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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84637完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃念祖(Nien-Tsu Huang) | |
| dc.contributor.author | Xiao-Wen Chen | en |
| dc.contributor.author | 陳曉汶 | zh_TW |
| dc.date.accessioned | 2023-03-19T22:18:32Z | - |
| dc.date.copyright | 2022-09-19 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-09-15 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84637 | - |
| dc.description.abstract | 血液離子濃度檢測為現今常用來作為免疫狀態監測及提供疾病診斷的方法之一。但傳統做法需要醫護人員進行冗長的樣本前處理並搭配大型儀器量測，導致量測結果無法即時反應病人當前的身體健康狀況。為解決上述問題，我們開發一個整合雙閘極離子敏感場效電晶體 (Dual-gate ion-sensitive field-effect transistor, DG-ISFET)的微流道裝置進行全血處理，並進行原位的血液離子濃度分析。本裝置主要分兩個部分進行。第一部分使用表面添加血球凝集因子(Anti-D)的凹槽陣列進行紅血球沉降，並搭配微米(μm)濾透膜進行高純度且快速的血清萃取。第二部分則使用DG-ISFET結合離子選擇膜 (Ion selective membrane, ISM) 進行血清中特定離子的濃度量測。為驗證上述構想，我們首先使用不同有機鹽類的標準液來最佳化ISM的厚度，接著進行DG-ISFET的血清離子濃度測試，此外也針對陣列凹槽所萃取出的血清進行溶血測試，並使用螢光珠模擬紅血球以探討濾透膜的攔截效果，一旦將上述的ISM參數及流道性能最佳化後，我們注入臨床血液樣本到流道晶片中進行血清的萃取及原位的鈉/鉀離子濃度量測。此實驗驗證了我們可在輸入500 μL的血液當中萃取200 μL的血清並在10分鐘內達到多離子的濃度量測目標，經由上述的結果我們證明此可攜式的檢測系統可用於即時且連續性的血液離子濃度檢測，並在未來將其應用在重症監護病房 (ICU)或是定點照護(POC) 的環境中。 | zh_TW |
| dc.description.abstract | Blood ion testing is commonly used to monitor immune status and physiological information for disease diagnosis. However, traditional methods often require well-trained medical operators to frequently conduct the tedious sample preparation procedures using bulky instruments, which means the results may not be able to reflect the patient's physical conditions in real-time. To solve these problems, we develop a microfluidic device that integrates a dual-gate ion-sensitive field-effect transistor (DG-ISFET) for whole blood pre-treatment and in situ ion concentrations analysis in blood. The system is made of serum extraction section and ion sensing section. In the first section, we used the trench array, coating with RBC agglutination reagent for red blood cells (RBCs) sedimentation, and integrated with a micrometer (μm) filter membrane for rapid and high purity serum extraction. In the second section, we combined DG-ISFET and ion-selective membrane (ISM) for specific ion concentrations sensing in the serum. For proof of concept, we used different standard organic salts solutions to optimize the thickness of ISM. Next, DG-ISFET ion concentrations measurement in serum was conducted. We also performed serum hemolysis tests extracted from the trench array and used fluorescent beads to simulate RBCs to investigate the trapping efficiency of the filter membrane. Once the above ISM parameters and flow channel performance were optimized, we injected the clinical blood sample into the microfluidic chip for serum extraction and in situ sodium/potassium ion concentrations test. This experiment verified that we could extract 200 μL serum from 500 μL of untreated whole blood and achieve the goal of multi-ion concentration measurement in 10 min. From the above results, we proved that this portable DG-ISFET system could be used for real-time and continuous blood ion concentration detection and application in an intensive care unit (ICU) or point-of-care (POC) environments in the future. