Digital monitoring of the microchannel filling flow dynamics using a non-contactless smartphone-based nano-liter precision flow velocity meter.

Microfluidic systems find widespread applications in diagnostics, biological research, chemistry, and engineering studies. Among their many critical parameters, flow rate plays a pivotal role in maintaining the functionality of microfluidic systems, including droplet-based microfluidic devices and those used in cell culture. It also significantly influences microfluidic mixing processes. Although various flow rate measurement devices have been developed, the challenge remains in accurately measuring flow rates within customized channels. This paper presents the development of a 3D-printed smartphone-based flow velocity meter. The 3D-printed platform is angled at 30° to achieve transparent flow visualization, and it doesn't require any external optical components such as external lenses and filters. Two LED modules integrated into the platform create a uniform illumination environment for video capture, powered directly by the smartphone. The performance of our platform, combined with a customized video processing algorithm, was assessed in three different channel types: uniform straight channels, straight channels with varying widths, and vessel-like channel patterns to demonstrate its versatility. Our device effectively measured flow velocities from 5.43 mm/s to 24.47 mm/s, with video quality at 1080p resolution and 60 frames per second, for which the measurement range can be extended by adjusting the frame rate. This flow velocity meter can be a useful analytical tool to evaluate and enhance microfluidic channel designs of various lab-on-a-chip applications.

Near-Infrared Triggered Degradation for Transient Electronics.

Electronics that disintegrate after stable operation present exciting opportunities for niche medical implant and consumer electronics applications. The disintegration of these devices can be initiated due to their medium conditions or triggered by external stimuli, which enables on-demand transition. An external stimulation method that can penetrate deep inside the body could revolutionize the use of transient electronics as implantable medical devices (IMDs), eliminating the need for secondary surgery to remove the IMDs. We report near-infrared (NIR) light-triggered transition of metastable cyclic poly(phthalaldehyde) (cPPA) polymers. The transition of the encapsulation layer is achieved through the conversion of NIR light to heat, facilitated by bioresorbable metals, such as molybdenum (Mo). We reported a rapid degradation of cPPA encapsulation layer about 1 min, and the rate of degradation can be controlled by laser power and exposure time. This study offers a new approach for light triggerable transient electronics for IMDs due to the deep penetration depth of NIR light through to organs and tissues.

A Wearable Touch-Activated Device Integrated with Hollow Microneedles for Continuous Sampling and Sensing of Dermal Interstitial Fluid.

Dermal interstitial fluid (ISF) is emerging as a rich source of biomarkers that complements conventional biofluids such as blood and urine. However, the impact of ISF sampling in clinical applications has been limited owing to the challenges associated with extraction. The implementation of microneedle-based wearable devices that can extract dermal ISF in a pain-free and easy-to-use manner has attracted growing attention in recent years. Here, a fully integrated touch-activated wearable device based on a laser-drilled hollow microneedle (HMN) patch for continuous sampling and sensing of dermal ISF is introduced. The developed platform can produce and maintain the required vacuum pressure (as low as ≈ -53 kPa) to collect adequate volumes of ISF (≈2 µL needle-1 h-1 ) for medical applications. The vacuum system can be activated through a one-touch finger operation. A parametric study is performed to investigate the effect of microneedle array size, vacuum pressure, and extraction duration on collected ISF. The capability of the proposed platform for continuous health monitoring is further demonstrated by the electrochemical detection of glucose and pH levels of ISF in animal models. This HMN-based system provides an alternative tool to the existing invasive techniques for ISF collection and sensing for medical diagnosis and treatment.

Miniaturized wireless sensor enables real-time monitoring of food spoilage.

