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A retinal prosthesis, also known as a bionic eye, is a device that can be implanted to partially restore vision in patients with retinal diseases that have resulted in the loss of photoreceptors (e.g., age-related macular degeneration and retinitis pigmentosa). Recently, there have been major breakthroughs in retinal prosthesis technology, with the creation of numerous types of implants, including epiretinal, subretinal, and suprachoroidal sensors. These devices can stimulate the remaining cells in the retina with electric signals to create a visual sensation. A literature review of the pre-clinical and clinical studies published between 2017 and 2023 is conducted. This narrative review delves into the retinal anatomy, physiology, pathology, and principles underlying electronic retinal prostheses. Engineering aspects are explored, including electrode-retina alignment, electrode size and material, charge density, resolution limits, spatial selectivity, and bidirectional closed-loop systems. This article also discusses clinical aspects, focusing on safety, adverse events, visual function, outcomes, and the importance of rehabilitation programs. Moreover, there is ongoing debate over whether implantable retinal devices still offer a promising approach for the treatment of retinal diseases, considering the recent emergence of cell-based and gene-based therapies as well as optogenetics. This review compares retinal prostheses with these alternative therapies, providing a balanced perspective on their advantages and limitations. The recent advancements in retinal prosthesis technology are also outlined, emphasizing progress in engineering and the outlook of retinal prostheses. While acknowledging the challenges and complexities of the technology, this article highlights the significant potential of retinal prostheses for vision restoration in individuals with retinal diseases and calls for continued research and development to refine and enhance their performance, ultimately improving patient outcomes and quality of life.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had severe consequences for health and the global economy. To control the transmission, there is an urgent demand for early diagnosis and treatment in the general population. In the present study, an automatic system for SARS-CoV-2 diagnosis is designed and built to deliver high specification, high sensitivity, and high throughput with minimal workforce involvement. The system, set up with cross-priming amplification (CPA) rather than conventional reverse transcription-polymerase chain reaction (RT-PCR), was evaluated using more than 1000 real-world samples for direct comparison. This fully automated robotic system performed SARS-CoV-2 nucleic acid-based diagnosis with 192 samples in under 180 min at 100 copies per reaction in a "specimen in data out" manner. This throughput translates to a daily screening capacity of 800-1000 in an assembly-line manner with limited workforce involvement. The sensitivity of this device could be further improved using a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based assay, which opens the door to mixed samples, potentially include SARS-CoV-2 variants screening in extensively scaled testing for fighting COVID-19., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

As a fundamental feature of solid surfaces, wettability is playing an increasingly important role in our daily life. Benefitting from the inspiration of biological paradigms and the development in manufacturing technology, numerous wettability materials with elaborately designed surface topology and chemical compositions have been fabricated. Based on these advances, wettability materials have found broad technological implications in various fields ranging from academy, industry, agriculture to biomedical engineering. Among them, the practical applications of wettability materials in biomedical-related fields are receiving remarkable researches during the past decades because of the increasing attention to healthcare. In this review, the research progress of materials with specific wettability is discussed. After briefly introducing the underlying mechanisms, the fabrication strategies of artificial materials with specific wettability are described. The emphasis is put on the application progress of wettability biomaterials in biomedical engineering. The prospects for the future trend of wettability materials are also presented., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The COVID-19 pandemic has affected life for everyone, and hospitals, in particular have been hard hit. In this study, we describe our efforts to develop personal protective equipment at a children's hospital early in the pandemic. We convened an innovation working group to organize our efforts and respond to the rapidly changing situation. We describe our work in four areas: (1) plexiglass shields for the emergency department, (2) face shields for clinical providers, (3) breath shields for ophthalmology, and (4) flip-up safety glasses for nurses. The hospital's supply chain is now caught up with addressing many pandemic-related shortages. Nevertheless, through our multidisciplinary approach to reacting to the pandemic's urgent needs, we demonstrated agility to bring stakeholders together to maximize the use of scarce resources and build resiliency. We believe this method can be rapidly replicated as future needs arise.

As the scope and scale of the COVID-19 pandemic became clear in early March of 2020, the faculty of the Malone Center engaged in several projects aimed at addressing both immediate and long-term implications of COVID-19. In this article, we briefly outline the processes that we engaged in to identify areas of need, the projects that emerged, and the results of those projects. As we write, some of these projects have reached a natural termination point, whereas others continue. We identify some of the factors that led to projects that moved to implementation, as well as factors that led projects to fail to progress or to be abandoned.

Despite the fast development of various energy harvesting and storage devices, their judicious integration into efficient, autonomous, and sustainable wearable systems has not been widely explored. Here, we introduce the concept and design principles of e-textile microgrids by demonstrating a multi-module bioenergy microgrid system. Unlike earlier hybrid wearable systems, the presented e-textile microgrid relies solely on human activity to work synergistically, harvesting biochemical and biomechanical energy using sweat-based biofuel cells and triboelectric generators, and regulating the harvested energy via supercapacitors for high-power output. Through energy budgeting, the e-textile system can efficiently power liquid crystal displays continuously or a sweat sensor-electrochromic display system in pulsed sessions, with half the booting time and triple the runtime in a 10-min exercise session. Implementing "compatible form factors, commensurate performance, and complementary functionality" design principles, the flexible, textile-based bioenergy microgrid offers attractive prospects for the design and operation of efficient, sustainable, and autonomous wearable systems.

