King Ho Holden Li

Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus.

Advanced management of dysmetabolic syndromes such as diabetes will benefit from a timely mechanistic insight enabling personalized medicine approaches. Herein, we present a rapid microfluidic neutrophil sorting and functional phenotyping strategy for type 2 diabetes mellitus (T2DM) patients using small blood volumes (fingerprick ~100 μL). The developed inertial microfluidics technology enables single-step neutrophil isolation (>90% purity) without immuno-labeling and sorted neutrophils are used to characterize their rolling behavior on E-selectin, a critical step in leukocyte recruitment during inflammation. The integrated microfluidics testing methodology facilitates high throughput single-cell quantification of neutrophil rolling to detect subtle differences in speed distribution. Higher rolling speed was observed in T2DM patients (P < 0.01) which strongly correlated with neutrophil activation, rolling ligand P-selectin glycoprotein ligand 1 (PSGL-1) expression, as well as established cardiovascular risk factors (cholesterol, high-sensitive C-reactive protein (CRP) and HbA1c). Rolling phenotype can be modulated by common disease risk modifiers (metformin and pravastatin). Receiver operating characteristics (ROC) and principal component analysis (PCA) revealed neutrophil rolling as an important functional phenotype in T2DM diagnostics. These results suggest a new point-of-care testing methodology, and neutrophil rolling speed as a functional biomarker for rapid profiling of dysmetabolic subjects in clinical and patient-oriented settings.

Advances in Single Cell Impedance Cytometry for Biomedical Applications

Microfluidics impedance cytometry is an emerging research tool for high throughput analysis of dielectric properties of cells and internal cellular components. This label-free method can be used in different biological assays including particle sizing and enumeration, cell phenotyping and disease diagnostics. Herein, we review recent developments in single cell impedance cytometer platforms, their biomedical and clinical applications, and discuss the future directions and challenges in this field.

A Compact CMOS Ring Oscillator with Temperature and Supply Compensation for Sensor Applications

This paper presents a 1MHz ring oscillator with simple temperature compensation circuit dedicated to MEMS sensor applications. A closed-loop PTAT voltage source follower coupled with an open-loop replica-biased source follower driving structure is proposed to power the CMOS ring oscillator and counteract its temperature-dependent effect. In conjunction with a pseudo-resistor based low-pass filter to lower the circuit noise, it significantly improves the jitter performance. The circuit is realized using 0.35μm CMOS technology at a 5V supply. The frequency variation of the compensated oscillator over the temperature range of - 40°C to +90°C is - 0.1% to +0.19% (22.3ppm/°C) with respect to the uncompensated frequency variation of -- 12.1% to +21.6% (2592ppm/°C) at typical process. For worst case process, the frequency deviates from - 1.5% to +1.9% for the stated temperature span and it deviates from - 1.2% to +1.2% at ±10% supply variation under 1 MHz oscillation frequency. The proposed ring oscillator is insensitive to the PVT variations. The simulated cycle-to-cycle RMS jitter value due to both the intrinsic circuit noise and the 200mV peak-to-peak power supply noise is only 64ps, which is about 50 times smaller than that of the standard ring oscillators under identical process technology and design conditions.

A tunable microfluidic 3D stenosis model to study leukocyte-endothelial interactions in atherosclerosis

Atherosclerosis, a chronic inflammatory disorder characterized by endothelial dysfunction and blood vessel narrowing, is the leading cause of cardiovascular diseases including heart attack and stroke. Herein, we present a novel tunable microfluidic atherosclerosis model to study vascular inflammation and leukocyte-endothelial interactions in 3D vessel stenosis. Flow and shear stress profiles were characterized in pneumatic-controlled stenosis conditions (0%, 50% and 80% constriction) using fluid simulation and experimental beads perfusion. Due to non-uniform fluid flow at the 3D stenosis, distinct monocyte (THP-1) adhesion patterns on inflamed [tumor necrosis factor-α (TNF-α) treated] endothelium were observed, and there was a differential endothelial expression of intercellular adhesion molecule-1 (ICAM-1) at the constriction region. Whole blood perfusion studies also showed increased leukocyte interactions (cell rolling and adherence) at the stenosis of healthy and inflamed endothelium, clearly highlighting the importance of vascular inflammation, flow disturbance, and vessel geometry in recapitulating atherogenic microenvironment. To demonstrate inflammatory risk assessment using leukocytes as functional biomarkers, we perfused whole blood samples into the developed microdevices (80% constriction) and observed significant dose-dependent effects of leukocyte adhesion in healthy and inflamed (TNF-α treated) blood samples. Taken together, the 3D stenosis chip facilitates quantitative study of hemodynamics and leukocyte-endothelial interactions, and can be further developed into a point-of-care blood profiling device for atherosclerosis and other vascular diseases.