Food spoilage results in food waste and food-borne diseases. Yet, standard laboratory tests to determine spoilage (mainly volatile biogenic amines) are not performed regularly by supply chain personnel or end customers. Here we developed a poly(styrene-co-maleic anhydride)-based, miniature (2 × 2 cm2) sensor for on-demand spoilage analysis via mobile phones. To demonstrate a real-life application, the wireless sensor was embedded into packaged chicken and beef; consecutive readings from meat samples using the sensor under various storage conditions enabled the monitoring of spoilage. While samples stored at room temperature showed an almost 700% change in sensor response on the third day, those stored in the freezer resulted in an insignificant change in sensor output. The proposed low-cost, miniature wireless sensor nodes can be integrated into packaged foods, helping consumers and suppliers detect spoilage of protein-rich foods on demand, and ultimately preventing food waste and food-borne diseases.

Biodegradable Piezoelectric Polymers: Recent Advancements in Materials and Applications.

Recent materials, microfabrication, and biotechnology improvements have introduced numerous exciting bioelectronic devices based on piezoelectric materials. There is an intriguing evolution from conventional unrecyclable materials to biodegradable, green, and biocompatible functional materials. As a fundamental electromechanical coupling material in numerous applications, novel piezoelectric materials with a feature of degradability and desired electrical and mechanical properties are being developed for future wearable and implantable bioelectronics. These bioelectronics can be easily integrated with biological systems for applications, including sensing physiological signals, diagnosing medical problems, opening the blood-brain barrier, and stimulating healing or tissue growth. Therefore, the generation of piezoelectricity from natural and synthetic bioresorbable polymers has drawn great attention in the research field. Herein, the significant and recent advancements in biodegradable piezoelectric materials, including natural and synthetic polymers, their principles, advanced applications, and challenges for medical uses, are reviewed thoroughly. The degradation methods of these piezoelectric materials through in vitro and in vivo studies are also investigated. These improvements in biodegradable piezoelectric materials and microsystems could enable new applications in the biomedical field. In the end, potential research opportunities regarding the practical applications are pointed out that might be significant for new materials research.

Photolithography-Based Microfabrication of Biodegradable Flexible and Stretchable Sensors.

Biodegradable sensors based on integrating conductive layers with polymeric materials in flexible and stretchable forms have been established. However, the lack of a generalized microfabrication method results in large-sized, low spatial density, and low device yield compared to the silicon-based devices manufactured via batch-compatible microfabrication processes. Here, a batch fabrication-compatible photolithography-based microfabrication approach for biodegradable and highly miniaturized essential sensor components is presented on flexible and stretchable substrates. Up to 1600 devices are fabricated within a 1 cm2 footprint and then the functionality of various biodegradable passive electrical components, mechanical sensors, and chemical sensors is demonstrated on flexible and stretchable substrates. The results are highly repeatable and consistent, proving the proposed method's high device yield and high-density potential. This simple, innovative, and robust fabrication recipe allows complete freedom over the applicability of various biodegradable materials with different properties toward the unique application of interests. The process offers a route to utilize standard micro-fabrication procedures toward scalable fabrication of highly miniaturized flexible and stretchable transient sensors and electronics.

Stretchable mesh microelectronics for the biointegration and stimulation of human neural organoids.

Advances in tridimensional (3D) culture approaches have led to the generation of organoids that recapitulate cellular and physiological features of domains of the human nervous system. Although microelectrodes have been developed for long-term electrophysiological interfaces with neural tissue, studies of long-term interfaces between microelectrodes and free-floating organoids remain limited. In this study, we report a stretchable, soft mesh electrode system that establishes an intimate in vitro electrical interface with human neurons in 3D organoids. Our mesh is constructed with poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) based electrically conductive hydrogel electrode arrays and elastomeric poly(styrene-ethylene-butylene-styrene) (SEBS) as the substrate and encapsulation materials. This mesh electrode can maintain a stable electrochemical impedance in buffer solution under 50% compressive and 50% tensile strain. We have successfully cultured pluripotent stem cell-derived human cortical organoids (hCO) on this polymeric mesh for more than 3 months and demonstrated that organoids readily integrate with the mesh. Using simultaneous stimulation and calcium imaging, we show that electrical stimulation through the mesh can elicit intensity-dependent calcium signals comparable to stimulation from a bipolar stereotrode. This platform may serve as a tool for monitoring and modulating the electrical activity of in vitro models of neuropsychiatric diseases.

