Implantable Sensor Research Articles

Implantable pH Sensing System Using Vertically Stacked Silicon Nanowire Arrays and Body Channel Communication for Gastroesophageal Reflux Monitoring.

Silicon nanowires (SiNWs) are emerging as versatile components in the fabrication of sensors for implantable medical devices because of their exceptional electrical, optical, and mechanical properties. This paper presents a novel top-down fabrication method for vertically stacked SiNWs, eliminating the need for wet oxidation, wet etching, and nanolithography. The integration of these SiNWs into body channel communication (BCC) circuits was also explored. The fabricated SiNWs were confirmed to be capable of forming arrays with multiple layers and rows. The SiNW-based pH sensors demonstrated a robust response to pH changes, and when tested with BCC circuits, they showed that it was possible to quantize based on pH when transmitting data through the human body. This study successfully developed a novel method for SiNW fabrication and integration into BCC circuits, which could lead to improvements in the reliability and efficiency of implantable medical sensors. The findings demonstrate significant potential for bioelectronic applications and real-time biochemical monitoring.

Room-Temperature Smart Sensor Based on Indium Acetate-Functionalized Perovskite CsPbBr3 Nanocrystals for Monitoring Electrolyte in Lithium-Ion Batteries.

Monitoring electrolyte components is an effective means of determining the safety status of lithium-ion batteries. In this study, indium acetate was taken as a ligand to functionalize perovskite CsPbBr3 nanocrystals, and then the room-temperature electrolyte sensor based on CsPbBr3 nanocrystals with ligand indium acetate was prepared. The sensor offers high response, long-term stability (21 days), and low detection limits for ethyl methyl carbonate (10 ppm), diethyl carbonate (10 ppm), and ethyl butyrate (1 ppm) gases at room temperature and boasts a fast response/recovery time (1500 ppm, 58.27/103.82 s, 33.58/40.62 s, and 45.05/103.08 s, respectively). Density functional theory results show that the gas sensitivity comes from the adsorption of an electrolyte, which changes the density-of-state distribution so that the electrical response curve changes. And using computational fluid dynamics simulation, it was found that the time required for gas detection by the built-in sensor (3.1 s) was 8.7 times shorter than that of the implantable sensor. This work provides inspiration and rationale for embedding and integrating room-temperature sensors into lithium-ion batteries to monitor safety and health conditions.

Recent Development of Implantable Chemical Sensors Utilizing Flexible and Biodegradable Materials for Biomedical Applications.

Implantable chemical sensors built with flexible and biodegradable materials exhibit immense potential for seamless integration with biological systems by matching the mechanical properties of soft tissues and eliminating device retraction procedures. Compared with conventional hospital-based blood tests, implantable chemical sensors have the capability to achieve real-time monitoring with high accuracy of important biomarkers such as metabolites, neurotransmitters, and proteins, offering valuable insights for clinical applications. These innovative sensors could provide essential information for preventive diagnosis and effective intervention. To date, despite extensive research on flexible and bioresorbable materials for implantable electronics, the development of chemical sensors has faced several challenges related to materials and device design, resulting in only a limited number of successful accomplishments. This review highlights recent advancements in implantable chemical sensors based on flexible and biodegradable materials, encompassing their sensing strategies, materials strategies, and geometric configurations. The following discussions focus on demonstrated detection of various objects including ions, small molecules, and a few examples of macromolecules using flexible and/or bioresorbable implantable chemical sensors. Finally, we will present current challenges and explore potential future directions.

The application of impantable sensors in the musculoskeletal system: a review.

As the population ages and the incidence of traumatic events rises, there is a growing trend toward the implantation of devices to replace damaged or degenerated tissues in the body. In orthopedic applications, some implants are equipped with sensors to measure internal data and monitor the status of the implant. In recent years, several multi-functional implants have been developed that the clinician can externally control using a smart device. Experts anticipate that these versatile implants could pave the way for the next-generation of technological advancements. This paper provides an introduction to implantable sensors and is structured into three parts. The first section categorizes existing implantable sensors based on their working principles and provides detailed illustrations with examples. The second section introduces the most common materials used in implantable sensors, divided into rigid and flexible materials according to their properties. The third section is the focal point of this article, with implantable orthopedic sensors being classified as joint, spine, or fracture, based on different practical scenarios. The aim of this review is to introduce various implantable orthopedic sensors, compare their different characteristics, and outline the future direction of their development and application.

