Biomedical Electronics

Biomedical Electronics

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Description: Department of Electronic and Computer Engineering, Advanced Medical Technology, Cancer Bio marker Discovery, Genome-Wide SNP Data Analysis, Ultrasound Image Analysis, Infectious Disease, Non-invasive Imaging of Early Cancer, IC Technology DNA Detection, Health care: Modeling Visual Function.

 
Author: Jianan Y. Qu (Fellow) | Visits: 2357 | Page Views: 3283
Domain:  Medicine Category: Equipment Subcategory: Medical Electronics 
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Contents:
Healthcare Forum

"Biomedical Electronics"
Presenter: Jianan Y. Qu
Department of Electronic and Computer Engineering, School of Engineering

Department of Electronic and Computer Engineering

RESEARCH AREAS:

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Biomedical Electronics Computer Engineering IC Design Microelectronics Photonics Signal & Information System & Automation Wireless Communications & Networking

Department of Electronic and Computer Engineering

RESEARCH AREAS:



Biomedical Electronics Core faculties:
Prof. Mansun Chan Dr. Emma MacPHERSON (visiting) Prof. Jianan Qu Dr. George Jie Yuan Prof. Bertram Shi Dr. Levent Yobas Dr. Weichuan Yu

Healthcare forum

Advanced medical technology:
Toward non-invasive and early diagnosis
Weichuan Yu: Levent Yabos: Jianan Y. Qu: Bioinformatics BioNanoFluidic MEMS Biophotonics

Department of Electronic and Computer Engineering (ECE), HKSUT

Cancer Biomarker Discovery
Blood Sample Protein/Peptide Mixture Liquid Chromatography
Mobile Phase

� Goal:
� Identify a subset of proteins or peptides as cancer biomarkers

Stationary Phase

� Technical challenges:
� What proteins are in the sample � What are their expression levels � Biological validation

Peptide 2 Peptide 1

I m/z

Time
Analysis .....

� Current achievement:
� Much better identification of protein mixtures from samples
Mass Spectrometry

� Future plan
� More stable estimation of protein expressions � Inclusion of measurement at different time points.

Weichuan YU / ECE

5

Genome-Wide SNP Data Analysis
� Single Nucleotide Polymorphism (SNP):
� Possibly the genetic cause of disease � 1: normal AACGGAT � 2: disease AACGAAT

� Technical challenges:
� Need to test so many of them
� Millions for single SNP-based test � 1010 tests needed for SNP-SNP pair-based test

� Maintain the statistical power and reduce false positive detection

� Current achievement:
� A new method which is about 63 times faster than the state-of-the-art testing method.

� Future plan:
� Inclusion of biological prior knowledge into the analysis framework � New testing strategies Weichuan YU / ECE
6

Ultrasound Image Analysis
� Non-invasive tumor detection and cardiac disease diagnosis. � Technical challenges:
� Accurate and reliable tissue deformation analysis

� Current achievement:
� A new ultrasound image-based analysis method that is capable of compensating the featuremotion decorrelation more robustly than previous analysis methods .

� Future plan:
� Clinic test of the new method. � Combine deformation analysis with image segmentation. Weichuan YU / ECE
7

Research Summary
Cancer Biomarker Discovery HKUST
Robert Qi/BICH Qiang Yang/CSE

Ultrasound Image Analysis HKUST/ECE Biomedical Electronics

Genome-wide SNP Data Analysis HKUST
Hong Xue/BICH Qiang Yang/CSE

Yale Univ.
Hongyu Zhao Erol Gulcicek Tukiet Lam

CUHK
Xiaodan Fan Nelson Tang

Recent Publications and Patent
1. X. Wan, C. Yang, Q. Yang, H. Xue, X. Fan, N. Tang, and W. Yu. BOOST: A Boolean Representation-based Method for Detecting SNP-SNP Interactions in Genome-wide Association Studies. submitted 2. Z. He, Ch. Yang, C. Yang, R.Z. Qi, J.P. Tam and W. Yu. Optimization-Based Peptide Mass Fingerprinting for Protein Mixture Identification. Journal of Computational Biology, 17:221-235, 2010. 3. X. Wan, C. Yang, Q. Yang, H. Xue, N. Tang, and W. Yu. SNPRuler: Predictive rule inference for epistatic interaction detection in genome-wide association studies. Bioinformatics, 26:30-37, 2010. 4. C. Yang, Z. He, X. Wan, Q. Yang, H. Xue, and W. Yu. SNPHarvester: A filtering-based approach for detecting epistatic interactions in genome-wide association studies. Bioinformatics, 25:504-511, 2009. 5. W. Yu, Z. He, J. Liu, and H. Zhao. Improving Mass Spectrometry Peak Detection Using Multiple Peak Alignment Results. Journal of Proteome Research, 7:123-129, 2008. 6. W. Yu and T. Liang. "Coupled filtering method for tissue motion analysis using ultrasound images." International patent, pending

