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This paper proposes a method that automatically measures non-invasive blood pressure (BP) based on an auscultatory approach using Korotkoff sounds (K-sounds). There have been methods utilizing K-sounds that were more accurate in general than those using cuff pressure signals only under well-controlled environments, but most were vulnerable to the measurement conditions and to external noise because blood pressure is simply determined based on threshold values in the sound signal. The proposed method enables robust and precise BP measurements by evaluating the probability that each sound pulse is an audible K-sound based on a deep learning using a convolutional neural network (CNN). Instead of classifying sound pulses into two categories, audible K-sounds and others, the proposed CNN model outputs probability values. These values in a Korotkoff cycle are arranged in time order, and the blood pressure is determined. The proposed method was tested with a dataset acquired in practice that occasionally contains considerable noise, which can degrade the performance of the threshold-based methods. The results demonstrate that the proposed method outperforms a previously reported CNN-based classification method using K-sounds. With larger amounts of various types of data, the proposed method can potentially achieve more precise and robust results.

A two-dimensional resistance temperature detector (RTD) array sensor for the measurement of temperature distribution inside a tissue-mimicking material was proposed to validate focused ultrasound (FUS) devices. The fully two-dimensional $10\times10$ RTD array sensor with 1 mm inter-RTD distance was fabricated on the $2.5~ \boldsymbol {\mu } \text{m}$ thick film and placed inside the tissue-mimicking material. The measurement uncertainty for the RTD array was 0.18 K. The temperature distribution inside the phantom caused by a FUS transducer was measured and compared depending on the input power and focal plane. A tissue-mimicking phantom with an implanted RTD array can be applied to validate the performance and safety of both high- and low-intensity focused ultrasound (HIFU and LIFU) devices.

The use of graphene and two-dimensional materials for industrial, scientific, and medical applications has recently received an enormous amount of attention due to their exceptional physicochemical properties. There have been numerous efforts to incorporate these two-dimensional materials into advanced flexible electronics, especially aimed for wearable biomedical applications. Here, recent advances in two-dimensional materials-based flexible electronic sensors for wearable biomedical applications with regard to both materials and devices are presented.

Optical coherence tomography (OCT) is one of imaging technologies to diagnose ophthalmic diseases and to monitor progresses of treatments. Therefore, OCT and OCT-angiography (OCTA) have actively developed in the field of ophthalmology, and retinal phantoms for evaluation of performance of OCT and OCTA also have been studied. In this presentation, we will show methods and results of a retinal phantom that can evaluate the optical performance of OCT and OCTA. The retinal phantom not only mimicked superficial vascular networks more realistically, but also implemented retinal layers with curvature. It consists of two microfluidic channels corresponding to superficial and deep retinal vessels, two multi-layered thin films, and base plate with retinal curvature. Each was attached with oxygen plasma for 1-min and fluorinated ethylene propylene (FEP) tubes was connected to the inlet and outlet holes. We could obtain cross-sectional OCT images and en-face OCTA images using lab-made OCT system.

The retinal imaging system, such as optical coherence tomography (OCT), OCT-angiography (OCTA) and fluorescein angiography (FA), is the important subject for ophthalmic. The use of such equipment continues to increase and retinal phantoms have also been developed to evaluate and modify its performance and image quality. In this presentation, we will show methods and results of a retinal phantom that can evaluate the optical performance of OCT, OCTA and FA. We implemented superficial vascular networks and full retinal layers which has curvature. We could obtain cross-sectional OCT images and en-face OCTA images using lab-made OCT system. In addition, FA image could also be obtained through sodium fluorescein dye injection.