A tissue-like neurotransmitter sensor for the brain and gut.

Neurotransmitters play essential roles in regulating neural circuit dynamics both in the central nervous system as well as at the peripheral, including the gastrointestinal tract1-3. Their real-time monitoring will offer critical information for understanding neural function and diagnosing disease1-3. However, bioelectronic tools to monitor the dynamics of neurotransmitters in vivo, especially in the enteric nervous systems, are underdeveloped. This is mainly owing to the limited availability of biosensing tools that are capable of examining soft, complex and actively moving organs. Here we introduce a tissue-mimicking, stretchable, neurochemical biological interface termed NeuroString, which is prepared by laser patterning of a metal-complexed polyimide into an interconnected graphene/nanoparticle network embedded in an elastomer. NeuroString sensors allow chronic in vivo real-time, multichannel and multiplexed monoamine sensing in the brain of behaving mouse, as well as measuring serotonin dynamics in the gut without undesired stimulations and perturbing peristaltic movements. The described elastic and conformable biosensing interface has broad potential for studying the impact of neurotransmitters on gut microbes, brain-gut communication and may ultimately be extended to biomolecular sensing in other soft organs across the body.

An ultra-compact and wireless tag for battery-free sweat glucose monitoring.

Glucose monitoring before, during, and after exercise is essential for people with diabetes as exercise increases the risk of activity-induced hyper- and hypo-glycemic events. The situation is even more challenging for athletes with diabetes as they have impaired metabolic control compared to sedentary individuals. In this regard, a compact and noninvasive wearable glucose monitoring device that can be easily worn is critical to enabling glucose monitoring. This report presents an ultra-compact glucose tag with a footprint and weight of 1.2 cm2 and 0.13 g, respectively, for sweat analysis. The device comprises a near field communication (NFC) chip, antenna, electrochemical sensor, and microfluidic channels implemented in different material layers. The device has a flexible and conformal structure and can be easily attached to different body parts. The battery-less operation of the device was enabled by NFC-based wireless power transmission and the compact antenna. Femtosecond laser ablation was employed to fabricate a highly compact and flexible NFC antenna. The proposed device demonstrated excellent operating characteristics with a limit of detection (LOD), limit of quantification (LOQ), and sensitivity of 24 µM, 74 µM, and 1.27 µA cm-2 mM-1, respectively. The response of the proposed sensor in sweat glucose detection and quantification was validated by nuclear magnetic resonance spectroscopy (NMR). Also, the device's capability in attachment to the body, sweat collection, and glucose measurement was demonstrated through in vitro and in vivo experiments, and satisfactory results were obtained.

Powering smart contact lenses for continuous health monitoring: Recent advancements and future challenges.

As the tear is noninvasively and continuously available, it has been turned into a convenient biological interface as a wearable medical device for out-of-hospital and self-monitoring applications. Recent progress in integrated circuits (ICs) and biosensors coupled with wireless data communication techniques have led to the implementation of smart contact lenses that can continuously sample tear fluid, analyze physiological conditions, and wirelessly transmit data to an electronic device such as smartphone, which can send data to relevant healthcare units. Continuous analyte monitoring is one of the significant characteristics of wearable biosensors. However, despite several advantages over other on-skin wearable medical devices, batteries cannot be incorporated on smart contact lenses for continuous electrical power supply due to the limited area. Herein, we review the progress of power delivery techniques of smart contact lenses for the first time. Different approaches, including wireless power transmission (WPT), biofuel cells, supercapacitors, flexible batteries, wired connections, and hybrid methods, are thoroughly discussed to understand the principles of self-sustainable contact lens biosensors comprehensively. Additionally, recent progress in contact lens biosensors is reviewed in detail, thereby providing the prospects for further developments of smart contact lenses as a common biosensing platform for various disease monitoring and diagnostic applications.

