From Biosensors to e-Health

Lin, Chii-Wann, Assoc. Prof.

Medical Micro-sensor and system Laboratory

Inst. of Biomed. Eng./Dept. of Elect. Eng.
National Taiwan University
cwlinx@ntu.edu.tw, (02)33665272
 Outline
• Miniature in Medical Devices
• Surface Plasmon Resonance Sensors
• Application examples
– Wearable micro-devices
– Minimum Invasive micro-devices
– Implantable micro-devices
– Research devices
 Biosensor –
Health and comfort monitoring
•Convergence of nano and biology
•Information capture
• Affinity microarrays for DNA, proteins
• Biosensors
• Biological lab on chip, electropheresis,
• DNA sequencers, mass spectrometry
•Drug delivery
•Bionics
BIOMICROTECHNOLOGIES
 經濟部學界科專計畫
先進無線生醫保健監測系統之開發
(Wireless Health Advanced
Monitoring Bio-Diagnosis System,
WHAM-BioS)
Wireless Health Monitoring System
Electrodes

INA A/D Wireless

Converter Module
Analog Digital Filter
Filter Including
Including 60
data coding,
Hz notch
GND Mode Switch frequency
filter
for modulation
EMG, ECG or
EEG signal Analog circuit Part
POWER Digital circuit Part
RF
signal

PC, Wireless
RS-232C,
Notebook Module
USB
or PDA interface
Including
data coding,
LCD LCD Data frequency
Display Driver Reconstruction modulation
Module
USER
USER interface
input
for Mode Switch

Display type
System Roadmap
Integrated valveless pump with
EC sensor
 Example devices under development

• Implantable microsensor with

actuator for drug delivery
– Needle type
– Sensor node for body network
製藥與生物技術國家型計畫
Diseases Diagnosis and
Drug Screening with
Multifunctional Opto-
electronic Biochip Systems
 Novel SPR devices & systems
System
• OBMorph – Multifunctional bio-
optical system for SPR chip (Lee
CK et.al. Taiwan/US Patents)
Algorithm

d1
• Depth resolved SPR with dual-

d2
wavelength (Lin CW et.al, λ2

Taiwan/US patent granted)

λ1

Devices
• Active SPR with alternative
dielectric layers (Lin CW et.al.
Taiwan/US Patents)
• Lateral propagation SPR (Lin CW
et.al. Taiwan/US Patent in review)
• Sinusoidal curve compensation
SPR waveguide (Lin CW et.al.
Taiwan/US Patent in review)
 Development of TBMorph system
Clinical requirement

Specimen Sample extraction/

Detection Sample separation
immobilization dilution

Microvalves integration Flow through chip

Microchannel operation
Micropumps Microreactor

TBMorph function
TBMorph System Integration
 Example devices under development
• Protein Array for TB
– Proprietary SPR chip & System – OBMorph
– 9 selected TB antigens from TB genome
(secreted proteins, lipoproteins, fibronectin
protein, heat shock protein)
– Array design for fast screening
– Preclinical test with 29 positive samples, 28
normal samples.
Mixture of 9 Ags
positive control

A B C D E
SPR
1
Sensitivity Analysis
W06 ELISA
2 1
W85 W10
3
0.5
4
W70 W14
0
5

Experimental set
W64 W19
Control set Ags Ags+Abs

A1~A3, B1,C1,D1,E1~E3
W38 W28
Experimental setup
Top view

sensing hole 200um

lens
1mm
Miniaturized SPR Sensing System based on Polymer Light-Emitting Diode

Miniaturize

Integrated system in
small box (2 X 3 inch2)

Sensing chip

Light source is replaced by PLED

 農委會
農業生物技術國家型科技計畫
應用生物科技技術發展重要動物疾病診
斷試劑及疫苗之生產系統
禽流感快速檢測技術平台之研發
The research and developemnt of fast screening
platform technology for Avian Influenza Virus
 SPR 相關產品與本平台比較
Desk top Desk top Hand held

Biacore 3000

TI Spreeta

體積 大 小
快速檢測技術平台獨特性
‧高靈敏度與穩定的結果
‧攜帶方便
‧方便操作
‧現場即時檢測 快速檢測技術平台
‧無線傳輸
 Design of lateral flow SPR sensor
substrate Step 1

