생체계측과신기술 New Technologies in Biomedical Instrumentation 2003 년 12 월 12 일 의공학교실김희찬
Specific Behavioral Objectives (SBO) 신기술에의한의료기기의새로운동향을설명할수있다.. 바이오센서 (Biosensor) 의원리와특성을설명할수있다.. 바이오칩 (Biochip) 의형태와요소기술들을설명할수있다.. Knowing is is not not enough; we we must must apply. apply. Willing Willing is is not not enough; we we must must do. do. - Johann Wolfgang von von Goethe
CONTENTS New Technology Boom (3T) New Trends in Medical Instruments New Trend Examples New Technology Examples Biosensors Biochips Epilogue
Medical Instruments & New Technologies
Bioelectronics Biocomputer Bioinformatics Telemedicine Biochips BioMEMS Biosensor Bioinstrumentation ALL (INDUSTRY, HOME, MEDICINE ) Computer(H/W, S/W) Semiconductor MEMS Telecommunication Internet Audio/Visual display IT New Technology POCT Map New IT devices : memory, display, sensor, actuator, computer materials Genomics Proteomics Molecular Biology Cell Technology Tissue Engineering MEDICINE BT Nano-Biosensor Nano-Biology Nano-Medicine NT Nano-material Nano-structure Nano-processing Nano-machine ALL ALL OR NONE
신기술붐 - 기술경쟁력확보필요 Genomics BT - 지속적인인프라구축요구 - 융합분야인프라확보절실 - 수익모델개발필요 PC, Telecommunication IT NT 1. 융합기술분야 2. 건강 의료기술분야 Nanotechnology - 일정수준의기술경쟁력확보 - 우수한인프라확보 - 융합분야인프라확보필요 - 수익모델다양화필요 - 본래목적의산업화시간필요 - 지속적인기초연구필요
건강 의료와신기술 신기술의대표적인응용분야 신기술의신속한적용에대해보수적시장 신기술적용을위한의료기기분야변화양상 1. 최소침습화 (minimally invasive) 2. 무구속화 (POC, portable, wireless) 3. 초소형화 (microminiaturized) 4. 대량정보화, 신정보화 (IT-based) 5. 바이오화 (biocompatible)
Minimally invasive
Trend in Glucose Sensor - continuous & noninvasive - Lifescan OneTouch Ultra 3 long, 1.5oz, 1.0 l sample & 5sec reading time MiniMed CGMS continuous glucose measurements for 72 hours Samsung Fine Chemicals Co., Ltd. & ArithMed GmbH GluControl GC300 uses "a non-invasive electromagnetic radiant ray" Medisense Sof-Tact integrated the blood glucose meter within a sampling device(built-in vacuum) Cygnus GlucoWatch automatic glucose measurements every 20 minutes, final FDA approval
Minimally Invasive & Robotic Surgery (JAMA. 2001;285:568-572)
Point-of-Care
Point-of-Care Devices - portable & wearable - www.envitec.com www.sonosite.com www.lifeshirts.com
Point-of-Care Testing Point-of-Care Testing : provision of laboratory testing at the point where patient care is rendered
Point-of-Care Testing ER, OR, ICUs Bed-side Outpatient Clinic Tele-Healthcare Ubiquitous Healthcare Satellite Lab Hand-held Device POCT Tele-care Device Central Lab Home, Office Total Laboratory Automation(TLA)
Thrust of POCT TECHNICAL ISSUES Biosensors BioMEMS/µfluidics Nanotechnology Telecommunication Network ECONOMICAL ISSUES High-cost reagent Sample rareness Low-cost Manufacturing Multifunction High High Throughput Quality Control POCT FUNCTIONAL ISSUES 최소침습화최소침습화 (minimally (minimally invasive) invasive) 무구속화무구속화 (POC, (POC, portable, portable, wireless) wireless) 초소형화초소형화 (microminiaturized) (microminiaturized) 대량정보화대량정보화,, 신정보화신정보화 (IT-based) (IT-based) 바이오화바이오화 (biocompatible) (biocompatible)
Essential Technologies Miniaturized Electro-optic Device Information Network Infra-structure Biomedical Science Biochip Biosensor
Microminiaturized
Endoscopic Microcapsule
The Smart Pill
IT-based
Bioinformatics for DNA µarray SOM K-means clustering Normalization MDS (using PCA) Hierarchical clustering preprocessing Gene expression Data set Class discovery (clustering) Known class info Marker gene selection (feature selection) Class prediction (classification) Soft thresholding ANN SVM CART Boosting And knn Nearest shrunken centroid LDA Logistic regression Bagging etc
Tele-/Ubiquitous- Healthcare Internet Health Monitoring thru Physical & Biochemical Parameters Wireless Wireless LAN LAN ECG, NIBP, SpO 2, temperature, motion, location ------------------- Ion, Gas, Drug, Metabolites, Tumor Marker, Cardiac Marker, Virus, etc.. RF RF Bluetooth Bluetooth TM TM Cellular Network, GPS etc Users anywhere Users anywhere Sensors Monitoring Sensors & Monitoring Device Device Tele-communication Tele-communication network network Medical Medical Service Service Provider Provider
Biocompatible
Bio-artificial Vessel Tissue engineering Bio-artificial Bio-artificial Organs Organs Bio-artificial Liver Bio-artificial Pancreas
Biosnesors & Biochips
Basic Instrumentation System BioSystem measurand target Diagnostic Instrument Sensor Analog signal processing A/D conversion Other types of Energy Electrical Energy Data Input Actuator Calibration Feedback Control Therapeutic Instrument Processor /Algorithm Main Control Unit Digital Signal Processing User Interface Display Storage Xmission
Biosensor Substances Detection Transduction Signal Conditioning analyte (substrate) transducer impurity electronic signal Output biological detection element biolayer High Selectivity & Sensitivity Biocatalysts Biocatalysts Enzymes Enzymes Microorganisms Microorganisms Plant & animal cells Plant & animal cells Subcellularorganelles Subcellularorganelles electronics Bioreceptors Bioreceptors Antibodies/Antigens Antibodies/Antigens Cell membrane receptors Cell membrane receptors Specific binding agents Specific binding agents DNA DNA sample nerve cell olfactory membrane brain
Analyte/Substrate Any substance that is consumed or produced in a biochemical process and exists inside human body Diverse examples Ions Gases Drugs Substrates Enzymes Microbiology Sodium Potassium Calcium ph Oxygen Ammonia CO 2 Paracetamol Slaicylate Amphetamine Barbiturates Cocaine Morphine Glucose Cholesterol Creatinine Creatine kinase Amylase Aspartate Aminotransferase Chlamydia Strep A Strep B H. Pylori I.M. Malaria Tuberculosis Hormones Cardiac Markers Proteins Allergy Renal Dysfunction Tumor Markers Viruses hcg FSH LH Prolactin TSH CK-MB Myoglobin TroponinI CRP IgE Micro- Albumin PSA Hemoglobin AFP Ferritin Adenovirus HBsAg HBsAb Rotavirus R.S.V.