BACKGROUND In a previous study, the modified Marsh and Schnider models respectively showed negatively- and positively-biased predictions in underweight patients. To overcome this drawback, we developed a new pharmacokinetic propofol model-the Choi model-for use in underweight patients. In the present study, we evaluated the predictive performance of the Choi model. METHODS Twenty underweight patients undergoing elective surgery received propofol via TCI using the Choi model. The target effect-site concentrations (Ces) of propofol were 2.5, 3, 3.5, 4, 4.5, and 2 μg/mL. Arterial blood samples were obtained at least 10 minutes after achieving pseudo-steady-state. Predicted propofol concentrations with the modified Marsh, Schnider, and Eleveld pharmacokinetic models were obtained by simulation (Asan pump, version 2.1.3; Bionet Co. Ltd., Seoul, Korea). The predictive performance of each model was assessed by calculation of four parameters: inaccuracy, divergence, bias, and wobble. RESULTS A total of 119 plasma samples were used to determine the predictive performance of the Choi model. Our evaluation showed that the pooled median (95% CI) bias and inaccuracy were 4.0 (-4.2 to 12.2) and 23.9 (17.6-30.3), respectively. The pooled biases and inaccuracies of the modified Marsh, Schnider, and Eleveld models were clinically acceptable. However, the modified Marsh and Eleveld models consistently produced negatively biased predictions in underweight patients. In particular, the Schnider model showed greater inaccuracy at a target Ce ≥ 3 µg/mL. CONCLUSION The new propofol pharmacokinetic model (the Choi model) developed for underweight patient showed adequate performance for clinical use.

A micropillar/microwell chip platform was applied to develop a 3D cell-based high-content screening (HCS) platform. Previously, 3D cell culture in the micropillar/microwell chip platform was only limited to cell viability measurements in a high-throughput manner. However, an HCS system could provide biological and phenotypic information which was very useful to understand complex biological functions and mechanisms of drug actions. To stain 3D cultured cells immobilized with alginate spots, we developed and optimized antibody staining procedures for 3D cultured cells. As a proof of concept, the phospho-EGFR (p-EGFR, a highly expressed receptor protein in cancer), F-actin (a protein of the actin cytoskeleton), and nuclei of 3D cultured cells were stained and analyzed after being treated with 72 different drugs. The p-EGFR inhibition of the drugs was successfully identified in the 3D cultured cells by comparing p-EGFR expression with that of F-actin and the nucleus. The p-EGFR expression levels were also measured by Western blot to verify the chip data.

In this study, we report the first experimental realization of an ultrathin (0.14λ, λ = 1.482 mm means wavelength at 1 MHz in the water medium) subwavelength focusing acoustic lens that can surpass the Rayleigh diffraction limit (0.61λ/NA, NA means numerical aperture). It is termed a Super-Oscillatory Acoustic Lens (SOAL), and it operates in the megasonic range. The SOAL represents an interesting feature allowing the achievement of subwavelength focusing without the need to operate in close proximity to the object to be imaged. The optimal layout of the SOAL is obtained by utilizing a systematic design approach, referred to here as topology optimization. To this end, the optimization formulation is newly defined. The optimized SOAL is fabricated using a photo-etching process and its subwavelength focusing performance is verified experimentally via an acoustic intensity measurement system. From these measurements, we found that the proposed optimized SOAL can achieve superior focusing features with a Full Width at Half Maximum (FWHM) of ~0.40λ/NA ≃ 0.84 mm (for our SOAL, NA = 0.707) with the transmission efficiency of 26.5%.

A thin-film resistance temperature detector (RTD) array is proposed to measure the temperature distribution inside a phantom. HIFU (high-intensity focused ultrasound) is a non-invasive treatment method using focused ultrasound to heat up a localized region, so it is important to measure the temperature distribution without affecting the ultrasonic field and heat conduction. The present 25 µm thick PI (polyimide) film is transparent not only to an ultrasonic field, because its thickness is much smaller than the wavelength of ultrasound, but also to heat conduction, owing to its negligible thermal mass compared to the phantom. A total of 33 RTDs consisting of Pt resistors and interconnection lines were patterned on a PI substrate using MEMS (microelectromechanical systems) technology, and a polymer phantom was fabricated with the film at the center. The expanded uncertainty of the RTDs was 0.8 K. In the experimental study using a 1 MHz HIFU transducer, the maximum temperature inside the phantom was measured as 70.1 °C just after a HIFU excitation of 6.4 W for 180 s. The time responses of the RTDs at different positions also showed the residual heat transfer inside the phantom after HIFU excitation. HIFU results with the phantom showed that a thin-film RTD array can measure the temperature distribution inside a phantom.

