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.

Diamond for High-Power, High-Frequency, and Terahertz Plasma Wave Electronics.

High thermal conductivity and a high breakdown field make diamond a promising candidate for high-power and high-temperature semiconductor devices. Diamond also has a higher radiation hardness than silicon. Recent studies show that diamond has exceptionally large electron and hole momentum relaxation times, facilitating compact THz and sub-THz plasmonic sources and detectors working at room temperature and elevated temperatures. The plasmonic resonance quality factor in diamond TeraFETs could be larger than unity for the 240-600 GHz atmospheric window, which could make them viable for 6G communications applications. This paper reviews the potential and challenges of diamond technology, showing that diamond might augment silicon for high-power and high-frequency compact devices with special advantages for extreme environments and high-frequency applications.

Paper-Based Supercapacitive Pressure Sensor for Wrist Arterial Pulse Waveform Monitoring.

Recent developments in wearable pressure sensors have led to the need for high sensitivity and a broad sensing range to accurately detect various physiological states. However, high sensitivity does not always translate to a wide sensing range, and manufacturing sensors with such high sensitivity is a complex and expensive process. In this study, we present a capacitive pressure sensor based on tissue paper that is simple to produce and cost-effective yet still exhibits high linear sensitivity of 2.9 kPa-1 in the 0-16 kPa range. The linear sensitivity of 1.5 kPa-1 was achieved from 16 to 90 kPa. The sensor also demonstrated a fast response time of 0.2 s, excellent pressure resolution at both low and high pressures, and a sufficient signal-to-noise ratio, making it ideal for detecting wrist arterial pulse waveforms. We were also able to demonstrate the sensor's practicality in real-world applications by cycling it 5000 times and showing its capability to capture pulse waveforms from different arterial locations. These low-cost sensors possess all the intrinsic features necessary for efficient measurement of pulse waveforms, which may facilitate the diagnosis of cardiovascular diseases.

A Review of Phase-Change Materials and Their Potential for Reconfigurable Intelligent Surfaces.

Phase-change materials (PCMs) and metal-insulator transition (MIT) materials have the unique feature of changing their material phase through external excitations such as conductive heating, optical stimulation, or the application of electric or magnetic fields, which, in turn, results in changes to their electrical and optical properties. This feature can find applications in many fields, particularly in reconfigurable electrical and optical structures. Among these applications, the reconfigurable intelligent surface (RIS) has emerged as a promising platform for both wireless RF applications as well as optical ones. This paper reviews the current, state-of-the-art PCMs within the context of RIS, their material properties, their performance metrics, some applications found in the literature, and how they can impact the future of RIS.

Monitoring and analysis of cardiovascular pulse waveforms using flexible capacitive and piezoresistive pressure sensors and machine learning perspective.

The growing interest in flexible electronics for physiological monitoring, particularly using flexible pressure sensors for cardiovascular pulse waveforms monitoring, has potential applications in cuffless blood pressure measurement and early diagnosis of cardiovascular disease. High sensitivity, fast response time, good pressure resolution and a high signal-to-noise ratio are essential for effective pulse waveform detection. This review focuses on flexible capacitive and piezoresistive pressure sensors, which have seen significant enhancements due to their simple operation, superior performance, wide range of materials, and easy fabrication. The comparison of sensing methods for acquiring pulse waveforms from the wrist artery, device integration configurations, high-quality pulse waveforms collection, and performance analysis of capacitive and piezoresistive sensors are discussed. The review also covers the use of machine learning for analyzing pulse waveforms for cardiovascular disease diagnosis and cuff-less blood pressure monitoring. Lastly, it provides perspectives on current challenges and further advancements in the field.

Selective area multilayer graphene synthesis using resistive nanoheater probe.

Graphene has been a material of interest due to its versatile properties and wide variety of applications. However, production has been one of the most challenging aspects of graphene and multilayer graphene (MLG). Most synthesis techniques require elevated temperatures and additional steps to transfer graphene or MLG to a substrate, which compromises the integrity of the film. In this paper, metal-induced crystallization is explored to locally synthesize MLG directly on metal films, creating an MLG-metal composite and directly on insulating substrates with a moving resistive nanoheater probe at much lower temperature conditions (~ 250 °C). Raman spectroscopy shows that the resultant carbon structure has properties of MLG. The presented tip-based approach offers a much simpler MLG fabrication solution by eliminating the photolithographic and transfer steps of MLG.