An in vitro demonstration of a passive, acoustic metamaterial as a temperature sensor with mK resolution for implantable applications

Wireless medical sensors typically utilize electromagnetic coupling or ultrasound for energy transfer and sensor interrogation. Energy transfer and management is a complex aspect that often limits the applicability of implantable sensor systems. In this work, we report a new passive temperature sensing scheme based on an acoustic metamaterial made of silicon embedded in a polydimethylsiloxane matrix. Compared to other approaches, this concept is implemented without additional electrical components in situ or the need for a customized receiving unit. A standard ultrasonic transducer is used for this demonstration to directly excite and collect the reflected signal. The metamaterial resonates at a frequency close to a typical medical value (5 MHz) and exhibits a high-quality factor. Combining the design features of the metamaterial with the high-temperature sensitivity of the polydimethylsiloxane matrix, we achieve a temperature resolution of 30 mK. This value is below the current standard resolution required in infrared thermometry for monitoring postoperative complications (0.1 K). We fabricated, simulated, in vitro tested, and compared three acoustic sensor designs in the 29–43 °C (~302–316 K) temperature range. With this concept, we demonstrate how our passive metamaterial sensor can open the way toward new zero-power smart medical implant concepts based on acoustic interrogation.

Ultrasensitive Optical Detection and Elimination of Residual Microtumors with a Postoperative Implantable Hydrogel Sensor for Preventing Cancer Recurrence.

In vivo optical imaging of trace biomarkers in residual microtumors holds significant promise for cancer prognosis but poses a formidable challenge. Here, a novel hydrogel sensor is designed for ultrasensitive and specific imaging of the elusive biomarker. This hydrogel sensor seamlessly integrates a molecular beacon nanoprobe with fibroblasts, offering both high tissue retention capability and an impressive signal-to-noise ratio for imaging. Signal amplification is accomplished through exonuclease I-mediated biomarker recycling. The resulting hydrogel sensor sensitively detects the biomarker carcinoembryonic antigen with a detection limit of 1.8pgmL-1 in test tubes. Moreover, it successfully identifies residual cancer nodules with a median diameter of less than 2mm in mice bearing partially removed primary triple-negative breast carcinomas (4T1). Notably, this hydrogel sensor is proven effective for the sensitive diagnosis of invasive tumors in post-surgical mice with infiltrating 4T1 cells, leveraging the role of fibroblasts in locally enriching tumor cells. Furthermore, the residual microtumor is rapidly photothermal ablation by polydopamine-based nanoprobe under the guidance of visualization, achieving ≈100% suppression of tumor recurrence and lung metastasis. This work offers a promising alternative strategy for visually detecting residual microtumors, potentially enhancing the prognosis of cancer patients following surgical interventions.

Fabrication of flexible glucose sensor based on heterostructure ZnO nanosheets decorated PU/Chitosan-PANI hybrid nanofiber

Designing and fabrication of immensely accurate, affordable, sensitive, and portable glucose sensors is rapidly increasing in clinical applications. However, commercialization of wearable sensors has been impeded by inadequate conductivity, insufficient durability, poor flexibility, and enzyme immobilization. Herein, a scalable approach for fabricating a nanofiber-based highly electroactive, flexible, and disposable (PUC-PANI-ZnO@GOx) sensor that can assess glucose stimuli with sufficient liquid permeability by anchoring ZnO nanosheets over polyaniline (PANI) coated polyurethane-chitosan (PU-Chitosan; PUC) fibrous mat followed by glucose oxidase (GOx) immobilization is described. Regarding the electrocatalytic performance, PUC-PANI-ZnO@GOx sensor showed a high sensitivity (∼998.72 µA mM−1 cm−2) and a low detection limit (∼7.31 µM) for a broad linear range of 0.01 – 9.48 mM with acceptable stability and reproducibility. The fabricated sensor was highly selective towards glucose in the presence of exogenous and endogenous interfering species. To the best of our knowledge, this novel polymer-based nanocomposite adorned on nanofiber substrate was utilized for the first time for the fabrication of a flexible glucose sensor. It can be used for producing a large-scale, cost-effective, and high-performing sensor. Hence, this sustainable and eco-friendly approach can lead to new techniques for designing next-generation wearable and implantable glucose sensors.