The fabrication of functional biomaterials for organ replacement and tissue repair remains a major goal of biomedical engineering. Advances in additive manufacturing (AM) technologies and computer-aided design (CAD) are advancing the tools available for the production of these devices. Ideally, these constructs should be matched to the geometry and mechanical properties of the tissue at the needed implant site. To generate geometrically defined and structurally supported multicomponent and cell-laden biomaterials, we have developed a method to integrate hydrogels with 3D-printed lattice scaffolds leveraging surface tension-assisted AM.

In the last decade, only 24% of class III life-saving devices approved by the U.S. Food and Drug Administration (FDA) were for pediatric use-and most of those were for children over 12. Of these, less than 4% were labeled for pediatric patients ages 0-2 years old and the number of approved devices is even lower for neonatal patients. For these young patients, adult medical devices are often manipulated by pediatric specialists in order to provide stop-gap solutions. However, these repurposed devices are not always able to fulfill the unique needs of children's biology and growth patterns.

The neuron behavioral models are inspired by the principle of the firing of neurons, and weighted accumulation of charge for a given set of input stimuli. Biological neurons show dynamic behavior through its feedback and feedforward time-dependent responses. The principle of the firing of neurons inspires threshold logic design by applying threshold functions on the weight summation of inputs. In this article, we present a recursive threshold logic unit that uses the output feedback from standard threshold logic gates to emulate Boolean expressions in a time-sequenced manner. The Boolean expression is implemented with an analog resistive divider in memristive crossbars and a hard-threshold function designed with CMOS comparator for realizing the sums (OR) and products (AND) operators. The method benefits from reliable programming of the memristors in 1T1R crossbar configuration to suppress sneak path currents and thus enable larger crossbar sizes, which in turn allow a higher number of Boolean inputs. The reference threshold voltage for the decision comparators is tuned to implement AND and OR logic. The threshold value range is limited by the number of inputs to the crossbar. Simultaneously, the resistance of the memristors is kept constant at R ON . The circuit's tolerance to the memristor variability and aging are analyzed, showing sufficient resilience. Also, the proposed recursive logic uses fewer cross-points, and has lower power dissipation than other memristive logic and CMOS implementation.

Background: The bispectral index (BIS) monitor has been available for clinical use for >20 years and has had an immense impact on academic activity in Anesthesiology, with >3000 articles referencing the bispectral index. Despite attempts to infer its algorithms by external observation, its operation has nevertheless remained undescribed, in contrast to the algorithms of other less commercially successful monitors of electroencephalogram (EEG) activity under anesthesia. With the expiration of certain key patents, the time is therefore ripe to examine the operation of the monitor on its own terms through careful dismantling, followed by extraction and examination of its internal software., Methods: An A-2000 BIS Monitor (gunmetal blue case, amber monochrome display) was purchased on the secondary market. After identifying the major data processing and storage components, a set of free or inexpensive tools was used to retrieve and disassemble the monitor's onboard software. The software executes primarily on an ARMv7 microprocessor (Sharp/NXP LH77790B) and a digital signal processor (Texas Instruments TMS320C32). The device software can be retrieved directly from the monitor's hardware by using debugging interfaces that have remained in place from its original development., Results: Critical numerical parameters such as the spectral edge frequency (SEF), total power, and BIS values were retraced from external delivery at the device's serial port back to the point of their calculation in the extracted software. In doing so, the locations of the critical algorithms were determined. To demonstrate the validity of the technique, the algorithms for SEF and total power were disassembled, comprehensively annotated and compared to their theoretically ideal behaviors. A bug was identified in the device's implementation of the SEF algorithm, which can be provoked by a perfectly isoelectric EEG., Conclusions: This article demonstrates that the electronic design of the A-2000 BIS Monitor does not pose any insuperable obstacles to retrieving its device software in hexadecimal machine code form directly from the motherboard. This software can be reverse engineered through disassembly and decompilation to reveal the methods by which the BIS monitor implements its algorithms, which ultimately must form the definitive statement of its function. Without further revealing any algorithms that might be considered trade secrets, the manufacturer of the BIS monitor should be encouraged to release the device software in its original format to place BIS-related academic literature on a firm theoretical foundation and to promote further academic development of EEG monitoring algorithms.

A bio-potential recorder working under 0.8 V supply voltage with a tunable low-pass filter is proposed in this paper. The prototype is implemented in TSMC 180 nm CMOS technology, featuring a power consumption of 2.27  μW, while preserving a high tolerance of power-line interference (PLI) up to 600 m V pp , a common-mode rejection ratio (CMRR) of higher than 100 dB, a THD of -65.5 dB, and a noise density of 50 nV/ √{Hz} by employing four new techniques, including 1) low noise chopper modulator, 2) feedback loop based common-mode cancellation loop (CMCL), 3) offset cancellation loop (OCL) with PMOS backgate control scheme, and 4) a very-lower transconductance (VLT) operational transconductance amplifier (OTA) using in the DC-servo-loop (DSL). The measured mid-band gain is 43.3 dB with a high-pass cut-off frequency of 1.2 Hz. The low-pass cut-off frequency can be configured from 650 Hz to 7.5 kHz. The measured input-referred integrated noise is 1.2 uVrms in the frequency band of 1-650 Hz and 4.1 uVrms in the 1 Hz-7.5 kHz frequency band, respectively, leading to a power efficiency factor (PEF) of 7.49 and 7.59.

