Implantable Sensor Research Articles

Physically crosslinked polyvinyl alcohol, phytic acid and glycerol hydrogels for wearable sensors with biocompatibility, antimicrobial stability and anti-freezing

Portable, miniaturized, intelligent and flexible electronic devices are more and more widely used in life areas. Conductive hydrogels with remarkable ion transport capabilities and tunable mechanical properties could be emerging materials for sensing devices. However, most of conductive hydrogels do not have antimicrobial activity, leading to microbial infections for human. Herein, a hydrogel with noteworthy biocompatibility, antimicrobial stability, anti-freezing, and anti-fatigue properties was designed and developed by introducing polyvinyl alcohol, phytic acid, and glycerol. Phytic acid and PVA formed hydrogen bonds by physically cross-linking, improving the fatigue resistance and toughness of the hydrogel. The hydrogel exhibited bacteriostatic zone against for Escherichia coli as well as Bacillus subtilis, and displayed antibacterial stability within 7 days. Hydrogels appeared distinguished biocompatibility due to the absence of allergic reactions in mouse subcutaneous tissue within 14 days. Hydrogels as sensors could monitor deformational movements such as speech and joint bending. Thus, hydrogels have the potential to be used as antimicrobial materials in medical applications such as implantable sensors and clinical information interventions.

Developing and validating an implantable suture tension sensor

IntroductionSuture tension has a direct influence on the sutured tissue. For abdominal wall closure, suture tension should be optimal without causing tissue necrosis, which can result in surgical site infection or incisional hernia. The purpose of the present study is to evaluate a device that can measure suture tension in-situ and in real-time. Materials and methodsA cheap, commercially available analog-to-digital converter was used, in conjunction with a force sensing resistor. A sensor probe housing was designed and 3D-printed. In order to test the sensor, a mechanical, computer controlled human abdominal wall model called the AbdoMAN was used. ResultsAn implantable suture tension sensor was developed, keeping cost-effectiveness in mind. This sensor can translate tension in the suture into a downward force, applied to the force sensing resistor. The sensor's raw readout was characterized using a set of weights, from which a formula correlating the readout to a specific force, was derived. Preliminary validation was successfully performed using the AbdoMANmodel, which showed a progressive rise in suture tension when the intra-abdominal pressure was artificially increased over time. ConclusionThe implantable suture tension sensor appeared to be capable of recording real time changes in suture tension, and the. validation process of this sensor has been initiated. With the information from devices like this, a much better understanding of the issues at play in the development of incisional hernia can be gained.

Cost-effectiveness of remote haemodynamic monitoring by an implantable pulmonary artery pressure monitoring sensor (CardioMEMS-HF system) in chronic heart failure in the Netherlands.

Remote haemodynamic monitoring with an implantable pulmonary artery (PA) sensor has been shown to reduce heart failure (HF) hospitalizations and improve quality of life. Cost-effectiveness analyses studying the value of remote haemodynamic monitoring in a European healthcare system with a contemporary standard care group are lacking. A Markov model was developed to estimate the cost-effectiveness of PA-guided therapy compared to the standard of care based upon patient-level data of the MONITOR-HF trial performed in the Netherlands in patients with chronic HF (New York Heart Association class III and at least one previous HF hospitalization). Cost-effectiveness was measured as the incremental cost per quality-adjusted life year (QALY) gained from the Dutch societal perspective with a lifetime horizon which encompasses a wide variety of costs including costs of hospitalizations, monitoring time, telephone contacts, laboratory assessments, and drug changes in both treatment groups. In the base-case analysis, PA-guided therapy increased costs compared to standard of care by €12 121. The QALYs per patient for PA-guided therapy and standard of care was 4.07 and 3.481, respectively, reflecting a gain of 0.58 QALYs. The resulting incremental cost-effectiveness ratio was €20 753 per QALY, which is below the Dutch willingness-to-pay threshold of €50 000 per QALY gained for HF. The current cost-effectiveness study suggests that remote haemodynamic monitoring with PA-guided therapy on top of standard care is likely to be cost-effective for patients with symptomatic moderate-to-severe HF in the Netherlands.