AO FRACTURE MONITOR: CONTINUOUS SENSOR MONITORING FOR PERSONALIZED FRACTURE CARE

In absence of available quantitative measures, the assessment of fracture healing based on clinical examination and X-rays remains a subjective matter. Lacking reliable information on the state of healing, rehabilitation is hardly individualized and mostly follows non evidence-based protocols building on common guidelines and personal experience. Measurement of fracture stiffness has been demonstrated as a valid outcome measure for the maturity of the repair tissue but so far has not found its way to clinical application outside the research space. However, with the recent technological advancements and trends towards digital health care, this seems about to change with new generations of instrumented implants – often unfortunately termed “smart implants” – being developed as medical devices.The AO Fracture Monitor is a novel, active, implantable sensor system designed to provide an objective measure for the assessment of fracture healing progression (1). It consists of an implantable sensor that is attached to conventional locking plates and continuously measures implant load during physiological weight bearing. Data is recorded and processed in real-time on the implant, from where it is wirelessly transmitted to a cloud application via the patient's smartphone. Thus, the system allows for timely, remote and X-ray free provision of feedback upon the mechanical competence of the repair tissue to support therapeutic decision making and individualized aftercare.The device has been developed according to medical device standards and underwent extensive verification and validation, including an in-vivo study in an ovine tibial osteotomy model, that confirmed the device's capability to depict the course of fracture healing as well as its long-term technical performance. Currently a multi-center clinical investigation is underway to demonstrate clinical safety of the novel implant system. Rendering the progression of bone fracture healing assessable, the AO Fracture Monitor carries potential to enhance today's postoperative care of fracture patients.

One-Dimensional Implantable Sensors for Accurately Monitoring Physiological and Biochemical Signals.

In recent years, one-dimensional (1D) implantable sensors have received considerable attention and rapid development in the biomedical field due to their unique structural characteristics and high integration capability. These sensors can be implanted into the human body with minimal invasiveness, facilitating real-time and accurate monitoring of various physiological and pathological parameters. This review examines the latest advancements in 1D implantable sensors, focusing on the material design of sensors, device integration, implantation methods, and the construction of the stable sensor-tissue interface. Furthermore, a comprehensive overview is provided regarding the applications and future research directions for 1D implantable sensors with an ultimate aim to promote their utilization in personalized healthcare and precision medicine.

Encapsulated stretchable amphibious strain sensors.

Soft and stretchable strain sensors have found wide applications in health monitoring, motion tracking, and robotic sensing. There is a growing demand for strain sensors in amphibious environments, such as implantable sensors, wearable sensors for swimmers/divers, and underwater robotic sensors. However, developing a sensitive, stretchable, and robust amphibious strain sensor remains challenging. This work presents an encapsulated stretchable amphibious strain sensor. The conductive layer, made of silver nanowires embedded below the surface of polydimethylsiloxane, was sandwiched by two layers of thermoplastic polyurethane. Periodic sharp cuts were introduced to change the direction of flow from across the sensor to along the conductive path defined by the opening cracks. The crack advancing and opening is controlled by a unique combination of weak/strong interfaces within the sandwich structure. The cut design and the interfacial interactions between the layers were investigated. The strain sensor exhibited a high gauge factor up to 289, a linear sensing response, a fast response time (53 ms), excellent robustness against over-strain, and stability after 16 000 loading cycles and 20 days in an aqueous saline solution. The functionality of this amphibious strain sensor was demonstrated by tracking the motion of a robotic fish, undertaking language recognition underwater, and monitoring the blood pressure of a porcine aorta. This illustrates the promising potential for this strain sensor for both underwater use and surgically implantable applications.

PVDF/ZnO piezoelectric nanofibers designed for monitoring of internal micro-pressure.