In neurostimulation, wireless power transfer is an efficient technology to overcome several limitations affecting medical devices currently used in clinical practice. Several methods were developed over the years for wireless power transfer. In this review article, we report and discuss the three most relevant methodologies for extremely miniaturised implantable neurostimulators: ultrasound coupling, inductive coupling and capacitive coupling. For each powering method, the discussion starts describing the physical working principle. In particular, we focus on the challenges given by the miniaturisation of the implanted integrated circuits and the related ad-hoc solutions for wireless power transfer. Then, we present recent developments and progresses in wireless power transfer for biomedical applications. Last, we compare each technique based on key performance indicators to highlight the most relevant and innovative solutions suitable for neurostimulation, with the gaze turned towards miniaturisation.

Continuous, battery-free operation of sensor nodes requires ultra-low-power sensing and data-logging techniques. Here we report that by directly coupling a sensor/transducer signal into globally asymptotically stable monotonic dynamical systems based on Fowler-Nordheim quantum tunneling, one can achieve self-powered sensing at an energy budget that is currently unachievable using conventional energy harvesting methods. The proposed device uses a differential architecture to compensate for environmental variations and the device can retain sensed information for durations ranging from hours to days. With a theoretical operating energy budget less than 10 attojoules, we demonstrate that when integrated with a miniature piezoelectric transducer the proposed sensor-data-logger can measure cumulative "action" due to ambient mechanical acceleration without any additional external power.

Realizing a clinical-grade electronic medicine for peripheral nerve disorders is challenging owing to the lack of rational material design that mimics the dynamic mechanical nature of peripheral nerves. Electronic medicine should be soft and stretchable, to feasibly allow autonomous mechanical nerve adaptation. Herein, we report a new type of neural interface platform, an adaptive self-healing electronic epineurium (A-SEE), which can form compressive stress-free and strain-insensitive electronics-nerve interfaces and enable facile biofluid-resistant self-locking owing to dynamic stress relaxation and water-proof self-bonding properties of intrinsically stretchable and self-healable insulating/conducting materials, respectively. Specifically, the A-SEE does not need to be sutured or glued when implanted, thereby significantly reducing complexity and the operation time of microneurosurgery. In addition, the autonomous mechanical adaptability of the A-SEE to peripheral nerves can significantly reduce the mechanical mismatch at electronics-nerve interfaces, which minimizes nerve compression-induced immune responses and device failure. Though a small amount of Ag leaked from the A-SEE is observed in vivo (17.03 ppm after 32 weeks of implantation), we successfully achieved a bidirectional neural signal recording and stimulation in a rat sciatic nerve model for 14 weeks. In view of our materials strategy and in vivo feasibility, the mechanically adaptive self-healing neural interface would be considered a new implantable platform for a wide range application of electronic medicine for neurological disorders in the human nervous system.

The substantial improvements and innovations in communication networks and bio-medical technologies have led to the adoption of networked medical devices due to which the attack surface has increased profoundly. Numerous devices in practice were designed and developed years ago without security measures. In such a scenario, the role of regulatory bodies has become evident. The Food and Drug Administration (FDA) validates and approves devices before commercialization. In contrast, the European Union (EU) follows a decentralized approach and Notified Bodies (NB) for assuring high standards, safety and quality of medical devices being marketed in Europe. Once the device has gone through stringent regulations including good manufacturing practices, Quality Management System (QMS), labeling, clinical tests, performance standards, adequate storage and packaging practices, a declaration of conformity will be granted, which is a legal binding document stating that the device is conformant with applicable European requirements and can be marketed in Europe. However, such regulations lack a systematic methodology to determine unified security, safety and privacy risk that eventually influence the health of patients. To cover these gaps, this research proposes Integrated Safety, Security, and Privacy (ISSP) Risk Assessment Framework to determine the risk level of the device and required security controls. It is, then applied to a case scenario of an infusion pump and further evaluated by comparing it with current standards and practices. The comparison shows that the framework provides a unified approach to consider different types of risks associated with devices.

This paper presents a 10-bit successive approximation analog-to-digital converter (ADC) that operates at an ultralow voltage of 0.3 V and can be applied to biomedical implants. The study proposes several techniques to improve the ADC performance. A pipeline comparator was utilized to maintain the advantages of dynamic comparators and reduce the kickback noise. Weight biasing calibration was used to correct the offset voltage without degrading the operating speed of the comparator. The incorporation of a unity-gain buffer improved the bootstrap switch leakage problem during the hold period and reduced the effect of parasitic capacitances on the digital-to-analog converter. The chip was fabricated using 90-nm CMOS technology. The data measured at a supply voltage of 0.3 V and sampling rate of 3 MSps for differential nonlinearity and integral nonlinearity were +0.83/-0.54 and +0.84/-0.89, respectively, and the signal-to-noise plus distortion ratio and effective number of bits were 56.42 dB and 9.08 b, respectively. The measured total power consumption was 6.6 μW at a figure of merit of 4.065 fJ/conv.-step.

E. coli expressed recombinant basic fibroblast growth factor (bFGF) with histidine-tag (bFGF-His) was immobilized onto the surface of a glass plate modified with a Ni(II)-chelated alkanethiol monolayer. The immobilization is expected to take place through the coordination between Ni(II) and His-tag. The bFGF-immobilized surface was exposed to citrate buffer solution to refold in situ the surface-immobilized bFGF. The secondary structure of immobilized bFGF-His was analyzed by solid-phase circular dichroism (CD) spectroscopy. Immortalized human mesenchymal stromal cells (hMSCs) were cultured on the bFGF-His-immobilized surface to examine their proliferation. CD spectroscopy revealed that the immobilized bFGF initially exhibited secondary structure rich in α-helix and that the spectrum was gradually transformed to exhibit the formation of β-strands upon exposure to citrate buffer solution, approaching to the spectrum of native bFGF. The rate of hMSC proliferation was 1.2-fold higher on the bFGF-immobilized surface treated with in situ citrate buffer, compared to the polystyrene surface. The immobilized bFGF-His treated in situ with citrate buffer solution seemed to be biologically active because its secondary structure approached its native state. This was well demonstrated by the cell culture experiments. From these results we conclude that immobilization of bFGF on the culture substrate serves to enhance proliferation of hMSCs.