A surface flow sensor is needed if turbulent drag force is to be measured over a vehicle, such as a car, a ship, and an airplane. In case of automobile industry, there are no automobile manufacturers which measure surface flow velocity over a car for wind tunnel testing. Instead, they rely on particle image velocimetry (PIV), pressure sensitive paint (PSP), laser Doppler anemometry (LDA), pitot tubes, and tufts to get information regarding the turbulent drag force. Surface flow sensors have not devised yet. This study aims at developing a surface flow sensor for measuring turbulent drag force over a rigid body in a wind tunnel. Two sensing schemes were designed for the fiber-optic distributed sensor and the thermal mass flow sensor. These concepts are introduced in this paper. As the first attempt, a thermal mass flow sensor has been fabricated. It was flush-mounted on the surface of a test section in the wind tunnel to measure the surface flow velocity. The thermal mass flow sensor was operated by either constant current or constant resistance modes. Resistance ratio was changed as the electric current was increased by the constant current mode, while power ratio was saturated as the resistance was increased by the constant resistance mode. Either the resistance ratio or the power ratio was changed with the flow velocity measured by a Pitot tube, located at the center of test section.

We developed an eye phantom that mimic retinal layers and blood vessels to evaluation of retinal OCT-angiography and fundus angiography. The phantom was made of polydimethylsiloxane and titanium dioxide using spin coater and microelectromechanical system (MEMS) technology.

Background Inaccuracies associated with target-controlled infusion (TCI) delivery systems are attributable to both software and hardware issues, as well as pharmacokinetic variability. However, little is known about the inaccuracy of the syringe pump operating in TCI mode. This study aimed to evaluate the accuracy of the TCI pump based on international standards. Methods A test apparatus for accuracy evaluation of a syringe pump (PION TCI®, Bionet Co. Ltd.) was designed to apply the gravimetric method. Pump accuracy was evaluated in terms of deviation defined by the following equation: infusion rate deviation (%) = (Ratemea - Rateest ) / Rateest × 100, where Ratemea is the infusion rate (ml/h) as measured by the gravimetric system, and Rateest is the infusion rate (ml/h) as estimated by the pump. An infusion rate representing TCI mode was determined from previous clinical trial data which evaluated the predictive performance of the pharmacokinetic model. The PION TCI pump used in that clinical trial was used to evaluate accuracy of the syringe pump. The distribution of infusion rates obtained from the clinical trial was calculated, and the median value of the distribution was determined as the representative value. Results The representative infusion rate representing TCI mode was 31 ml/h, at which the infusion rate deviation was 4.5 ± 1.6%. Conclusions The inaccuracy of the syringe pump contributing to TCI system inaccuracy is insignificant.

Date Presented 04/13/21 It is important to monitor the status of motor development in children. Standardization for comparing pre- and postintervention results for children with suspected developmental coordination disease should also be implemented. In this study, a digital device for testing manual dexterity was developed, and its accuracy was verified. This device will be used to provide data for early screening and intervention program planning for infants at risk of delayed motor development or disability. Primary Author and Speaker: Yeshin Woo Contributing Authors: Allison J. L'Hotta, Anna H. Bauer, Chih-Hung Chang, Taniya Easow Varughese, Regina A. Abel, Allison King

We present a clinical device for simple, rapid, and viable isolation of circulating tumor cells (CTCs) from cancer patient bloods. In spite of the clinical importance of CTCs, the lack of easy and non-biased isolation methods is a big hurdle for implementing CTC into clinical use. The present device made of photosensitive polymer was designed to attach to conventional syringe to isolate the CTCs at minimal resources. Its unique tapered-slits on the filter are capable not only to isolate the cell based on their size and deformability, but also to increase sample flow rate, thus achieving label-free rapid viable CTC isolation. We verified our device performance using 9 different types of cancer cells at the cell concentration from 5 to 100cells/ml, showing that the device capture 77.7% of the CTCs while maintaining their viability of 80.6%. We extended our study using the 18 blood samples from lung, colorectal, pancreatic and renal cancer patients and captured 1-172 CTCs or clustered CTCs by immunofluorescent or immunohistochemical staining. The captured CTCs were also molecularly assayed by RT-PCR with three cancer-associated genes (CK19, EpCAM, and MUC1). Those comprehensive studies proved to use our device for cancer study, thereby inaugurating further in-depth CTC-based clinical researches.