Wearable Capacitive Pressure Sensor for Contact and Non-Contact Sensing and Pulse Waveform Monitoring.

Sensitive and flexible pressure sensors have invoked considerable interest for a broad range of applications in tactile sensing, physiological sensing, and flexible electronics. The barrier between high sensitivity and low fabrication cost needs to be addressed to commercialize such flexible pressure sensors. A low-cost sacrificial template-assisted method for the capacitive sensor has been reported herein, utilizing a porous Polydimethylsiloxane (PDMS) polymer and a multiwalled carbon nanotube (MWCNT) composite-based dielectric layer. The sensor shows high sensitivity of 2.42 kPa-1 along with a low limit of detection of 1.46 Pa. The high sensitivity originates from adding MWCNT to PDMS, increasing the composite polymer's dielectric constant. Besides this, the pressure sensor shows excellent stability at a cyclic loading of 9000 cycles, proving its reliability for long-lasting application in tactile and physiological sensing. The high sensitivity of the sensor is suitable for the detection of small deformations such as pulse waveforms as well as tactile pressure sensing. In addition, the paper demonstrates a simultaneous contact and non-contact sensing capability suitable for dual sensing (pressure and proximity) with a single data readout system. The dual-mode sensing capability may open opportunities for realizing compact systems in robotics, gesture control, contactless applications, and many more. The practicality of the sensor was shown in applications such as tactile sensing, Morse code generator, proximity sensing, and pulse wave sensing.

Design Rules for a Wearable Micro-Fabricated Piezo-Resistive Pressure Sensor.

Wearable flexible piezo-resistive pressure sensors hold a wide-ranging potential in human health monitoring, electronic skin, robotic limbs, and other human-machine interfaces. Out of the most successful recent efforts for arterial pulse monitoring are sensors with micro-patterned conductive elastomers. However, a low-current output signal (typically in the range of nano-amperes) and bulky and expensive measurement equipment for useful signal acquisition inhibits their wearability. Herein, through a finite element analysis we establish the design rules for a highly sensitive piezo-resistive pressure sensor with an output that is high enough to be detectable by simple and inexpensive circuits and therefore ensure wearability. We also show that, out of four frequently reported micro-feature shapes in micro-patterned piezo-resistive sensors, the micro-dome and micro-pyramid yield the highest sensitivity. Furthermore, investigations of different conductivity values of micro-patterned elastomers found that coating the elastomer with a conductive material (usually metallic) leads to higher current response when compared to composited conductive elastomers. Finally, the geometric parameters and spatial configurations of micro-pyramid design of piezo-resistive sensors were optimized. The results show that an enhanced sensitivity and higher current output is achieved by the lower spatial density configuration of three micro-features per millimeter length, a smaller feature size of around 100 µm, and a 60-50 degrees pyramid angle.

VO2-based ultra-reconfigurable intelligent reflective surface for 5G applications.

As demand for higher capacity wireless communications increases, new approaches are needed to improve capacity. The lack of configurable radio platforms and power consumed to create new signals are some of the limitations preventing further advancements. To address these limitations, we propose an Ultra-Reconfigurable Intelligent Surface (URIS) platform based on the metal-to-insulator transition property of VO2. A VO2 layer is placed on a high-density micro-heater matrix consisting of pixels that can be electronically switched on. With this manner of control, heat can be transferred to selected areas of the VO2 layer and convert it to highly conductive metallic phase. This technique allows dynamically changing the shape of the reflection surface with high speed. We numerically investigated the heat activated switching and RF reflection characteristics of a reflectarray designed for potential 5G applications operating at 32 GHz. It consists of heating pixels with the size of 40 × 40 µm which can generate metallic VO2 patches or arbitrary shapes with ~ 100 × 100 µm spatial resolution. Our analyses resulted in large phase range of ~ 300° and approximate losses of -2 dB. The proposed device can serve as a novel platform for ultra-reconfigurable reflectarrays, other IRSs, and various wide spectral range RF applications.

In-Situ Integration of 3D C-MEMS Microelectrodes with Bipolar Exfoliated Graphene for Label-Free Electrochemical Cancer Biomarkers Aptasensor.