The importance of advanced technologies in functional rehabilitation of the hand

Abstract: This systematic review examines groundbreaking advancements in hand rehabilitation, driven by significant progress in medical technology. Adhering to PRISMA guidelines, the review surveyed articles from various databases, emphasizing the utilization of advanced technologies for hand rehabilitation across diverse conditions such as fractures, burns, amputations, and postoperative care. Out of the 1562 studies analyzed, ten articles that met the inclusion criteria were identified. Key technologies like IMES (Implantable Myoelectric Sensor) technology are scrutinized for their potential to transform prosthetic control, providing intuitive functionality and substantial physiological hand function for individuals with limb loss. Similarly, advancements in orthotic devices like the VacoHand Orthosis are showcased for their improvements in stabilizing and aiding the healing process in wrist immobilization and rehabilitation. The integration of virtual reality (VR) emerges as a pivotal convergence point, offering supplementary therapy to enhance direction-specific improvements in wrist and forearm mobility, hand function, and work-related tasks. Additional advantages include program customization, heightened engagement through interactive approaches, and improved functional outcomes such as hand strength and range of motion. While showcasing transformative potential, the review acknowledges the need for further research through larger sample sizes, standardized methodologies and more in-depth investigations to optimize these technologies. Overall, this review underlines the remarkable advancements achieved in hand rehabilitation through technological innovations, offering hope and improved outcomes for individuals grappling with various hand-related challenges.

Recent Progress and Challenges of Implantable Biodegradable Biosensors.

Implantable biosensors have evolved to the cutting-edge technology of personalized health care and provide promise for future directions in precision medicine. This is the reason why these devices stand to revolutionize our approach to health and disease management and offer insights into our bodily functions in ways that have never been possible before. This review article tries to delve into the important developments, new materials, and multifarious applications of these biosensors, along with a frank discussion on the challenges that the devices will face in their clinical deployment. In addition, techniques that have been employed for the improvement of the sensitivity and specificity of the biosensors alike are focused on in this article, like new biomarkers and advanced computational and data communicational models. A significant challenge of miniaturized in situ implants is that they need to be removed after serving their purpose. Surgical expulsion provokes discomfort to patients, potentially leading to post-operative complications. Therefore, the biodegradability of implants is an alternative method for removal through natural biological processes. This includes biocompatible materials to develop sensors that remain in the body over longer periods with a much-reduced immune response and better device longevity. However, the biodegradability of implantable sensors is still in its infancy compared to conventional non-biodegradable ones. Sensor design, morphology, fabrication, power, electronics, and data transmission all play a pivotal role in developing medically approved implantable biodegradable biosensors. Advanced material science and nanotechnology extended the capacity of different research groups to implement novel courses of action to design implantable and biodegradable sensor components. But the actualization of such potential for the transformative nature of the health sector, in the first place, will have to surmount the challenges related to biofouling, managing power, guaranteeing data security, and meeting today's rules and regulations. Solving these problems will, therefore, not only enhance the performance and reliability of implantable biodegradable biosensors but also facilitate the translation of laboratory development into clinics, serving patients worldwide in their better disease management and personalized therapeutic interventions.

Ultra-sensitive LC MEMS for bladder pressure monitoring using modified slotted diaphragm

In this paper, we have designed and simulated an implantable MEMS-based LC pressure sensor for bladder pressure monitoring. The device is composed of metal-insulator-metal capacitive sensor in which the size of the diaphragm is 1 mm × 1 mm of 5 µm thickness. Besides, novel modified-slotted diaphragm is developed to improve the sensitivity by decreasing the mechanical rigidity of the membrane. We used the COMSOL Multiphysics a tool for design and simulation. According to the results, the frequency response to the variable pressure is varied within the range of 35.23 to 119.72 MHz, the results also yield a value obtained of the quality factor is worth 32 with high value of 4.22 kHz/Pa sensor sensitivity. Hence, this sensor with a novel modified-slotted diaphragm has a high-pressure sensitivity, which shows 2.91 times more sensitivity than clamped diaphragm.