Real-time precision pedestrian navigation solution using Inertial Navigation System and Global Positioning System

Global Positioning System and Inertial Navigation System can be used to determine position and velocity. A Global Positioning System module is able to accurately determine position without sensor drift, but its usage is limited in heavily urbanized environments and heavy vegetation. While high-cost tactical-grade Inertial Navigation System can determine position accurately, low-cost micro-electro-mechanical system Inertial Navigation System sensors are plagued by significant errors. Global Positioning System is coupled with Inertial Navigation System to correct the errors, while Inertial Navigation System itself can be used to provide navigation solution during a Global Positioning System outage. Data from Global Positioning System and Inertial Navigation System can be integrated by extensive Kalman filtering, using loosely coupled integration architecture to provide navigation solutions. In this study, real-time low-cost loosely coupled micro-electro-mechanical system Inertial Navigation System/Global Positioning System sensors have been used for pedestrian navigation. Trial runs of Global Positioning System outages have been conducted to determine the accuracy of the system described. The micro-electro-mechanical system Inertial Navigation System/Global Positioning System can successfully project a trajectory during a Global Positioning System outage and produces a root mean square error of 9.35 m in latitude direction and 10.8 m in longitude direction. This technology is very suitable for visually impaired pedestrians.

Stability test of the silicon Fiber Bragg Grating embroidered on textile for joint angle measurement

Recently, Fiber Bragg Grating (FBG) sensors are being used for motion tracking applications. However, the sensitivity, linearity and stability of the systems have not been fully studied. Herein, an embroidered optical Fiber Bragg Grating (FBG) on a stretchable supportive textile for elbow movement measurement was developed. The sensing principle of this system is based on the alteration of Bragg wavelength due to strain from the elbow movements. The relationship between elbow movements and reflected Bragg wavelength was found to be linear. The dynamic range of FBG sensor on elbow support is between 0 and 120 degree. Finally, the stability of the FBG sensor on the supportive textile was tested during the exercise and the cleaning process with water. The sensitivity of FBG sensors for joint angle measurement and the effect of the movement and cleaning process to signals from FBG sensors after using in the real activity will be the basis knowledge for design and actual implementation of future optical fiber based wearable devices.

Low-cost, disposable microfluidics device for blood plasma extraction using continuously alternating paramagnetic and diamagnetic capture modes

Blood plasma contains biomarkers and substances that indicate the physiological state of an organism, and it can be used to diagnose various diseases or body condition. To improve the accuracy of diagnostic test, it is required to obtain the high purity of blood plasma. This paper presents a low-cost, disposable microfluidics device for blood plasma extraction using magnetophoretic behaviors of blood cells. This device uses alternating magnetophoretic capture modes to trap and separate paramagnetic and diamagnetic cells away from blood plasma. The device system is composed of two parts, a disposable microfluidics chip and a non-disposable (reusable) magnetic field source. Such modularized device helps the structure of the disposable part dramatically simplified, which is beneficial for low-cost mass production. A series of numerical simulation and parametric study have been performed to describe the mechanism of blood cell separation in the microchannel, and the results are discussed. Furthermore, experimental feasibility test has been carried out in order to demonstrate the blood plasma extraction process of the proposed device. In this experiment, pure blood plasma has been successfully extracted with yield of 21.933% from 75 μl 1:10 dilution of deoxygenated blood.

Design enhancement of overall Paralympics wheelchair for para table tennis competition

This study focused on enhancing the performance of the para table tennis player by implementing design modifications to the wheelchair to increase the sweep area of the player. In this article, a detailed study of pressure distribution on the player’s seat during play was performed to facilitate potential enhancements to the wheelchair that would alleviate issues that could arise from long hours of training and actual competition. Some of these issues include the discomfort and fatigue that could develop from an imbalanced posture resulting in imbalanced seat pressure distribution exerted on the gluteus maximus, as well as pressure sores that could develop during training and competition. Such issues impact the immediate and long-term development of competitiveness in the player. Through a systematic and quantitative understanding of the situation, further structural enhancements to the wheelchair as well as modifications to the training methodologies, strategies and techniques of gameplay could be implemented.

Label-free leukocyte sorting and impedance-based profiling for diabetes testing

Circulating leukocytes comprise of approximately 1% of all blood cells and efficient enrichment of these cells from whole blood is critical for understanding cellular heterogeneity and biological significance in health and diseases. In this work, we report a novel microfluidic strategy for rapid (< 1 h) label-free leukocyte sorting and impedance-based profiling to determine cell activation in type 2 diabetes mellitus (T2DM) using whole blood. Leukocytes were first size-fractionated into different subtypes (neutrophils, monocytes, lymphocytes) using an inertial spiral sorter prior to single-cell impedance measurement in a microfluidic device with coplanar electrode design. Significant changes in membrane dielectric properties (size and opacity) were detected between healthy and activated leukocytes (TNF-α/LPS stimulated), during monocyte differentiation and among different monocyte subsets (classical, intermediate, non-classical). As proof-of-concept for diabetes testing, neutrophil/monocyte dielectric properties in T2DM subjects (n = 8) were quantified which were associated with cardiovascular risk factors including lipid levels, C-reactive protein (CRP) and vascular functions (LnRHI) (P < 0.05) were observed. Overall, these results clearly showed that T2DM subjects have pro-inflammatory leukocyte phenotypes and suggest leukocyte impedance signature as a novel surrogate biomarker for inflammation.

Compact combined antenna with slit for monopolar input pulse

In this paper, a compact combined antenna with slit for monopolar input pulse is proposed. The slit is introduced in the antenna to avoid high short circuit current of DC component. This also makes the field energy in the computation domain to decay during simulation, when fed with rectangular pulse waveform. The field energy in the computation domain, along with return loss and realized gain, are simulated to investigate the locations of slit at the corner and center of the antenna. The combined antenna with corner slit is fabricated. The simulated and measured realized gain and return loss are presented. The −10 dB bandwidth ratio is 10:1, which is from 0.4 GHz to 4 GHz.