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We describe a miniaturized, high-throughput, time-resolved fluorescence lifetime sensor implemented in a 0.13 m CMOS process, combining single photon detection, multiple channel timing and embedded pre-processing of fluorescence lifetime estimations on a single device. Detection is achieved using an array of single photon avalanche diodes (SPADs) arranged in a digital silicon photomultiplier (SiPM) architecture with 400 ps output pulses and a 10% fill-factor. An array of time-to-digital converters (TDCs) with ≈50 ps resolution records up to 8 photon events during each excitation period. Data from the TDC array is then processed using a centre-of-mass method (CMM) pre-calculation to produce fluorescence lifetime estimations in real-time. The sensor is believed to be the first reported implementation of embedded fluorescence lifetime estimation. The system is demonstrated in a practical laboratory environment with measurements of a variety of fluorescent dyes with different single exponential lifetimes, successfully showing the sensor's ability to overcome the classic pile-up limitation of time-correlated single photon counting (TCSPC) by over an order of magnitude.

Tongue drive system (TDS) is a tongue-operated, minimally invasive, unobtrusive, and wireless assistive technology (AT) that infers users' intentions by detecting their voluntary tongue motion and translating them into user-defined commands. Here we present the new intraoral version of the TDS (iTDS), which has been implemented in the form of a dental retainer. The iTDS system-on-a-chip (SoC) features a configurable analog front-end (AFE) that reads the magnetic field variations inside the mouth from four 3-axial magnetoresistive sensors located at four corners of the iTDS printed circuit board (PCB). A dual-band transmitter (Tx) on the same chip operates at 27 and 432 MHz in the Industrial/Scientific/Medical (ISM) band to allow users to switch in the presence of external interference. The Tx streams the digitized samples to a custom-designed TDS universal interface, built from commercial off-the-shelf (COTS) components, which delivers the iTDS data to other devices such as smartphones, personal computers (PC), and powered wheelchairs (PWC). Another key block on the iTDS SoC is the power management integrated circuit (PMIC), which provides individually regulated and duty-cycled 1.8 V supplies for sensors, AFE, Tx, and digital control blocks. The PMIC also charges a 50 mAh Li-ion battery with constant current up to 4.2 V, and recovers data and clock to update its configuration register through a 13.56 MHz inductive link. The iTDS SoC has been implemented in a 0.5-μm standard CMOS process and consumes 3.7 mW on average.

Bioartificial livers (BALs) are bioreactors containing liver cells that provide extracorporeal liver support to liver-failure patients. Theoretically, the plasma perfusion flow rate through a BAL is an important determinant of its functionality. Low flow rates can limit functionality due to limited substrate availability, and high flow rates can induce cell damage. This hypothesis was tested by perfusing the AMC-BAL loaded with the liver cell line HepaRG at four different medium flow rates (0.3, 1.5, 5, and 10 mL/min). Hepatic functions ammonia elimination, urea production, lactate consumption, and 6β-hydroxylation of testosterone showed 2-20-fold higher rates at 5 mL/min compared to 0.3 mL/min, while cell damage remained stable. However, at 10 mL/min cell damage was twofold higher, and maximal hepatic functionality was not changed, except for an increase in lactate elimination. On the other hand, only a low flow rate of 0.3 mL/min allowed for an accurate measurement of the ammonia and lactate mass balance across the bioreactor, which is useful for monitoring the BAL's condition during treatment. These results show that (1) the functionality of a BAL highly depends on the perfusion rate; (2) there is a universal optimal flow rate based on various function and cell damage parameters (5 mL/min for HepaRG-BAL); and (3) in the current set-up the mass balance of substrate, metabolite, or cell damage markers between in-and out-flow of the bioreactor can only be determined at a suboptimal, low, perfusion rate (0.3 mL/min for HepaRG-BAL)., (Copyright © 2012 Wiley Periodicals, Inc.)

A wirelessly powered and controlled implantable device capable of locomotion in a fluid medium is presented. Two scalable low-power propulsion methods are described that achieve roughly an order of magnitude better performance than existing methods in terms of thrust conversion efficiency. The wireless prototype occupies 0.6 mm × 1 mm in 65 nm CMOS with an external 2 mm × 2 mm receive antenna. The IC consists of a matching network, a rectifier, a bandgap reference, a regulator, a demodulator, a digital controller, and high-current drivers that interface directly with the propulsion system. It receives 500 μW from a 2 W 1.86 GHz power signal at a distance of 5 cm. Asynchronous pulse-width modulation on the carrier allows for data rates from 2.5-25 Mbps with energy efficiency of 0.5 pJ/b at 10 Mbps. The received data configures the propulsion system drivers, which are capable of driving up to 2 mA at 0.2 V and can achieve speed of 0.53 cm/sec in a 0.06 T magnetic field.