Clinical Trial Inclusion and Impact on Early Adoption of Medical Innovation in Diverse Populations

BackgroundInadequate inclusion in clinical trial enrollment may contribute to health inequities by evaluating interventions in cohorts that do not fully represent target populations. ObjectivesThe aim of this study was to determine if characteristics of patients with heart failure (HF) enrolled in a pivotal trial are associated with who receives an intervention after approval. MethodsDemographics from 2,017,107 Medicare patients hospitalized for HF were compared with those of the first 10,631 Medicare beneficiaries who received implantable pulmonary artery pressure sensors. Characteristics of the population studied in the pivotal CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) clinical trial (n = 550) were compared with those of both groups. All demographic data were analyzed nationally and in 4 U.S. regions. ResultsThe Medicare HF cohort included 80.9% White, 13.3% African American, 1.9% Hispanic, 1.3% Asian, and 51.5% female patients. Medicare patients <65 years of age were more likely to be African American (33%) and male (58%), whereas older patients were mostly White (84%) and female (53%). Forty-one percent of U.S. HF hospitalizations occurred in the South; demographic characteristics varied significantly across all U.S. regions. The CHAMPION trial adequately represented African Americans (23% overall, 35% <65 years of age), Hispanic Americans (2%), and Asian Americans (1%) but underrepresented women (27%). The trial’s population characteristics were similar to those of the first patients who received pulmonary artery sensors (82% White, 13% African American, 1% Asian, 1% Hispanic, and 29% female). ConclusionsDemographics of Centers for Medicare and Medicaid Services beneficiaries hospitalized with HF vary regionally and by age, which should be considered when defining “adequate” representation in clinical studies. Enrollment diversity in clinical trials may affect who receives early application of recently approved innovations.

Molecular Ferroelastic Induced by Mono‐/Double‐Protonation Strategy

Comprehensive SummaryMolecular ferroelastics with the natural features of mechanical flexibility and switchable spontaneous strain have attracted widespread attention in the scientific community due to their potential applications in tunable gratings, flexible memorizers, strain sensors, and intelligent actuators. However, most designs of molecular ferroelastics remain in the stage of blind exploration, posing a challenge to achieve a functional ferroelastic more effectively. Herein, we have successfully obtained a molecular ferroelastic, [Me2NH(CH2)2NH3](ReO4)2 (Me2NH(CH2)2NH3 = N,N‐dimethylethylenediammonium), under the guidance of the mono‐/double‐protonation strategy. The double‐protonated [Me2NH(CH2)2NH3](ReO4)2 undergoes a paraelastic‐ferroelastic phase transition with the Aizu notation of 2/mF at 322 K. Meanwhile, the theoretical calculation and experimental measurement simultaneously show that [Me2NH(CH2)2NH3](ReO4)2 possesses good mechanical flexibility, because its elastic modulus (E) of 8.26 GPa and hardness (H) of 0.45 GPa are smaller than the average values of organic crystals (E of 12.05 GPa and H of 0.5 GPa), which makes it promising to apply in wearable pressure sensors, implantable medical sensors, high‐precision tuners, etc. This work further enriches the molecular ferroelastic family and demonstrates that mono‐/double‐protonation is one of the effective molecular modification strategies for designing ferroelastics.

Millimeter-scale magnetic implants paired with a fully integrated wearable device for wireless biophysical and biochemical sensing.

Implantable sensors can directly interface with various organs for precise evaluation of health status. However, extracting signals from such sensors mainly requires transcutaneous wires, integrated circuit chips, or cumbersome readout equipment, which increases the risks of infection, reduces biocompatibility, or limits portability. Here, we develop a set of millimeter-scale, chip-less, and battery-less magnetic implants paired with a fully integrated wearable device for measuring biophysical and biochemical signals. The wearable device can induce a large amplitude damped vibration of the magnetic implants and capture their subsequent motions wirelessly. These motions reflect the biophysical conditions surrounding the implants and the concentration of a specific biochemical depending on the surface modification. Experiments in rat models demonstrate the capabilities of measuring cerebrospinal fluid (CSF) viscosity, intracranial pressure, and CSF glucose levels. This miniaturized system opens the possibility for continuous, wireless monitoring of a wide range of biophysical and biochemical conditions within the living organism.

