Challenges of Integrated Low-Cost, Disposable Devices for Type 2 Diabetes Mellitus Patients based on Leukocyte studies
Chayakorn Petchakup, Hui Min Tay, Rinkoo Dalan^, Han Wei Hou, Holden Li*
Nanyang Technological University
Tan Tock Seng Hospital ^
holdenli@ntu.edu.sg
Abstract
Advanced management of dysmetabolic syndromes such as diabetes will benefit from a timely mechanistic insight enabling personalized medicine approaches. The integrated microfluidics technology enables such testing methodology, which facilitates high throughput single-cell quantification of leukocytes in a lab-on-a chip setting. To develop such platform, it is important to understand the pros and cons of various microfabrication techniques, their challenges for integration and the ability to be scaled up for large scale production.
In this talk, the various techniques like blood plasma extraction, blood cells separation, study of multi-way microvalves, micro-mixers, single cell impedance measurement are compared and analyzed. Based on our studies, we have achieved 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.
Short Bio
Holden Li graduated in NUS with a Bachelor of Engineering (Honors) in 1997. In 2000 Holden enrolled in Stanford University for his graduate studies under Professor Thomas Kenny. During his PhD studies, Holden was actively involved in MEMS process development in finding suitable packaging solutions to MEMS and BioMEMS devices. Besides, he worked closely with several industrial partners who benefited from the on-going research activities in Kenny’s group at that time. He was awarded his MSc and PhD in Mechanical Engineering in 2001 and 2005 respectively.
Back in Singapore in September 2005, Holden started to lead a research team in MEMS sensors research effort in the area of MEMS R&D and reliability study. He is currently holding a concurrent appointment of Micro Sensors Research Director in Temasek Laboratories at NTU. Beyond this, Holden’s passion for research and development in microelectronics and BioMEMS, coupled with his strong academic interest in the area of micro and nanotechnology propelled him to seek for funding opportunity in these areas. He is currently working closely with several senior faculties in the area of microelectronics and MEMS research both in NTU and Temasek Laboratories at NTU.