This paper presents analysis and design of a radio frequency power and data link for a novel Bone Conduction Implant (BCI) system. Patients with conductive and mixed hearing loss and single-sided deafness can be rehabilitated by bone-anchored hearing aids (BAHA). Whereas the conventional hearing aids transmit sound to the tympanic membrane via air conduction, the BAHA transmits sound via vibrations through the skull directly to the cochlea. It uses a titanium screw that penetrates the skin and needs life-long daily care; it may cause skin infection and redness. The BCI is developed as an alternative to the percutaneous BAHA since it leaves the skin intact. The BCI comprises an external audio processor with a transmitter coil and an implanted unit called the bridging bone conductor with a receiver coil. Using amplitude modulation of the Class-E power amplifier that drives the inductive link, the sound signal is transmitted to the implant through the intact skin. It was found that the BCI can generate enough output force level for candidate patients. Maximum power output of the BCI was designed to occur at 5-mm skin thickness and the variability was within 1.5 dB for 1-8-mm skin thickness variations.

Congenital pulmonary hypoplasia is a devastating condition affecting fetal and newborn pulmonary physiology, resulting in great morbidity and mortality. The fetal lung develops in a fluid-filled environment. In this work, we describe a novel, implantable pressure sensing and recording device which we use to study the pressures present in the fetal pulmonary tree throughout gestation. The system achieves 0.18 cm H2O resolution and can record for twenty one days continuously at 256 Hz. Sample tracings of in vivo fetal lamb recordings are shown.

We have designed, built and tested an anthropomorphic-scale surrogate spinal canal, for use in preliminary evaluations of the performance characteristics of a novel intradural spinal cord stimulator. The surrogate employs a silicone mock spinal cord with semi-major and semi-minor diameters of 10 and 6 mm, respectively, commensurate with those of actual thoracic-level spinal cord. The axial restoring force provided by the 300 µm thick silicone denticulate ligament constructs on the mock cord is ~ 0.32 N mm(-1) over a 1.5 mm range of displacement, which is within a factor of 2 of that measured by others in human cadaver specimens. Examples of testing protocols of prototype intradural stimulators that employ this device are discussed.

We report an analog front-end prototype designed in 0.25 μm CMOS process for hybrid integration into 3-D neural recording microsystems. For scaling towards massive parallel neural recording, the prototype has investigated some critical circuit challenges in power, area, interface, and modularity. We achieved extremely low power consumption of 4 μW/channel, optimized energy efficiency using moderate inversion in low-noise amplifiers (K of 5.98 × 10⁸ or NEF of 2.9), and minimized asynchronous interface (only 2 per 16 channels) for command and data capturing. We also implemented adaptable operations including programmable-gain amplification, power-scalable sampling (up to 50 kS/s/channel), wide configuration range (9-bit) for programmable gain and bandwidth, and 5-bit site selection capability (selecting 16 out of 128 sites). The implemented front-end module has achieved a reduction in noise-energy-area product by a factor of 5-25 times as compared to the state-of-the-art analog front-end approaches reported to date.

Wireless power and data transmission have created promising prospects in biomedical research by enabling perpetual data acquisition and stimulation systems. We present a work in progress towards such a system, called the EnerCage, equipped with scalable arrays of overlapping planar spiral coils (PSC) and 3-axis magnetic sensors for focused wireless power transmission to randomly moving targets, such as small freely behaving animal subjects. The EnerCage system includes a stationary unit for 3D non-line-of-sight localization and inductive power transmission through a geometrically optimized PSC array. The localization algorithm compares the magnetic sensor outputs with a threshold to activate a PSC. All PSCs are optimized based on the worst-case misalignment, considering parasitics from the overlapping and adjacent PSCs. EnerCage also has a mobile unit attached to or implanted in the subject's body, which includes a permanent magnetic tracer for localization and back telemetry circuit for efficient closed-loop inductive power regulation. The EnerCage system is designed to enable long-term electrophysiology experiments on freely behaving small animal subjects in large experimental arenas without requiring them to carry bulky batteries. A prototype of the EnerCage system with five PSCs and five magnetic sensors achieved power transfer efficiency (PTE) of 19.6% at the worst-case horizontal misalignment of 49.1 mm (√1/3 of the PSC radius) and coupling distance of 78 mm with a mobile unit coil, 20 mm in radius. The closed-loop power management mechanism maintains the mobile unit received power at 20 mW despite misalignments, tilting, and distance variations up to a maximum operating height of 120 mm (PTE = 5%).