Weichuan YU / ECE

8

Infectious Disease Control by On-site Screening
Cell Separation DNA Micro Extraction

Status: Microdevice building blocks � Cell separation � DNA/RNA Purification � Enzymatic Amplification � DNA/RNA Detection Need: � A self-contained fully-enclosed cartridge integrating the blocks � Microfluidic valving & pumping Challenges: � A simplified integration scheme for a low-cost cartridge � Ability to process diverse & complex set of bodily fluids � Sensitive & robust biosensors

Viral RNA Micro Extrac. SiNW Biosensor

PCR Amplification

Levent Yobas/ ECE

Cancer Monitoring by the Enumeration of CTC
CTC Circulating Tumor Cells Cancer progresses w/CTC level

Status: � Cell trapping & monitoring their electrical activities through integrated glass microcapillaries � Label-free isolation of cancer cells from whole blood via their distinct mechanical properties Need: � A high-accuracy microdevice through concurrent probing of mechanical and electrical properties of CTC Challenges: � Very rare (a few CTC among billions of blood cells in 1ml) � To be able to distinguish CTC from epithelial non-tumor cells Levent Yobas/ ECE

Collaborators, Publications & Patents:
Platform Technologies: D.A. Weitz, Physics, Harvard.........................................................Scalable generation of emulsions in microfluidics N.T. Nguyen, Mechanical & Aerospace Eng, NTU Singapore...............Droplet-based micro/nano fluidics D. Poenar, EEE, NTU Singapore....................................................Microspectrophotometer on chip for diagnostics D.W. Trau, Bioengineering, NUS....................................................Generation of polyelectrolyte multi-layered capsules M.L. Buist, Bioengineering, NUS....................................................Dielectrophoresis for cell positioning Infectious Diseases Screening: Cancer Monitoring: Chew-Kiat Heng, Pediatrics, National University of Singapore Chwee Teck Lim, Bioengineering, NUS Tit-Meng Lim, Biological Sciences, National University of Singapore J.P. Thiery, A*STAR, Inst of Molecular & Cell Biology Martin Hibberd, A*STAR, Genome Institute of Singapore 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. S.J. Tan, R.L. Lakshmi, T.K.K. Lin, H.L. Tan, P.F. Chen, L. Yobas, M.H. Tan, and C.T. Lim, Size and Deformability based Isolation and Detection of Circulating Tumor Cells of Renal Cell Carcinoma Patients. Submitted. K.-C. Tang, J. Reboud, Y.L. Kwok, S.L. Peng, and L. Yobas, "Lateral patch-clamping in a standard 1536-well microplate format," Lab Chip, 2010, 10 (8), 1044-1050. S.P.C. Sim, T.G. Kang, L. Yobas, C. Holtze, and D.A. Weitz, "Shape of a step structure as a design aspect to control droplet generation in microfluidics," J Micromech & Microeng, 2009, 20(3), 035010 L. Yobas, L.F. Cheow, K.-C. Tang, S.-E. Yong, E.K.-Z. Ong, L. Wong, W. Teo, H.M. Ji, S. Rafaeh, and C. Yu, "A self-contained fullyenclosed microfluidic cartridge for lab-on-a-chip," Biomedical Microdevices 2009, 11 (6), 1279-1288 S.J. Tan, L. Yobas, G.Y.H. Lee, C.N. Ong, and C.T. Lim, "Microdevice for the isolation and enumeration of cancer cells from blood," Biomedical Microdevices, 2009, 11 (4), 883-892 L. Yobas, K.-C. Tang, S.-E. Yong, and E.K.-Z. Ong, "A disposable planar peristaltic pump for Lab-on-a-Chip," Lab Chip, 2008, 8, 660-662 (Communication) J.K. Sheng, D.P. Poenar, P. Neuzil, and L. Yobas, "Monolithic integration of Poly(dimethylsiloxane) waveguides and microfluidics for onchip absorbance measurements," Sensors and Actuators B 2008, 134 (2), 532-538, DOI:10.1016/j.snb.2008.05.040. H.M. Ji, V. Samper, Y. Chen, C.K. Heng, T.M. Lim, and L. Yobas, "Silicon-based microfilters for whole blood cell separation," Biomedical Microdevices, 2008, 10, 251-257. W.-L. Ong, K.-C. Tang, A. Agarwal, R. Nagarajan, L.-W. Luo, and L. Yobas, "Microfluidic integration of substantially round glass capillaries for lateral patch clamping on chip," Lab Chip, 2007, 7, 1357-1366. L. Yobas, H. Ji, W. Hui, Y. Chen, T-M. Lim, C-K. Heng, and D-L Kwong, "Nucleic acid extraction, amplification, and detection on Si-based microfluidic platforms," IEEE Journal of Solid-State Circuits 2007, 42 (8), 1803 � 1813. W.C. Hui, L. Yobas, V.D. Samper, C.K. Heng, S. Liw, H.M. Ji, Y. Chen, C. Lin, J. Li, and T.M. Lim, "Microfluidic systems for extracting nucleic acids for DNA and RNA analysis," Sensors and Actuators A 2007, 133 (2), 335-339 L. Yobas, and L.F. Cheow, "Fluid cartridge, pump, and fluid valve arrangement," WO2008118908. W.L. Ong, L. Yobas, K.C. Tang, A. Agarwal, and N. Ranganathan "Microfluidic Device for Analyzing the Status of a Particle," WO2007108779A1