At this time many (if not all) colleges and universities are on lockdown, students have returned home, and classes have transitioned to online instruction. Students in capstone design courses around the country have no access to their school's maker spaces and test equipment. Their prototype parts may be stored in a locked maker space, making it difficult to build, test, and deliver prototypes to sponsors or clients at the end of the semester.z.

In today's clinics, a cell-resolution view of the cornea can be achieved only with a confocal microscope (IVCM) in contact with the eye. Here, we present a common-path full-field/spectral-domain OCT microscope (FF/SD OCT), which enables cell-detail imaging of the entire ocular surface in humans (central and peripheral cornea, limbus, sclera, tear film) without contact and in real-time. Real-time performance is achieved through rapid axial eye tracking and simultaneous defocusing correction. Images contain cells and nerves, which can be quantified over a millimetric field-of-view, beyond the capability of IVCM and conventional OCT. In the limbus, palisades of Vogt, vessels, and blood flow can be resolved with high contrast without contrast agent injection. The fast imaging speed of 275 frames/s (0.6 billion pixels/s) allows direct monitoring of blood flow dynamics, enabling creation of high-resolution velocity maps. Tear flow velocity and evaporation time can be measured without fluorescein administration.

This paper presents an adaptable dictionary-based feature extraction approach for spike sorting offering high accuracy and low computational complexity for implantable applications. It extracts and learns identifiable features from evolving subspaces through matched unsupervised subspace filtering. To provide compatibility with the strict constraints in implantable devices such as the chip area and power budget, the dictionary contains arrays of {-1, 0 and 1} and the algorithm need only process addition and subtraction operations. Three types of such dictionary were considered. To quantify and compare the performance of the resulting three feature extractors with existing systems, a neural signal simulator based on several different libraries was developed. For noise levels σ N between 0.05 and 0.3 and groups of 3 to 6 clusters, all three feature extractors provide robust high performance with average classification errors of less than 8% over five iterations, each consisting of 100 generated data segments. To our knowledge, the proposed adaptive feature extractors are the first able to classify reliably 6 clusters for implantable applications. An ASIC implementation of the best performing dictionary-based feature extractor was synthesized in a 65-nm CMOS process. It occupies an area of 0.09 mm 2 and dissipates up to about 10.48 μW from a 1 V supply voltage, when operating with 8-bit resolution at 30 kHz operating frequency.

This study aims to design and implement a very large scale integration (VLSI) chip of the extend InfoMax independent component analysis (ICA) algorithm which can separate the super-Gaussian source signals. In order to substantially reduce the circuit area, the proposed circuit utilizes the time sharing matrix multiplication array (MMA) to realize a series of matrix multiplication operations and employs the coordinate rotation digital computer (CORDIC) algorithm to calculate the hyperbolic functions sinh(θ) and cosh(θ) with the rotation of the hyperbolic coordinate system. Also, the rotation of the linear coordinate system of the CORDIC is adopted for the design of a divider used for obtaining the required function value of tanh(θ) simply by evaluating sinh(θ)/cosh(θ). Implemented in a TSMC 90-nm CMOS technology, the proposed ICA has an operation frequency of 100 MHz with 90.8 K gate counts. Furthermore, the measurement results show the ICA core can be successfully applied to separating mixed medical signals into independent sources.

Advances in areas such as data analytics, genomics, and imaging have revealed individual patient complexities and exposed the inherent limitations of generic therapies for patient treatment. These observations have also fueled the development of precision medicine approaches, where therapies are tailored for the individual rather than the broad patient population. 3D printing is a field that intersects with precision medicine through the design of precision implants with patient-directed shapes, structures, and materials or for the development of patient-specific in vitro models that can be used for screening precision therapeutics. Toward their success, advances in 3D printing and biofabrication technologies are needed with enhanced resolution, complexity, reproducibility, and speed and that encompass a broad range of cells and materials. The overall goal of this progress report is to highlight recent advances in 3D printing technologies that are helping to enable advances important in precision medicine., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel mono-surface antisymmetric 16-element transmit/receive (Tx/Rx) coil array was designed, simulated, constructed, and tested for cardiac magnetic resonance imaging (cMRI) in pigs at 7 T. The cardiac array comprised of a mono-surface 16-loops with two central elements arranged anti-symmetrically and flanked by seven elements on either side. The array was configured for parallel transmit (pTx) mode to have an eight channel transmit and 16-channel receive (8Tx/16Rx) coil array. Electromagnetic (EM) simulations, bench-top measurements, phantom, and MRI experiments with two pig cadavers (68 and 46 kg) were performed. Finally, the coil was used in pilot in-vivo measurements with a 60 kg pig. Flip angle (FA), geometry factor (g-factor), signal-to-noise ratio (SNR) maps, and high-resolution cardiac images were acquired with an in-plane resolution of 0.6 mm × 0.6 mm (in-vivo) and 0.3 mm × 0.3 mm (ex-vivo). The mean g-factor over the heart was 1.26 (R = 6). Static phase [Formula: see text] shimming in a pig body phantom with the optimal phase vectors makes possible to improve the [Formula: see text] homogeneity by factor > 2 and transmit efficiency by factor > 3 compared to zero phases (before RF shimming). Parallel imaging performed in the in-vivo measurements demonstrated well preserved diagnostic quality of the resulting images at acceleration factors up to R = 6. The described hardware design can be adapted for arrays optimized for animals and humans with a larger number of elements (32-64) while maintaining good decoupling for various MRI applications at UHF (e.g., cardiac, head, and spine).

