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Innovative GaN HEMT based Biosensor Group 4 Instructor: • National Chiao Tung University Compound Semiconductor Device Laboratory Professor Edward Yi Chang • National Tsing Hua University Professor Chuan-Kai Lee GROUP 4 CVO Eileen CTO Simon CEO Celine CFO Annie CPO Zoey Outline • What is our aim target on GaN based biosensor • First disease: Diabetes • Second disease: Breast cancer • Third disease: Prostate cancer • New way: Can’tDia • Suggestions Why we want to aim on Biosensor The market is growing! The Advantages of GaN HEMT Based Biosensor 1 2 3 Low noise due to high eletron mobility Very sensitive to surface charges’ change Good stability to chemical Therefore, we can use GaN based Biosensor to replace the original Silicon Based Biosensor Summary of surface functional layers used with GaN HEMT-based sensor Detection Mechanism Surface Functionalization H2 Catalytic Pd, Pt Pressure change Polarization Polyvinylidence difluoride Botulinum toxin antibody Thioglycolic acid/ antibody Proteins Conjugation/ hybridization Aminopropylsilane/ biotin PH Adsorption of polar molecules Sc2O3, ZnO Hg2+ chelation Thioglycolic acid/ Au KIM-1 antibody KIM-1 antibody Glucose GOX immobilization ZnO nanorods Prostate Specific Antigen PSA antibody Carboxylate succimdyl ester/ PSA antibody Lactic acid LOX immobilization ZnO nanorods Chloride ions Anodization Ag/ AgCl electrodes; InN Breast Cancer antibody Thyioglycolic acid/c-erbB antibody CO2 Absorption of water/ charge Polyethylenimine/ starch DNA hybridization 3’-thiol-modified oligonucleotides O2 oxidation InGaZnO Summary of surface functional layers used with GaN HEMT-based sensor Detection Mechanism Surface Functionalization H2 Catalytic Pd, Pt Pressure change Polarization Polyvinylidence difluoride Botulinum toxin antibody Thioglycolic acid/ antibody Proteins Conjugation/ hybridization Aminopropylsilane/ biotin PH Adsorption of polar molecules Sc2O3, ZnO Hg2+ chelation Thioglycolic acid/ Au KIM-1 antibody KIM-1 antibody Glucose GOX immobilization ZnO nanorods Prostate Specific Antigen PSA antibody Carboxylate succimdyl ester/ PSA antibody Lactic acid LOX immobilization ZnO nanorods Chloride ions Anodization Ag/ AgCl electrodes; InN Breast Cancer antibody Thyioglycolic acid/c-erbB antibody CO2 Medical part Absorption of water/ charge DNA hybridization 3’-thiol-modified oligonucleotides O2 oxidation InGaZnO Polyethylenimine/ starch 1st Applications of biosensor based on GaN in medical field Cancer is leading cause of death Applications of biosensor based on GaN in medical field We should develop the GaN based biosensor in the usage of diabetes, breast cancer and prostate cancer Diabetes ------------------------------------------------ Number of people with diabetes In Taiwan 2,000,000 1,500,000 1,000,000 500,000 2002 2003 2004 2005 2006 Total Male Female 2007 2008 2009 Glucose as diabetes biomarker Quantitation of the glucose content is of extreme importance, as it is the main diabetes biomarker. Optimal management of diabetes involves patients measuring and recording their own blood glucose levels. Blood Glucose Monitoring Traditional Home Blood Glucose Monitoring The traditional method of testing blood glucose involves: • pricking finger with a lancet • putting a drop of blood on a test strip • placing the strip into a meter that displays blood glucose level. Imperfection • uncomfortable for the user • complex procedures Meters That Test Alternative Sites Newer meters allow test sites other than fingertip, include: • upper arm • forearm • base of the thumb • thigh Imperfection • Results are different from the blood glucose levels obtained from the fingertip . • The results are not reliable. Continuous Glucose Monitoring System Some of these devices are combined with insulin pumps. They can be used to see patterns and trends. Imperfection • is not as accurate as finger stick glucose results • expensive in terms of costs 3~4 times/day However, frequent self-monitoring of glucose concentrations is difficult, given: • the time • the inconvenience • the