Levent Yobas/ ECE

Non-invasive imaging of early cancer
Ultrasound imaging X-ray computer tomography (CT)

Jianan Qu, Biophotonics Research Laboratory, Hong Kong University of Science and Technology

Non-invasive imaging of early cancer
Positron emission tomography (PET) Magnetic resonance imaging (MRI)

Jianan Qu, Biophotonics Research Laboratory, Hong Kong University of Science and Technology

Non-invasive imaging of early cancer
Endoscopy � an optical imaging technology
Colon A physician using an endoscope.

Endoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope, an optical instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are Esophagus inserted directly into the organ. A medical procedure using any type of endoscope is called endoscopy.
An example of a flexible endoscope.

Jianan Qu, Biophotonics Research Laboratory, Hong Kong University of Science and Technology

Non-invasive imaging of early cancer
Challenge: 90% early cancer originate from epithelium. epithelium
Nonlinear optical imaging
Epithelium:
Thickness ranging from a few tens to a few hundred microns

Nonlinear dependence on excitation intensity gives NLO microscopy inherent 3-D imaging and high-resolution capability. NLO microscopy utilizes near-IR excitation that provides both superior optical penetration into tissues and reduced photodamage due to reduced interaction with endogenous molecules NLO imaging modalities are sensitive for probing different cellular structures and functionality.

Jianan Qu, Biophotonics Research Laboratory, Hong Kong University of Science and Technology

Non-invasive imaging of early cancer
Epithelium Collagen fibers Capillaries

Nonlinear optical imaging
Nonlinear dependence on excitation intensity gives NLO microscopy inherent 3-D imaging and high-resolution capability. NLO microscopy utilizes near-IR excitation that provides both superior optical penetration into tissues and reduced photodamage due to reduced interaction with endogenous molecules NLO imaging modalities are sensitive for probing different cellular structures and functionality.

Protein

Mitochondria

Collagen

Jianan Qu, Biophotonics Research Laboratory, Hong Kong University of Science and Technology

Non-invasive imaging of early cancer
Challenge: miniaturization
Nonlinear optical imaging
Nonlinear dependence on excitation intensity gives NLO microscopy inherent 3-D imaging and high-resolution capability. NLO microscopy utilizes near-IR excitation that provides both superior optical penetration into MEMS scanner tissues and reduced photodamage due to reduced Micro-optics interaction with endogenous molecules

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Fiber optics � PCF NLO imaging laser Ultrafast fibermodalities are sensitive for probing different Clinical collaborators cellular structures and
functionality.

