Implantable Biosensors Research Articles

Effect of protein adsorption on electrospun hemoglobin/gelatin-MWCNTs microbelts modified electrode: Toward electrochemical measurement of hydrogen peroxide

The on-line electrochemical analysis is one of powerful strategies in analytical chemistry and pathophysiology. To achieve high sensitivity and long-term stability of electrochemical biosensor, the bottleneck challenge is the spontaneous proteins adsorption onto the electrode surface within the biological fluids or in vivo environments. In this work, a hemoglobin/gelatin-multiwalled carbon nanotubes microbelts modified electrode (Hb/gelatin-MWCNTs/GC electrode) was successfully fabricated via one-step electrospinning process. The results of atomic force microscopy (AFM), scanning electron microscopy (SEM) and water contact angle test confirmed the electrospun Hb/gelatin-MWCNTs microbelts possessed smooth and hydrophilic surfaces. Furthermore, the electrospun Hb/gelatin-MWCNTs/GC electrode after protein adsorption displayed an excellent electrocatalytic sensitivity toward the reduction of hydrogen peroxide (H2O2). Moreover, the Hb/gelatin-MWCNTs/GC electrode presented very high biological affinity to H2O2 (Kmapp=503.4 ± 2.8 μmol L−1) after 360 min protein adsorption compared to that of the electrode before protein adsorption (Kmapp=298.1 ± 3.1 μmol L−1). The microbelts constructed H2O2 biosensor showed high selectivity, stability and reproducibility after protein adsorption. Therefore, this work provided the proof of the concept that the electrospun Hb/gelatin-MWCNTs/GC electrode displayed excellent sensing performance to H2O2 after protein adsorption, which could enable the implantable electrochemical biosensor for the on-line analysis.

Anti-Biofouling Strategies for Long-Term Continuous Use of Implantable Biosensors

The growing trend for personalized medicine calls for more reliable implantable biosensors that are capable of continuously monitoring target analytes for extended periods (i.e., >30 d). While promising biosensors for various applications are constantly being developed in the laboratories across the world, many struggle to maintain reliable functionality in complex in vivo environments over time. In this review, we explore the impact of various biotic and abiotic failure modes on the reliability of implantable biosensors. We discuss various design considerations for the development of chronically reliable implantable biosensors with a specific focus on strategies to combat biofouling, which is a fundamental challenge for many implantable devices. Briefly, we introduce the process of the foreign body response and compare the in vitro and the in vivo performances of state-of-the-art implantable biosensors. We then discuss the latest development in material science to minimize and delay biofouling including the usage of various hydrophilic, biomimetic, drug-eluting, zwitterionic, and other smart polymer materials. We also explore a number of active anti-biofouling approaches including stimuli-responsive materials and mechanical actuation. Finally, we conclude this topical review with a discussion on future research opportunities towards more reliable implantable biosensors.

Egg white based biological microlasers

Biolasers made of biological materials hold great potential for implantable biosensing and cell-tracking. However, the current bio-extracted materials used for biolasers generally require a complicated synthesis process and therefore suffer from high cost. In this work, we demonstrate that low-cost natural egg white is an excellent biomaterial for a laser cavity. Using a simple dehydration method, dye-doped goose egg white microspheres are obtained with various sizes from 20 to 160 µm in diameter. These microspheres can act as excellent laser sources under optical excitation with lasing threshold of ∼26 µJ mm−2 and quality (Q) factor up to 3 × 103. The lasing mechanism is studied and ascribed to the whispering gallery mode. Size-dependence of the lasing spectrum and Q factor are also investigated. Owing to the ease of fabrication, the cost-effectiveness, goose egg white based microlasers are promising for biosensing and bioimaging applications.