This paper presents a low power switchable current mode driver/receiver I/O pair for high speed serial transmission of asynchronous address event representation (AER) information. The sparse nature of AER packets (also called events) allows driver/receiver bias currents to be switched off to save power. The on/off times must be lower than the bit time to minimize the latency introduced by the switching mechanism. Using this technique, the link power consumption can be scaled down with the event rate without compromising the maximum system throughput. The proposed technique has been implemented on a typical push/pull low voltage differential signaling (LVDS) circuit, but it can easily be extended to other widely used current mode standards, such as current mode logic (CML) or low-voltage positive emitter-coupled logic (LVPECL). A proof of concept prototype has been fabricated in 0.35 μm CMOS incorporating the proposed driver/receiver pair along with a previously reported switchable serializer/deserializer scheme. At a 500 Mbps bit rate, the maximum event rate is 11 Mevent/s for 32-bit events. In this situation, current consumption is 7.5 mA and 9.6 mA for the driver and receiver, respectively, while differential voltage amplitude is ±300 mV. However, if event rate is lower than 20-30 Kevent/s, current consumption has a floor of 270 μA for the driver and 570 μA for the receiver. The measured ON/OFF switching times are in the order of 1 ns. The serial link could be operated at up to 710 Mbps bit rate, resulting in a maximum 32-bit event rate of 15 Mevent/s . This is the same peak event rate as that obtained with the same SerDes circuits and a non-switched driver/receiver pair.

Monitoring blood flow rate inside prosthetic vascular grafts enables an early detection of the graft degradation, followed by the timely intervention and prevention of the graft failure. This paper presents an inductively powered implantable blood flow sensor microsystem with bidirectional telemetry. The microsystem integrates silicon nanowire (SiNW) sensors with tunable piezoresistivity, an ultralow-power application-specific integrated circuit (ASIC), and two miniature coils that are coupled with a larger coil in an external monitoring unit to form a passive wireless link. Operating at 13.56-MHz carrier frequency, the implantable microsystem receives power and command from the external unit and backscatters digitized sensor readout through the coupling coils. The ASIC fabricated in 0.18-μm CMOS process occupies an active area of 1.5 × 1.78 mm (2) and consumes 21.6 μW only. The sensors based on the SiNW and diaphragm structure provide a gauge factor higher than 300 when a small negative tuning voltage (-0.5-0 V) is applied. The measured performance of the pressure sensor and ASIC has demonstrated 0.176 mmHg/√Hz sensing resolution.

Many researchers and engineers are busy in their laboratories working on devices that will bring mobility to people who have lost function in the lower body due to an accident, stroke, multiple sclerosis, or other disorders. "Several pretty sophisticated exoskeletons are already on the market now, and they are all similar to each other in terms of technologies, but we're not ready to replace the wheelchair yet," said exoskeleton developer Homayoon Kaz Kazerooni, Ph.D., professor of mechanical engineering at the University of California (UC) at Berkeley. "Eventually, we will have devices that are used by individuals on a daily basis to replace wheelchairs but not with the existing technology. We're at the beginning of a much bigger era in exoskeletons."

Vibrotactile displays can extend the perception capabilities of visually impaired persons. Placing such devices on the head promises easy attachment and detachment without reducing other interaction abilities. However, the effectiveness of head-attached vibrotactile displays has never been thoroughly tested. This paper presents the results obtained from experiments with 22 subjects equipped with a display containing 12 coin-type motors equally spaced in a horizontal plane around the upper head region. Our display allowed single- as well as multimotor activation with up to six simultaneously active motors. We identified the minimum and comfort strength of vibrotactile stimulation, and measured the precision in perceiving the accurate number of active motors as well as the precision in localizing the stimuli on the head. While subjects identified the correct number of active motors in 94% of the cases when presented with only one active motor, this precision dropped to 40% for two and down to 5% for five simultaneously active motors. This strongly suggests to avoid multipoint stimulation even though the precision of localizing a position of a stimulus on the head is barely affected by the number of simultaneously active motors. Localization precision, however, varied significantly with the region of the head suggesting that the most front and back regions of the head should be avoided if high precision is required.