NC Step 2
spin 1000 rpm

Sample pad Step 3

Adsorption pad Step 4

Polymer substrate:
Filter membrane : -visible substrate (PVC, PDMS，PC…
(PVC, PDMS， PC…)
nitrocellulose，cellulose acetate
-nitrocellulose， 5 cm

Absorption pad :
nitrocellulose，cellulose acetate
-nitrocellulose，
Guided layer

<100um Sensor chip

Au
1 cm

Support
accessory Waveguide
Smart living space
Medical home
雃博公司
 Digital Finger
Pulse Oximeter GPS Locator Watch For Alzheimer's Patients

Telemonitoring Services
http://www.nonin.com/products/9500.html

Actiwatch Actigraphs
Bracelet Vivago

http://www.vivago.org/home.htm
http://www.wirelesshomesecurityalarmsystems.com/
http://www.minimitter.com/products/Actiwatch/
Exercise Set
(extended exercise profiles)

http://www.polar.fi/polar/channels/eng/segments/Running/S810i/allfeatures.html
HEART RHYTHM (ECG) MEASUREMENT DEVICE
 Wearable breath sensor
正常呼吸のダイメデックス・エアーフローセンサと空気圧トランスジュー
サ（口鼻カニューレ）と比較
APT

ダイメデッ
クス
口呼吸のダイメデックス・エアーフローセンサと空気圧トランスジュー
サ（口鼻カニューレ）と比較
APT

ダイメデッ
クス

The breath sensor which uses the PVDF film

it meaning accuracy of the ripple mark, and
that sensitivity is superior gives the appraisal
which is good to diagnosis.
PVDF (Poly-vinylla-dene-Fluoride)

http://www.miyuki-net.co.jp/hpage/respsensor.htm
 Wearable Polysomnograph
Advanced Medical Electronics Corporation
A full-featured 16-channel wearable
polysomnograph that records locally, or transfers
data off-body using a plastic optical fiber
connection or wireless digital radio.
FEATURES:
· 16 data channels, including:
· Pulse Oximetry and Heart Rate,
· EEG (4 channels),
· EOG (2 channels),
· EMG (2 channels),
· EKG,
· Chest Effort (2 channels),
· Airflow (thermoresistive or optional pressure based),
· Body Position,
· Snore Sensor.

· Small Package: 0.85 x 3 x 6.5 inches.

· Lightweight: 8 ounces.
· Low Power: 2 AA batteries last 12 hours.
· Impedance Testing.
· Optical fiber connection (option).
· Wireless digital radio connection (option).
· Solid-state recording memory module (option).
http://www.ame-corp.com/Wearable_Polysomnograph.htm
 Adaptive Vision Aid
室內

視覺系統所見影像
視覺系統的
硬體部分 原始影像 教室
視力衰退

Enhanced
電子擴影系統 process
軟體部分

室外 適應性影像 臨床量測視覺 NET

1st Client End
強化處理 系統特性

DSP
網際網路教學閱讀系統 2nd Client End
HMD

可攜式閱讀系統

Server End
 NTU Nano-BioMEMS Group
NTU BioMEMS Group Project leader : Consultant member:
Human resources and 李世光、林啟萬、林世明
equipments integration OBMorph

Signal Detection and Morph Biochips fabrication and Solid-liquid interface techniques
duplications
李世光、王安邦、張所鋐 張培仁、楊龍杰、黃榮山、吳造中 李世元、賴信智