The ability to image pressure distribution over complex three-dimensional surfaces would significantly augment the potential applications of electronic skin. However, existing methods show poor spatial and temporal fidelity due to their limited pixel density, low sensitivity, or low conformability. Here, we report an ultraflexible and transparent electroluminescent skin that autonomously displays super-resolution images of pressure distribution in real time. The device comprises a transparent pressure-sensing film with a solution-processable cellulose/nanowire nanohybrid network featuring ultrahigh sensor sensitivity (>5000 kPa -1 ) and a fast response time (<1 ms), and a quantum dot-based electroluminescent film. The two ultrathin films conform to each contact object and transduce spatial pressure into conductivity distribution in a continuous domain, resulting in super-resolution (>1000 dpi) pressure imaging without the need for pixel structures. Our approach provides a new framework for visualizing accurate stimulus distribution with potential applications in skin prosthesis, robotics, and advanced human-machine interfaces.

Challenges in drug development of neurological diseases remain mainly ascribed to the blood-brain barrier (BBB). Despite the valuable contribution of animal models to drug discovery, it remains difficult to conduct mechanistic studies on the barrier function and interactions with drugs at molecular and cellular levels. Here we present a microphysiological platform that recapitulates the key structure and function of the human BBB and enables 3D mapping of nanoparticle distributions in the vascular and perivascular regions. We demonstrate on-chip mimicry of the BBB structure and function by cellular interactions, key gene expressions, low permeability, and 3D astrocytic network with reduced reactive gliosis and polarized aquaporin-4 (AQP4) distribution. Moreover, our model precisely captures 3D nanoparticle distributions at cellular levels and demonstrates the distinct cellular uptakes and BBB penetrations through receptor-mediated transcytosis. Our BBB platform may present a complementary in vitro model to animal models for prescreening drug candidates for the treatment of neurological diseases.

Uncontrolled bleeding contributes to 30% to 40% of trauma-related deaths and is the leading cause of potentially preventable deaths. Currently, there is no effective method available to first responders for temporary control of noncompressible intraabdominal bleeding while patients are transported to the hospital. Our previous studies demonstrated that abdominal insufflation provides effective temporary bleeding control. The study aims to prove the feasibility (insufflation to a target pressure) and safety (cardiovascular and respiratory effects) of a novel portable abdominal insufflation device (PAID) designed to control the intraperitoneal bleeding caused by abdominal trauma. The PAID prototype is based on a patented design and manufactured via additive manufacturing. PAID contains a 16-g CO 2 cartridge and an electronic pressure transducer. PAID was tested on a bench top and a swine animal model. For the animal model study, the intraperitoneal pressure as well as cardiorespiratory parameters (hearth rate, SpO 2 [peripheral capillary oxygen saturation], and blood pressure) were continuously monitored during the insufflation procedure. The prototype functioned according to specifications on both bench top and animal models. CO 2 insufflation of the peritoneal cavity was delivered up the target 20 mm Hg and maintained for 30 minutes from 1 or 2 cartridges in the swine model. No intraoperative incidents were registered, and all the recorded physiological parameters were within normal limits. The PAID prototype is a feasible, easy to use device that provides quick, controlled, and safe insufflation of the peritoneal cavity. Future studies will focus on testing the next-generation, semiautomatic PAID prototype in a severe intraabdominal injury model.

Objectives. Thoracic drainage is a common procedure to drain fluid, blood, or air from the pleural cavity. Some attempts to develop approaches to new thoracic drainage systems have been made; however, a simple tube is often currently used. The existing drain presupposes that it is placed correctly and that the tip does not require moving after insertion into the thoracic cavity. However, in some cases, the drain is not correctly placed and reinsertion of an additional drain is required, resulting in significant invasiveness to the patient. Therefore, a more effective drainage system is needed. This study aimed to develop and assess a new thoracic drain via a collaboration between medical and engineering personnel. Methods. We developed the concept of a controllable drain system using magnetic actuation. A dry laboratory trial and accompanying questionnaire assessment were performed by a group of thoracic and general surgeons. Objective mechanical measurements were obtained. Porcine experiments were also carried out. Results. In a dry laboratory trial, use of the controllable drain required significantly less time than that required by replacing the drain. The average satisfaction score of the new drainage system was 4.07 out of 5, indicating that most of the research participants were satisfied with the quality of the drain with a magnetic actuation. During the porcine experiment, the transfer of the tip of the drain was possible inside the thoracic cavity and abdominal cavity. Conclusion. This controllable thoracic drain could reduce the invasiveness for patients requiring thoracic or abdominal cavity drainage.

Objective: The purpose of this paper is to demonstrate the ultrasound tracking strategy for the acoustically actuated bubble-based microswimmer., Methods: The ultrasound tracking performance is evaluated by comparing the tracking results with the camera tracking. A benchtop experiment is conducted to capture the motion of two types of microswimmers by synchronized ultrasound and camera systems. A laboratory developed tracking algorithm is utilized to estimate the trajectory for both tracking methods., Results: The trajectory reconstructed from ultrasound tracking method compares well with the conventional camera tracking, exhibiting a high accuracy and robustness for three different types of moving trajectories., Conclusion: Ultrasound tracking is an accurate and reliable approach to track the motion of the acoustically actuated microswimmers., Significance: Ultrasound imaging is a promising candidate for noninvasively tracking the motion of microswimmers inside the body in biomedical applications and may further promote the real-time control strategy for the microswimmers.