A unified high-throughput screening (HTS) platform is proposed for both 2D and 3D cell culture models in a single chip platform. Comparison studies between well-established 2D models and in vivo-like 3D models are important to understand the underlying mechanisms of chemotherapeutic drugs. In the present unified platform, cells were seeded on top of micropillars and cultured with 2D or 3D cell culture protocols. Through a simple assembly of a micropillar/microwell chip, the cells on the micropillars were dipped into a microwell array, thus providing a one-step quick media exchange without additional washing steps. To demonstrate the utility of the proposed platform, drug-response assays for human lung cancer cells (A375) in both 2D and 3D models were done with 12 different compounds. Most of the IC 50 values of the drugs in the 3D model were higher than those in the 2D case; however, cancer cells exposed to a hypoxia-activated drug (TPZ) showed higher resistance in the 2D model. The proposed unified platform represents an opportunity to achieve effective and reliable cell assessment standards by linking various model-based studies with biochemical and pharmaceutical applications.

Hepatocellular carcinoma (HCC), a major histological subtype of liver cancer, is the third most common cause of cancer-related death worldwide. Currently, many curative standard treatments using target-specific chemotherapeutic agents are being developed. However, drug efficacy tests based on the 2D monolayer cell culture model do not effectively screen the best drug candidates because they do not accurately reflect in vivo tumor microenvironments. Thus, to select the best drug candidates or repositioning drugs, we developed new 3D in vitro hepatic tumor models, including 3D forming and preformed sphere models. A micropillar and microwell chip platform was used for the 3D in vitro liver cell-based model for high-throughput screening. We measured the efficacy of 60 drugs and sorted the most efficacious drugs by comparing the drug response of the 2D monolayer model with the 3D forming and preformed sphere models. Among the 60 drugs, 17 drugs (28.3%) showed a significant high efficacy in the 3D preformed sphere model, while 45 drugs (75%) showed an efficacy in the 2D model. We also calculated the IC50 values of the 17 drugs and found that 7 drugs exhibited a high sensitivity in HCC, which was in agreement with previous studies.

This study proposes a skin analysis device using a truncate hollow cone (THC) probe for measuring both transepidermal water loss (TEWL) and skin hardness. Because skin health is closely related to the epidermal barrier function and skin mechanical property, it is important to measure their biophysical indicators at the same time, to understand skin conditions and diagnose skin disorders such as atopic dermatitis and systemic sclerosis. Previous skin analyzers, however, required different probes with different protocols for each biophysical indicators, which makes the measurement inconvenient and increases the measurement uncertainty. The present device consists of a THC probe equipped with humidity and force sensors, and an actuator that simultaneously measure both TEWL and skin hardness which indicate the integrity of the epidermal barrier function and the skin mechanical property, respectively. Using artificial reference skins, the prototype device showed the TEWL with a sensitivity and linearity of 0.011 (%/s)/(g/m

Blood pressure (BP) is one of the most important pieces of information to diagnose cardiovascular diseases but the measurement readings could be easily changed by various factors. If these readings are wrong, it may ultimately lead to a misdiagnosis. In addition, there is a problem when there are different devices used to read blood pressure because these devices may give different readings. Four different BP measurement devices were used, including two mercury sphygmomanometers and two automatic digital devices. Thirty-eight healthy young people (mean age = 27.1±6.1 years) stayed one night at a clinical center and the BPs were measured from their right arms on the following day. Factors such as exercise, food, and smoking that may affect the BP were controlled and prohibited. All tests were repeated three times and all devices were calibrated before the test. Absolute BP value difference between a mercury sphygmomanometer and an automatic digital device was counted for the BP difference between devices ≥ 5 mmHg and ≥ 10 mmHg of each measurement. Significant inter-device BP differences were found between a mercury sphygmomanometer and two automatic devices (p 0.5); all subjects showed BP difference less than 5 mmHg between two mercury sphygmomanometers while only 32% and 38% of subjects showed BP difference less than 5 mmHg for two out of three repeated tests between a mercury sphygmomanometer and an automatic device, and even 26% ~ 36% of subjects showed BP difference ≥ 10 mmHg. This study result stresses that it is necessary to check the reliability of automatic blood pressure devices used in the hospitals. In addition, an easier and more convenient protocol should be developed for the routine calibration of automatic devices.

