Band-Selection of a Portal LED-Induced Autofluorescence Multispectral Imager to Improve Oral Cancer Detection.

This aim of this study was to find effective spectral bands for the early detection of oral cancer. The spectral images in different bands were acquired using a self-made portable light-emitting diode (LED)-induced autofluorescence multispectral imager equipped with 365 and 405 nm excitation LEDs, emission filters with center wavelengths of 470, 505, 525, 532, 550, 595, 632, 635, and 695 nm, and a color image sensor. The spectral images of 218 healthy points in 62 healthy participants and 218 tumor points in 62 patients were collected in the ex vivo trials at China Medical University Hospital. These ex vivo trials were similar to in vivo because the spectral images of anatomical specimens were immediately acquired after the on-site tumor resection. The spectral images associated with red, blue, and green filters correlated with and without nine emission filters were quantized by four computing method, including summated intensity, the highest number of the intensity level, entropy, and fractional dimension. The combination of four computing methods, two excitation light sources with two intensities, and 30 spectral bands in three experiments formed 264 classifiers. The quantized data in each classifier was divided into two groups: one was the training group optimizing the threshold of the quantized data, and the other was validating group tested under this optimized threshold. The sensitivity, specificity, and accuracy of each classifier were derived from these tests. To identify the influential spectral bands based on the area under the region and the testing results, a single-layer network learning process was used. This was compared to conventional rules-based approaches to show its superior and faster performance. Consequently, four emission filters with the center wavelengths of 470, 505, 532, and 550 nm were selected by an AI-based method and verified using a rule-based approach. The sensitivities of six classifiers using these emission filters were more significant than 90%. The average sensitivity of these was about 96.15%, the average specificity was approximately 69.55%, and the average accuracy was about 82.85%.

A High-Efficiency Driver Circuit for a Gas-Sensor Microheater Based on a Switch-Mode DC-to-DC Converter.

Low power consumption is one of the critical factors for successful Internet of Things (IoT) applications. In such applications, gas sensors have become a main source of power consumption because energy conversion efficiency of the microheater is relative over a wide range of operating temperatures. To improve the energy-conversion efficiency of gas-sensor microheaters, this paper proposes integrated switch-mode DC-to-DC power converter technology which we compare with traditional driving methods such as pulse-width modulation and the linear mode. The results indicate that energy conversion efficiency with this proposed method remains over 90% from 150 °C to 400 °C when using a 3.0, 4.2 and 5.0 V power supply. Energy-conversion efficiency increases by 1-74% compared with results obtained using the traditional driving methods, and the sensing film still detects alcohol and toluene at 200 °C and 280 °C, respectively, with high energy conversion efficiency. These results show that the proposed method is useful and should be further developed to drive gas-sensor microheaters, and then integrated into the circuits of the complementary metal-oxide-semiconductor micro electro mechanical systems (CMOS-MEMS).

A Wirelessly Powered Smart Contact Lens with Reconfigurable Wide Range and Tunable Sensitivity Sensor Readout Circuitry.

This study presented a wireless smart contact lens system that was composed of a reconfigurable capacitive sensor interface circuitry and wirelessly powered radio-frequency identification (RFID) addressable system for sensor control and data communication. In order to improve compliance and reduce user discomfort, a capacitive sensor was embedded on a soft contact lens of 200 µm thickness using commercially available bio-compatible lens material and a standard manufacturing process. The results indicated that the reconfigurable sensor interface achieved sensitivity and baseline tuning up to 120 pF while consuming only 110 µW power. The range and sensitivity tuning of the readout circuitry ensured a reliable operation with respect to sensor fabrication variations and independent calibration of the sensor baseline for individuals. The on-chip voltage scaling allowed the further extension of the detection range and prevented the implementation of large on-chip elements. The on-lens system enabled the detection of capacitive variation caused by pressure changes in the range of 2.25 to 30 mmHg and hydration level variation from a distance of 1 cm using incident power from an RFID reader at 26.5 dBm.

Effects of Operating Temperature on Droplet Casting of Flexible Polymer/Multi-Walled Carbon Nanotube Composite Gas Sensors.