Implantable medical devices have been used for real-time monitoring of physical parameters (temperature, pressure and biopotentials), sustained drug release, cardiovascular and pulmonary stents and other clinical applications. Several biocompatible materials (titanium and its alloys, aluminium, cobalt-alloys, stainless steel, poly-ethylene, polyurethanes, polyglycolide and polylactides) have been commercially used for fabricating implantable devices. However, these devices require retrieval operations after a certain period. Bioresorbable materials disintegrate gradually in vivo and their derivatives get absorbed completely in the body fluid with no residue and with minimal toxic effects, thus, eliminating the need for retrieval operations. In this article, state-of-the-art advances in materials, fabrication techniques and clinical applications of bioresorbable implantable devices are reviewed. We first discuss the bioresorbable materials (e.g., magnesium, molybdenum, tungsten, silicon, germanium, silicon dioxide, silicon nitride, silk and synthetic polymers) used in the fabrication of implantable devices. Later, an overview of processes to fabricate pressure, temperature, electrical and chemical sensors are discussed, followed by their applications as implantable devices in biomedical engineering., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Medical device industry encompasses a wide range of technologies and applications, which makes the process validation approach (IQ/OQ/PQ framework) and OQ/PQ implementation method difficult to be defined in the industry's regulation and process validation guidance documents. Based on two-level (component production level and device assembly level) process validation approach, this article proposes 1) a typical section structure & contents for production equipment/system/process validation OQ/PQ protocols, 2) a typical subsection structure & contents for the protocols' most critical section - Test Plan, and 3) the validation approach and OQ Detailed Test Plan for both common equipment and test equipment.

Capabilities in real-time monitoring of internal physiological processes could inform pharmacological drug-delivery schedules, surgical intervention procedures and the management of recovery and rehabilitation. Current methods rely on external imaging techniques or implantable sensors, without the ability to provide continuous information over clinically relevant timescales, and/or with requirements in surgical procedures with associated costs and risks. Here, we describe injectable classes of photonic devices, made entirely of materials that naturally resorb and undergo clearance from the body after a controlled operational lifetime, for the spectroscopic characterization of targeted tissues and biofluids. As an example application, we show that the devices can be used for the continuous monitoring of cerebral temperature, oxygenation and neural activity in freely moving mice. These types of devices should prove useful in fundamental studies of disease pathology, in neuroscience research, in surgical procedures and in monitoring of recovery from injury or illness.

Parkinson's disease (PD) is a degenerative disorder of the brain characterized by the impairment of the nigrostriatal system. This impairment leads to specific motor manifestations (i.e., bradykinesia, tremor, and rigidity) that are assessed through clinical examination, scales, and patient-reported outcomes. New sensor-based and wearable technologies are progressively revolutionizing PD care by objectively measuring these manifestations and improving PD diagnosis and treatment monitoring. However, their use is still limited in clinical practice, perhaps because of the absence of external validation and standards for their continuous use at home. In the near future, these systems will progressively complement traditional tools and revolutionize the way we diagnose and monitor patients with PD.

The microfluidics field is at a critical crossroads. The vast majority of microfluidic devices are presently manufactured using micromolding processes that work very well for a reduced set of biocompatible materials, but the time, cost, and design constraints of micromolding hinder the commercialization of many devices. As a result, the dissemination of microfluidic technology-and its impact on society-is in jeopardy. Digital manufacturing (DM) refers to a family of computer-centered processes that integrate digital three-dimensional (3D) designs, automated (additive or subtractive) fabrication, and device testing in order to increase fabrication efficiency. Importantly, DM enables the inexpensive realization of 3D designs that are impossible or very difficult to mold. The adoption of DM by microfluidic engineers has been slow, likely due to concerns over the resolution of the printers and the biocompatibility of the resins. In this article, we review and discuss the various printer types, resolution, biocompatibility issues, DM microfluidic designs, and the bright future ahead for this promising, fertile field.

Human body communication (HBC) has emerged as an alternative to radio wave communication for connecting low power, miniaturized wearable, and implantable devices in, on, and around the human body. HBC uses the human body as the communication channel between on-body devices. Previous studies characterizing the human body channel has reported widely varying channel response much of which has been attributed to the variation in measurement setup. This calls for the development of a unifying bio-physical model of HBC, supported by in-depth analysis and an understanding of the effect of excitation, termination modality on HBC measurements. This paper characterizes the human body channel up to 1 MHz frequency to evaluate it as a medium for the broadband communication. The communication occurs primarily in the electro-quasistatic (EQS) regime at these frequencies through the subcutaneous tissues. A lumped bio-physical model of HBC is developed, supported by experimental validations that provide insight into some of the key discrepancies found in previous studies. Voltage loss measurements are carried out both with an oscilloscope and a miniaturized wearable prototype to capture the effects of non-common ground. Results show that the channel loss is strongly dependent on the termination impedance at the receiver end, with up to 4 dB variation in average loss for different termination in an oscilloscope and an additional 9 dB channel loss with wearable prototype compared to an oscilloscope measurement. The measured channel response with capacitive termination reduces low-frequency loss and allows flat-band transfer function down to 13 KHz, establishing the human body as a broadband communication channel. Analysis of the measured results and the simulation model shows that instruments with 50 Ω input impedance (Vector Network Analyzer, Spectrum Analyzer) provides pessimistic estimation of channel loss at low frequencies. Instead, high impedance and capacitive termination should be used at the receiver end for accurate voltage mode loss measurements of the HBC channel at low frequencies. The experimentally validated bio-physical model shows that capacitive voltage mode termination can improve the low frequency loss by up to 50 dB, which helps broadband communication significantly.

