Implantable Biosensors Research Articles

Electrochemical and Electrical Biosensors for Wearable and Implantable Electronics Based on Conducting Polymers and Carbon-Based Materials.

Bioelectronic devices are designed to translate biological information into electrical signals and vice versa, thereby bridging the gap between the living biological world and electronic systems. Among different types of bioelectronics devices, wearable and implantable biosensors are particularly important as they offer access to the physiological and biochemical activities of tissues and organs, which is significant in diagnosing and researching various medical conditions. Organic conducting and semiconducting materials, including conducting polymers (CPs) and graphene and carbon nanotubes (CNTs), are some of the most promising candidates for wearable and implantable biosensors. Their unique electrical, electrochemical, and mechanical properties bring new possibilities to bioelectronics that could not be realized by utilizing metals- or silicon-based analogues. The use of organic- and carbon-based conductors in the development of wearable and implantable biosensors has emerged as a rapidly growing research field, with remarkable progress being made in recent years. The use of such materials addresses the issue of mismatched properties between biological tissues and electronic devices, as well as the improvement in the accuracy and fidelity of the transferred information. In this review, we highlight the most recent advances in this field and provide insights into organic and carbon-based (semi)conducting materials' properties and relate these to their applications in wearable/implantable biosensors. We also provide a perspective on the promising potential and exciting future developments of wearable/implantable biosensors.

(Invited) Wearable Intelligent Sensors and Electronic (WISE)- Problem, Progress and Perspective

Artificial intelligence (AI) and wearable sensors are crucial in achieving the goal of precision medicine, which is to customize the best treatment for each individual patient. The recent combination of these two fields is improving patient data acquisition and the design of wearable sensors for monitoring health, fitness, and surroundings. Wearable sensors aim to address the limitations of centralized and reactive healthcare by providing individuals with insight into their own physiology. However, the relationship between disease and therapeutic platforms is very complex, making it difficult to analyze their output. Integrating AI can bridge this gap by using pattern analysis and classification algorithms to improve diagnostic and therapeutic accuracy. The future of AI-biosensors (such as AI wearable sweat biosensors, AI ingestible biosensors, AI glass biosensors, AI implantable biosensors, etc.) will mainly focus on AI diagnosis (where the diagnostic algorithm in the microprocessor can verify the sensor output and present diagnostic information), big data processing (using self-contained space for historical data and various necessary parameters of data storage, significantly improving the controller's performance), and self-learning/adaptation (embedded microprocessors with advanced programming functions, allowing the AI-biosensor to reconstruct the structure and parameters according to certain behavioral criteria and have adaptive functions).

MXene-Coated Ion-Selective Electrode Sensors for Highly Stable and Selective Lithium Dynamics Monitoring.

Lithium holds immense significance in propelling sustainable energy and environmental systems forward. However, existing sensors used for lithium monitoring encounter issues concerning their selectivity and long-term durability. Addressing these challenges is crucial to ensure accurate and reliable lithium measurements during the lithium recovery processes. In response to these concerns, this study proposes a novel approach involving the use of an MXene composite membrane with incorporated poly(sodium 4-styrenesulfonate) (PSS) as an antibiofouling layer on the Li+ ion selective electrode (ISE) sensors. The resulting MXene-PSS Li+ ISE sensor demonstrates exceptional electrochemical performance, showcasing a superior slope (59.42 mV/dec), lower detection limit (10-7.2 M), quicker response time (∼10 s), higher selectivity to Na+ (-2.37) and K+ (-2.54), and reduced impedance (106.9 kΩ) when compared to conventional Li+ ISE sensors. These improvements are attributed to the unique electronic conductivity and layered structure of the MXene-PSS nanosheet coating layer. In addition, the study exhibits the long-term accuracy and durability of the MXene-PSS Li+ ISE sensor by subjecting it to real wastewater testing for 14 days, resulting in sensor reading errors of less than 10% when compared to laboratory validation results. This research highlights the great potential of MXene nanosheet coatings in advancing sensor technology, particularly in challenging applications, such as detecting emerging contaminants and developing implantable biosensors. The findings offer promising prospects for future advancements in sensor technology, particularly in the context of sustainable energy and environmental monitoring.