Biological Components Can attach/combine to one particular substrate but not to others High selectivity & sensitivity Examples Enzyme Antibodies Nucleic acids Receptors Microorganisms Cell/Tissue/Organ materials
Immobilization Adsorption B B B Microencapsulation B B B Entrapment Cross-linking Covalent bonding B B B B B B B B B
Transducers Electrochemical potentiometric, amperometric, voltammetric, conductometric electrode, FET-based Optical absorption, fluorescence, luminescence, IRS(ATR, TIRF, SPR), light scattering Piezoelectric : QCM, EQCM Surface Acoustic Waves Thermal
Biochips Cookie Chips DNA/Protein chip CHIPS chip 1 [t íp] n. a piece; a bit; a strip; a slip; a slice; a scrap; a cut;a chop; a fragment; chip 2 n. a piece of silicon semiconductor on which integrated circuit(ic) is fabricated; chip 3 n. a piece of substrate biological detection elements are immobilized; chip 4 n. a piece of silicon semiconductor on which a micro total analysis system is fabricated; IC chip Lab-on-a-chip
Biochips GeneChip, Affymetrix DNA chip, Macrogen Lab-on-a-chip, Michigan Univ. HPV DNA chip, Biomedlab Labchip, Caliper Tech.
Classification of Biochip Biomaterials Test Kit DNA chip cdna oligomer Diagnostics Analysis µtas Screening Lab-ona-chip Protein chip Cell chip Enzyme, Antibody, Antigen Biochip Microorganism Animal cell Neuron Prosthetic device Bioinstrumentation Biocomputing Bio-memory Bioelectronic chip Implantable chip Courtesy of Prof. J.K. Park at KAIST Usage
Elements of Biochip Biosensor Micro- Fluidics Biochip MEMS Bio-MEMS
MEMS Micro-Electro-Mechanical Systems (MEMS) is the integration of mechanical elements, sensors, actuators, and electronics on a common silicon substrate through microfabrication technology. The micromechanical components are fabricated using compatible micromachining processes that selectively etch away parts of the silicon wafer or add new structural layers to form the mechanical and electromechanical devices. For mass production of microstructures with controlled quality
Photolithography Photolithography is the process of transferring geometric shapes on a mask to the surface of a silicon wafer. The steps involved in the photolithographic process are wafer cleaning; barrier layer formation; photoresist application; soft baking; mask alignment; exposure and development; and hardbaking
Disposable pressure transducers MEMS in Medical Devices Accelerometer Wireless Capsule Endoscope DEBIOTECH, Swiss Insulin pump
BioMEMS & µfluidics BioMEMS : new notion of MEMS for Biomedical application, typically using glass of plastic materials Microfluidics : science of designing, manufacturing, and formulating devices and processes that deal with volumes of fluid on the order of 10-9 ~10-12 liter Needs -High-cost reagent -Sample rareness - Lower chip cost (Glass or plastic chips) - Transparency for optical study - Compatible with conventional biological works (Wet or Fluidic System)
Biosensor on a biochip Biosensor on a biochip POCT Blood Analyzer, i-stat Co. Cartridge label Sample entry well gasket Fluid channel Cartridge cover Sample entry well Tape gasket Biosensor chips Calibrant pouch Puncturing barb Cartridge base Air bladder
EPILOGUE 한국산업이선진국과후발국사이에서 nut-cracked 되면서성장잠재력이 5% 대로떨어지는시점에서성장잠재력확충을위한차세대성장동력산업의발굴이절실히요청되고있다.. 특히 1996 년이후 1 인당국민소득이 1 만달러의수렁에빠져증가하지못하면서세계경제의불확실성에대한대처가어려워지고있는데대해국민적공감대를형성하고적극대처할필요가있다.. 보건복지부는차세대성장동력산업의일환으로추진하게될 바이오신약 / 장기 산업육성을위한 5 개추진사업으로 휴대형진단치료기기,, 나노메디컬소재,, 바이오신약,, 바이오장기,, 바이오칩 을선정하였다..