The electrochemical label-free aptamer-based biosensors (also known as aptasensors) are highly suitable for point-of-care applications. The well-established C-MEMS (carbon microelectromechanical systems) platforms have distinguishing features which are highly suitable for biosensing applications such as low background noise, high capacitance, high stability when exposed to different physical/chemical treatments, biocompatibility, and good electrical conductivity. This study investigates the integration of bipolar exfoliated (BPE) reduced graphene oxide (rGO) with 3D C-MEMS microelectrodes for developing PDGF-BB (platelet-derived growth factor-BB) label-free aptasensors. A simple setup has been used for exfoliation, reduction, and deposition of rGO on the 3D C-MEMS microelectrodes based on the principle of bipolar electrochemistry of graphite in deionized water. The electrochemical bipolar exfoliation of rGO resolves the drawbacks of commonly applied methods for synthesis and deposition of rGO, such as requiring complicated and costly processes, excessive use of harsh chemicals, and complex subsequent deposition procedures. The PDGF-BB affinity aptamers were covalently immobilized by binding amino-tag terminated aptamers and rGO surfaces. The turn-off sensing strategy was implemented by measuring the areal capacitance from CV plots. The aptasensor showed a wide linear range of 1 pM-10 nM, high sensitivity of 3.09 mF cm-2 Logc-1 (unit of c, pM), and a low detection limit of 0.75 pM. This study demonstrated the successful and novel in-situ deposition of BPE-rGO on 3D C-MEMS microelectrodes. Considering the BPE technique's simplicity and efficiency, along with the high potential of C-MEMS technology, this novel procedure is highly promising for developing high-performance graphene-based viable lab-on-chip and point-of-care cancer diagnosis technologies.

Implantable Devices for the Treatment of Breast Cancer.

Breast cancer is one of the leading causes of death in the female population worldwide. Standard treatments such as chemotherapy show noticeable results. However, along with killing cancer cells, it causes systemic toxicity and apoptosis of the nearby healthy cells, therefore patients must endure side effects during the treatment process. Implantable drug delivery devices that enhance therapeutic efficacy by allowing localized therapy with programmed or controlled drug release can overcome the shortcomings of conventional treatments. An implantable device can be composed of biopolymer materials, nanocomposite materials, or a combination of both. This review summarizes the recent research and current state-of-the art in these types of implantable devices and gives perspective for future directions.

A Review of THz Technologies for Rapid Sensing and Detection of Viruses including SARS-CoV-2.

Virus epidemics such as Ebola virus, Zika virus, MERS-coronavirus, and others have wreaked havoc on humanity in the last decade. In addition, a coronavirus (SARS-CoV-2) pandemic and its continuously evolving mutants have become so deadly that they have forced the entire technical advancement of healthcare into peril. Traditional ways of detecting these viruses have been successful to some extent, but they are costly, time-consuming, and require specialized human resources. Terahertz-based biosensors have the potential to lead the way for low-cost, non-invasive, and rapid virus detection. This review explores the latest progresses in terahertz technology-based biosensors for the virus, viral particle, and antigen detection, as well as upcoming research directions in the field.

Perspectives on C-MEMS and C-NEMS biotech applications.

Carbon microelectromechanical system (C-MEMS) and carbon nanoelectromechanical system (C-NEMS) have been identified as promising technologies for a range of biotech applications, including electrochemical biosensors, biofuel cells, neural probes, and dielectrophoretic cell trapping. Research teams around the world have devoted more and more time to this field. After almost two decades of efforts on developing C-MEMS and C-NEMS, a review of the relevant progress and addressing future research opportunities and critical issues is in order. This review first introduces C-MEMS and C-NEMS fabrication processes that fall into two categories: photolithography- and non-photolithography- based techniques. Next, a detailed discussion of the state of the art, and technical challenges and opportunities associated with C-MEMS and C-NEMS devices used in biotech applications are presented. These devices are discussed in the relevant sub-sections of biosensors, biofuel cells, intracorporeal neural probe, dielectrophoresis cell trapping, and cell culture. The review concludes with an exposition of future perspectives in C-MEMS and C-NEMS.

Novel application of electrochemical bipolar exfoliated graphene for highly sensitive disposable label-free cancer biomarker aptasensors.