A Biodegradable Piezoelectric Sensor for Real‐Time Evaluation of the Motor Function Recovery After Nerve Injury

AbstractNerve injury can lead to defects in related motor functions. It is critical to achieve long‐term and convenient real‐time evaluation of motor function recovery status during nerve injury repair. In this study, an implantable PLLA/BTO piezoelectric sensor (PBPS) with good biodegradability and biocompatibility for real time evaluation of the motor function recovery after nerve injury is developed. PLLA fibers doped with BTO are employed as piezoelectric material in PBPS, which can convert the biomechanical signals generated by motion into electrical signals. PBPS can be implant simultaneously with commonly used tissue scaffolds for treatment in the rats with sciatic nerve injury. The linearity of the pressure and the output voltage of PBPS is ≈0.9445. For the evaluation effectiveness, as the treatment process progresses, the signals generated by PBPS exhibited good consistency with EMG signals, indicating effectively evaluation of the motor function. Moreover, the integration of PBPS and wireless module can break the limitations of time and space for sensing and realize wireless evaluation of motor function in rat. The implantable sensor based on PBPS may bring new ideas for the development of implantable bioelectronics.

A combined technique of implantable sensors and probabilistic localization method for monitoring acoustic events on concrete slab

Continuous monitoring of acoustic events in concrete such as cracking and impacting, and providing their location information is a significant topic in structural health monitoring (SHM). This paper develops a combined technique of concrete implantable cube (CIC) and probabilistic localization method to monitor acoustic sources on concrete slabs. The CIC that integrates an octahedron-shaped piezoelectric sensor array can be implanted in concrete structures in long term and supply an omni-dimensional sensing capacity. Aiming at the designed sensor array and the impacts of randomness and heterogeneity of concrete material on the localization accuracy, a probabilistic localization method was proposed. To demonstrate the feasibility of the proposed technique, an experiment including 48 impact tests was conducted on a concrete slab specimen. The acoustic signals received by the implanted CIC were used to reconstruct localization maps to predict the impact areas. The results were quantified using three matrixes including accuracy, precision, and recall; consequently, the accuracy obtained the highest average score close to 0.98 and performed most steadily. In addition, to optimize the proposed technique furtherly, the sensitivity of two key parameters associated with this method were discussed. Overall, the experimental study showed a great potential of this developed technique for long-term monitoring acoustic events on concrete structures.

Miniaturized implantable temperature sensors for the long-term monitoring of chronic intestinal inflammation.

Diagnosing and monitoring inflammatory bowel diseases, such as Crohn's disease, involves the use of endoscopic imaging, biopsies and serology. These infrequent tests cannot, however, identify sudden onsets and severe flare-ups to facilitate early intervention. Hence, about 70% of patients with Crohn's disease require surgical intestinal resections in their lifetime. Here we report wireless, miniaturized and implantable temperature sensors for the real-time chronic monitoring of disease progression, which we tested for nearly 4 months in a mouse model of Crohn's-disease-like ileitis. Local measurements of intestinal temperature via intraperitoneally implanted sensors held in place against abdominal muscular tissue via two sutures showed the development of ultradian rhythms at approximately 5 weeks before the visual emergence of inflammatory skip lesions. The ultradian rhythms showed correlations with variations in the concentrations of stress hormones and inflammatory cytokines in blood. Decreasing average temperatures over the span of approximately 23 weeks were accompanied by an increasing percentage of inflammatory species in ileal lesions. These miniaturized temperature sensors may aid the early treatment of inflammatory bowel diseases upon the detection of episodic flare-ups.

Исследование способа измерения артериального давления ёмкостным интегрированным датчиком

A method of wireless measurement of blood flow parameters is investigated using an implantable passive capacitive sensor and an external reader. This device is designed to measure the parameters of blood flow in the human body, through the installation of a passive capacitive sensor and inductive coupling with an external reader device. The method of wireless measurement is based on the connection of resonant circuits at an operating frequency of 10 MHz. The mathematical calculation of the device circuit is presented. The result of the calculation was the dependence of the output voltage of the external reader on the change of capacitance in the implanted passive sensor. The values of the potential sensitivity of the device are obtained. The manufactured layout of the device and its parameters are presented. The mock-up allowed to investigate the dependences of the coupling factor of the circuits when using coils of an external reader of different sizes. Also the measurement of the output voltage of the external reader from the value of the passive sensor capacitance was made. The value of real sensitivity of the device layout was measured.