This study examined the performance of a flexible polymer/multi-walled carbon nanotube (MWCNT) composite sensor array as a function of operating temperature. The response magnitudes of a cost-effective flexible gas sensor array equipped with a heater were measured with respect to five different operating temperatures (room temperature, 40 °C, 50 °C, 60 °C, and 70 °C) via impedance spectrum measurement and sensing response experiments. The selected polymers that were droplet cast to coat a MWCNT conductive layer to form two-layer polymer/MWCNT composite sensing films included ethyl cellulose (EC), polyethylene oxide (PEO), and polyvinylpyrrolidone (PVP). Electrical characterization of impedance, sensing response magnitude, and scanning electron microscope (SEM) morphology of each type of polymer/MWCNT composite film was performed at different operating temperatures. With respect to ethanol, the response magnitude of the sensor decreased with increasing operating temperatures. The results indicated that the higher operating temperature could reduce the response and influence the sensitivity of the polymer/MWCNT gas sensor array. The morphology of polymer/MWCNT composite films revealed that there were changes in the porous film after volatile organic compound (VOC) testing.

A double-sided, single-chip integration scheme using through-silicon-via for neural sensing applications.

We present a new double-sided, single-chip monolithic integration scheme to integrate the CMOS circuits and MEMS structures by using through-silicon-via (TSV). Neural sensing applications were chosen as the implementation example. The proposed heterogeneous device integrates standard 0.18 µm CMOS technology, TSV and neural probe array into a compact single chip device. The neural probe array on the back-side of the chip is connected to the CMOS circuits on the front-side of the chip by using low-parasitic TSVs through the chip. Successful fabrication results and detailed characterization demonstrate the feasibility and performance of the neural probe array, TSV and readout circuitry. The fabricated device is 5 × 5 mm(2) in area, with 16 channels of 150 µm-in-length neural probe array on the back-side, 200 µm-deep TSV through the chip and CMOS circuits on the front-side. Each channel consists of a 5 × 6 probe array, 3 × 14 TSV array and a differential-difference amplifier (DDA) based analog front-end circuitry with 1.8 V supply, 21.88 µW power consumption, 108 dB CMRR and 2.56 µVrms input referred noise. In-vivo long term implantation demonstrated the feasibility of presented integration scheme after 7 and 58 days of implantation. We expect the conceptual realization can be extended for higher density recording array by using the proposed method.

Design and analysis of wearable pupillometer for autonomic neuropathy of diabetic patients.

Diabetes is a familiar disease in modern society. In the early stage of diabetes, symptoms are unobvious, but they usually induce diabetic autonomic neuropathy or, worse, cardiovascular autonomic neuropathy. Pupillometers are effective instruments for observing human pupils. This article presents a novel wearable pupillometer design, without external light artifacts, and an embedded algorithm with blinking elimination, which investigates autonomic neuropathy through recording pupil dynamics triggered by an external sensitive invisible light source. The pupillometer is experimented on 36 healthy subjects and 10 diabetic patients under four different colors (white, red, green, and blue) as well as two different light intensities: 50 and 500 mcd. Ten parameters derived from pupil diameter, pupil response time, and pupil response speed will be evaluated for the healthy subjects and diabetic patients. The results show that three in four parameters related to pupil diameters, one in four related to light intensities, and one in two related to pupil response speed could have significant differences (p<0.05) between healthy subjects and diabetic patients. These parameters obtain over 85% sensitivity, 83% specificity, and 88% accuracy. The pupillometer is proven reliable, effective, portable, and inexpensive for diagnosing diabetes in an early stage.

Research of accommodative microfluctuations caused by visual fatigue based on liquid crystal and laser displays.

Different levels of visual fatigue in the human eye depend on different color-formation methods and image quality. This paper uses the high-frequency component of the spectral power of accommodative microfluctuations as a major objective indicator for analyzing the effects of visual fatigue based on various displays, such as color-formation displays and 3D displays. Also, a questionnaire is used as a subjective indicator. The results are that 3D videos cause greater visual fatigue than 2D videos (p<0.001), the shutter-type 3D display causes visual fatigue more than the polarized type (p=0.012), the display of the time-sharing method causes greater visual fatigue than the spatial-formation method (p=0.008), and there is no significance between various light source modules of displays (p=0.162). In general, people with normal color discrimination have more visual fatigue than those with good color discrimination (p<0.001). Therefore, this paper uses the high-frequency component of accommodative microfluctuations to evaluate the physiological stress or strain by overexerting the visual system, and can compare the level of visual fatigue between various displays.