Multiphase Chemistry under Nanoconfinement: An Electrochemical Perspective.

Most relevant systems of interest to modern chemists rarely consist of a single phase. Real-world problems that require a rigorous understanding of chemical reactivity in multiple phases include the development of wearable and implantable biosensors, efficient fuel cells, single cell metabolic characterization techniques, and solar energy conversion devices. Within all of these systems, confinement effects at the nanoscale influence the chemical reaction coordinate. Thus, a fundamental understanding of the nanoconfinement effects of chemistry in multiphase environments is paramount. Electrochemistry is inherently a multiphase measurement tool reporting on a charged species traversing a phase boundary. Over the past 50 years, electrochemistry has witnessed astounding growth. Subpicoampere current measurements are routine, as is the study of single molecules and nanoparticles. This Perspective focuses on three nanoelectrochemical techniques to study multiphase chemistry under nanoconfinement: stochastic collision electrochemistry, single nanodroplet electrochemistry, and nanopore electrochemistry.

Cellulose-Based Conductive Materials for Energy and Sensing Applications.

Cellulose-based conductive materials (CCMs) have emerged as a promising class of materials with various applications in energy and sensing. This review provides a comprehensive overview of the synthesis methods and properties of CCMs and their applications in batteries, supercapacitors, chemical sensors, biosensors, and mechanical sensors. Derived from renewable resources, cellulose serves as a scaffold for integrating conductive additives such as carbon nanotubes (CNTs), graphene, metal particles, metal-organic frameworks (MOFs), carbides and nitrides of transition metals (MXene), and conductive polymers. This combination results in materials with excellent electrical conductivity while retaining the eco-friendliness and biocompatibility of cellulose. In the field of energy storage, CCMs show great potential for batteries and supercapacitors due to their high surface area, excellent mechanical strength, tunable chemistry, and high porosity. Their flexibility makes them ideal for wearable and flexible electronics, contributing to advances in portable energy storage and electronic integration into various substrates. In addition, CCMs play a key role in sensing applications. Their biocompatibility allows for the development of implantable biosensors and biodegradable environmental sensors to meet the growing demand for health and environmental monitoring. Looking to the future, this review emphasizes the need for scalable synthetic methods, improved mechanical and thermal properties, and exploration of novel cellulose sources and modifications. Continued innovation in CCMs promises to revolutionize sustainable energy storage and sensing technologies, providing environmentally friendly solutions to pressing global challenges.

Implantable biosensor tracks temperature to detect early transplant rejection in rats.

Implantable biosensor tracks temperature to detect early transplant rejection in rats.

The challenges in developing implantable biosensors

Advanced implantable sensors offer preemptive disease-fighting capabilities, if they can overcome challenges around engineering, regulation, patients, and clinicians.

Survey: Self-Empowered Wireless Sensor Networks Security Taxonomy, Challenges, and Future Research Directions

In the recent past, patient wearable devices and implantable biosensors revealed exponential growth in digital healthcare, because they have the capability to allow access to the information anywhere and every time to improve the life standard of multifarious disease effected patients followed by healthy people. Following these advantages, digital healthcare demands a secure wireless communication infrastructure for interconnected self-empowered biosensor devices to maintain the trust of patients, doctors, pharmacologists, nursing staff, and other associated stakeholders, etc. Several authentications, privacy, and data preservation schemes had been used in the literature to ensure the security of this emerging technology, but with time, these counteraction prototypes become vulnerable to new security threats, as the hackers work tirelessly to compromise them and steal the legitimate information of user’s or disrupt the operation of an employed self-empowered wireless sensor network (SWSN). To discuss the security problems of SWSN applications, in this review article, we have presented a detailed survey of the present literature from 2019 to 2022, to familiarize the readers with different security threats and their counteraction schemes. Following this, we will highlight the pros and cons of these countermeasure techniques in the context of SWSN security requirements to underscore their limitations. Thereafter, we will follow-up the underlined limitations to discuss the open security challenges of SWSN that need the concerned authorities’ attention. Based on this, we will pave a road map for the future research work that could be useful for every individual associated with this technology. For the novelty and uniqueness of this work, we will make comparative analysis with present survey papers published on this topic to answer the question of reviewers, readers, editors, and students that why this paper is in time and needed in the presence of rival papers.