This paper describes the construction of a static 3D ultrasonography image by tracking the radiation beam position during the handy operation of a 1D array probe to enable point-of-care use. The theoretical model of the transformation from the translational and rotational information of the sensor mounted on the probe to the reference Cartesian coordinate system was given. The signal amplification and serial communication interface module was made using a commercially available sensor. A test phantom was also made using silicone putty in a donut shape. During the movement of the hand-held probe, B-mode movie and sensor signals were recorded. B-mode images were periodically selected from the movie, and the gray levels of the pixels for each image were converted to the gray levels of 3D voxels. 3D and 2D images of arbitrary cross-section of the B-mode type were also constructed from the voxel data, and agreed well with the shape of the test phantom. Keywords: Ultrasound, 3D Image, Position Angle Sensor, Beam Tracking Method[Received: January 9, 2015, Revised: February 3, 2015, Accepted: February 3, 2015] *한국표준과학연구원 의료융합측정표준센터, **과학기술연합대학원대학교 의학물리학과, ***㈜메타바이오메드 HCP사업부, ✝Corresponding Author: Center for Medical Metrology, Korea Research Institute of Standards and Science, Daejeon 305-340, Korea (E-mail: il.doh@kriss.re.kr)

Blood pressure is one of the most important vital signs used to monitor a patient's medical condition and is widely measured in hospitals and at home. Automatic, non-invasive blood pressure (NIBP) monitoring devices measure systolic and diastolic blood pressures from the analysis of cuff pressure oscillations caused by periodic variations of blood pressure in an artery. Currently, clinical validation by comparing them to the auscultatory reference has been used to verify the performance of NIBP devices. However, there are presently no calibration methods for NIBP devices. Here, we propose an SI-traceable calibration method for oscillometric NIBP devices. The calibration system generates pressure-pulses at pre-determined cuff pressures, and with pre-determined amplitude, to the device-under-test. The uncertainty of each pulse is analyzed and used for the calculation of blood pressure (BP) uncertainty. The maximum uncertainty for systolic and diastolic BP using the newly developed calibration system is (0.74 and 0.60) mmHg (k = 2) depending on the pressure and amplitude of each pulse, as well as the number of pulses applied. The present method can be used for calibration of oscillometric NIBP devices.

The volumetric analysis of three-dimensional (3-D)-cultured colonies in alginate spots has been proposed to increase drug efficacy. In a previously developed pillar/well chip platform, colonies within spots are usually stained and dried for analysis of cell viability using two-dimensional (2-D) fluorescent images. Since the number of viable cells in colonies is directly related to colony volume, we proposed the 3-D analysis of colonies for high-accuracy cell viability calculation. The spots were immersed in buffer, and the 3-D volume of each colony was calculated from the 2-D stacking fluorescent images of the spot with different focal positions. In the experiments with human gastric carcinoma cells and anticancer drugs, we compared cell viability values calculated using the 2-D area and 3-D volume of colonies in the wet and dried alginate spots, respectively. The IC50 value calculated using the 3-D volume of the colonies (9.5 μM) was less than that calculated in the 2-D area analysis (121.5 μM). We observed that the colony showed a more sensitive drug response regarding volume calculated from the 3-D image reconstructed using several confocal images than regarding colony area calculated in the 2-D analysis.

Glioblastoma multiforme (GBM) is recognized as the most common and lethal form of central nervous system cancer. To cure GBM patients, many target-specific chemotherapeutic agents have been developing. However, 2D monolayer cell-based toxicity and efficacy tests did not efficiently screen agents due to the pool reflection of in vivo microenvironments (cell-to-cell and cell-to-extracellular matrix interaction). In this study, we used a 3D cell-based, high-throughput screening method reflecting the microenvironments using a micropillar and microwell chip platform to draw a high-dose heat map of the cytotoxicity and efficacy of 70 compounds, with two DMSO controls. Moreover, the high-dose heat map model compared the responses of four 3D-cultured patient-derived GBM cells and astrocytes to high dosages of compounds with respect to efficacy and cytotoxicity, respectively, to discern the most efficacious drug for GBM. Among the 70 compounds tested, cediranib (a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases) exhibited the lowest cytotoxicity to astrocytes and high efficacy to GBM cells in a high-dose heat map model.