Unconventional Device and Material Approaches for Monolithic Biointegration of Implantable Sensors and Wearable Electronics

AbstractImplantable biosensors and wearable bioelectronics need to be intimately interfaced with soft human tissues for a high‐quality health diagnosis and feedback therapy. Despite the recent developments in these devices, it is essential to further enhance their performance and functionalities in order to facilitate the formation of intimate interfaces between the devices and the human body. This will help minimize the unwanted injuries to target tissues, enhance the efficiency of sensing and therapy, and achieve long‐term biocompatibility. In this regard, the physiological and mechanical properties of the target tissues need to be considered carefully when designing the materials and devices to be employed in implantable and wearable electronics. Herein, a discussion of the recent developments in implantable biosensors and wearable electronics, based on unconventional device designs and material approaches, is presented. This review particularly focuses on the design principles of devices and materials that enable an intimate integration of biosensing devices with soft tissues and target organs. In addition, recent developments of electronics employed in stand‐alone wearable biomedical systems, such as wearable displays and energy devices, are presented. Moreover, future prospects for emerging approaches that could enable further developments of implantable biosensors and wearable electronics are also discussed.

Skin-Integrated Wearable Systems and Implantable Biosensors: A Comprehensive Review

Biosensors devices have attracted the attention of many researchers across the world. They have the capability to solve a large number of analytical problems and challenges. They are future ubiquitous devices for disease diagnosis, monitoring, treatment and health management. This review presents an overview of the biosensors field, highlighting the current research and development of bio-integrated and implanted biosensors. These devices are micro- and nano-fabricated, according to numerous techniques that are adapted in order to offer a suitable mechanical match of the biosensor to the surrounding tissue, and therefore decrease the body’s biological response. For this, most of the skin-integrated and implanted biosensors use a polymer layer as a versatile and flexible structural support, combined with a functional/active material, to generate, transmit and process the obtained signal. A few challenging issues of implantable biosensor devices, as well as strategies to overcome them, are also discussed in this review, including biological response, power supply, and data communication.

Streaming potential in bio-mimetic microvessels mediated by capillary glycocalyx

Implantable medical devices and biosensors are pivotal in revolutionizing the field of medical technology by opening new dimensions in the field of disease detection and cure. These devices need to harness a biocompatible and physiologically sustainable safe power source instead of relying on external stimuli, overcoming the constraints on their applicability in-vivo. Here, by appealing to the interplay of electromechanics and hydrodynamics in physiologically relevant microvessels, we bring out the role of charged endothelial glycocalyx layer (EGL) towards establishing a streaming potential across physiological fluidic conduits. We account for the complex rheology of blood-mimicking fluid by appealing to Newtonian fluid model representing the blood plasma and a viscoelastic fluid model representing the whole blood. We model the EGL as a poroelastic layer with volumetric charge distribution. Our results reveal that for physiologically relevant micro-flows, the streaming potential induced is typically of the order of 0.1 V/mm, which may turn out to be substantial towards energizing biosensors and implantable medical devices whose power requirements are typically in the range of micro to milliwatts. We also bring out the specific implications of the relevant physiological parameters towards establishment of the streaming potential, with a vision of augmenting the same within plausible functional limits. We further unveil that the dependence of streaming potential on EGL thickness might be one of the key aspects in unlocking the mystery behind the angiogenesis pattern. Our results may open up novel bio-sensing and actuating possibilities in medical diagnostics as well as may provide a possible alternative regarding the development of physiologically safe and biocompatible power sources within the human body.

Wireless In Vivo Biofuel Cell Monitoring

Enzymatic reactions involving glucose hold the potential for building implantable biosensors and embedded power generators for various medical applications. While Biofuel cells (BFCs) such as enzymatic glucose/O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> are ensured to benefit from abundant chemical resources that can be harvested in the immediate environment of the human body, the highly critical in vivo kinetics of biofuel cell is not yet fully understood. Unfortunately, existing solutions for real-time monitoring of the reaction on rodents are not possible today, or too bulky, which has a biasing impact on the animal behavior. This work presents a light, battery-less, and wireless strategy to continuously monitor a BFC implanted in a laboratory rat using a Frequency Identification (RFID) link. An extremely lightweight and flexible tag antenna of footprint lower than 10 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> is presented with communication capability above 60 cm in field environment. The operational capabilities are demonstrated with a 24-hour continuous monitoring of an enzymatic glucose/O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> reaction, both in vitro and in vivo.