Wireless power transfer is commonly realized by means of near-field inductive coupling and is critical to many existing and emerging applications in biomedical engineering. This paper presents a closed form analytical solution for the optimum load that achieves the maximum possible power efficiency under arbitrary input impedance conditions based on the general two-port parameters of the network. The two-port approach allows one to predict the power transfer efficiency at any frequency, any type of coil geometry and through any type of media surrounding the coils. Moreover, the results are applicable to any form of passive power transfer such as provided by inductive or capacitive coupling. Our results generalize several well-known special cases. The formulation allows the design of an optimized wireless power transfer link through biological media using readily available EM simulation software. The proposed method effectively decouples the design of the inductive coupling two-port from the problem of loading and power amplifier design. Several case studies are provided for typical applications.

Deep tissue injury (DTI) is a life-threatening type of pressure ulcer which initiates subdermally with muscle necrosis at weight-bearing anatomical locations, where localized elevated tissue strains exist. Though it has been suggested that excessive sustained soft tissue strains might compromise cell viability, which then initiates the DTI, there is no experimental evidence to describe how specifically such a process might take place. Here, we experimentally test the hypothesis that macroscopic tissue deformations translated to cell-level deformations and in particular, to localized tensile strains in the plasma membrane (PM) of cells, increase the permeability of the PM which could disrupt vital transport processes. In order to determine whether PM permeability changes can occur due to static stretching of cells we measured the uptake of fluorescein isothiocyanate (FITC)-labeled Dextran (molecular weight = 4 kDa) by deformed vs. undeformed myoblasts, using a fluorescence-activated cell sorting (FACS) method. These PM permeability changes were then correlated with tensile strains in the PM which correspond to the levels of substrate tensile strain (STS) that were applied in the experiments. The PM strains were evaluated by means of confocal-microscopy-based cell-specific finite element (FE) modeling. The FACS studies demonstrated a statistically significant rise in the uptake of the FITC-labeled Dextran with increasing STS levels in the STS ≤ 12% domain, which thereby indicates a rise in the permeability of the PM of the myoblasts with the extent of the applied cellular deformation. The cell-specific FE modeling simulating the experiments further demonstrated that applying average PM tensile strains which exceed 3%, or, applying peak PM tensile strains over 9%, substantially increases the permeability of the PM of myoblasts to the Dextran. Moreover, the permeability of the PM grew rapidly with any further increase in PM strains, though there were no significant changes in the uptake above average and peak PM tensile strain values of 9 and 26%, respectively. These results provide an experimental basis for studying the theory that cell-level deformation-diffusion relationships may be involved in determining the tolerance of soft tissues to sustained mechanical loading, as relevant to the etiology of DTI.

To introduce bio- and micro-technologies into general undergraduate thermal-fluids classes, a hands-on interdisciplinary in-class demonstration is described that juxtaposes classical pressure loss pipe flow experiments against a modern micro-characterization technique, AFM profilometry. Both approaches measure surface roughness and can segue into classroom discussions related to material selection and design of bio-medical devices to handle biological fluids such as blood. Appealing to the range of engineering students populating a general thermal-fluids course, a variety of pipe/hose/tube materials representing a spectrum of disciplines can be tested using both techniques. This in-class demonstration relies on technical content already available in standard thermal-fluids textbooks, provides experimental juxtaposition between classical and micro-technology-enabled approaches to the same experiment, and can be taught by personnel with no specialized micro- or bio-technology expertise.

Optical tweezers which enables to trap micron to nanometer sized objects by radiation pressure force is utilized for manipulation of particles under a microscope and for measurement of forces between biomolecules. Weak force of optical tweezers causes some limitations such as particle adhesion or steric barrier like lipid membrane in a cell prevent further movement of objects. For biomedical applications we need to overcome these difficulties. We have developed a technique to exert strong instantaneous force by use of a pulse laser beam and to assist conventional optical tweezers. A pulse laser beam has huge instantaneous laser power of more than 1000 times as strong as a conventional continuous-wave laser beam so that the instantaneous force is strong enough to break chemical bonding and molecular force between objects and obstacles. We derive suitable pulse duration for pulse assist of optical tweezers and demonstrate particle manipulation in difficult situations through an experiment of particle removal from sticky surface of glass substrate.