Anti-biofouling strategies for implantable biosensors of continuous glucose monitoring systems

Anti-biofouling strategies for implantable biosensors of continuous glucose monitoring systems

Challenges and strategies faced in the electrochemical biosensing analysis of neurochemicals in vivo: A review

Our brain is an intricate neuromodulatory network, and various neurochemicals, including neurotransmitters, neuromodulators, gases, ions, and energy metabolites, play important roles in regulating normal brain function. Abnormal release or imbalance of these substances will lead to various diseases such as Parkinson’s and Alzheimer’s diseases, therefore, in situ and real-time analysis of neurochemical interactions in pathophysiological conditions is beneficial to facilitate our understanding of brain function. Implantable electrochemical biosensors are capable of monitoring neurochemical signals in real time in extracellular fluid of specific brain regions because they can provide excellent temporal and spatial resolution. However, in vivo electrochemical biosensing analysis mainly faces the following challenges: First, foreign body reactions induced by microelectrode implantation, non-specific adsorption of proteins and redox products, and aggregation of glial cells, which will cause irreversible degradation of performance such as stability and sensitivity of the microsensor and eventually lead to signal loss; Second, various neurochemicals coexist in the complex brain environment, and electroactive substances with similar formal potentials interfere with each other. Therefore, it is a great challenge to design recognition molecules and tailor functional surfaces to develop in vivo electrochemical biosensors with high selectivity. Here, we take the above challenges as a starting point and detail the basic design principles for improving in vivo stability, selectivity and sensitivity of microsensors through some specific functionalized surface strategies as case studies. At the same time, we summarize surface modification strategies for in vivo electrochemical biosensing analysis of some important neurochemicals for researchers’ reference. In addition, we also focus on the electrochemical detection of low basal concentrations of neurochemicals in vivo via amperometric waveform techniques, as well as the stability and biocompatibility of reference electrodes during long-term sensing, and provide an outlook on the future direction of in vivo electrochemical neurosensing.

P-280 Continuous in-situ monitoring of female hormone levels as a tool to improve the efficacy of assisted reproductive technology (ART) and in-vitro fertilization (IVF) treatment

Abstract Study question Is it possible to remotely monitor a patient’s hormone levels during an ART cycle using an unobtrusive and subcutaneously injectable biosensor for real-time monitoring? Summary answer It is possible for in-situ remote continuous monitoring implantable devices to successfully measure patient blood hormone levels over a clinically relevant concentration range. What is known already Worldwide 48.5 million couples suffer from infertility. In the UK, assisted reproductive treatments (ART) have increased by almost ten-fold in the last 20 years. Hormonal imbalances are the leading cause of female infertility and the success rate of ART tremendously depends on the accurate measurement of the levels of hormones, namely Luteinizing Hormone, Progesterone and Beta Estradiol. These hormone levels change and pulsate during each patient cycle, requiring women undergoing ART treatments to have a blood draw and endocrinology analysis every 2-3 days, making ART treatment highly invasive to a patient’s lifestyle and at a high cost. Study design, size, duration In order to determine the feasibility and potential of the study question, a minimally invasive biosensor to monitor ART hormone levels in real time was developed. The biosensor was tested in vitro for the range of 1 pg/ml to 1 µg/ml in three analytical replicates. The resulting sensitivity of testing was measured in order to evaluate real-work applications. Participants/materials, setting, methods A gold working electrode was utilized and activated using cyclic voltammetry. After activation, a self-assembled monolayer (Thiol-EDC-NHS), was formed on the gold surface, followed by the separate addition of anti-Progesterone4 and Beta-estradiol antibodies. After the addition of each layer, the Differential Pulse Voltammetry (DPV) of the gold electrode was measured. Based on the peak current, calibration curves were plotted and the sensitivity of the sensors was calculated. All electrochemical measurements were performed using CHI potentiostat. Main results and the role of chance This electrochemical hormone biosensor technology) is based on the detection of Progesterone4 and Beta-estradiol biosensor electrodes which can continuously detect hormone levels with a limit of detection (LOD) and limit of quantification (LOQ) of 2.01 and 6.72 pg/ml, respectively. Further to this, the biosensor covers the detection of a wide range of hormone concentrations in the blood from 1 pg/ml to 1 µg/ml. The sensor was also characterised by microscopy techniques such as scanning electron microscope (SEM) and Raman microscopy. Next, the biosensors will be validated in-vivo by conducting animal trials allowing for the main parameters of the biosensors to be optimized according to the in-vivo study. Limitations, reasons for caution This novel implantable biosensor technology requires more upcoming validation in animal models before then being tested clinically to order to assess its ability for widespread use. Wider implications of the findings The development and implementation of an unobtrusive remote and continuous monitoring implantable system for hormonal concentrations monitoring that are vital for success in an ART procedure could transform the entirety of the process as well as positively influence patient's access to care. Trial registration number NA