Longitudinal CT-based finite element analyses provide objective fracture healing measures in an ovine tibia model.

Measuring the healing status of a bone fracture is important to determine the clinical care a patient receives. Implantable devices can directly and continuously assess the healing status of fracture fixation constructs, while subject-specific virtual biomechanical tests can noninvasively determine callus structural integrity at single time points. Despite their potential for objectification, both methods are not yet integrated into clinical practice with further evidence of their benefits required. This study correlated continuous data from an implantable sensor assessing healing status through implant load monitoring with computer tomography (CT) based longitudinal finite element (FE) simulations in a large animal model. Eight sheep were part of a previous preclinical study utilizing a tibial osteotomy model and equipped with such a sensor. Sensor signal was collected over several months, and CT scans were acquired at six interim time points. For each scan, two FE analyses were performed: a virtual torsional rigidity test of the bone and a model of the bone-implant construct with the sensor. The longitudinal simulation results were compared to the sensor data at corresponding time points and a cohort-specific empirical healing rule was employed. Healing status predicted by both in silico simulations correlated significantly with the sensor data at corresponding time points and correctly identified a delayed and a nonunion in the cohort. The methodology is readily translatable with the potential to be applied to further preclinical or clinical cohorts to find generalizable healing criteria. Virtual mechanical tests can objectively measure fracture healing progressing using longitudinal CT scans.

A Highly Selective Implantable Electrochemical Fiber Sensor for Real-Time Monitoring of Blood Homovanillic Acid.

Homovanillic acid (HVA) is a major dopamine metabolite, and blood HVA is considered as central nervous system (CNS) dopamine biomarker, which reflects the progression of dopamine-associated CNS diseases and the behavioral response to therapeutic drugs. However, facing blood various active substances interference, particularly structurally similar catecholamines and their metabolites, real-time and accurate monitoring of blood HVA remains a challenge. Herein, a highly selective implantable electrochemical fiber sensor based on a molecularly imprinted polymer is reported to accurately monitor HVA in vivo. The sensor exhibits high selectivity, with a response intensity to HVA 12.6 times greater than that of catecholamines and their metabolites, achieving 97.8% accuracy in vivo. The sensor injected into the rat caudal vein tracked the real-time changes of blood HVA, which paralleled the brain dopamine fluctuations and indicated the behavioral response to dopamine increase. This study provides a universal design strategy for improving the selectivity of implantable electrochemical sensors.

Advancements in Brain Research: The In Vivo/In Vitro Electrochemical Detection of Neurochemicals.

Neurochemicals, crucial for nervous system function, influence vital bodily processes and their fluctuations are linked to neurodegenerative diseases and mental health conditions. Monitoring these compounds is pivotal, yet the intricate nature of the central nervous system poses challenges. Researchers have devised methods, notably electrochemical sensing with micro-nanoscale electrodes, offering high-resolution monitoring despite low concentrations and rapid changes. Implantable sensors enable precise detection in brain tissues with minimal damage, while microdialysis-coupled platforms allow in vivo sampling and subsequent in vitro analysis, addressing the selectivity issues seen in other methods. While lacking temporal resolution, techniques like HPLC and CE complement electrochemical sensing's selectivity, particularly for structurally similar neurochemicals. This review covers essential neurochemicals and explores miniaturized electrochemical sensors for brain analysis, emphasizing microdialysis integration. It discusses the pros and cons of these techniques, forecasting electrochemical sensing's future in neuroscience research. Overall, this comprehensive review outlines the evolution, strengths, and potential applications of electrochemical sensing in the study of neurochemicals, offering insights into future advancements in the field.

In Situ Polymer-Solution-Processed Graphene-PDMS Nanocomposites for Application in Intracranial Pressure Sensors.