A new set of manufacturing technologies has emerged in the past decades to address market requirements in a customized way and to provide support for research tasks that require prototypes. These new techniques and technologies are usually referred to as rapid prototyping and manufacturing technologies, and they allow prototypes to be produced in a wide range of materials with remarkable precision in a couple of hours. Although they have been rapidly incorporated into product development methodologies, they are still under development, and their applications in bioengineering are continuously evolving. Rapid prototyping and manufacturing technologies can be of assistance in every stage of the development process of novel biodevices, to address various problems that can arise in the devices' interactions with biological systems and the fact that the design decisions must be tested carefully. This review focuses on the main fields of application for rapid prototyping in biomedical engineering and health sciences, as well as on the most remarkable challenges and research trends.

The long-term stability of three clinical electronic portal imaging devices (EPIDs) was studied to determine if longer times between calibrations can be justified. This would make alternatives to flood-field calibration of EPIDs clinically feasible, allowing for more effective use of EPIDs for dosimetry. Images were acquired monthly for each EPID as part of regular clinical quality assurance over a time period of approximately 3 years. The images were analysed to determine (1) the long-term stability of the EPID positioning system, (2) the dose response of the central pixels and (3) the long term stability of each pixel in the imager. The position of the EPID was found to be very repeatable with variations less than 0.3 pixels (0.27 mm) for all imagers (1 standard deviation). The central axis dose response was found to reliably track ion chamber measurements to better than 0.5%. The mean variation in pixel response (1 standard deviation), averaged over all pixels in the EPID, was found to be at most 0.6% for the three EPIDs studied over the entire period. More than 99% of pixels in each EPID showed less than 1% variation. Since the EPID response was found to be very stable over long periods of time, an annual calibration should be sufficient in most cases. More complex dosimetric calibrations should be clinically feasible.

Purpose: The present study introduced the application of cytodetachment technology--the examination of single cell responses to implant material surfaces--to the analysis of implant surfaces with a view to significantly improving upon conventional methods of studying cell interactions with implant surfaces., Materials and Methods: With the new cytodetachment technology, osteoblasts (MG-63) were allowed to attach to a surface, and a nanoprobe was positioned adjacent to the cell. The probe was then moved using a piezo-actuator to completely detach the cell. The detachment forces were calculated and analyzed statistically for three different groups of implant disks: a titanium (Ti) grit-blasted (TiOblast) surface (n = 15, group 1), a fluoride-modified (OsseoSpeed) surface (n = 15, group 2), and a machined titanium surface (n = 6, group 3)., Results: The detachment force was slightly higher for the OsseoSpeed surface than the TiOblast surface, but this difference was not statistically significant. The detachment force on the machined surface was statistically significantly lower than that seen in the other groups, thus supporting the rationale that changes in surface properties would be reflected in the measured detachment force. The OsseoSpeed and TiOblast surfaces demonstrated stronger osteoblast adhesion compared to the machined titanium surface., Conclusions: Within the limitations of this study, this report is a good proof-of-principle for the application of cytodetachment technology to testing implant surfaces. It might represent a new parameter to judge implant surface properties and might have broad applications in product development and research protocols for future implant surfaces.

Developing tools to reproduce and manipulate the cell micro-environment, including the location and shape of cell patterns, is essential for tissue engineering. Parallel to inkjet printing and pressure-operated mechanical extruders, laser-assisted bioprinting (LAB) has emerged as an alternative technology to fabricate two- and three-dimensional tissue engineering products. The objective of this work was to determine laser printing parameters for patterning and assembling nano-hydroxyapatite (nHA) and human osteoprogenitors (HOPs) in two and three dimensions with LAB. The LAB workstation used in this study comprised an infrared laser focused on a quartz ribbon that was coated with a thin absorbing layer of titanium and a layer of bioink. The scanning system, quartz ribbon and substrate were piloted by dedicated software, allowing the sequential printing of different biological materials into two and/or three dimensions. nHA printing material (bioink) was synthesized by chemical precipitation and was characterized prior and following printing using transmission electron microscopy, Fourier transformed infrared spectroscopy and x-ray diffraction. HOP bioink was prepared using a 30 million cells ml(-1) suspension in culture medium and cells were characterized after printing using a Live/Dead assay and osteoblastic phenotype markers (alcaline phosphatase and osteocalcin). The results revealed that LAB allows printing and organizing nHA and HOPs in two and three dimensions. LAB did not alter the physico-chemical properties of nHA, nor the viability, proliferation and phenotype of HOPs over time (up to 15 days). This study has demonstrated that LAB is a relevant method for patterning nHA and osteoblastic cells in 2D, and is also adapted to the bio-fabrication of 3D composite materials.