Current Innovations in Intraocular Pressure Monitoring Biosensors for Diagnosis and Treatment of Glaucoma—Novel Strategies and Future Perspectives

Biosensors are devices that quantify biologically significant information required for diverse applications, such as disease diagnosis, food safety, drug discovery and detection of environmental pollutants. Recent advancements in microfluidics, nanotechnology and electronics have led to the development of novel implantable and wearable biosensors for the expedient monitoring of diseases such as diabetes, glaucoma and cancer. Glaucoma is an ocular disease which ranks as the second leading cause for loss of vision. It is characterized by the increase in intraocular pressure (IOP) in human eyes, which results in irreversible blindness. Currently, the reduction of IOP is the only treatment used to manage glaucoma. However, the success rate of medicines used to treat glaucoma is quite minimal due to their curbed bioavailability and reduced therapeutic efficacy. The drugs must pass through various barriers to reach the intraocular space, which in turn serves as a major challenge in glaucoma treatment. Rapid progress has been observed in nano-drug delivery systems for the early diagnosis and prompt therapy of ocular diseases. This review gives a deep insight into the current advancements in the field of nanotechnology for detecting and treating glaucoma, as well as for the continuous monitoring of IOP. Various nanotechnology-based achievements, such as nanoparticle/nanofiber-based contact lenses and biosensors that can efficiently monitor IOP for the efficient detection of glaucoma, are also discussed.

Recent advances in enzymatic biofuel cells enabled by innovative materials and techniques.

The past few decades have seen increasingly rapid advances in the field of sustainable energy technologies. As a new bio- and eco-friendly energy source, enzymatic biofuel cells (EBFCs) have garnered significant research interest due to their capacity to power implantable bioelectronics, portable devices, and biosensors by utilizing biomass as fuel under mild circumstances. Nonetheless, numerous obstacles impeded the commercialization of EBFCs, including their relatively modest power output and poor long-term stability of enzymes. To depict the current progress of EBFC and address the challenges it faces, this review traces back the evolution of EBFC and focuses on contemporary advances such as newly emerged multi or single enzyme systems, various porous framework-enzyme composites techniques, and innovative applications. Besides emphasizing current achievements in this field, from our perspective part we also introduced novel electrode and cell design for highly effective EBFC fabrication. We believe this review will assist readers in comprehending the basic research and applications of EBFCs as well as potentially spark interdisciplinary collaboration for addressing the pressing issues in this field.

An Implantable Bio-Signal Sensor SoC with Low-Standby-Power 8K-Bit SRAM for Continuous Long-Term Monitoring

Individualized treatment of chronic diseases opens up great opportunities for implantable biosensor systems capable of tracking vital signals over long periods of time. To this end, low-power techniques in standby mode and the efficient utilization of storage space will be important issues for the implementation of such rechargeable implants with a built-in memory. This paper presents key circuit techniques, including a leakage-current-based clock generator that eliminates the need for an internal reference clock source, a low-standby-power 8Kbit SRAM with negative wordline and dynamic supply voltage scaling, and an adaptive sensing scheme to improve storage space utilization. When implemented with commercial 180 nm CMOS technology for the circuit simulation, approximately 70% (100 nW) of power dissipation was reduced from internal clock source, about 70% of power consumed by 8Kbit SRAM was saved, and the storage space utilization was improved by about 42.8%. In the end, the proposed implantable biosensor SoC consumes about 82.5 nW of standby power, saving about 42% from the previous approach and can last for 2.5 days using a 5 uAh thin-film battery (CYMBET® 1.7 × 2.2 mm2).