Jianan Qu, Biophotonics Research Laboratory, Hong Kong University of Science and Technology

Non-invasive imaging of early cancer
Preliminary work
Nonlinear optical imaging
Nonlinear dependence on excitation intensity gives NLO microscopy inherent 3-D imaging and high-resolution capability. NLO microscopy utilizes near-IR excitation that provides both superior optical penetration into tissues and reduced photodamage due to reduced interaction with endogenous molecules. NLO imaging modalities are sensitive for probing different cellular structures and functionality.
Jianan Qu, Biophotonics Research Laboratory, Hong Kong University of Science and Technology

Non-invasive imaging of early cancer
Quantitative imaging of early cervical cancer: A clinical study Abnormal cervix Normal cervix
Before application of acetic acid

After application of acetic acid

Jianan Qu, Biophotonics Research Laboratory, Hong Kong University of Science and Technology

Non-invasive imaging of early cancer
Quantitative imaging of early cervical cancer: A clinical study

Normal: 12 HPV: CIN 1: 66 15

CIN 2-3 HPV

CIN 2-3: 44

Normal CIN 1

Jianan Qu, Biophotonics Research Laboratory, Hong Kong University of Science and Technology

Healthcare forum

Advanced bio-instrumentation for medical and life science research
Mansun Chan: Bert Shi: George Yuan:
Bio-chips Neuromorphic engineering Integrated bio-sensing/imaging

Department of Electronic and Computer Engineering (ECE), HKSUT

IC Technology DNA Detection
Research Accomplishment/ Sub topics

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Resistive based DNA detection technique Optical DNA detection with CMOS sensor Micro-concentration and other sensitivity enhancement technique

Optical DNA detection chip photo, schematic, packaging and measurement result

[1] Y. Wang, C. Xu, J. Li, J. He and M. Chan, "A CMOS Image Sensor Utilizing Opacity of Nano-Metallic Particles for DNA Detection", IEEE Trans. on Electron Devices, Vol. 54, No. 6, pp. 1549-1554 [2] J. Li, Y. Wang, Z. Lu, and M. Chan, "Enhancing Deoxyribonucleic acid (DNA) Detection Sensitivity through Micro-Concentration on Patterned Fluorocarbon Polymer Surface", Analytica Chimica Acta, Vol. 571, No. 1, pp. 34-39, June 2006

Mansun CHAN/ ECE

Micro-Array for Cell Signal Study
Research Accomplishment/ Sub topics

� Hypoxic study and model development � Effects of preconditioning on cell responses � Effects of drug on cell responses
[1] Chi-Kong Yeung, Jessica Ka-Yan Law, Sze-Wing Sam, Sven Ingebrandt, Hang-Yung Alaster Lau, John Anthony Rudd, and Mansun Chan, "Modulatory Action of Potassium Channel Openers on Field Potential and Histamine Release from Rat Peritoneal Mast Cells", Canadian Journal of Physiology and Pharmacology, vol. 87, no. 8, August 2009, pp. 624-632 [2] J. K. Y. Law, C. K. Yeung, B. Hofmann, S. Ingebrandt, J. A. Rudd, A. Offenh�usser and M. Chan, "The Use of Microelectrode Array (MEA) to Study the Protective Effects of Potassium Channel Openers on Metabolically-Compromised HL-1 Cardiomyocytes", Physiological Measurements, vol. 30, pp. 155-167, January 2009

Micro-Electrode Array and packaging, together with measurement result of Cardiac Cells

Mansun CHAN/ ECE

Healthcare: Modeling Visual Function
Ongoing Research Projects
� Virtual Cat
� Build an artificial vision system that can take the place of a cat in neurophysiological experiments � with P. Kara, Dept. of Neurosciences, MUSC



Hand-Eye Coordination
� Use robotics to study how organisms learn the relationship between visual signals and the external world � with M. Rucci, Dept. of Psychology, Boston U

Technical Goal: Develop hardware/robotic models linking results from visual neurophysiology with visual psychophysics Application: Generate insights/technologies for restoring lost or missing function



Perceptual Learning
� Model task related improvements in performance through training and their effect on neural responses � with W. Li, State Key Lab of Cognitive Neuroscience and Learning, Beijing Normal University