Polydimethylsiloxane (PDMS) has emerged as a promising candidate for the dielectric layer in implantable sensors due to its exceptional biocompatibility, stability, and flexibility. This study introduces an innovative approach to produce graphene-reinforced PDMS (Gr-PDMS), where graphite powders are exfoliated into mono- and few-layer graphene sheets within the polymer solution, concurrently forming cross-linkages with PDMS. This method yields a uniformly distributed graphene within the polymer matrix with improved interfaces between graphene and PDMS, significantly reducing the percolation threshold of graphene dispersed in PDMS from 10% to 5%. As-synthesized Gr-PDMS exhibits improved mechanical and electrical properties, tested for potential use in capacitive pressure sensors. The results demonstrate an impressive pressure sensitivity up to 0.0273 kpa-1, 45 times higher than that of pristine PDMS and 2.5 times higher than the reported literature value. The Gr-PDMS showcases excellent pressure sensing ability and stability, fulfilling the requirements for implantable intracranial pressure (ICP) sensors.

Biomimetic dual sensing polymer nanocomposite for biomedical applications.

There is a growing need for sensing materials that can provide multiple sensing capabilities for wearable devices, implantable sensors, and diagnostics tools. As complex human physiology requires materials that can simultaneously detect and respond to slow and fast pressure fluctuations. Mimicking the slow adaptive (SA) and fast adaptive (FA) mechanoreceptors in skin can lead to the development of dual sensing electrospun polymer nanocomposites for biomedical applications. These dual sensing nanocomposites can provide simultaneous sensing of both slow and fast pressure fluctuations, making them ideal for applications such as monitoring vital signs, detecting a wider range of movements and pressures. Here we develop a novel dual sensing PVDF-HFP-based nanocomposite that combines the advantages of capacitive and piezoelectric properties through controling electrospinning environment and processing parameters, polymer solution composition, and addition of nucleating agents such as Carbon Black (CB) to enhance the crystalline development of β-phase, fibre thickness, and morphology. The developed PVDF-HFP/CB nanocomposite presents and response to both slow and fast pressure fluctuations with high capacitance (5.37nF) and output voltage (1.51V) allowing for accurate and reliable measurements.

Robust Ionics Reinforced Fiber As Implantable Sensor for Early Operando Monitoring Cell Thermal Safety of Commercial Lithium-Ion Batteries.

Commercial batteries have been largely applied in mobile electronics, electric vehicles, and scalable energy storage systems. However, thermal runaway of batteries still obstructs the reliability of electric equipment. Considering this, building upon recent investigations of energy thermal safety, commercially available organogel fiber-based implantable sensors have been developed through 3D printing technology for first operando implantable monitoring of cell temperature. The printed fibers present excellent reliability and superelasticity because of internal supramolecular cross-linking. High temperature sensitivity (-39.84% °C-1/-1.557% °C-1) within a wide range (-15 to 80 °C) is achieved, and the corresponding mechanism is clarified based on in situ temperature-dependent Raman technology. Furthermore, taking the pouch cell as an example, combined with finite element analysis, the real-time observation system of cell temperature is successfully demonstrated through an implanted sensor with wireless Bluetooth transmission. This enlightening approach paves the way for achieving safety monitoring and smart warnings for various electric equipment.

One-step prepared of e-Gelatin-CNTs nano-composite fiber modified carbon fiber microelectrode for continuous dopamine monitoring: Characterization, biocompatibility evaluation and in vivo experiment

Fabricating electrochemical sensor capable of stable sensing in complex organism's environment will undoubtedly underpin key in the development of implanted electrochemical sensor. However, nonspecific protein adsorption can greatly reduce sensing sensitivity of electrode due to the abundance of protein in vivo. Herein, we aim to fabricating a modified layer of good protein adsorption resistance. The nano-composite fibers from gelatin with good hydrophily and multiwall carbon nanotubes (CNTs) for constructing on the surface of carbon fiber microelectrode using one-step electrospinning technology (e-Gelatin-CNTs/CFME). A comprehensive discussing on the protein adsorption resistance of e-Gelatin-CNTs/CFME that are, through the use of SEM, AFM, water contact angle, UV–vis, cyclic voltammetry and I-T. The resulting electrochemical sensor revealed stable sensing sensitivity in protein solution, a slightly decrease (0.02nA/μM). Furthermore, the sensor was successfully used for the detection of DA in human blood. More remarkable, e-Gelatin-CNTs nano-composite fibers presented excellent biocompatibility, which could meet the biosafety as implantation materials in vivo. This work provided a platform for the development of implantable electrochemical sensor.