Unlabelled: Abstract Background and Purpose: The Single Port Instrument Delivery Extended Reach (SPIDER) surgical system was developed for true continuous instrument triangulation during laparoendoscopic single site (LESS) surgery. We present our initial preclinical experience with the SPIDER surgical system during renal surgery., Material and Methods: Bilateral laparoscopic nephrectomies were performed in a live adult porcine animal model using the SPIDER device. A standard surgical approach was used via direct video guidance., Results: The procedure was successfully performed without surgical error or complication. The SPIDER system proved easy to use with only a minimal learning curve. Intracorporeal surgical knots were tied without difficulty using this single site system., Conclusions: Our initial experience with the SPIDER surgical system during renal surgery is promising. SPIDER allows for true single port instrument triangulation offering a superior operative experience to currently available LESS surgical systems.

In human motion analysis, in situ calibration of the force plate is necessary to improve the accuracy of the measured ground reaction force (GRF) and center of pressure (COP). Few existing devices are capable of both static and dynamic calibration of the usually non-linear GRF and COP errors, while are also easy to move and/or set up without damaging the building. The current study developed a small device (160 cm × 88 cm × 43 cm) with a mass of 50 kg, equipped with auxiliary wheels and fixing suction pads for rapid deployment and easy set-up. A PC-based controller enabled quick movement and accurate positioning of the applied force to the calibration point. Static calibration at 100 validation points and dynamic calibration of a force plate were performed using the device. After correction by an artificial neural network (ANN) trained with the static data from another 121 points, the mean errors for the GRF were all reduced from a maximum of 0.64% to less than 0.01%, while those for the COP were all reduced from a maximum of about 1.37 mm to less than 0.04 mm. For dynamic calibration, the mean errors for the GRF were reduced from a maximum of 0.46% to less than 0.28%, while those for the COP were reduced from a maximum of 0.95 mm to less than 0.11 mm. The results suggest that the calibration device with the ANN method will be useful for obtaining more accurate GRF and COP measurements in human motion analysis., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: In Nigeria, manual methods of heartbeat monitoring are commonly used which are subject to a number of human errors and problems., Objective: This paper describes the development of a noninvasive EPROM based heartbeat monitor using optical biomedical engineering technique to detect and count the user's heartbeat digitally as well as provide a visual indication of the result obtained., Methods: This design and construction work employed the optical biomedical engineering technique in which tiny subcutaneous blood vessels in any patch of skin preferably the fingers furnished with a good supply of blood alternately expand and contract in time with the heartbeat. The optical sensors were planted in a peg which provides firm grip of the finger tip to sense these contraction and expansion processes., Results: The results of the tests carried out on fingers of different individuals at rest showed that the thumb, middle finger and forefinger responded more accurately to the heartbeat measurements taken. The thickness of the individual's fingers contributed greatly to the accuracy of the measurement taken., Conclusion: The EPROM based heartbeat monitor is a very efficient tool for monitoring the heartbeat of patients. However, its efficiency is determined by the thickness of the individual's finger.

The hydraulic resistance R across osteochondral tissue, especially articular cartilage, decreases with degeneration and erosion. Clinically useful measures to quantify and diagnose the extent of cartilage degeneration and efficacy of repair strategies, especially with regard to pressure maintenance, are still developing. The hypothesis of this study was that hydraulic resistance provides a quantitative measure of osteochondral tissue that could be used to evaluate the state of cartilage damage and repair. The aims were to (1) develop a device to measure R in an arthroscopic setting, (2) determine whether the device could detect differences in R for cartilage, an osteochondral defect, and cartilage treated using a hydrogel ex vivo, and (3) determine how quickly such differences could be discerned. The apparent hydraulic resistance of defect samples was ~35% less than intact cartilage controls, while the resistance of hydrogel-filled groups was not statistically different than controls, suggesting some restoration of fluid pressurization in the defect region by the hydrogel. Differences in hydraulic resistance between control and defect groups were apparent after 4 s. The results indicate that the measurement of R is feasible for rapid and quantitative functional assessment of the extent of osteochondral defects and repair. The arthroscopic compatibility of the device demonstrates the potential for this measurement to be made in a clinical setting.