Organic piezoelectric materials are emerging as integral components in the development of advanced implantable self-powered sensors for the next generation. Despite their promising applications, a key limitation lies in their reduced mechanical force-to-electricity conversion efficiency. In this study, we present a breakthrough in the fabrication of soft poly(vinylidene fluoride) (PVDF) organic electrospun piezoelectric nanofibers (OEPNs) with exceptional piezoelectric performance achieved through the incorporation of zinc oxide nanorods (ZnO NR). The inclusion of ZnO NR proved instrumental in augmenting the nanocrystallization of PVDF organic electrospun piezoelectric nanofibers (OEPNs), leading to a highly efficient crystal phase transformation from the α phase to the β/γ phase, serving as superior piezoelectric working dipoles. The resulting PVDF/ZnO NR OEPNs exhibited unparalleled piezoelectric output voltage and current density, particularly noteworthy under a micro-pressure of 1 kPa and a low frequency of 1.5 Hz. Utilizing the obtained PVDF/ZnO NR OEPNs as the piezoelectric working element, we engineered a soft self-powered micro-pressure sensor. This sensor was implanted simultaneously on the cardiovascular walls of the heart and femoral artery in pigs. The sensor demonstrated precise monitoring and recording capabilities for micro-pressure changes during various physiological states, spanning from wakefulness to coma, euthanasia, and notably, the formation of cardiac thrombus. These findings underscore the immense potential of the implantable self-powered sensor for the assessment and diagnosis of pressure-related cardiovascular diseases, such as thrombus and atherosclerosis, during the postoperative recovery phase. This innovative technology offers valuable insights into the dynamic physiological states, paving the way for enhanced postoperative care and management of cardiovascular conditions.

Nucleic acid-based wearable and implantable electrochemical sensors.

The rapid advancements in nucleic acid-based electrochemical sensors for implantable and wearable applications have marked a significant leap forward in the domain of personal healthcare over the last decade. This technology promises to revolutionize personalized healthcare by facilitating the early diagnosis of diseases, monitoring of disease progression, and tailoring of individual treatment plans. This review navigates through the latest developments in this field, focusing on the strategies for nucleic acid sensing that enable real-time and continuous biomarker analysis directly in various biofluids, such as blood, interstitial fluid, sweat, and saliva. The review delves into various nucleic acid sensing strategies, emphasizing the innovative designs of biorecognition elements and signal transduction mechanisms that enable implantable and wearable applications. Special perspective is given to enhance nucleic acid-based sensor selectivity and sensitivity, which are crucial for the accurate detection of low-level biomarkers. The integration of such sensors into implantable and wearable platforms, including microneedle arrays and flexible electronic systems, actualizes their use in on-body devices for health monitoring. We also tackle the technical challenges encountered in the development of these sensors, such as ensuring long-term stability, managing the complexity of biofluid dynamics, and fulfilling the need for real-time, continuous, and reagentless detection. In conclusion, the review highlights the importance of these sensors in the future of medical engineering, offering insights into design considerations and future research directions to overcome existing limitations and fully realize the potential of nucleic acid-based electrochemical sensors for healthcare applications.

Electrochemical sensors for analyte in saliva: recent update

Purpose This review provides an overview of recent advances in electrochemical sensors for analyte detection in saliva, highlighting their potential applications in diagnostics and health care. The purpose of this paper is to summarize the current state of the field, identify challenges and limitations and discuss future prospects for the development of saliva-based electrochemical sensors. Design/methodology/approach The paper reviews relevant literature and research articles to examine the latest developments in electrochemical sensing technologies for saliva analysis. It explores the use of various electrode materials, including carbon nanomaterial, metal nanoparticles and conducting polymers, as well as the integration of microfluidics, lab-on-a-chip (LOC) devices and wearable/implantable technologies. The design and fabrication methodologies used in these sensors are discussed, along with sample preparation techniques and biorecognition elements for enhancing sensor performance. Findings Electrochemical sensors for salivary analyte detection have demonstrated excellent potential for noninvasive, rapid and cost-effective diagnostics. Recent advancements have resulted in improved sensor selectivity, stability, sensitivity and compatibility with complex saliva samples. Integration with microfluidics and LOC technologies has shown promise in enhancing sensor efficiency and accuracy. In addition, wearable and implantable sensors enable continuous, real-time monitoring of salivary analytes, opening new avenues for personalized health care and disease management. Originality/value This review presents an up-to-date overview of electrochemical sensors for analyte detection in saliva, offering insights into their design, fabrication and performance. It highlights the originality and value of integrating electrochemical sensing with microfluidics, wearable/implantable technologies and point-of-care testing platforms. The review also identifies challenges and limitations, such as interference from other saliva components and the need for improved stability and reproducibility. Future prospects include the development of novel microfluidic devices, advanced materials and user-friendly diagnostic devices to unlock the full potential of saliva-based electrochemical sensing in clinical practice.

