2 [period 1-2, F (59) = 22.60, p < 0.0001]. In this short-term study, melanoma survivors managed their daily UV exposure to stay below their maximum tolerated UV dose. ClinicalTrials.gov Protocol Record NCT0334796, date of registration Nov 15, 2017.

Wirelessly controlled, bioresorbable drug delivery device with active valves that exploit electrochemically triggered crevice corrosion.

Implantable drug release platforms that offer wirelessly programmable control over pharmacokinetics have potential in advanced treatment protocols for hormone imbalances, malignant cancers, diabetic conditions, and others. We present a system with this type of functionality in which the constituent materials undergo complete bioresorption to eliminate device load from the patient after completing the final stage of the release process. Here, bioresorbable polyanhydride reservoirs store drugs in defined reservoirs without leakage until wirelessly triggered valve structures open to allow release. These valves operate through an electrochemical mechanism of geometrically accelerated corrosion induced by passage of electrical current from a wireless, bioresorbable power-harvesting unit. Evaluations in cell cultures demonstrate the efficacy of this technology for the treatment of cancerous tissues by release of the drug doxorubicin. Complete in vivo studies of platforms with multiple, independently controlled release events in live-animal models illustrate capabilities for control of blood glucose levels by timed delivery of insulin.

Catheter-integrated soft multilayer electronic arrays for multiplexed sensing and actuation during cardiac surgery.

The rigidity and relatively primitive modes of operation of catheters equipped with sensing or actuation elements impede their conformal contact with soft-tissue surfaces, limit the scope of their uses, lengthen surgical times and increase the need for advanced surgical skills. Here, we report materials, device designs and fabrication approaches for integrating advanced electronic functionality with catheters for minimally invasive forms of cardiac surgery. By using multiphysics modelling, plastic heart models and Langendorff animal and human hearts, we show that soft electronic arrays in multilayer configurations on endocardial balloon catheters can establish conformal contact with curved tissue surfaces, support high-density spatiotemporal mapping of temperature, pressure and electrophysiological parameters and allow for programmable electrical stimulation, radiofrequency ablation and irreversible electroporation. Integrating multimodal and multiplexing capabilities into minimally invasive surgical instruments may improve surgical performance and patient outcomes.