Effect of protein adsorption on bioelectrochemistry of electrospun core-shell MWCNTs/gelatin-Hb nanobelts on electrode surface

Implantable electrochemical biosensor is one powerful tool for the accurate and reliable measurements of small molecules in vivo. However, the electrode is inevitably subjected to the protein adsorption when implanted into the living animals, affecting the sensitivity and stability of biosensor. Herein, we designed the multi-walled carbon nanotubes/gelatin-hemoglobin (MWCNTs/gelatin-Hb) core-shell nanobelts constructed on glassy carbon electrode (GC) using the one-step electrospinning technique for studying the effect of protein adsorption on the electrode surface properties. The results of the water contact angle and the scanning electron microscopy (SEM) showed that the electrospun core-shell MWCNTs/gelatin-Hb nanobelts present hydrophilic and certain anti-protein adsorption properties. Direct electron transfer between the Hb molecules in the electrospun core-shell nanobelts and electrode and catalysis of hydrogen peroxide (H2O2) can be still achieved after the electrospun core-shell MWCNTs/gelatin-Hb nanobelts adsorbed protein. Moreover, compared with before protein adsorption (Kmapp =0.0155 mmol/L), the electrospun core-shell MWCNTs/gelatin-Hb nanobelts after protein adsorption still displayed high biological affinity to H2O2 (Kmapp =0.0382 mmol/L). The constructed H2O2 biosensor by using the electrospun core-shell MWCNTs/gelatin-Hb nanobelts showed high sensitivity, great reproducibility and stability after protein adsorption. This study provides a novel design and an effective platform for the development of implantable electrochemical biosensors.

Anisotropic Conductive Hydrogels with High Water Content.

High water content is hard to be achieved in conductive hydrogels because a mass of conductive constituent is needed to form an internal conductive pathway. Here, we developed anisotropic electrically conductive hydrogels with high water content based on bacterial cellulose (BC). Polystyrene sulfonate (PSS) was grafted to the acryloyl chloride-modified BC to provide a template for the subsequent synthesis of poly(3,4-ethylenedioxythiophene) (PEDOT). The BC-g-PSS/PEDOT hydrogels obtained were electrically conductive owing to the immobilization of PEDOT on the surface of cellulose nanofibers. The hydrogels exhibited an electrical conductivity of 0.24 S cm-1. Further, they demonstrated suppleness in compression (compiled to external compression stress >2.8 MPa and recoverable), inherent high water content (∼95.0 wt %), and anisotropy (anisotropic index of 4.1 in conductivity) from BC. The incorporation of a thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel into the BC-g-PSS/PEDOT hydrogel demonstrated a uniaxial thermoresponsive actuation with resistance change. The expected size and resistance change were only observed in the direction vertical to the cellulose nanofiber layers. These hydrogels could accommodate further developments in novel tissue engineering scaffolds, implantable biosensors, and smart soft electronic devices.

Using implantable biosensors and wearable scanners to monitor dairy cattle's core body temperature in real-time