Peripheral blood lymphocytes (PBLs) are mature lymphocytes that circulate in the blood rather than being localized to organs. A reliable label-free collection approach that can viably and appropriately isolate PBLs to establish in vitro culture systems is crucial for basic research and clinical requirements. However, isolation of PBLs from whole blood is difficult, and so the development of a rapid and safe method to perform this task is required. Microfluidic technology offers opportunities that challenge the performance of macroscale methods. In this study, we proposed a simple spiral microfluidic chip for efficient and high-throughput isolation of lymphocytes from a sample with prelysed RBCs. This spiral microfluidic platform does not rely on antibodies or biological markers for labeling cells of interest while isolating lymphocytes but rather enriches B and T lymphocytes through the different physical properties that are intrinsic to lymphocytes and other blood cells. The device was used to achieve high-throughput (~1.3 × 10 5 cells/min) separation of lymphocytes with high viability (>95%). Compared with previous approaches, our device provided rapid, label-free, high-throughput, and safe lymphocyte separation.

Objective: Prosthetic electrical stimulation delivered to the vestibular nerve could provide therapy for people suffering from bilateral vestibular dysfunction. Common encoding methods use pulse-frequency modulation (PFM) to stimulate the semicircular canals of the vestibular system. We previously showed that delivery of ionic direct current (iDC) can also modulate the vestibular system. In this study, we compare the dynamic range of head velocity encoding from iDC modulation to that of PFM controls., Methods: Gentamicin-treated wild-type chinchillas were implanted with microcatheter tubes that delivered ionic current to the left ear vestibular canals and stimulated with steps of anodic/cathodic iDC or PFM. Evoked vestibulo-ocular reflex eye velocity was used to compare PFM and iDC vestibular modulation., Results: Cathodic iDC steps effectively elicited eye rotations consistent with an increased firing rate of the implanted semicircular canal afferents. Anodic iDC current steps elicited eye rotations in the opposite direction that, when paired with an adapted cathodic offset, increased the dynamic range of eye rotation velocities in comparison to PFM controls., Conclusion: Our results suggest that iDC modulation can effectively modulate the vestibular system across a functional range of rotation vectors and velocities, with a potential benefit over a PFM stimulation paradigm., Significance: In conjunction with a safe dc delivery system, iDC modulation could potentially increase the range of simulated head rotation velocities available to neuroelectric vestibular prostheses.

Objective: In teleoperated robot-assisted tasks, the user interacts with manipulators to finely control remote tools. Manipulation of robotic devices, characterized by specific kinematic and dynamic proprieties, is a complex task for the human sensorimotor system due to the inherent biomechanical and neuronal redundancies that characterize the human arm and its control. We investigate how master devices with different kinematics structures and how different task constraints influence users capabilities in exploiting arm redundancy., Methods: A virtual teleoperation workbench was designed and the arm kinematics of seven users was acquired during the execution of two planar virtual tasks, involving either the control of position only or position-orientation of a tool. Using the uncontrolled manifold analysis of arm joint variability, we estimated the logarithmic ratio between the task irrelevant and the task relevant manifolds ( R v )., Results: The R v values obtained in the position-orientation task were higher than in the position only task, while no differences were found between the master devices. A modulation of R v was found through the execution of the position task and a positive correlation was found between task performance and redundancy exploitation., Conclusion: Users exploited additional portions of arm redundancy when dealing with the tool orientation. The R v modulation seems influenced by the task constraints and by the users possibility of reconfiguring the arm position., Significance: This paper advances the general understanding of the exploitation of arm redundancy in complex tasks, and can improve the development of future robotic devices.

Background: There exists a growing need for a cost-effective, reliable, and portable pulsation simulator that can generate a wide variety of pulses depending on age and cardiovascular disease. For constructing compact pulsation simulator, this study proposes to use a pneumatic actuator based on cam-follower mechanism controlled by a DC motor. The simulator is intended to generate pulse waveforms for a range of pulse pressures and heart beats that are realistic to human blood pulsations., Methods: This study first performed in vivo testing of a healthy young man to collect his pulse waveforms using a robotic tonometry system (RTS). Based on the collected data a representative human radial pulse waveform is obtained by conducting a mathematical analysis. This standard pulse waveform is then used to design the cam profile. Upon fabrication of the cam, the pulsatile simulator, consisting of the pulse pressure generating component, pressure and heart rate adjusting units, and the real-time pulse display, is constructed. Using the RTS, a series of testing was performed on the prototype to collect its pulse waveforms by varying the pressure levels and heart rates. Followed by the testing, the pulse waveforms generated by the prototype are compared with the representative, in vivo, pulse waveform., Results: The radial Augmentation Index analysis results show that the percent error between the simulator data and human pulse profiles is sufficiently small, indicating that the first two peak pressures agree well. Moreover, the phase analysis results show that the phase delay errors between the pulse waveforms of the prototype and the representative waveform are adequately small, confirming that the prototype simulator is capable of simulating realistic human pulse waveforms., Conclusions: This study demonstrated that a very accurate radial pressure waveform can be reproduced using the cam-based simulator. It can be concluded that the same testing and design methods can be used to generate pulse waveforms for other age groups or any target pulse waveforms. Such a simulator can make a contribution to the research efforts, such as development of wearable pressure sensors, standardization of pulse diagnosis in oriental medicine, and training medical professionals for pulse diagnosis techniques.