Stretchable fabric-based lithium-ion battery

In many applications ranging from wearable devices to implantable biosensors, next-generation electronics are expected to be stretchable which necessitates a concomitant development of fully stretchable batteries. Stretchable lithium-ion batteries must provide stable performance while subjected to mechanical deformations such as stretching, bending, and twisting. Although there has been a noticeable progress in the development of flexible energy storage devices, stretchable lithium-ion batteries still face several persistent challenges. While in a prior work we successfully presented a proof-of-concept that rendered just the cathode to be stretchable, in this work we present the design, fabrication and characterization of a complete fully stretchable fabric-based lithium ion battery. The electrochemical and mechanical performances of the fabric-based battery are investigated and discussed. Solid polymer electrolyte stretchable fabric-based battery offers a more compatible and safer alternative to liquid based batteries, especially for the application of textile wearable devices that may involve intimate contact with human skin and organs. We demonstrate that our fabric-based battery can stretch up to 15% strain without a significant increase in its internal impedance.

Material Design in Implantable Biosensors toward Future Personalized Diagnostics and Treatments

The growing demand for personalized treatments and the constant observation of vital signs for extended periods could positively solve the problematic concerns associated with the necessity for patient control and hospitalization. The impressive development in biosensing devices has led to the creation of man-made implantable devices that are temporarily or permanently introduced into the human body, and thus, diminishing the pain and discomfort of the person. Despite all promising achievements in this field, there are some critical challenges to preserve reliable functionality in the complex environment of the human body over time. Biosensors in the in vivo environment are required to have specific features, including biocompatibility (minimal immune response or biofouling), biodegradability, reliability, high accuracy, and miniaturization (flexible, stretchable, lightweight, and ultra-thin). However, the performance of implantable biosensors is limited by body responses and insufficient power supplies (due to minimized batteries/electronics and data transmission without wires). In addition, the current processes and developments in the implantable biosensors field will open new routes in biomedicine and diagnostic systems that monitor occurrences happening inside the body in a certain period. This topical paper aims to give an overview of the state-of-the-art implantable biosensors and their design methods. It also discusses the latest developments in material science, including nanomaterials, hydrogel, hydrophilic, biomimetic, and other polymeric materials to overcome failures in implantable biosensors’ reliability. Lastly, we discuss the main challenges faced and future research prospects toward the development of dependable implantable biosensors.

Plasma surface functionalization: A comprehensive review of advances in the quest for bioinstructive materials and interfaces

Surface biofunctionalization aims to create cell-instructive surfaces that control the behavior of cells and modulate cellular interactions by incorporating cell signaling moieties at the materials–biosystem interface. Despite advances in developing bioinert and biocompatible materials, blood clotting, inflammation, and cell death continue to be observed upon the contact of foreign materials with living tissues leading to the materials' rejection. Specific examples include the application of foreign materials in implantable devices (e.g., bone implants, antimicrobial surfaces, and cardiovascular stents), biosensors, drug delivery, and 3D-bioprinting. Biofunctionalization of materials to date has been predominantly realized using wet chemical approaches. However, the complexity of wet chemistry, toxicity of reactants, waste disposal issues, reaction time, poor reproducibility, and scalability drive a need for a paradigm shift from wet chemical approaches to dry methods of surface biofunctionalization. Plasma-based technologies that enable covalent surface immobilization of biomolecules have emerged as dry, reagent-free, and single-step alternatives for surface biofunctionalization. This review commences by highlighting the need for bioinstructive surfaces and coatings for various biomedical applications such as bone implants, antimicrobial surfaces, biosensors, and 3D-bioprinted structures, followed by a brief review of wet chemical approaches for developing biofunctionalized surfaces and biomimetic devices. We then provide a comprehensive review of the development of plasma-based technologies for biofunctionalization, highlighting the plasma–surface interactions and underpinning mechanisms of biomolecule immobilization.