Label-free aptasensors can be a promising point-of-care biosensor for detecting various cancer diseases due to their selectivity, sensitivity, and lower cost of production and operation. In this study, a highly sensitive aptasensor based on gold-covered polyethylene terephthalate electrodes (PET/Au) decorated with bipolar exfoliated graphene is proposed as a possible contender for disposable label-free aptasensor applications. Bipolar electrochemical exfoliation enables simultaneous exfoliation, reduction, and deposition of graphene nanosheets on prospective electrodes. Our comparative study confirms that the bipolar exfoliated graphene deposited on the negative feeding electrode (i.e., reduced graphene oxide) possesses better electrochemical properties for aptasensing. The optimized aptasensor based on bipolar exfoliated graphene deposited on PET/Au electrodes exhibits a highly sensitive response of 4.07 µA log c -1 (unit of c, pM) which is linear in the range of 0.0007-20 nM, and has a low limit of detection of 0.65 pM (S/N = 3). The aptasensor establishes highly selective performance with a stability of 91.2% after 6 days. This study demonstrates that bipolar electrochemistry is a simple yet efficient technique that could provide high-quality graphene for biosensing applications. Considering its simplicity and efficiency, the BPE technique promises the development of feasible and affordable lab-on-chip and point-of-care cancer diagnosis technologies.

Highly sensitive label-free electrochemical aptasensors based on photoresist derived carbon for cancer biomarker detection.

-Label-free electrochemical aptasensors for cancer biomarker detection can be a promising means for early detection of cancer due to their high sensitivity, selectivity, and stability, and low cost. In this study, a highly sensitive and selective label-free electrochemical aptasensor based on carbon microelectromechanical systems (C-MEMS) was developed for the detection of platelet-derived growth factor-BB (PDGF-BB). The active electrodes of the aptasensors were synthesized via carbonization of SU-8 derived electrodes at high temperatures in an oxygen-free furnace. An oxygen-plasma oxidation treatment was used to functionalize the C-MEMS electrodes, which provided efficient covalent immobilization of amino terminated affinity aptamers. The turn-off and turn-on detection strategies-based on capacitance and resistance measurement, respectively-were employed. The capacitance detection strategies exhibited a wide linear response range of 0.01-50 nM, with a high sensitivity of 3.33 mF cm-2 Logc-1 (unit of c, nM) and a low limit of detection of 7 pM (S/N = 3). The resistance detection strategies exhibited an even wider linear response range of 0.005-50 nM, and a lower limit of detection of 1.9 pM (S/N = 3), with a high sensitivity of 1.65 × 103 Ω Logc-1 (unit of c, nM). Both detection strategies provided high selectivity for PDGF-BB and high stability of 90.34% after 10 days. This research demonstrates that the developed label-free electrochemical C-MEMS based PDGF-BB aptasensor is highly sensitive, selective, and robust. This aptasensor is a promising prospect for the highly demanding task of early detection of cancer biomarkers.

Magneto-plasmonic nanostars for image-guided and NIR-triggered drug delivery.

Smart multifunctional nanoparticles with magnetic and plasmonic properties assembled on a single nanoplatform are promising for various biomedical applications. Owing to their expanding imaging and therapeutic capabilities in response to external stimuli, they have been explored for on-demand drug delivery, image-guided drug delivery, and simultaneous diagnostic and therapeutic (i.e. theranostic) applications. In this study, we engineered nanoparticles with unique morphology consisting of a superparamagnetic iron oxide core and star-shaped plasmonic shell with high-aspect-ratio gold branches. Strong magnetic and near-infrared (NIR)-responsive plasmonic properties of the engineered nanostars enabled multimodal quantitative imaging combining advantageous functions of magnetic resonance imaging (MRI), magnetic particle imaging (MPI), photoacoustic imaging (PAI), and image-guided drug delivery with a tunable drug release capacity. The model drug molecules bound to the core-shell nanostars were released upon NIR illumination due to the heat generation from the core-shell nanostars. Moreover, our simulation analysis showed that the specific design of the core-shell nanostars demonstrated a pronounced multipolar plasmon resonance, which has not been observed in previous reports. The multimodal imaging and NIR-triggered drug release capabilities of the proposed nanoplatform verify their potential for precise and controllable drug release with different applications in personalized medicine.

Lactate biosensing: The emerging point-of-care and personal health monitoring.