The complex mechanical properties of skin have been the subject of much study in recent years. Several experimental methods developed to measure the mechanical properties of skin in vivo, such as suction or torsion, are unable to measure skin's anisotropic characteristics. An experiment characterising the mechanical properties of in vivo human skin using a novel force-sensitive micro-robot is presented. The micro-robot applied in-plane deformations to the anterior forearm and the posterior upper arm. The behaviour of the skin in each area is highly nonlinear, anisotropic, and viscoelastic. The response of the upper arm skin is very dependent on the orientation of the arm. A finite element model consisting of an Ogden strain energy function and quasi-linear viscoelasticity was developed to simulate the experiments. An orthogonal initial stress field, representing the in vivo skin tension, was used as an additional model parameter. The model simulated the experiments accurately with an error-of-fit of 17.5% for the anterior lower forearm area, 6.5% for the anterior upper forearm and 9.3% for the posterior upper arm. The maximum in vivo tension in each area determined by the model was 6.2 Nm(-1) in the anterior lower forearm, 11.4 Nm(-1) in anterior upper forearm and 5.6 Nm(-1) in the posterior upper arm. The results also show that a finite element model with a neo-Hookean strain energy function cannot simulate the experiments with the same accuracy.

This review is motivated by the growing demand for low-cost, easy-to-use, compact-size yet powerful micro-nanofabrication technology to address emerging challenges of fundamental biology and translational medicine in regular laboratory settings. Recent advancements in the field benefit considerably from rapidly expanding material selections, ranging from inorganics to organics and from nanoparticles to self-assembled molecules. Meanwhile a great number of novel methodologies, employing off-the-shelf consumer electronics, intriguing interfacial phenomena, bottom-up self-assembly principles, etc., have been implemented to transit micro-nanofabrication from a cleanroom environment to a desktop setup. Furthermore, the latest application of micro-nanofabrication to emerging biomedical research will be presented in detail, which includes point-of-care diagnostics, on-chip cell culture as well as bio-manipulation. While significant progresses have been made in the rapidly growing field, both apparent and unrevealed roadblocks will need to be addressed in the future. We conclude this review by offering our perspectives on the current technical challenges and future research opportunities.

The integration of living, human smooth muscle cells in biosynthesized cellulose scaffolds was monitored by nonlinear microscopy toward contractile artificial blood vessels. Combined coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy was applied for studies of the cell interaction with the biopolymer network. CARS microscopy probing CH(2)-groups at 2845 cm(-1) permitted three-dimensional imaging of the cells with high contrast for lipid-rich intracellular structures. SHG microscopy visualized the fibers of the cellulose scaffold, together with a small signal obtained from the cytoplasmic myosin of the muscle cells. From the overlay images we conclude a close interaction between cells and cellulose fibers. We followed the cell migration into the three-dimensional structure, illustrating that while the cells submerge into the scaffold they extrude filopodia on top of the surface. A comparison between compact and porous scaffolds reveals a migration depth of <10 μm for the former, whereas the porous type shows cells further submerged into the cellulose. Thus, the scaffold architecture determines the degree of cell integration. We conclude that the unique ability of nonlinear microscopy to visualize the three-dimensional composition of living, soft matter makes it an ideal instrument within tissue engineering.

A wireless and passive pressure sensor was developed for biomedical applications such as monitoring pressure in an abdominal aortic aneurysm sac after a stenting procedure to detect potential leakage from the stent graft. The sensor, referred to as the magneto-harmonic pressure sensor, was an airtight chamber consisting of a rigid well structure capped with an elastic membrane. A magnetically soft material was placed at the bottom of the well, while a magnetically hard material was attached to the membrane. Under the excitation of a magnetic AC field, the magnetically soft material produced a magnetic field at frequencies higher than the excitation frequency (the higher-order harmonic fields) that can be remotely detected with an external detection system. The pattern of the higher-order harmonic fields was dependent on the magnitude of the magnetic DC field produced by the magnetically hard material. When the ambient pressure varied, the membrane of the sensor deflected, changing the separation distance between the magnetically hard and soft materials. This in turn changed the magnitude of the magnetic DC field, causing a shift in the higher-order harmonic field pattern. This paper describes the design and fabrication of the sensor, and its implementation to mice to evaluate its performance in a biological environment.