Artificial multimodal receptors based on ion relaxation dynamics.

Human skin has different types of tactile receptors that can distinguish various mechanical stimuli from temperature. We present a deformable artificial multimodal ionic receptor that can differentiate thermal and mechanical information without signal interference. Two variables are derived from the analysis of the ion relaxation dynamics: the charge relaxation time as a strain-insensitive intrinsic variable to measure absolute temperature and the normalized capacitance as a temperature-insensitive extrinsic variable to measure strain. The artificial receptor with a simple electrode-electrolyte-electrode structure simultaneously detects temperature and strain by measuring the variables at only two measurement frequencies. The human skin-like multimodal receptor array, called multimodal ion-electronic skin (IEM-skin), provides real-time force directions and strain profiles in various tactile motions (shear, pinch, spread, torsion, and so on).

A Review of Bioresorbable Implantable Medical Devices: Materials, Fabrication, and Implementation.

Implantable medical devices (IMDs) are designed to sense specific parameters or stimulate organs and have been actively used for treatment and diagnosis of various diseases. IMDs are used for long-term disease screening or treatments and cannot be considered for short-term applications since patients need to go through a surgery for retrieval of the IMD. Advances in bioresorbable materials has led to the development of transient IMDs that can be resorbed by bodily fluids and disappear after a certain period. These devices are designed to be implanted in the adjacent of the targeted tissue for predetermined times with the aim of measurement of pressure, strain, or temperature, while the bioelectronic devices stimulate certain tissues. They enable opportunities for monitoring and treatment of acute diseases. To realize such transient and miniaturized devices, researchers utilize a variety of materials, novel fabrication methods, and device design strategies. This review discusses potential bioresorbable materials for each component in an IMD followed by programmable degradation and safety standards. Then, common fabrication methods for bioresorbable materials are introduced, along with challenges. The final section provides representative examples of bioresorbable IMDs for various applications with an emphasis on materials, device functionality, and fabrication methods.

A bioinspired stretchable membrane-based compliance sensor.

Compliance sensation is a unique feature of the human skin that electronic devices could not mimic via compact and thin form-factor devices. Due to the complex nature of the sensing mechanism, up to now, only high-precision or bulky handheld devices have been used to measure compliance of materials. This also prevents the development of electronic skin that is fully capable of mimicking human skin. Here, we developed a thin sensor that consists of a strain sensor coupled to a pressure sensor and is capable of identifying compliance of touched materials. The sensor can be easily integrated into robotic systems due to its small form factor. Results showed that the sensor is capable of classifying compliance of materials with high sensitivity allowing materials with various compliance to be identified. We integrated the sensor to a robotic finger to demonstrate the capability of the sensor for robotics. Further, the arrayed sensor configuration allows a compliance mapping which can enable humanlike sensations to robotic systems when grasping objects composed of multiple materials of varying compliance. These highly tunable sensors enable robotic systems to handle more advanced and complicated tasks such as classifying touched materials.

A Novel Technology for Free Flap Monitoring: Pilot Study of a Wireless, Biodegradable Sensor.