Lactate plays a crucial role in the anaerobic metabolic pathway of humans. In situations of oxygen deficit, its production increases; leading to several life-threatening conditions such as hemorrhage, respiratory failure, trauma or ischemia from lactate acidosis. Lactate level detection and point-of-care (POC) monitoring in a fast, accurate and non-invasive manner is ultimately important for many health care applications. Optical and electrochemical techniques are employed in lactate sensing to achieve high sensitivity and selectivity, miniaturization, portability, simplicity, and low cost. To improve the selectivity and sensitivity, two important enzymes, lactate oxidase (LOx) and lactate dehydrogenese (LDH) are employed. Conventional methods for lactate detection are not fast enough to be used in point-of-care or personal health monitoring settings. Moreover, the existing point-of-care lactate sensing tools follow invasive or partially invasive sampling protocols such as finger pricking. In this review, a comprehensive overview of different lactate biosensing devices is presented. Particularly, the state-of-the-art and prospects of wearable, non-invasive lactate sensing from different biofluids are discussed.

Prospects and Challenges of Volatile Organic Compound Sensors in Human Healthcare.

The chemical signatures of volatile organic compounds (VOCs) in humans can be utilized for point-of-care (POC) diagnosis. Apart from toxic exposure studies, VOCs generated in humans can provide insights into one's healthy and diseased metabolic states, acting as a biomarker for identifying numerous diseases noninvasively. VOC sensors and the technology of e-nose have received significant attention for continuous and selective monitoring of various physiological and pathophysiological conditions of an individual. Noninvasive detection of VOCs is achieved from biomatrices of breath, sweat and saliva. Among these, detection from sweat and saliva can be continuous in real-time. The sensing approaches include optical, chemiresistive and electrochemical techniques. This article provides an overview of such techniques. These, however, have limitations of reliability, precision, selectivity, and stability in continuous monitoring. Such limitations are due to lack of sensor stability and complexity of samples in a multivariate environment, which can lead to false readings. To overcome selectivity barriers, sensor arrays enabling multimodal sensing, have been used with pattern recognition techniques. Stability and precision issues have been addressed through advancements in nanotechnology. The use of various forms of nanomaterial not only enhance sensing performance, but also plays a major role in detection on a miniaturized scale. The rapid growth in medical Internet of Things (IoT) and artificial intelligence paves a pathway for improvements in human theranostics.

Extreme sensitive metasensor for targeted biomarkers identification using colloidal nanoparticles-integrated plasmonic unit cells.

Engineered terahertz (THz) plasmonic metamaterials have emerged as promising platforms for quick infection diagnosis, cost-effective and real-time pharmacology applications owing to their non-destructive and harmless interaction with biological tissues in both in vivo and in vitro assays. As a recent member of THz metamaterials family, toroidal metamaterials have been demonstrated to be supporting high-quality sharp resonance modes. Here we introduce a THz metasensor based on a plasmonic surface consisting of metamolecules that support ultra-narrow toroidal resonances excited by the incident radiation and demonstrate detection of an ultralow concertation targeted biomarker. The toroidal plasmonic metasurface was designed and optimized through extensive numerical studies and fabricated by standard microfabrication techniques. The surface then functionalized by immobilizing the antibody for virus-envelope proteins (ZIKV-EPs) for selective sensing. We sensed and quantified the ZIKV-EP in the assays by measuring the spectral shifts of the toroidal resonances while varying the concentration. In an improved protocol, we introduced gold nanoparticles (GNPs) decorated with the same antibodies onto the metamolecules and monitored the resonance shifts for the same concentrations. Our studies verified that the presence of GNPs enhances capturing of biomarker molecules in the surrounding medium of the metamaterial. By measuring the shift of the toroidal dipolar momentum (up to Δω~0.35 cm-1) for different concentrations of the biomarker proteins, we analyzed the sensitivity, repeatability, and limit of detection (LoD) of the proposed toroidal THz metasensor. The results show that up to 100-fold sensitivity enhancement can be obtained by utilizing plasmonic nanoparticles-integrated toroidal metamolecules in comparison to analogous devices. This approach allows for detection of low molecular-weight biomolecules (≈13 kDa) in diluted solutions using toroidal THz plasmonic unit cells.

Azimuthally and radially excited charge transfer plasmon and Fano lineshapes in conductive sublayer-mediated nanoassemblies.

Here, the plasmon responses of both symmetric and antisymmetric oligomers on a conductive substrate under linear, azimuthal, and radial polarization excitations are analyzed numerically. By observing charge transfer plasmons under cylindrical vector beam (CVB) illumination for what we believe is the first time, we show that our studies open new horizons to induce significant charge transfer plasmons and antisymmetric Fano resonance lineshapes in metallic substrate-mediated plasmonic nanoclusters under both azimuthal and radial excitation as CVBs.