A wireless and batteryless microsystem with implantable grid electrode/3-dimensional probe array for ECoG and extracellular neural recording in rats.

This paper presents the design and implementation of an integrated wireless microsystem platform that provides the possibility to support versatile implantable neural sensing devices in free laboratory rats. Inductive coupled coils with low dropout regulator design allows true long-term recording without limitation of battery capacity. A 16-channel analog front end chip located on the headstage is designed for high channel account neural signal conditioning with low current consumption and noise. Two types of implantable electrodes including grid electrode and 3D probe array are also presented for brain surface recording and 3D biopotential acquisition in the implanted target volume of tissue. The overall system consumes less than 20 mA with small form factor, 3.9 × 3.9 cm2 mainboard and 1.8 × 3.4 cm2 headstage, is packaged into a backpack for rats. Practical in vivo recordings including auditory response, brain resection tissue and PZT-induced seizures recording demonstrate the correct function of the proposed microsystem. Presented achievements addressed the aforementioned properties by combining MEMS neural sensors, low-power circuit designs and commercial chips into system-level integration.

A low-power bio-potential acquisition system with flexible PDMS dry electrodes for portable ubiquitous healthcare applications.

This work describes a bio-potential acquisition system for portable ubiquitous healthcare applications using flexible polydimethylsiloxane dry electrodes (FPDEs) and a low-power recording circuit. This novel FPDE used Au as the skin contact layer, which was made using a CO2 laser and replica method technology. The FPDE was revised from a commercial bio-potential electrode with a conductive snap using dry electrodes rather than wet electrodes that proposed reliable and robust attachment for the purpose of measurement, and attaching velcro made it wearable on the forearm for bio-potential applications. Furthermore, this study proposes a recording device to store bio-potential signal data and provides portability and low-power consumption for the proposed acquisition system. To acquire differential bio-potentials, such as electrocardiogram (ECG) signals, the proposed recording device includes a low-power front-end acquisition chip fabricated using a complementary metal-oxide-semiconductor (CMOS) process, a commercial microcontroller (MSP430F149), and a secure digital (SD) card for portable healthcare applications. The proposed system can obtain ECG signals efficiently and are comfortable to the skin. The power consumption of the system is about 85 mW for continuous working over a 3 day period with two AA batteries. It can also be used as a compact Holter ECG system.

Dielectrophoretically Assembled SWCNTs Networks on SU-8 Substrate for PEG/SWCNTs Composite Gas Sensor.

This study proposed a SU-8 based gas sensor, integrated with heater and sensing electrodes, to develop a multi-channel gas sensor with PEG/SWCNTs composite films. The impedance of single-walled carbon nanotubes (SWCNTs) on each sensing electrode was well controlled via dielectrophoresis technology. To investigate dielectrophoretic mobility characteristics, the concentric circular sensing electrode has three different spacing between the inner and outer electrodes, including 10 µm, 15 µm, and 20 µm. The electrodes were applied with a 5 MHz AC source with a voltage ranging from 1 Vpp to 5 Vpp. Polyethylene glycol (PEG) was deposited on the gas sensor via drop casting. The fabricated gas sensor was operated at different working temperatures, including 25 °C, 40 °C, 50 °C and 60 °C, to examine the sensing response. The response results revealed that the PEG/SWCNTs composites gas sensor with 60 °C working temperature exhibited the ability to detect 80 ppm ethanol vapor.

Nanosurface design of dental implants for improved cell growth and function.

A strategy was proposed for the topological design of dental implants based on an in vitro survey of optimized nanodot structures. An in vitro survey was performed using nanodot arrays with dot diameters ranging from 10 to 200 nm. MG63 osteoblasts were seeded on nanodot arrays and cultured for 3 days. Cell number, percentage undergoing apoptotic-like cell death, cell adhesion and cytoskeletal organization were evaluated. Nanodots with a diameter of approximately 50 nm enhanced cell number by 44%, minimized apoptotic-like cell death to 2.7%, promoted a 30% increase in microfilament bundles and maximized cell adhesion with a 73% increase in focal adhesions. An enhancement of about 50% in mineralization was observed, determined by von Kossa staining and by Alizarin Red S staining. Therefore, we provide a complete range of nanosurfaces for growing osteoblasts to discriminate their nanoscale environment. Nanodot arrays present an opportunity to positively and negatively modulate cell behavior and maturation. Our results suggest a topological approach which is beneficial for the design of dental implants.