Recent Developments in the Design and Fabrication of Electrochemical Biosensors Using Functional Materials and Molecules.

Electrochemical biosensors are superior technologies that are used to detect or sense biologically and environmentally significant analytes in a laboratory environment, or even in the form of portable handheld or wearable electronics. Recently, imprinted and implantable biosensors are emerging as point-of-care devices, which monitor the target analytes in a continuous environment and alert the intended users to anomalies. The stability and performance of the developed biosensor depend on the nature and properties of the electrode material or the platform on which the biosensor is constructed. Therefore, the biosensor platform plays an integral role in the effectiveness of the developed biosensor. Enormous effort has been dedicated to the rational design of the electrode material and to fabrication strategies for improving the performance of developed biosensors. Every year, in the search for multifarious electrode materials, thousands of new biosensor platforms are reported. Moreover, in order to construct an effectual biosensor, the researcher should familiarize themself with the sensible strategies behind electrode fabrication. Thus, we intend to shed light on various strategies and methodologies utilized in the design and fabrication of electrochemical biosensors that facilitate sensitive and selective detection of significant analytes. Furthermore, this review highlights the advantages of various electrode materials and the correlation between immobilized biomolecules and modified surfaces.

Recent Advances in Cardiovascular Disease Biosensors and Monitoring Technologies.

Cardiovascular disease (CVD) causes significant mortality and remains the leading cause of death globally. Thus, to reduce mortality, early diagnosis by measurement of cardiac biomarkers and heartbeat signals presents fundamental importance. Traditional CVD examination requires bulky hospital instruments to conduct electrocardiography recording and immunoassay analysis, which are both time-consuming and inconvenient. Recently, development of biosensing technologies for rapid CVD marker screening attracted great attention. Thanks to the advancement in nanotechnology and bioelectronics, novel biosensor platforms are developed to achieve rapid detection, accurate quantification, and continuous monitoring throughout disease progression. A variety of sensing methodologies using chemical, electrochemical, optical, and electromechanical means are explored. This review first discusses the prevalence and common categories of CVD. Then, heartbeat signals and cardiac blood-based biomarkers that are widely employed in clinic, as well as their utilizations for disease prognosis, are summarized. Emerging CVD wearable and implantable biosensors and monitoring bioelectronics, allowing these cardiac markers to be continuously measured are introduced. Finally, comparisons of the pros and cons of these biosensing devices along with perspectives on future CVD biosensor research are presented.

Accelerating the development of implantable neurochemical biosensors by using existing clinically applied depth electrodes

In this study, an implantable stereo-electroencephalography (sEEG) depth electrode was functionalised with an enzyme coating for enzyme-based biosensing of glucose and L-glutamate. This was done because personalised medicine could benefit from active real-time neurochemical monitoring on small spatial and temporal scales to further understand and treat neurological disorders. To achieve this, the sEEG depth electrode was characterised using cyclic voltammetry (CV), differential pulse voltammetry (DPV), square wave voltammetry (SWV), and electrochemical impedance spectroscopy (EIS) using several electrochemical redox mediators (potassium ferri/ferrocyanide, ruthenium hexamine chloride, and dopamine). To improve performance, the Pt sensors on the sEEG depth electrode were coated with platinum black and a crosslinked gelatin-enzyme film to enable enzymatic biosensing. This characterisation work showed that producing a useable electrode with a good electrochemical response showing the expected behaviour for a platinum electrode was possible. Coating with Pt black improved the sensitivity to H2O2 over unmodified electrodes and approached that of well-defined Pt macro disc electrodes. Measured current showed good dependence on concentration, and the calibration curves report good sensitivity of 29.65 nA/cm2/μM for glucose and 8.05 nA/cm2/μM for L-glutamate with a stable, repeatable, and linear response. These findings demonstrate that existing clinical electrode devices can be adapted for combined electrochemical and electrophysiological measurement in patients and obviate the need to develop new electrodes when existing clinically approved devices and the associated knowledge can be reused. This accelerates the time to use and application of in vivo and wearable biosensing for diagnosis, treatment, and personalised medicine.Graphical abstract