A high-throughput clonogenic assay with a micropillar-microwell chip platform is proposed by using the colony area of glioblastoma multiforme (GBM) patient-derived cells (PDCs) from colony images. Unlike conventional cell lines, PDCs from the tumor are composed of heterogeneous cell populations, and some clonogenic populations form colonies during culture while the rest die off or remain unchanged, thus causing the diverse distribution of colony size. Therefore, area-based analysis of the total colonies is not sufficient to estimate total cell viability or toxicity responses. In this work, the average and standard deviation of an individual colony's area calculated from the colony images were used as indicators for cell clonogenicity and heterogeneity, respectively. Two parameters (the total and average area of colonies) were compared to draw the colony's growth curve and measure a doubling time and dose-response curve (IC50). Based on both analyses of two PDCs, 464T PDCs show a higher heterogeneity and clonogenicity than 448T PDCs. The differences in the doubling time and the IC50 according to the analysis methods suggest that the average area of colonies, rather than their total area, is suitable for heterogeneous and clonogenic samples.

This paper presents a cell electroporation characterization chip using a single tapered channel for a continuous gradient of electric fields. In the cell electroporation study, it is required to find the optimal electric field strength for obtaining the maximum number of both viable and electroporated cells possible. The previous electroporation chip with a single stepwise channel generated a limited number of electric fields. However, the present chip, where continuous electric fields (0.3–.5 kV/cm) are generated by a pair of external electrodes across a tapered single channel, provides a more finely tuned electric field for stable cell electroporation with high viability. In the experimental study, we characterize H23 non-small-cell lung cancer (NSCLC) cells. In the previous electroporation chip, the percentages of viable electroporated H23 cells were 51.4% and 44.5% at 0.4 and 0.45 kV/cm, respectively. The present chip was measured to have an electric field of 0.44 kV/cm with a maximum percentage of viable electroporated cells of 54.7±4.8%. The present cell electroporation characterization chip has potential for use in integrated cell chips to find fine optimal electric field conditions for the study of electroporation.

Optical coherence tomography (OCT) angiography (OCTA) has been actively studied as a noninvasive imaging technology to generate retinal blood vessel network maps for the diagnoses of retinal diseases. Given that the uses of OCT and OCTA have increased in the field of ophthalmology, it is necessary to develop retinal phantoms for clinical OCT for product development, performance evaluation, calibration, certification, medical device licensing, and production processes. We developed a retinal layer-mimicking phantom with microfluidic channels based on microfluidic fabrication technology using polydimethylsiloxane (PDMS) and titanium dioxide (TiO(2)) powder. We implemented superficial and deep retinal vessels using microfluidic channels. In addition, multilayered thin films were synthesized with multiple spin-coating processes that comprised layers that corresponded to the retinal layers, including the ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL). The phantom was formed by merging the multilayered thin film, and microfluidic channels were assembled with an optical lens, water chamber, and an aluminum tube case. Finally, we obtained cross-sectional OCT images and en-face OCTA images of the retinal phantom using lab-made ophthalmic OCT. From the cross-sectional OCT image, we could compare each of the layer thicknesses of the phantom with the corresponding layer thicknesses of the human retina. In addition, we obtained en-face OCTA images with injections of intralipid solutions. It is shown that this phantom will be able to be potentially used as a convenient tool to evaluate and standardize the quality and accuracy of OCT and OCTA images.