Catheter-Free Urodynamics Testing: Current Insights and Clinical Potential.

Lower urinary tract dysfunction not only interferes with the health-related quality of life of patients but may also lead to acute kidney injury and infections. To assess the bladder, urodynamic studies (UDS) have been implemented but the use of catheters leads to discomfort for the patient. Catheter-free long-term UDS would be useful and a potential solution could be ambulatory wireless devices that communicate via telemetry. Such sensors can detect pressure or volume. Numerous types of potential catheter-free sensors have been proposed for bladder monitoring. Despite substantial innovation in the manufacturing of implantable biomedical electronic systems, such sensors have remained at the laboratory stage due to a number of critical challenges. These challenges primarily concern hermeticity and biocompatibility, sensitivity and artifacts, drift, telemetry, and energy management. Having overcome these challenges, catheter-free ambulatory urodynamic monitoring could combine a synchronized intravesical pressure sensor with a volume analyzer but only the steps of cystometry and volume measurement are currently sufficiently reproducible to simulate UDS results. The measurement of volume by infrared optical sensors, in the form of abdominal patches, appears to be promising and studies are underway to market a telemetric ambulatory urodynamic monitoring system that includes an intravesical pressure sensor. There has been considerable progress in wearable and conformable electronics on many fronts, and continued collaboration between engineers and urologists could quickly overcome current challenges. In addition, to the diagnosis of UDS, such sensors could be useful in the development of a long-term closed-loop neuromodulation system. In this review, we explore the various types of catheter-free bladder sensors, inherent challenges and solutions to overcome these challenges, and the clinical potential of such long-term implantable sensors.

Electrospun polarity-controlled molecular orientation for synergistic performance of an artifact-free piezoelectric anisotropic sensor.

Anisotropy in mechanical, optical and thermal sensors in a spatial direction has many applications in health care, robotics, aerospace, and tissue engineering. In particular, wearable and implantable sensors respond to stretching and bending strains that probe mechanical energy and track physiological signals. Hence, the development of anisotropic pressure sensors with true piezoelectric (PE) signals is of utmost importance to achieve efficient devices. Herein, a simple and efficient method is developed for high longitudinal and transverse responses, with an approach to isolating a true piezoelectric signal. The electrospun (ES) polarity of oriented dipoles inside flexible fibers gives rise to a high longitudinal/transverse PE response of both lateral and transverse strains. Nanofibers of poly(vinylidene-chlorotrifluoroethylene) copolymers contain poled dipoles, up to 86%, that promote an enhanced PE coefficient of 42 pm V-1 in the case of negative polarity-based electrospinning. It is 40% higher in composition than the commonly adopted positive polarity-biased electrospinning process. We demonstrated the advantage of such a high PE coefficient by the enhanced sensitivity of the longitudinal (VLs = 0.3 V kPa-1, ILs = 0.07 μA kPa-1) as well as transverse (VTs = 1.0 V kPa-1, ITs = 0.8 μA kPa-1) PE response. To counter the ambiguity of high transverse response as compared to longitudinal in electrospun fiber-based devices, a facile method is proposed to isolate the ferroelectret, triboelectric and piezoelectric signals in a fiber-based hybrid device with their independent charge generation mechanisms.

Piezoelectric PVDF and its copolymers in biomedicine: innovations and applications.