A minimally invasive method that involves using implantable biosensors with radio-frequency identification (RFID) capabilities was tested in regard to its ability to continuously measure the ear base subdermal temperature of a dairy cow. An increase in subdermal temperature, reflective of vasodilation, could, we surmised, potentially detect the level of heat stress. This could provide a better way to control dairy-barn cooling systems, which are commonly controlled solely on the basis of either air temperature or some other such non-ideal environmental parameters. Concurrent with the development of new technologies, the Long-Range (LoRa) wireless communication technology and a concept known as the “Internet of Things” (IoT) were utilized to extract temperature data from the base of a cow’s ear every 30 s in real-time. To test the method, an implant temperature sensor was injected, at the base of the ear, into three Holstein cows, and each was equipped with a wearable RFID scanner (mounted on an existing collar) for five days during a summer season in Wisconsin. The primary objective was to determine the efficacy of using implantable biosensors and wireless communication technology to monitor the heat-stress levels experienced by these dairy cows, in real-time, over the five days. Overall, the recorded subdermal temperature data obtained from implantable biosensors closely corresponded to the changes that occurred in core (vaginal) body temperature, and the developed wireless communication nodes successfully measured and monitored the temperature readings in real-time. Each cow showed different heat stress responses despite the fact that all three were in virtually the same location and subject to the same temperature-humidity index (THI) throughout the study. The study also found that the temperature readings obtained by the implantable biosensor began to more closely match in value the corresponding core body temperature (CBT) readings as the THI increased. Furthermore, the CBT of a cow could be reasonably predicted by applying a machine-learning (ML) algorithm to measured subdermal-temperature and THI data. The present study also found that the dairy cows tested displayed no obvious adverse effects that could have resulted from the biosensor implanted at the base of the ear. This study’s findings should serve as the first step toward any future research and development that may take place in the field of precision agriculture, especially research that considers even smaller and more practical electronics.

A novel antimicrobial electrochemical glucose biosensor based on silver–Prussian blue‐modified TiO2 nanotube arrays

AbstractGlucose biosensors play an important role in the diagnosis and continued monitoring of the disease, diabetes mellitus. This report proposes the development of a novel enzymatic electrochemical glucose biosensor based on TiO2 nanotubes modified by AgO and Prussian blue (PB) nanoparticles (NPs), which has an additional advantage of possessing antimicrobial properties for implantable biosensor applications. In this study, we developed two high‐performance glucose biosensors based on the immobilization of glucose oxidase (GOx) onto Prussian blue (PB)‐modified TiO2 nanotube arrays functionalized by Au and AgO NPs. AgO‐deposited TiO2 nanotubes were synthesized through an electrochemical anodization process followed by Ag electroplating process in the same electrolyte. Deposition of PB particles was performed from an acidic ferricyanide solution. The surface morphology and elemental composition of the two fabricated biosensors were investigated by scanning electron microscopy (SEM) and energy‐dispersive X‐ray spectroscopy (EDS) which indicate the successful deposition of Au and AgO nanoparticles as well as PB nanocrystals. Cyclic voltammetry and chronoamperometry were used to investigate the performance of the modified electrochemical biosensors. The results show that the developed electrochemical biosensors display excellent properties in terms of electron transmission, low detection limit and high stability for the determination of glucose. Under the optimized conditions, the amperometric response shows a linear dependence on the glucose concentration to a detection limit down to 4.91 µM with sensitivity of 185.1 mA M−1 cm−2 in Au‐modified biosensor and detection limit of 58.7 µM with 29.1 mA M−1 cm−2 sensitivity in AgO‐modified biosensor.

Improved operational stability of mediated glucose enzyme electrodes for operation in human physiological solutions

Stability of glucose-oxidising enzyme electrodes is affected by substances in physiological solutions, hampering deployment as long-term implantable biosensors or fuel cells. The performance of Nafion over-coated enzyme electrodes, consisting of multiwalled carbon nanotubes and flavin adenine dinucleotide-dependent glucose dehydrogenase (FADGDH) or glucose oxidase (GOx) crosslinked with osmium-complex based redox polymer, was compared to uncoated electrodes in presence of uric acid and artificial plasma. Nafion over-coating resulted in lower glucose oxidation current densities compared to no over-coating. The highest initial current density for Nafion over-coated electrodes in artificial plasma in 100 mM glucose was 8.0 ± 2.0 mA cm−2 for GOx electrodes with 0.5% w/v Nafion coating. These electrodes retained 83% of initial current after 12 h continuous operation in artificial plasma while similarly prepared FADGDH electrodes retained 58% signal. This is compared to retention of only 73% or 31% observed for GOx or FADGDH electrodes in artificial plasma with no Nafion membrane. Enzyme electrodes over-coated with Nafion maintain improved signal stability when tested continuously in the presence of uric acid, identified as being the main contributing substance to FADGDH enzyme electrode instability, showing promise for application to continuous use glucose-oxidising enzyme electrodes.