We present a high-efficient particle trapping chip, where a wide and uniform slit is formed by a deformable membrane barrier with air bubble plugs. The previous particle trapping methods based on membrane barriers resulted in low trapping efficiency due to the non-uniform slit gap between the membrane and the substrate, especially at the side walls of rectangular channel. In the present method, the air bubble plugs remained in the extended microchannel during sample filling process, block the particle passage at the both side ends of the membrane, thus all particles flow through the uniform slit gap. Therefore, high-efficient particle trapping without particle loss can be achieved. The present particle trapping chip was composed of three layers: pneumatic (top), membrane and channel (bottom) layers. The membrane was deformed by the pneumatic pressure applied from the top layer. In the experimental study using 10.3 μm-diameter polystyrene beads, the membrane barrier with the air bubble plugs successfully trapped the injected beads with the trapping efficiency of 100% at the flow rate of 10 μl/min, while the barrier without the air bubble plugs showed low efficiency of 20%. At the increased flow rate of 20 μl/min, beads were still trapped with trapping efficiency over 98% in the present device. By using a mixture of 5.7 and 10.3 μm-diameter beads, we also verified the present method was capable to trap and release the beads selectively according to their size with the release efficiency of 95.1%. The present simple and effective particle trapping device is applicable for the high-efficient bioparticle isolation and recovery in the micro total analysis system.

We present a rapid and low-temperature polymer fabrication method based on the direct patterning by UV light. Compared to the conventional polymer micromolding method for polydimethylsiloxane (PDMS) and cyclic olefin copolymers (COC), the present method has advantages of rapid fabrication in low-temperature environment. We used an AEO3000, UV-curable low-stress hyper-branched polymer (HBP), as a polymer material. The AEO3000 layer was selectively exposed to UV light by a photomask at room temperature for 3 min. Using the present method, we designed the rigid substrate for the microelectrofluidic bench. The measured electrical and fluidic interconnection characteristics in the bench were 0.75 ± 0.44 Ω and 8.3 kPa (at the flow rate of 100 μl/min), respectively. Both electric and fluidic characteristics were equivalent or lower than the sum of individual devices. We also successfully verified the bio-sample analysis through the interconnected devices on the microelectrofluidic bench using yeast cell samples. The proposed method offers fast and bio-compatible process applicable to biomedical micro total analysis systems.

This paper presents a three-dimensional (3D) tumor spheroid chip where the pharmacokinetic (PK) drug elimination model is developed by balanced droplet dispensing. The PK model should reflect the exponential decrease of drug concentration in a body to improve the reliability of cell-based screening assay. The previous cell chips, however, maintain the concentration of anti-cancer agents at constant or discretely decrease the concentration level by manual process. In the present chip where medium droplet dispensers are integrated on a well array, the small droplets of fresh medium and well waste are autonomously replaced each other, the exponential elimination of drug concentration in the well is provided. In the experimental study, we demonstrated that the present chip successfully develops the exponential elimination model using fluorescein isothiocyanate (FITC) and cisplatin. Although the exponential decay of cisplatin in the present chip did not show significant effect biologically due to the current protocol where 3 days of constant concentration pre-treatment is performed, we observed different growth pattern of H358 spheroids depending on peak concentration of 0, 1, 10, and 100 μM. The present chip has potential for analyzing the response of 3D tumor spheroids in the pharmacokinetically relevant drug elimination model for high-reliability spheroid-based drug screening chip.

We performed a dynamic characterization of passive flow-rate regulators, which compensate for inlet pressure variation and maintain a constant flow rate for precise liquid control in microfluidic systems. To measure the flow rate for a short time, much less than the period of the dynamic inlet pressure, we use the particle image velocimetry (PIV) method. DI water containing fluorescent beads with a diameter was supplied to the flow-rate regulators, and two successive images of the particles were taken by a pulse laser and a fluorescent microscope to measure the flow velocity. For a dynamic inlet pressure of frequency 60 Hz, the flow velocity was constant with an average of 0.194 0.014 m/s as the inlet pressure varied between 20 kPa to 50 kPa. The flow-rate regulators provided a constant flow rate of in the frequency range of the inlet pressure from 1 Hz to 60 Hz.

There are numerous biological processes which are related to heat production, and the heat information can be used in various applications, for example the diagnosis of disease or the investigation of antibiotics by measuring metabolism of biological samples. Therefore, it is very useful to develop a device which can measure small amounts of heating power corresponding to sub-microwatt level. In this study, a chip calorimeter is developed which can measure sub-microwatt power level. The size of the chip calorimeter is 8 mm × 10 mm and the chip is designed to have four identical measurement units. In each chip, there is a platinum (Pt) electrode to generate heat in the centre and two thermopiles on both sides of the heater. Thermopile consists of a serial connection of 73 bismuth (Bi) and aluminium (Al) thermopiles. The whole chip unit is inserted in the double thermostat which is maintained within 20 mK using film heater and natural convection with two temperature controllers. The generated heat from the heater was measured with the depicted thermopile and the resolution was found to be less than sub-microwatt. Various methods to improve the heat power resolution are discussed. The developed chip calorimeter can be used for biological research by measuring metabolic heat of cells in the future research.