Optical metrology Biochip microstructure Chip thin-film and

and system design fabrication interface stoichiometry

Precision opto- Micro fluidic system Chip/Biomolecular

mechanical design construction interface

Signal processing and SPR fiber biomedical Multi-function immuno-

electronics design detection techniques reactive biotechnology

Micro fluid arraying Semiconductor processing

Affinities and Kinetics at
techniques and packaging
protein-protein interface
Note: 李世光、張培仁、王安邦 、黃榮山 (台大應力所)，張所鋐(台大機械所)， 林世明(台大光電生物
中心) ，李世元(淡江化學所) 、賴信智(台大醫技) 、吳造中(台大內科) 、楊龍杰(淡江機械)。楊燿州
、趙福杉
 References
• Related products
– http://www.CleveMed.com
– http://www.minimed.com/index.html
– http://www.cozmore.com/default.cfm?PID=1.3
– http://www.drugdeliverytech.com/cgi-bin/articles.cgi?idArticle=235
– http://www.medgadget.com/archives/2005/02/dexcoms_continu.html
– http://www.pulsemetric.com
– http://www.apexmedical.com.tw
• Papers
– F-R Liao, C.-A. Chen, S.-S. Lu, N.-F. Chiu, C.-W. Lin, J.-Y. Li, C.-N. Chien, F.-S. Jaw, J.-M. Wang, L.-J. Yang, T.-C.
Hsiao, and C.-K. Lee, “An Implantable Integrated SIGE FM Transmitter for HRV Biotelemetry”, IEEE BioCAS2004,
S1.8-9 – 11 (2004). (EI)
– C.-K. Chen, W.-J. Wu, S.-A. Yu, J.-G. Huang, Y.-H. Lin, Y.-F. Chen, M.-H. Jin, C.-M. Wen, C.-Y. Kao, S.-M. Lin, S.-S.
Lu, C.-W. Lin, J.-Y. Yen, F.-S. Jaw, C.-A. Chen, F.-J. Liao, N.-F. Chiu, C.-N. Chien, and C.-K. Lee, “In vivo wireless
biodiagnosis system for long-term bioactivity monitoring network”, Proc. SPIE 5394:288-297 (2004) (EI)
– N.-F. Chiu, T.-C. Hsiao, C.-W. Lin*, “Low power consumption design of micro-machined thermal sensor for portable
spirometer”, Tamkang J. Sci. Eng., 8:225-230 (2005) (EI)
– C.-W. Lin, K.-P. Chen, S.-M. Lin, C.-K.Lee, “Design and Fabrication of an Alternative Dielectric Multilayer device for
Surface Plasmon Resonance Sensor”, Sensors and Actuators B: Chemical, 113: 169-176 (2006), (SCI)
– C.-W. Lin, K.-P. Chen, M.-C. Su, T.-C. Hsiao, S.-S. Lee, S. Lin, X.-J. Shi, C.-K. Lee, “Admittance Loci Design Method
for Multilayer Surface Plasmon Resonance Devices”, Sensors and Actuators B: Chemical in press (SCI)
– C.-W. Lin, K.-P. Chen, M.-C. Su, C.-K. Lee, C.-C. Yang, “Bio-Plasmonics: Nano/Micro structure of Surface Plasmon
Resonance devices for Biomedicine”, OQE 37: 1423-1437 (2005) (SCI)
– Y.-S. Chu, W.-H. Hsu, C.-W. Lin, and W.-S. Wang, "Surface plasmon resonance sensors using silica-on-silicon optical
waveguides," will appear in the May 2006 issue of Microwave and Optical Technology Letters (MOTL) (SCI)
– Lin, H.-C., Hsiao, T.-C., C.-W. Lin, “A web-reader vision aid for low vision”, NIWeek 2001
– C.-W. Lin, Lin Chii-Ming, Lin Hsin-Chih, “An Adaptive Vision Aid for Low Vision with Wavelet Transform”, Annual
Meeting of Chinese Biomedical Engineering Society, Taiwan, R.O.C., Dec. 2002,
• Patents
– 具個別調適功能之數位弱視影像輔助系統林啟萬、林鑫志、蕭子健中華民國00541504,07/11/2003通過
– DIGITAL AMBLYOPIA IMAGE AID SYSTEM WITH INDIVIDUAL ADJUSTABLE CONTRAST SENSITIVITY FUNCTIONLIN, CHII-WANN; LIN,
HSIN-CHIH; HSIAO, TZE-CHIEN美國09/989,427, 03/29/2005通過US6,912,301B1
– 一種多功光電生物醫學晶片檢測儀李世光、薛順成、李舒昇、吳俊彥、林啟萬、林世明中華民國194931, 5/15/2004
– MULTUFUNCTIONAL OPTO-ELECTRONIC BIOCHIP DETECTION SYSTEM LEE, CHIH KUNG, SHIUE, SHUEN-CHEN; LEE, SHU SHENG;
WU, JIUN YAN; LIN, CHII-WANN; LIN, SHIMING LIN美國6,844,935 January 18, 2005
– 以有機光電元件為光源之微型化表面電漿共振感測晶片林啟萬、王子賓、段啟聖、李世光中華民國、美國06/30/2006
Thank you and have a
great meeting!

NTU Nano-BioMEMS Group