In recent years, poly(vinylidene fluoride) (PVDF) has emerged as a versatile polymer with a wide range of applications across various fields. PVDF's piezosensitivity, versatility, crystalline structure, and tunable parameters have established it as a highly sought-after material. Furthermore, PVDF and its copolymers exhibit excellent processability and chemical resistance to a diverse array of substances. Of particular significance is its remarkable structural stability in physiological media, which highlights its potential for use in the development of biomedical products. This review offers a comprehensive overview of the latest advancements in PVDF-based biomedical systems. It examines the fabrication of stimulus-responsive delivery systems, bioelectric therapy devices, and tissue-regenerating scaffolds, all of which harness the piezosensitivity of PVDF. Moreover, the potential of PVDF in the fabrication of both invasive and non-invasive diagnostic tools is investigated, with particular emphasis on its flexibility, transparency, and piezoelectric efficiency. The material's high biocompatibility and physiological stability are of paramount importance in the development of implantable sensors for long-term health monitoring, which is crucial for the management of chronic diseases and postoperative care. Additionally,we discuss a novel approach to photoacoustic microscopy that employs a PVDF sensor, thereby eliminating the necessity for external contrast agents. This technique provides a new avenue for non-invasive imaging in biomedical applications. Finally, we explore the challenges and prospects for the development of PVDF-based systems for a range of biomedical applications. This review is distinctive in comparison to other reviews on PVDF due to its concentrated examination of biomedical applications, including pioneering imaging techniques, long-term health monitoring, and a detailed account of advancements in the field. Collectively, these elements illustrate the potential of PVDF to markedly influence biomedical engineering and patient care, distinguishing it from existing literature. By leveraging the distinctive attributes of PVDF and its copolymers, researchers can continue to advance the frontiers of biomedical engineering, with the potential to transform patient care and treatment outcomes.

The Implant-Induced Foreign Body Response Is Limited by CD13-Dependent Regulation of Ubiquitination of Fusogenic Proteins.

Implanted medical devices, from artificial heart valves and arthroscopic joints to implantable sensors, often induce a foreign body response (FBR), a form of chronic inflammation resulting from the inflammatory reaction to a persistent foreign stimulus. The FBR is characterized by a subset of multinucleated giant cells (MGCs) formed by macrophage fusion, the foreign body giant cells (FBGCs), accompanied by inflammatory cytokines, matrix deposition, and eventually deleterious fibrotic implant encapsulation. Despite efforts to improve biocompatibility, implant-induced FBR persists, compromising the utility of devices and making efforts to control the FBR imperative for long-term function. Controlling macrophage fusion in FBGC formation presents a logical target to prevent implant failure, but the actual contribution of FBGCs to FBR-induced damage is controversial. CD13 is a molecular scaffold, and invitro induction of CD13KO bone marrow progenitors generates many more MGCs than the wild type, suggesting that CD13 regulates macrophage fusion. In the mesh implant model of FBR, CD13KO mice produced significantly more peri-implant FBGCs with enhanced TGF-β expression and increased collagen deposition versus the wild type. Prior to fusion, increased protrusion and microprotrusion formation accompanies hyperfusion in the absence of CD13. Expression of fusogenic proteins driving cell-cell fusion was aberrantly sustained at high levels in CD13KO MGCs, which we show is due to a novel CD13 function, to our knowledge, regulating ubiquitin/proteasomal protein degradation. We propose CD13 as a physiologic brake limiting aberrant macrophage fusion and the FBR, and it may be a novel therapeutic target to improve the success of implanted medical devices. Furthermore, our data directly implicate FBGCs in the detrimental fibrosis that characterizes the FBR.