Refreshable Nanobiosensor Based on Organosilica Encapsulation of Biorecognition Elements.

Implantable and wearable biosensors that enable monitoring of biophysical and biochemical parameters over long durations are highly attractive for early and presymptomatic diagnosis of pathological conditions and timely clinical intervention. Poor stability of antibodies used as biorecognition elements and the lack of effective methods to refresh the biosensors upon demand without severely compromising the functionality of the biosensor remain significant challenges in realizing protein biosensors for long-term monitoring. Here, we introduce a novel method involving organosilica encapsulation of antibodies for preserving their biorecognition capability under harsh conditions, typically encountered during the sensor refreshing process, and elevated temperature. Specifically, a simple aqueous rinsing step using sodium dodecyl sulfate (SDS) solution refreshes the biosensor by dissociating the antibody-antigen interactions. Encapsulation of the antibodies with an organosilica layer is shown to preserve the biorecognition capability of otherwise unstable antibodies during the SDS treatment, thus ultimately facilitating the refreshability of the biosensor over multiple cycles. Harnessing this method, we demonstrate the refreshability of plasmonic biosensors for anti-IgG (model bioanalyte) and neutrophil gelatinase-associated lipocalin (NGAL) (a biomarker for acute and chronic kidney injury). The novel encapsulation approach demonstrated can be easily extended to other transduction platforms to realize refreshable biosensors for monitoring of protein biomarkers over long durations.

A Glucose Biosensor Based on Direct Electron Transfer of Glucose Oxidase on PEDOT Modified Microelectrode

Implantable glucose biosensor based on poly (3,4-ethylenedioxythiophene) (PEDOT) modified carbon fiber (CF) microelectrode was fabricated for the first time. Main appeal of this work was the immobilization of glucose oxidase (GOx) on PEDOT film by electrostatic interaction, which resulted in the direct electron transfer (DET) between the active sites of enzyme and electrode in the help of PEDOT. The sensor exhibited selective response to glucose in the presence of some common interference. The biosensor operates at a low potential of −0.65 V vs Ag/AgCl, and the amperometric response was linear over range from 0.5 mM to 15 mM for glucose with a sensitivity of 8.5 μA·cm−2·mM−1. The Michaelis-Menten constant was calculated as 6.5 mM, and the sensor retain 81.3% sensitivity after 60 d storage. Moreover, the extremely simple process of DET construction could be potentially extended for the mass production.

A Minimally Invasive Implantable Sensor for Continuous Wireless Glucose Monitoring Based on a Passive Resonator

An implantable biosensor for the long-range continuous glucose monitoring is proposed in this letter. A fully passive, miniaturized circuit composed of an LC (inductor–capacitor) tank resonator with a volume of 16 mm $^3$ is developed. This passive circuit can be implanted under the human skin, where the interstitial dermal fluid surrounds the LC tank resonator. Variations in glucose concentration result in variations in the permittivity of the fluid. In turn, this variation changes the capacitance of the LC tank resonator and, thus, its resonant frequency. The change in the resonant frequency is observed by the inductively coupled reader antenna located outside the tissue. Measurements are performed for various glucose concentrations in deionized water and human serum albumin, to check the validity of the proposed method in the presence of skin and fat phantom tissues. The results indicate a linear variation of the sensor's resonant frequency with respect to the glucose concentration within the range 0–500 mg/dL and a sensitivity of about 150 kHz/(mg/dL). Measurement results are reliable up to a distance of 10 mm between the reader and the sensor.

