Retinal Prostheses: Engineering and Clinical Perspectives for Vision Restoration.

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.

Automatic system for high-throughput and high-sensitivity diagnosis of SARS-CoV-2.

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.

Tailoring Materials with Specific Wettability in Biomedical Engineering.

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.

Responding to a Pandemic: COVID-19 Projects in the Malone Center.

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.

Innovation at a Children's Hospital: Personal Protective Equipment Efforts During the Pandemic.

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.

A self-sustainable wearable multi-modular E-textile bioenergy microgrid system.

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.

Solving Unmet Needs With Innovative Pediatric Medical Devices.

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.

Surface Tension-Assisted Additive Manufacturing of Tubular, Multicomponent Biomaterials.

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.

Miniaturised Wireless Power Transfer Systems for Neurostimulation: A Review.

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.

Design of a Low Noise Bio-Potential Recorder With High Tolerance to Power-Line Interference Under 0.8 V Power Supply.

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 Vpp, 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.

A self-powered analog sensor-data-logging device based on Fowler-Nordheim dynamical systems.

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.

A Forensic Disassembly of the BIS Monitor.

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.

Recursive Threshold Logic-A Bioinspired Reconfigurable Dynamic Logic System With Crossbar Arrays.

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 RON. 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.

Adaptive self-healing electronic epineurium for chronic bidirectional neural interfaces.

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.

Finding Alternate Resources for Completing Senior Design Projects During the Current COVID-19 Pandemic.

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.

Oriented immobilization of basic fibroblast growth factor: Bioengineered surface design for the expansion of human mesenchymal stromal cells.

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 ß-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.

A 0.3V 10b 3MS/s SAR ADC With Comparator Calibration and Kickback Noise Reduction for Biomedical Applications.

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.

Real-time non-contact cellular imaging and angiography of human cornea and limbus with common-path full-field/SD OCT.

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.

Ultraflexible and transparent electroluminescent skin for real-time and super-resolution imaging of pressure distribution.

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.