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T22:18:32Z (GMT). No. of bitstreams: 1 U0001-1309202216141000.pdf: 6533281 bytes, checksum: c501b88ffbb5af523fbb6a8650e3cc74 (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | Contents 口試委員審定書 II 誌謝……….. III 摘要………….. IV Abstract………… V Chapter 1. Introduction 1 1.1. Research background and motivation 1 1.2. Literature review 4 1.2.1. Monitoring of electrolytes in the blood 4 1.2.2. Optical measurement 4 1.2.3. Chemical measurement 5 1.2.4. Electrical measurement- ion-selective electrodes (ISE) 6 1.2.5. Electrical measurement- Ion-sensitive field-effect transistor (ISFET) 7 1.2.6. Summary of current electrolyte monitoring technologies 8 1.3. Applications of ISFET 8 1.4. Applications of ISM- ISFET 13 1.5. On-chip whole blood preparation techniques 18 1.5.1. Microfluidic for the whole blood process 18 1.6. Current challenges and limitations of blood ion detection 19 Chapter 2. Experimental Design 21 2.1. The principle of dual-gate ion-sensitive field-effect transistor (ISFET) 21 2.2. The principle of ISM 24 2.3. The working principle of ISM-modified DG-ISFETs 25 Chapter 3. Material and methods 27 3.1. Experimental setup 27 3.2. Operation procedures of the microfluidic platform 28 3.3. ISFET sensor fabrication 30 3.4. Multiple ISM deposition process 31 3.5. PMMA microfluidic device fabrication 32 3.6. Standard solution preparation 33 3.7. ISM solution preparation 34 3.8. Blood sample preparation 35 Chapter 4. Results and Discussion 36 4.1. Pure ISFET performance 36 4.1.1. pH and Na/K performance 36 4.1.2. The correlation between the cover glass gap and ISM thickness 37 4.2. ISM deposited ISFET performance 38 4.2.1. ISM sensitivity and specificity 38 4.2.2. Mixed solution test 42 4.2.3. The ISM reproducibility test 44 4.2.4. The signal stability of Na/K ISM 45 4.3. Channel performance 46 4.3.1. Na/K ion sensitivity with the channel and filter 46 4.3.2. Beads trapping efficiency 47 4.4. Real clinical sample performance 49 4.4.1. Serum measurement 49 4.4.2. Whole blood processing performance 51 4.4.3. On-chip whole blood ion concentration test 53 Chapter 5. Conclusion 55 Chapter 6. Future work 56 6.1. Standardization of the ISMs fabrication process 56 6.2. The filter-integrated array trench microchamber 56 6.3. Different blood sample types measurement 57 6.4. Heavy metal ion-sensing 57 References 58 LITS OF FIGURES Figure. 1 1 (A) symptoms of abnormal ion concentration balance in serum; (B) the current commercial instrument for ion sensing; (C) the traditional process for detecting blood ion concentrations. 3 Figure. 1 2 Schematic of how LIBS was used for bacterial cells . 5 Figure. 1 3 The zinc half-cell. 6 Figure. 1 4 ISE-based in-line monitoring electrolytes and urea system. 7 Figure. 1 5 ISFET applications (A) identify gram-positive and gram-negative bacteria; (B) DNA amplification and detection; (C) sweat pH value and temperature monitoring; (D) continuous blood ion detection; (E) industrial waste water monitoring. 10 Figure. 1 6 Ion implantation (A) FET structure formation; (B) Si3N4-surface oxidation; (C) deposited Al buffer layer by electron-beam evaporation; (D) introduce Na+ into the oxide layer through the Al buffer layer; (E) Post-implantation treatment, remove the Al buffer layer with an etching solution 11 Figure. 1 7 Applications of ISM-ISFET-based ion detection. (A) bacterial antimicrobial susceptibility test (AST); (B) brain dialysate monitoring; (C) in vitro sweat electrolyte sensing; (D) urine quality test; (E) serum metal ion detection; (F) industrial waste water monitoring. 15 Figure. 