discomfort • the complex procedures • the expensive cost involved with the traditional measurement technique. The American Diabetes Association recommends that: • insulin-dependent type 1 diabetics selfmonitor blood glucose 3–4 times daily • insulin-dependent type 2 diabetics monitor oncedaily So Difficult! It is necessary to develop such a approach: NONINVASIVE ACCURATE SENSITIVE S!MPLE MICROVOLUME LOW-COST Non-invasive glucose sensing is the ultimate goal of glucose monitoring The main approaches being pursued for glucose sensor development are: • Near infrared spectroscopy • Excreted physiological fluid (tears, sweat, urine, saliva) analysis • Microcalorimetry, enzyme • Electrodes • Optical sensors • Sonophoresis and iontophoresis, both of which extract glucose from the skin Glucose biosensors A D V A N T A G E Relative easy of use Speed Minimal risk of infection involved with infrared spectroscopy Low sensitivity Poor selectivity Frequently required calibrations Difficulties with miniaturization D I S A D V A N T A G E GaN High Electron Mobility Transistor Based Biosensors Breast Cancer ----------------------------------------------- Estimated New Cancer Cases and Deaths Worldwide for Leading Cancer Sites by Level of Economic Development, 2008 Estimated New Cases Worldwide Estimated Deaths Incidence of Cancer In Taiwan Death Rate Early Detection Breast cancer screening for women at average risk includes clinical breast exam and mammography. Mammography can often detect breast cancer at an early stage, when treatment is more effective and a cure is more likely. Numerous studies have shown that early detection with mammography saves lives and increases treatment options. - American Cancer Society Breast Cancer Examination Breast Self-examination 20+ Monthly • Not sensitive • Low performance rate Clinical Breast Examination 20s-30s Every Three Years • Hospital only Mammography & Breast Ultrasound & Magnetic Resonance Imaging 40+ Annually • Radiation exposure and uncomfortable process • Rely on doctor experience, supporting Mammography • Injection contrast medium and costly Breast cancer marker: c-erbB-2 antigen Normal patient 4-6 µg/ml Breast Cancer Patient 9-13 µg/ml • • • • Patient Saliva The limit of detection of this device was 0.25 μg/ml c-erbB-2 antigen in PBS buffer solution. Sensitive Portability Non-Invasive Easy to use Prostate Cancer ----------------------------------------------- Estimated New Cancer Cases and Deaths Worldwide for Leading Cancer Sites by Level of Economic Development, 2008 Estimated New Cases Worldwide Estimated Deaths Incidence of Cancer Death Rate Prostate Cancer Examination Prostate cancer antigen blood test Digital rectal exam (DRE) 50+ Every Year • Hospital only • • • Costly Time-consuming Need sample transportation Prostate cancer marker: Prostate-specific antigen (PSA) Normal patient <4 ng/ml Blood 25% chance 4-10 ng/ml 50% chance >10 ng/ml The range of detection of this device was 1 μg/ml 10 pg/ml PSA Can’t Dia The Linkage between Diabetes and Cancers • Type 2 diabetes is associated with increased risk for some cancers. (liver, pancreas, endometrium, colon and rectum, breast, bladder). • Only for prostate cancer is diabetes associated with a lower risk. ---Adopted from Diabetes and Cancer (a consensus report) Find a New Way!!! Diabetes + Breast Cancer = A Biosensor can both diabetes breast cancer detect and Conclusion and Suggestion Possible Collaborator Target Customer Diabetes 五鼎生物技術股份有限公司 台欣科技研發股份有限公司 華廣生技股份有限公司 Diabetic Prostate Cancer 亞諾法生技股份有限公司 台灣基康股份有限公司 Hospital and Clinics Breast Cancer 超微基因偵測科技股份有限公司 Hospital and Clinics 台灣基康股份有限公司 麥利亞德基因科技公司 Diabetes+ Breast Cancer 超微基因偵測科技股份有限公司 40+ years old women 台灣基康股份有限公司 who get diabetes 麥利亞德基因科技公司 Suggestion • Biosensor is a potential market, especially in diagnosis application, according to our study, the potential is diabetes > breast cancer > prostate cancer. • Can’t Dia is from the concept of combination drug, through the same testing procedure but monitoring patient’s cancer risk at the same time, having niche to enter the market. Thank You