Tritium Power Supply Sources Based on AlGaAs/GaAs Heterostructures

The results of the development of a radioisotope power supply source based on a semiconductor (AlxGa1 –xAs/GaAs) β-radiation energy converter and tritium as a radiation source are presented. The efficiency of this converter with a tritium saturated titanium disk, a green luminescent tritium lamp, or tritium gas as a radioisotope radiation source is compared. For a converter based on the Al0.35Ga0.65As/GaAs heterostructure in a capsule with tritium, efficiency η = 5.9% at a maximum specific output electrical power of 0.56 μW/cm2. Due to their long service life, such stand-alone and compact power supply sources can be used in space and subsea technologies, implantable cardiac pacemakers, biosensors, and portable equipment of high reliability.

Sterilization of Drug-Loaded Composite Coatings for Implantable Glucose Biosensors.

An anti-inflammatory drug-loaded composite coating (dexamethasone-loaded poly (lactic-co-glycolic acid) [PLGA] microspheres/polyvinyl alcohol [PVA] hydrogel) was previously developed to counter the foreign body reaction to a fully implantable continuous glucose monitoring biosensor. The long-term sensor functionality was ensured in the presence of the drug-loaded composite coating thus facilitating better diabetes control and management. In order to advance such a drug-device combination product toward clinical testing, addressing sterilization remains a key step due to the heterogeneity of the product components. The main objective of this research was to investigate the effect of two terminal sterilization techniques: gamma radiation and ethylene oxide (EO) on the stability of the anti-inflammatory coatings as well as retention of the glucose sensing ability of the implantable sensor. The composite coatings, their individual components, and the glucose-sensing elements of the biosensor were subjected to low-temperature gamma radiation and EO cycles. Detailed characterization was conducted on all components before and after sterilization. Exposure to gamma radiation affected dexamethasone crystallinity and glucose response linearity of the sensing element, whereas physical aging of microspheres in composite coatings was observed poststerilization with EO. Despite these effects, dexamethasone drug release from coatings was not significantly affected by either technique. The research findings indicate that both sterilization techniques are feasible for the sterilization of the dexamethasone-loaded PLGA microspheres/PVA hydrogel composite coatings, while EO was preferred for the sterilization of the glucose-sensing element of the biosensor.

Coatings Releasing the Relaxin Peptide Analogue B7-33 Reduce Fibrotic Encapsulation.

The development of antifibrotic materials and coatings that can resist the foreign body response (FBR) continues to present a major hurdle in the advancement of current and next-generation implantable medical devices, biosensors, and cell therapies. From an implant perspective, the most important issue associated with the FBR is the prolonged inflammatory response leading to a collagenous capsule that ultimately blocks mass transport and communication between the implant and the surrounding tissue. Up to now, most attempts to reduce the capsule thickness have focused on providing surface coatings that reduce protein fouling and cell attachment. Here, we present an approach that is based on the sustained release of a peptide drug interfering with the FBR. In this study, the biodegradable polymer poly(lactic-co-glycolic) acid (PLGA) was used as a coating releasing the relaxin peptide analogue B7-33, which has been demonstrated to reduce organ fibrosis in animal models. While in vitro protein quantification was used to demonstrate controlled release of the antifibrotic peptide B7-33 from PLGA coatings, an in vitro reporter cell assay was used to demonstrate that B7-33 retains activity against the relaxin family peptide receptor 1 (RXFP1). Subcutaneous implantation of PLGA-coated polypropylene samples in mice with and without the peptide demonstrated a marked reduction in capsule thickness (49.2%) over a 6 week period. It is expected that this novel approach will open the door to a range of new and improved implantable medical devices.