1 8 Methods of serum extraction by microfluidics. (A) centrifugation; (B) gravity sedimentation; (C) cross-flow filtration. 19 Figure. 2 1 (A) Schematic of site binding model for a SiO 2 layer. (B) Cross-section view of DG-ISFET with a back-side sensing structure [70]. 23 Figure. 2 2 (A) Structure of valinomycin and Na ionophore X [62]. (B) Scheme of ion to electron process for ISE. The ISM contains a neutral ionophore (L) and an anionic site (R-). I+ is the primary ion. X- is the anion in solution [75]. 25 Figure. 2 3 The principle of ISM-ISFET sensing. (A) system setup for measuring the electrolytic solution; (B) schematic of how ion concentrations affect the ISM-ISFET surface potential; (C) a change in potential surface causes the shift in the current Ids [38]. 26 Figure. 3 1 The experimental setup of the on-chip in-situ multi-ion detection in whole blood: (A) photograph of the portable reader to record and process Ids signal; (B) the photograph of the DISM-ISFET device. The device dimension is 35 mm × 60 mm; (C) 0.22 μm PVDF-filter membrane; (D) microscopic images of the DISM-ISFET sensor deposited Na and K ISM. The sensor dimension is 4 mm × 4 mm; (E) Schematic of the DISM-ISFET device. It consists of (1) top cover layer; (2) filter membrane; (3) bottom chamber with RBC trapping trenches and detection chamber; (4) DISM-ISFET sensor wire bonded onto the PCB board. 28 Figure. 3 2 (A) The cross-sectional view and (B) Operational procedure of the ISM-IFET device. It can be divided into six steps. (1) blood sample loading; (2) RBC trapping and buffer loading; (3) serum purification and buffer withdrawing; (4) serum guiding to the filter chamber; (5) serum withdrawing; (6) recording; (C) The continuous Ids profile at step 2 to 6 to represent in situ Na+/K+ ions sensing features. 30 Figure. 3 3 (A) The real image of the stage. (B) Schematic of multiple ISMs casting. 32 Figure. 3 4 (A) Photo of the Roland EGX-400 CNC machine. (B) The detailed scale of the microfluidic channel. 33 Figure. 4 1 (A) The continuous Ids profile with sequentially loading of three pH solutions (pH 8, 7, 6); (B) five NaCl solutions (10-1.5, 10-1.25,10-1,10-0.75, 10-0.5 M) and five KCl solutions (10-3, 10-2.75, 10-2.5, 10-2.25, 10-2 M); (C) ΔIds of pH solution and (D) NaCl and KCl solutions. 37 Figure. 4 2 The average thickness of the stage-casting Na/K ISM measured by the probe-type surface analyzer at 0.2, 0.3, 0.4, 0.5, and 0.6 mm gap. 38 Figure. 4 3 (A-F) Continuous Ids profile of sequentially loaded NaCl solution (10-1.5, 10-1.25, 10-1, 10-0.75, 10-0.5 M) (solid line) and KCl solution (10-3, 10-2.75, 10-2.5, 10-2.25, 10-2 M) (dash line). (A) without Na ISM; (B-F) with Na ISM formed at (B) 0.2; (C) 0.3; (D) 0.4; (E) 0.5; (F) 0.6 mm gap; ΔIds of (G) NaCl and (H) KCl solution. 39 Figure. 4 4 (A-F) Continuous Ids profile of sequentially loaded NaCl solution (10-1.5, 10-1.25, 10-1, 10-0.75, 10-0.5 M) (solid line) and KCl solution (10-3, 10-2.75, 10-2.5, 10-2.25, 10-2 M) (dash line). (A) without K ISM; (B-F) with K ISM formed at gap of (B) 0.2; (C) 0.3; (D) 0.4; (E) 0.5; (F) 0.6 (mm); ΔIds of (G) NaCl and (H) KCl solution. 41 Figure. 4 5 The continuous ΔIds profile for off-chip H+ ion sensing (A) with and without Na/K ISM; (B) the averaged ΔIds. 42 Figure. 4 6 (A, C) Continuous Ids profiles and (B, D) ΔIds of standard NaCl, KCl, and mixed solution using Na ISM and K ISM, respectively. 