Prism-type holographic optical element design and verification for the blue-light small-form-factor optical pickup head.

This paper presents the prism-type holographic optical element (PT-HOE) design for a small-form-factor (SFF) optical pickup head (OPH). The surface of the PT-HOE was simulated by three steps of optimization and generated by binary optics. Its grating pattern was fabricated on the inclined plane of a microprism by using the standard photolithography and specific dicing procedures. The optical characteristics of the device were verified. Based on the virtual image method, the SFF-OPH with the device was assembled and realized.

Self-assembly of an antireflective moth-like structure using antibody-functionalized nanowires and nanopore arrays.

A novel framework to fabricate moth-like nanopillar arrays was proposed. In this scheme, nanowires were first cross-linked with anti-gold nanoparticle (GNP) antibodies and mixed with the nanopore array pre-deposited by GNP, which was then followed by centrifugation. An optimal success rate of 95% was finally obtained by choosing nanorods with an aspect ratio of 5:1 by modifying with 10 ng mL⁻¹ antibodies, and by inserting them into a pore array pre-deposited with 54.4 µM GNP. The nanopillar arrays thus fabricated showed high levels of antireflective efficiency across a broad wavelength. Here we demonstrate the assembly of nanowires and nanopores into nanopillar arrays by the assistance of antibody-antigen binding. The application of bio-nano-interaction provides an economic, time-saving, and throughput approach to manipulating objects on the nanoscale.

Development of a three dimensional neural sensing device by a stacking method.

This study reports a new stacking method for assembling a 3-D microprobe array. To date, 3-D array structures have usually been assembled with vertical spacers, snap fasteners and a supporting platform. Such methods have achieved 3-D structures but suffer from complex assembly steps, vertical interconnection for 3-D signal transmission, low structure strength and large implantable opening. By applying the proposed stacking method, the previous techniques could be replaced by 2-D wire bonding. In this way, supporting platforms with slots and vertical spacers were no longer needed. Furthermore, ASIC chips can be substituted for the spacers in the stacked arrays to achieve system integration, design flexibility and volume usage efficiency. To avoid overflow of the adhesive fluid during assembly, an anti-overflow design which made use of capillary action force was applied in the stacking method as well. Moreover, presented stacking procedure consumes only 35 minutes in average for a 4 × 4 3-D microprobe array without requiring other specially made assembly tools. To summarize, the advantages of the proposed stacking method for 3-D array assembly include simplified assembly process, high structure strength, smaller opening area and integration ability with active circuits. This stacking assembly technique allows an alternative method to create 3-D structures from planar components.

A power-efficient bio-potential acquisition device with DS-MDE sensors for long-term healthcare monitoring applications.

This work describes a power-efficient bio-potential acquisition device for long-term healthcare applications that is implemented using novel microelectromechanical dry electrodes (MDE) and a low power bio-potential processing chip. Using micromachining technology, an attempt is also made to enhance the sensing reliability and stability by fabricating a diamond-shaped MDE (DS-MDE) that has a satisfactory self-stability capability and superior electric conductivity when attached onto skin without any extra skin tissue injury technology. To acquire differential bio-potentials such as ECG signals, the proposed processing chip fabricated in a standard CMOS process has a high common mode rejection ratio (C.M.R.R.) differential amplifier and a 12-bit analog-to-digital converter (ADC). Use of the proposed system and integrate simple peripheral commercial devices can obtain the ECG signal efficiently without additional skin tissue injury and ensure continuous monitoring more than 70 hours with a 400 mAh battery.

Sensitivity Enhancement of Acetone Gas Sensor using Polyethylene Glycol/Multi-Walled Carbon Nanotubes Composite Sensing Film with Thermal Treatment.