(Invited) Calibration-Free Ion-Selective Electrodes and Optodes for Decentralized Electrolyte Monitoring

Ionophore-based ion-selective sensors have been used in hospital analyzers for decades to measure electrolytes. Recently, there has been growing interest in affordable and accessible electrolyte measurements via at-home sensors, wearable sensors, transdermal sensors, and implantable sensors. However, the commercial success of ion-selective sensors in these new sensing modalities is hindered by the need for technically demanding on-site calibration. In fact, all ionophore-based sensors in clinical analyzers need to be calibrated with standard solutions at the point of use. We are developing calibration-free ionophore-based sensors, including ion-selective electrodes and optodes, to enable decentralized electrolyte measurements for the management of chronic heart, renal, and parathyroid diseases.In the first approach, we have designed self-calibrating solid-contact ion-selective electrodes. Due to microheterogeneities and variabilities in multiple phases and interfaces of the indicator and reference electrodes, the absolute electromotive force (EMF) varies among identically fabricated and stored sensors. We create an EMF baseline that corrects for the EMF variabilities by connecting two electrodes using an appropriately formulated ionic conductor. Upon the introduction of a sample, such as a drop of blood, the EMF change relative to this baseline allows for ion measurements with high sensor-to-sensor consistency in the absence of any calibration protocols. Surprisingly, when the cross-sectional area, viscosity, and formulation of the ionic conductor are precisely controlled and the ionic conductor is insulated from the sample, its presence does not compromise the Nernstian response slope of the primary ion in the sample. In other words, this built-in ionic bridge serves for one-point calibration before the sample addition but does not need to be removed for the sample testing, representing a novel self-calibration strategy for electrochemical sensors.In the second approach, we have for the first time functionalized the oil stream of droplet microfluidics with sensing chemicals to convert oil segments to sensors for adjacent aqueous droplets. Ionophores, ion exchangers, and dyes are dissolved in the oil to form highly selective fluorescent ion sensors. Analyte ions from the aqueous droplets are extracted into the oil segments to alter their fluorescence and absorbance. The composition of all oil segments is highly consistent, as they are from the same homogenous solution, avoiding the need for any on-site calibration. As the optical property of the oil segment is measured in a fashion that is spatially and temporally separated from the aqueous sample, this biphasic sensing method works for complicated samples such as undiluted whole blood.In the third approach, we have designed a home-use sensor based on a calibration-free oil sensor contained in a capillary tube. Only one segment of sensing oil is used for analysis of one segment of sample of a few microliters. By continuously alternating the relative position of the oil and the sample controlled by a stepper motor, efficient mass transfer between two phases is obtained. The color of the oil segment is acquired and analyzed by a smartphone to indicate the electrolyte concentration in an aqueous sample. The accuracy and precision of an at-home calcium monitor in this format have been validated in > 50 human blood samples.

Non-contact monitoring of glucose concentration and pH by integration of wearable and implantable hydrogel sensors with optical coherence tomography.

Optical coherence tomography (OCT) is a noninvasive imaging technique with large penetration depth into the tissue, but limited chemical specificity. By incorporating functional co-monomers, hydrogels can be designed to respond to specific molecules and undergo reversible volume changes. In this study, we present implantable and wearable biocompatible hydrogel sensors combined with OCT to monitor their thickness change as a tool for continuous and real-time monitoring of glucose concentration and pH. The results demonstrate the potential of combining hydrogel biosensors with OCT for non-contact continuous in-vivo monitoring of physiological parameters.

Bio-Inspired Untethered Robot-Sensor Platform for Minimally Invasive Biomedical Sensing.

Conventional catheter- or probe-based in vivo biomedical sensing is uncomfortable, inconvenient, and sometimes infeasible for long-term monitoring. Existing implantable sensors often require an invasive procedure for sensor placement. Untethered soft robots with the capability to deliver the sensor to the desired monitoring point hold great promise for minimally invasive biomedical sensing. Inspired by the locomotion modes of snakes, we present here a soft kirigami robot for sensor deployment and real-time wireless sensing. The locomotion mechanism of the soft robot is achieved by kirigami patterns that offer asymmetric tribological properties that mimic the skin of the snake. The robot exhibits good deployability, excellent load capacity (up to 150 times its own weight), high-speed locomotion (0.25 body length per step), and wide environmental adaptability with multimodal movements (obstacle crossing, locomotion in wet and dry conditions, climbing, and inverted crawling). When integrated with passive sensors, the versatile soft robot can locomote inside the human body, deliver the passive sensor to the desired location, and hold the sensor in place for real-time monitoring in a minimally invasive manner. The proof-of-concept prototype demonstrates that the platform can perform real-time impedance monitoring for the diagnosis of gastroesophageal reflux disease.