P6308Use of cell-embedded fully implantable biosensor system for real-time, in-vivo monitoring of NF-Kappa B inflammatory pathway

Abstract Background 21st century health care remains anchored to sporadic measurements of traditional physiologic variables such as heart rate, blood pressure, weight, physical exam findings and general biochemical values. Currently there is no sensor capable of monitoring in intra-cellular protein and gene level signaling in real-time and in-vivo. This gap between biological signaling and its translation into clinically relevant therapeutics targeting the individual has limited precision medicine approaches to heart and vascular diseases. Inflammatory processes have been implicated in numerous cardiovascular diseases providing an ideal target for using Biologically based-Implantable Electronic Devices (BIED) approaches. Objective We aimed to test an implantable electro-photonic biosensor system in which living cells are integrated within the BIED and 1) serve as the primary sensor element providing in-vivo, real-time monitoring of intra-cellular processes such as gene expression, protein signaling, and target pathway activation, and 2) provide intelligent biologically based-processing in which the the output reflects biological response to an event. The engineered sensor cells provide real-time monitoring and respond to prespecified biologic signals using green fluorescence protein (GFP). The fluorescence is then detected via the BIED's photonic system and the cellular response data transmitted providing remote monitoring capabilities to facilitate the development of innovative personalized therapeutics. Methods A biologically-based implantable biosensor (BIED) platform which provides fluorescence detection, data acquisition and transmission from living cells integrated within the device was tested. The sensor cells communicate with the surrounding implant environment via a biomembrane. NRK rat cells engineered to express GFP in response to NF-κB pathway activation were cultured and housed within the sensor. Prior implant studies confirmed NRK sensor cells remained viable for 21 days in-vivo as part of a fully functional implanted BIED hardware system. Ex-vivo experiments characterized the expected magnitude and time course of NRK response to TNF-α and Lipopolysaccharide (LPS) exposure used to elicit a proinflammatory inflammatory response. The biosensor was implanted in the subcutaneous space of male Sprague Dawley rats (n=2) for a total of 11 days consisting of a baseline post-surgical recovery period of 7 days, with subsequent challenge with intraperitoneal LPS on Day 8 and 96 hours of post LPS monitoring. Results Rats implanted with the Biological based sensor and challenged with intraperitoneal LPS showed real-time expression of GFP under NF-κB transcriptional control following time course similar to ex-vivo experiments (p&lt;0.05) (Figure 1). Figure 1. Implantable Cell-Embedded Biosensor Conclusion We present the first in-vivo use of a new class of BIEDs to detect biological cell response which may herald real-time personalize health management at the molecular and cellular level. Acknowledgement/Funding Clinical and Translational Sciences Institute-University of Rochester, Efferent Labs

Wave propagation in microtubule-based bio-nano-architected networks: A lesson from nature

Microtubules, bio-polymeric hollow tubes forming entangled radial networks from the nucleus to the cell membrane, are considered the main part of the cytoskeleton providing mechanical stiffness, organization and shape for the cytoplasm of the eukaryotic cells and playing substantial roles in some cellular processes such as mechanotransduction, cell division, intercellular transports, internal organization of the cell components, etc. In all of the mentioned functions, the network structure of the microtubules has the main responsibility proving the importance of more in-depth studies of their mechanical properties. This paper addresses the elastic wave propagation in various two-dimensional microtubule-based bio-nano-architected periodic networks to analyze their dynamic characteristics for possible further utilizations. The study starts with selecting a proper beam model for a single microtubule, as proved by previous experiments, and continues with creating ten widely used periodic structures, namely square, triangle, triangle–square, triangle–diamond, negative Poisson's ratio, semi-honeycomb, star–honeycomb, zig-zag, hexagram, and Sierpinski triangle, thereof. To obtain the dispersion curves, finite element models are developed for both individual and networked microtubules, and the phononic band structures are calculated based on Bloch's theorem. The results reveal the possibility of designing bandgaps in specific ranges for the low- and high-frequency bio-filter applications depending on the topologies of the selected unit cells as well as the considered periodicities. This application helps researchers control the ways to absorb some unwanted or hazardous vibrations using architected periodic structures and, thanks to the higher biocompatibility resulted from their biomaterial origin, the networks can be applied in next-generation nano-biomechanical instruments such as implantable biosensors.