There is a need to develop a chemiresistive gas sensor equipped with a thermostat over a wide area for the sensor, which can protect the sensor from the influence of ambient temperature due to the uniform temperature of the thermostat. In this paper, we demonstrated an acetone gas sensor based on a polyethylene glycol (PEG)/Multi-walled Carbon Nanotubes (MWCNTs) composite film, which was equipped with a thermostat. The sensor was operated at modest working temperatures for sensor sensitivity enhancement. The optimum design of the polyimide-based thermostat with widely uniform thermal distribution was investigated in detail. It was found that the temperature uniformity of the thermostat was achieved using double spiral geometry. The experimental results of the sensor response showed that the PEG/MWCNTs composite film with a moderate working temperature revealed a higher sensitivity than that without thermal treatment. Moreover, the sensing mechanisms of the PEG/MWCNTs composite gas sensor to acetone vapor were studied as well.

Micro objective lens with NA 0.65 for the blue-light small-form-factor optical pickup head.

A micro objective lens with the numerical aperture (NA) of 0.65 and clear aperture of 1.1mm was designed, fabricated, and tested for the proposed blue-light small-form-factor optical pickup head system. It adopted the finite optical conjugation and could be produced by using the glass molding technique. The experimental results verify the optical performance near the diffraction-limited focus spot for the applications of high-density portable optical storage systems.

A Wearable and Wireless Gas-Sensing System Using Flexible Polymer/Multi-Walled Carbon Nanotube Composite Films.

In this study, an integrated flexible gas sensor was developed based on a polymer/multi-walled carbon nanotube composite film by using Bluetooth wireless communication/interface technology. Polymer/multi-walled carbon nanotube composite films were deposited over a polyimide flexible substrate for building a gas sensor array by using a drop-casting method. Sensor response was acquired through interdigitated electrodes and multi-channel sensor boards, which were linked to a Bluetooth wireless transceiver. Additionally, a double-spiral-shaped heater was built into the backside of the gas sensor array as a thermostat to protect it from the influence of ambient temperature. Multi-channel sensing responses were read on a display screen via a smartphone application (app). The advantages of this system include light weight, low cost, highly integrated sensors, wireless telecommunication, and real-time functioning. Thus, it is a promising candidate for deployment in a wearable gas-sensing system used to study air pollution.

Portable LED-induced autofluorescence spectroscopy for oral cancer diagnosis.

Oral cancer is a serious and growing problem in many developing and developed countries. To improve the cancer screening procedure, we developed a portable light-emitting-diode (LED)-induced autofluorescence (LIAF) imager that contains two wavelength LED excitation light sources and multiple filters to capture ex vivo oral tissue autofluorescence images. Compared with conventional means of oral cancer diagnosis, the LIAF imager is a handier, faster, and more highly reliable solution. The compact design with a tiny probe allows clinicians to easily observe autofluorescence images of hidden areas located in concave deep oral cavities. The ex vivo trials conducted in Taiwan present the design and prototype of the portable LIAF imager used for analyzing 31 patients with 221 measurement points. Using the normalized factor of normal tissues under the excitation source with 365 nm of the central wavelength and without the bandpass filter, the results revealed that the sensitivity was larger than 84%, the specificity was not smaller than over 76%, the accuracy was about 80%, and the area under curve of the receiver operating characteristic (ROC) was achieved at about 87%, respectively. The fact shows the LIAF spectroscopy has the possibilities of ex vivo diagnosis and noninvasive examinations for oral cancer.

Ultrahigh-Density 256-Channel Neural Sensing Microsystem Using TSV-Embedded Neural Probes.

Highly integrated neural sensing microsystems are crucial to capture accurate signals for brain function investigations. In this paper, a 256-channel neural sensing microsystem with a sensing area of 5 × 5 mm 2 is presented based on 2.5-D through-silicon-via (TSV) integration. This microsystem composes of dissolvable µ-needles, TSV-embedded µ-probes, 256-channel neural amplifiers, 11-bit area-power-efficient successive approximation register analog-to-digital converters, and serializers. This microsystem can detect 256 electrocorticography and local field potential signals within a small area of 5 mm × 5 mm. The neural amplifier realizes 57.8 dB gain with only 9.8 µW per channel. The overall power of this microsystem is only 3.79 mW for 256-channel neural sensing. A smaller microsystem with dimension of 6 mm × 4 mm has been also implanted into rat brain for somatosensory evoked potentials (SSEPs) recording by using contralateral and ipsilateral electrical stimuli with intensity from 0.2 to 1.0 mA, and successfully observed different SSEPs from left somatosensory cortex of a rat.