The mechanical behavior of human femurs has been described in the literature with regard to torsion and tension but only as independent measurements. However, in this study, human femurs were subjected to torsion to determine if a simultaneous axial tensile load was generated. Fresh frozen human femurs (n=25) were harvested and stripped of soft tissue. Each femur was mounted rigidly in a specially designed test jig and remained at a fixed axial length during all experiments. Femurs were subjected to external and internal rotation applied at a constant angulation rate of 0.1 deg/s to a maximum torque of 12 N m. Applied torque and generated axial tension were monitored simultaneously. Outcome measurements were extracted from torsion-versus-tension graphs. There was a strong relationship between applied torsion and the resulting tension for external rotation tests (torsion/tension ratio=551.7±283.8 mm, R(2)=0.83±0.20, n=25), internal rotation tests (torsion/tension ratio=495.3±233.1 mm, R(2)=0.87±0.17, n=24), left femurs (torsion/tension ratio=542.2±262.4 mm, R(2)=0.88±0.13, n=24), and right femurs (torsion/tension ratio=506.7±260.0 mm, R(2)=0.82±0.22, n=25). No statistically significant differences were found for external versus internal rotation groups or for left versus right femurs when comparing torsion/tension ratios (p=0.85) or R(2) values (p=0.54). A strongly coupled linear relationship between torsion and tension for human femurs was exhibited. This suggests an interplay between these two factors during activities of daily living and injury processes.

A signal processor/compressor dedicated to implantable neural recording microsystems is presented. Signal compression is performed based on Haar wavelet. It is shown in this paper that, compared to other mathematical transforms already used for this purpose, compression of neural signals using this type of wavelet transform can be of almost the same quality, while demanding less circuit complexity and smaller silicon area. Designed in a 0.13-μm standard CMOS process, the 64-channel 8-bit signal processor reported in this paper occupies 113 μm x 110 μm of silicon area. It operates under a 1.8-V supply voltage at a master clock frequency of 3.2 MHz.

On-chip implementation of Hilbert-Huang transform (HHT) has great impact to analyze the non-linear and non-stationary biomedical signals on wearable or implantable sensors for the real-time applications. Cubic spline interpolation (CSI) consumes the most computation in HHT, and is the key component for the HHT processor. In tradition, CSI in HHT is usually performed after the collection of a large window of signals, and the long latency violates the realtime requirement of the applications. In this work, we propose to keep processing the incoming signals on-line with small and overlapped data windows without sacrificing the interpolation accuracy. 58% multiplication and 73% division of CSI are saved after the data reuse between the data windows.

The area of Micro and Nano systems (MNS) focuses on heterogeneous integration of technologies (e.g. electronics, mechanics and biotechnology) and implementation of multiple functionalities (e.g. sensing, processing, communication, energy and actuation) into small systems. A significant amount of MNS activities targets development and testing of systems enabling biomedicine and personal health solutions. Convergence of micro-nano-bio and Information & communication technologies is being leading to enabling innovative solutions e.g. for in-vitro testing and in vivo interaction with the human body for early diagnosis and minimally invasive therapy. Of particular interest are smart wearable systems such as smart textiles aiming at the full integration of sensors/actuators, energy sources, processing and communication within the clothes to enable non-invasive personal health, lifestyle, safety and emergency applications. The paper presents on going major R&D activities on micro-nano-bio systems (MNBS) and wearable systems for pHealth under the European Union R&D Programs, Information and Communication Technologies (ICT) priority; it also identifies gaps and discusses key challenges for the future.

A series of pressurization and tensile loading experiments on mouse carotid arteries is performed with deformation measurements acquired during each experiment using three-dimensional digital image correlation. Using a combination of finite element analysis and a microstructure-based constitutive model to describe the response of biological tissue, the measured surface strains during pressurization, and the average axial strains during tensile loading, an inverse procedure is used to identify the optimal constitutive parameters for the mouse carotid artery. The results demonstrate that surface strain measurements can be combined with computational methods to identify material properties in a vascular tissue. Additional computational studies using the optimal material parameters for the mouse carotid artery are discussed with emphasis on the significance of the qualitative trends observed.