Bertram Shi/ECE

Healthcare: Analog Front-End Integrated Circuits for Bio-signal Acquisition
Our group is developing new analog front-end techniques to acquire weak bio-potentials or bio-currents from various new bio-related devices Completed and on-going projects include:
1. Developing chip to transmit/receive data through the body channel 2. Developing chip to acquire �V cell potential from microelectrode array 3. Developing chip to acquire weak electro-chemical redox currents from microelectrodes array 4. High-speed ultrasound front-end integrated chip with beamforming
Publications:
� � � J. Guo, B. Liu, and J. Yuan, "Wide dynamic range front-end amplifier for cell recording with microelectrode arrays", 2009 IEEE Biomedical Circuits and Systems Conference, pp. 65-68, Nov. 26-28, 2009 R. Xu, H. Zhu, and J. Yuan, "Electrical-field intra-body communication channel modeling with finite element method", IEEE Trans. BioMedical Eng., submitted J. Yuan, K.L.Tsang, "The Design and Optimization Methodology of A Low-Distortion sub-uW Sample-and-Hold Stage for Weak BioCurrents", Microelectronics Journal, Vol. 41, pp. 121-128, Feb./Mar., 2010

Jie George Yuan/ ECE

Healthcare: Highly-sensitive CMOS Imaging Sensor IC for Bio-medical Imaging
Our group is developing specialized CMOS camera chip for bio-medical imaging with new features that existing CCD camera can not provide
Completed and on-going projects include:
1. Wide dynamic range CMOS imaging sensor with the highest reported linearity 2. High-speed artifact-free CMOS computed tomography scanner 3. High-speed low-noise CMOS imaging sensor for fluorescence intensity microscopy 4. Single-photon pico-second CMOS imaging sensor for fluorescence lifetime microscopy
Publications: � J. Yuan, H.Chan, S.W. Fung, B. Liu,"An Activity-Triggered 95.3dB DR -75.6dB THD CMOS Imaging Sensor with Digital Calibration", IEEE Journal of Solid-State Circuits, Vol. 44, pp. 2834-2843, Oct. 2009. � B. Liu, and J. Yuan, "An artifact-free monolithic CMOS CT scanner with synchronous partial quantization", IEEE J. SolidState Circuits, submitted

George Jie Yuan/ ECE

Healthcare:

Biomedical Terahertz Imaging
Research Accomplishment/ Sub topics In vivo THz Imaging Development of a THz probe Biomedical tissue characterization in reflection geometry

� � �
Epidermis Quartz window Incident THz Incident THz A Stratum corneum Quartz

B

Reflected THz

Healthy skin is the simplest example. We are also investigating applications in skin cancer, breast cancer and osteoarthritis. Emma MacPherson/ECE

Smartphone-Centric Platform for Remote Health Monitoring
Project demo: http://www.ee.ust.hk/~eewhmow/ppg_demo/ppg_demo_v5.wmv
Wearable Biosensors

Central Server and Database

Research Accomplishment/subtopics
� Remote health monitoring hardwaresoftware platform co-design using commerical-off-the-shelf building blocks (fast time to market)
� Tested on multi-brands phones: Symbian (Nokia N79, Sony Ericsson K550i), and Linux (Moto E6) phones Designed & fabricated hardware interface with commercial PPG & other sensors & wireless bluetooth modules Filed a patent on novel power saving support for most commercial modules Embedded software implementation for bio-signal processing algorithms for heart rate, breathing rate, OSA, etc. Emergency detection and SMS alert

Bluetooth/ WLAN

GPRS/HSPA

GPRS/HSPA

SMS/MMS

Doctor

User

Fig.1: System Block Diagram


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Fig.2: Hardware/software/algorithms developed for commercial smartphones



Wai Ho MOW/ ECE

Healthcare: Localization and Communication
Services for Silver Population
Wearable AGPS Terminal GPS RF Web Client HTML / Javascript Dojoroot Flash AJAX
Location/Cell ID IMS I

3G RF

GPS Reference Station GPS Receiver ARM7 Processor UDP
Proprietary AGPS Protocol

3G Baseband + Processor
SUPL Assistance Data

Location Server ANS.1 Web Engine Web Server Django (PYTHON) Location / Users Groups / Geofencing ELC Server AGPS / Locator

AGPS Update Collector Server (Java) SSL AGPS Data Store Server (Java)

MYSQL Database

Sub topics � An Assisted GPS Elderly Tracking Trial System � Energy Efficient Location Fix and Tracking � Path Reconstruction � Data Fusion for MultiLocalization Systems � Distributed Conferencing and Messaging for Body-Worn Device � Activity Detection System

Albert Wong, Tim Woo, Chin-Tau Lea/ECE

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