BACKGROUND: Accurate monitoring of free flap perfusion after complex reconstruction is critical for early recognition of flap compromise. Surgeons use a variety of subjective and objective measures to evaluate flap perfusion postoperatively. However, these measures have some limitations. We have developed a wireless, biodegradable, and flexible sensor that can be applied to real-time postoperative free flap monitoring. Here we assess the biocompatibility and function of our novel sensor. METHODS: Seven Sprague-Dawley (SD) rats were used for biocompatibility studies. The sensor was implanted around the femoral artery near the inguinal ligament on one leg (implant side) and sham surgery was performed on the contralateral leg (control side). At 6 and 12 weeks, samples were harvested to assess the inflammation within and around the implant and artery. Two animals were used to assess sensor function. Sensor function was evaluated at implantation and 7 days after the implantation. Signal changes after venous occlusion were also assessed in an epigastric artery island flap model. RESULTS: In biocompatibility studies, the diameter of the arterial lumen and intima thickness in the implant group were not significantly different than the control group at the 12-week time point. The number of CD-68 positive cells that infiltrated into the soft tissue, surrounding the femoral artery, was also not significantly different between groups at the 12-week time point. For sensor function, accurate signaling could be recorded at implantation and 7 days later. A change in arterial signal was noted immediately after venous occlusion in a flap model. CONCLUSION: The novel wireless, biodegradable sensor presented here is biocompatible and capable of detecting arterial blood flow and venous occlusion with high sensitivity. This promising new technology could combat the complications of wired sensors, while improving the survival rate of flaps with vessel compromise due to its responsive nature.

An Electrochemical Gelation Method for Patterning Conductive PEDOT:PSS Hydrogels.

Due to their high water content and macroscopic connectivity, hydrogels made from the conducting polymer PEDOT:PSS are a promising platform from which to fabricate a wide range of porous conductive materials that are increasingly of interest in applications as varied as bioelectronics, regenerative medicine, and energy storage. Despite the promising properties of PEDOT:PSS-based porous materials, the ability to pattern PEDOT:PSS hydrogels is still required to enable their integration with multifunctional and multichannel electronic devices. In this work, a novel electrochemical gelation ("electrogelation") method is presented for rapidly patterning PEDOT:PSS hydrogels on any conductive template, including curved and 3D surfaces. High spatial resolution is achieved through use of a sacrificial metal layer to generate the hydrogel pattern, thereby enabling high-performance conducting hydrogels and aerogels with desirable material properties to be introduced into increasingly complex device architectures.

Biodegradable and flexible arterial-pulse sensor for the wireless monitoring of blood flow.

The ability to monitor blood flow is critical to patient recovery and patient outcomes after complex reconstructive surgeries. Clinically available wired implantable monitoring technology requires careful fixation for accurate detection and needs to be removed after use. Here, we report the design of a pressure sensor, made entirely of biodegradable materials and based on fringe-field capacitor technology, for measuring arterial blood flow in both contact and non-contact modes. The sensor is operated wirelessly through inductive coupling, has minimal hysteresis, fast response times, excellent cycling stability, is highly robust, allows for easy mounting and eliminates the need for removal, thus reducing the risk of vessel trauma. We demonstrate the operation of the sensor with a custom-made artificial artery model and in vivo in rats. This technology may be advantageous in real-time post-operative monitoring of blood flow after reconstructive surgery.

Energy harvesting from cerebrospinal fluid pressure fluctuations for self-powered neural implants.

In this paper, a novel method to generate electrical energy by converting available mechanical energy from pressure fluctuations of the cerebrospinal fluid within lateral ventricles of the brain is presented. The generated electrical power can be supplied to the neural implants and either eliminate their battery need or extend the battery lifespan. A diaphragm type harvester comprised of piezoelectric material is utilized to convert the pressure fluctuations to electrical energy. The pressure fluctuations cause the diaphragm to bend, and the strained piezoelectric materials generate electricity. In the framework of this study, an energy harvesting structure having a diameter of 2.5 mm was designed and fabricated using microfabrication techniques. A 1:1 model of lateral ventricles was 3D-printed from raw MRI images to characterize the harvester. Experimental results show that a maximum power of 0.62 nW can be generated from the harvester under similar physical conditions in lateral ventricles which corresponds to energy density of 12.6 nW/cm2. Considering the available area within the lateral ventricles and the size of harvesters that can be built using microfabrication techniques it is possible to amplify to power up to 26 nW. As such, the idea of generating electrical energy by making use of pressure fluctuations within brain is demonstrated in this work via the 3D-printed model system.