44 Figure. 4 7 (A) the ΔIds and (B) the averaged ΔIds in the six repeated stage-casting Na ISM measurements. (C) the ΔIds and (D) the averaged ΔIds in the six repeated stage-casting K ISM measurements. 45 Figure. 4 8 The real-time Ids changed (ΔIds) and averaged ΔIds of long-term Na/K ion sensing with the same Na/K ISM repeated 10 times. 46 Figure. 4 9 The real-time Ids changed (ΔIds) and averaged ΔIds for on-chip (A) Na+ ion sensing with and without filter; (B) K+ ion sensing with and without the filter. 47 Figure. 4 10 (A) Photograph of the PMMA microchamber filled with 6 μL beads at 108 beads/mL; the fluorescent images of beads seeding at (B) the inlet, (C) top of the filter membrane, and (D) the outlet. Scale bar is 50 μm. 48 Figure. 4 11 (A) The real-time Ids change (ΔIds) for off-chip Na/K ion sensing in different serum samples (n=3) and photo of the commercial Na/K meter.; (B) DG-ISFET sensor compared with commercial Na/K meter. The Green zone represents the average Na/K ion concentration level. Each data point represents an individual patient with n = 3. 50 Figure. 4 12 The Anti-D pre-treatment protocol. 51 Figure. 4 13 Plasma extraction performance under different whole blood processing methods. (A) The UV-VIS absorption spectra of the extracted plasma from (1) artificially hemolyzed whole blood (red line); (2) 3 min sedimentation + filter membrane (blue line); (3) 7 min sedimentation + filter membrane (green line); (4) 3 min sedimentation + anti-D treatment + filter membrane (purple line); (5) 7 min sedimentation + anti-D treatment + filter membrane (orange line); (6) centrifuged whole blood (black line). The light bandwidth represents the corresponding standard deviations (n = 3). (B) The absorbance spectra at 414 nm (A414) of the six whole blood processing methods; (C) The real image of the different steps of serum extraction. 53 Figure. 4 14 On-chip blood ions measurement results using DISM-ISFET system and Horiba pocket Na/K meters. The corresponded (A) Na+ ion and (B) K+ ion comparison of two devices. Each point represents an individual clinical sample. (C) the detailed measured Na+ and K+ ion values of nine clinical samples. 54 LITS OF TABLES Table. 1 1 ISFET application for DNA amplification and detection 12 Table. 1 2 Applications of PVC-based ISM-ISFET 16 Table. 3 1 The detailed specification of H, Na, and K pocket meters. 34 | |
| dc.language.iso | en | |
| dc.title | 利用雙閘極敏感場效應電晶體結合多離子選擇膜以及溝槽濾膜流道進行全血處理與血液離子濃度檢測 | zh_TW |
| dc.title | Multi-ion Selective Membrane Deposited Dual-gate Ion-Sensitive Field-Effect Transistor (DG-ISFET) Integrating the Microchamber Embedded Trench and Filter Membrane for Whole Blood Preparation and Ions Concentration Test in Blood | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 盧彥文(Yen-Wen Lu),陳建甫(Chien-Fu Chen),林致廷(Chih-Ting Lin) | |
| dc.subject.keyword | 雙閘極敏感場效應電晶體,離子選擇膜,血液離子濃度檢測, | zh_TW |
| dc.subject.keyword | dual-gate ion-sensitive field-effect transistor (DG-ISFET),ion-selective membrane (ISM),blood ion concentration test, | en |
| dc.relation.page | 63 | |
| dc.identifier.doi | 10.6342/NTU202203357 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2022-09-16 | |
| dc.contributor.author-college | 電機資訊學院 | zh_TW |
| dc.contributor.author-dept | 生醫電子與資訊學研究所 | zh_TW |
| dc.date.embargo-lift | 2022-09-19 | - |
| 顯示於系所單位： | 生醫電子與資訊學研究所 | |
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