In the past decades, wireless milli and micro devices have been incorporated into medical procedures as a way to reduce invasiveness. However, the commercially available methods still consist of passive locomotion devices, which is a limiting factor to the development of minimally invasive devices. Magnetism simplifies the design of small-scale devices since it does not require on-board batteries or motors. This review presents locomotion techniques and features using magnetic actuation towards minimally invasive procedures. Requirements, advantages, and challenges are discussed.

In this paper, we investigate the feasibility of harvesting energy from cardiac valvular perturbations to self-power a wireless sonomicrometry sensor. Compared to the previous studies involving piezoelectric patches or encasings attached to the cardiac or aortic surface, the proposed study explores the use of piezoelectric sutures that can be implanted in proximity to the valvular regions, where non-linear valvular perturbations could be exploited for self-powering. Using an ovine animal model, the magnitude of valvular perturbations are first measured using an array of sonomicrometry crystals implanted around the tricuspid valve. These measurements were then used to estimate the levels of electrical energy that could be harvested using a simplified piezoelectric suture model. These results were revalidated across seven different animals, before and after valvular regurgitation was induced. Our study shows that power harvested from different annular planes of the tricuspid valve (before and after regurgitation) could range from nano-watts to milli-watts, with the maximum power harvested from the leaflet plane. We believe that these results could be useful for determining optimal surgical placement of wireless and self-powered sonomicrometry sensor, which in turn could be used for investigating the pathophysiology of ischemic regurgitation.

Human neuroblastoma cells, SH-SY5Y, are often used as a neuronal model to study Parkinson's disease and dopamine release in the substantia nigra, a midbrain region that plays an important role in motor control. Using amperometric single-cell recordings of single vesicle release events, we can study molecular manipulations of dopamine release and gain a better understanding of the mechanisms of neurological diseases. However, single-cell analysis of neurotransmitter release using traditional techniques yields results with very low throughput. In this paper, we will discuss a monolithically-integrated CMOS sensor array that has the low-noise performance, fine temporal resolution, and 1024 parallel channels to observe dopamine release from many single cells with single-vesicle resolution. The measured noise levels of our transimpedance amplifier are 415, 622, and 1083 [Formula: see text], at sampling rates of 10, 20, and 30 kS/s, respectively, without additional filtering. Post-CMOS processing is used to monolithically integrate 1024 on-chip gold electrodes, with an individual electrode size of 15 μm × 15 μm, directly on 1024 transimpedance amplifiers in the CMOS device. SU-8 traps are fabricated on individual electrodes to allow single cells to be interrogated and to reject multicellular clumps. Dopamine secretions from 76 cells are simultaneously recorded by loading the CMOS device with SH-SY5Y cells. In the 42-s measurement, a total of 7147 single vesicle release events are monitored. The study shows the CMOS device's capability of recording vesicle secretion at a single-cell level, with 1024 parallel channels, to provide detailed information on the dynamics of dopamine release at a single-vesicle resolution.

In this minireview, we summarize the recent development of liquid-infused slippery surfaces (LISS) for biomedical applications. The selected topics are divided into two parts: the material designs and emerging strategies to fabricate slippery surface, and their applications with strong and direct relevance to biomedical areas including antibiofouling, antithrombosis, medical device coatings and surface enhanced/assisted detection. We also describe the most critical directions in need of development to adapt this new approach to biomedical use., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: Motivated by the fact that palpation skills are challenging to learn and teach, particularly during Digital Rectal Examinations (DRE), and the lack of understanding of what constitutes adequate performance, we present a visualisation and analysis system that uses small position and pressure sensors located on the examining finger, allowing the quantitative analysis of duration, steps and pressure applied., Methods: The system is first described, followed by an experimental study of twenty experts from four clinical specialties performing ten DREs each on a benchtop model using the proposed system. Analysis of the constitutive steps was conducted to improve understanding of the examination. A Markov model representing executed tasks and analysis of pressure applied is also introduced., Results: The proposed system successfully allowed the visualisation and analysis during the experimental study. General Practitioners and Nurses were found to execute more tasks compared to Urologists and Colorectal Surgeons. Urologists executed the least number of tasks and were the most consistent group compared to others., Conclusion: The ability to "see through" allowed us to better characterise the performance of experts when conducting a DRE on a benchtop model, comparing the performance of relevant specialties, and studying executed tasks and the pressure applied. The Markov model presented summarises task execution of experts and could be used to compare performance of novices against that of experts., Significance: This approach allows for the analysis of performance based on continuous sensor data recording that can be easily extended to real subjects and other types of physical examinations.

Cancer has become the most prevalent cause of deaths, placing a huge economic and healthcare burden worldwide. Nanoparticles (NPs), as a key component of nanomedicine, provide alternative options for promoting the efficacy of cancer therapy. Current conventional cancer models have limitations in predicting the effects of various cancer treatments. To overcome these limitations, biomimetic and novel 'tumor-on-a-chip' platforms have emerged with other innovative biomedical engineering methods that enable the evaluation of NP-based cancer therapy. In this review, we first describe cancer models for evaluation of NP-based cancer therapy techniques, and then present the latest advances in 'tumor-on-a-chip' platforms that can potentially facilitate clinical translation of NP-based cancer therapies.

Innovative researchers are employing flexible, rather than rigid materials in combination with new design approaches as part of the emerging field of biomedical soft robotics. The idea is to generate tools that conform to and interact with the human body in a much more natural and lightweight way, providing better treatment options for clinicians and translating into better outcomes for patients.