In this paper an improved Lab-on-a-Chip device has been proposed for focusing the particle at the center of the channel to separate the desired particles from the main stream at the exit. The design methodology is kept simple and a two fluidic port device with geometric description is proposed. The induced dielectric force responsible for focusing particle is accomplished by means of two electrodes separated by dielectric material. Compared to the previous particle focusing devices; this device provides simple and effective mean of particle focusing with numerical study highlighting the importance of geometric improvements and efficiency.

This research aimed to develop a simulator capable of oscillometric pressure pulses recorded from the participants for the validation of oscillometric noninvasive blood pressure (NIBP) devices. The simulator generates the pressure pulses to the cuff connected to NIBP devices depending on the oscillometric waveforms obtained from the participants. Device readings were compared with auscultatory references (systolic and diastolic blood pressures) of the participants. A total of 94 oscillometric waveforms from participants were used in the simulator for the validation of two automated NIBP devices (Omron HEM-7221 and UA-787Plus). For Omron HEM-7221, the differences between device readings and auscultation references for systolic and diastolic blood pressures were 2.82±7.27 and -4.74±6.73 mmHg, respectively. UA-787Plus showed differences of 3.26±5.69 and -3.53±6.61 mmHg, respectively. Although the number of individual measurements did not fulfill the ISO 81060-2 requirement for clinical validation, criterion 1, where the average of the difference and SD should be lower than ±5 and -8 mmHg, was fulfilled. Although the simulator still needs extensive comparative studies to be verified, it could be a potential candidate for a simple and robust tool for the validation and quality control of NIBP devices.

We present a method for sub-population analysis of deformability distribution using single-cell microchamber array (SiCMA) technology. It is a unique method allowing the correlation of overall cellular characteristics with surface and cytosolic characteristics to define the distribution of individual cellular characteristics in heterogeneous cell populations. As a proof of principle, reticulocytes, the immature sub-population of red blood cells (RBC), were recognized from RBC population by a surface marker and different characteristics on deformability between these populations were characterized. The proposed technology can be used in a variety of applications that would benefit from the ability to measure the distribution of cellular characteristics in complex populations, especially important to define hematologic disorders.

We present a handheld device for the simple, stable, high-throughput, and viable circulating tumor cell (CTC) isolation with the whole blood processing capacity of 3.3ml/hr. The device uses the microfabricated tapered-slit filters having wider slit entrances and gradually narrower slit exits. Compared to the conventional straight-slit filters, the tapered-slit filters are capable to increase blood flowrate with the minimal cell stress. We verified the device's performance using the 4 different lung cancer cells at 5 different concentrations in the range of 5–100cells per 1ml of whole blood; thus achieving the average capture efficiency of 80.4% with the viability of 82.3%. Furthermore, the device captured 1 to 9 CTCs from the experiments using 5 different lung cancer patients' blood samples; thus, demonstrating the device's potential for clinical applications.

We present a high-throughput continuous cell separation chip using hydrodynamic dielectrophoresis (DEP) process. The continuous cell separation chip uses three planar electrodes in a separation channel, where the positive DEP cells are moved away from the central streamline while the negative DEP cells remain in the central streamline. In the experimental study, we use the mixture of viable (live) and nonviable (dead) yeast cells in order to obtain the continuous cell separation conditions. For the conditions of the electric fields frequency of 5 MHz and the medium conductivity of 5 μS/cm, the fabricated chip performs a continuous separation of the yeast cell mixture at the varying flow-rate in the range of 0.1–1 μl/min; thereby, resulting in the purity ranges of 95.9–97.3 and 64.5–74.3%, respectively, for the viable and nonviable yeast cells. The present chip demonstrates the constant cell separation performance for varying mixture flow-rates.