臺灣博碩士論文加值系統

場效電晶體(field-effect transistor, FET) 長久以來在生物感測上是具有高靈敏度的工具，然而若要應用在醫學臨床上卻有一大限制，即被偵測的生物分子樣本不能在高鹽類濃度的環境下進行檢測，如常見的人體血液和尿液。此類溶液含有高濃度的離子，會屏蔽待測分子給予偵測通道的作用電場(interacting electric field )，此現象稱為Debye screening effect。為了克服這項障礙，我們發展出新穎的光電生物感測技術(optoelectronic biosensor)，可以在高濃度鹽類的緩衝液中(例如：10× PBS(phosphate buffered saline) 其Debye length為~0.23 nm；10× NMG buffer其Debye length為~0.7 nm) 偵測到不同濃度的目標生物分子。此項技術是利用光激發半導體元件裡的帶電載子，而非傳統之場效電晶體是由外在電場誘發帶電載子的機制；由於高濃度離子溶液不易影響光的穿透，因此由光激發而產生的帶電載子之訊號，可順利被半導體元件偵測。
我們設計的光電生物檢測元件是由二維半導體材料之二硫化錫作為基底的場效電晶體(SnS2-FET) ，並和上轉換奈米粒子(upconverting nanoparticles, UCNPs) 連結所組成；兩材料間由適體(aptamer) 鍵結，作為目標生物分子的受體。二硫化錫為n-型半導體具有2.2 eV（~560 nm）的能隙，當UCNP/SnS2-FET受980 nm的紅外光照射後，UCNP會釋放530 nm的綠光，此綠光會激發SnS2-FET內之電子而產生光致電流。而在目標分子與適體結合時，適體因和目標分子相互作用產生纏繞而彎曲，縮短了UCNP和SnS2間的距離，SnS2-FET感受到的光強度會因而上升，造成SnS2-FET被激發的電子數目增加，所以在目標分子與適體的鍵結前後，我們可量測SnS2-FET元件的電流訊號變化來感測目標分子的存在與否，並可定量目標分子的濃度。
本研究主題利用檢測兩項目標分子：多巴胺和鉀離子來確認此技術的可行性、靈敏度、及偵測極限，結果顯示UCNP/SnS2-FET可成功於1× PBS和10× NMG 緩衝溶液下分別偵測到1 pM的多巴胺和100 pM的鉀離子。

Field-effect transistors (FETs) have long been employed as high-sensitive biosensors for detecting biomolecules, but they also encounter a stringent challenge of the Debye screening effect on the signal detection in physiological buffers, which hinders the further applications of FETs in clinical diagnosis. For the Debye screening effect, because the ions and charged molecules in a high-salt buffer, e.g., human serum or urine, will shield the interacting potential exerted by the charged targets toward the sensing channel of an FET, the signals are severely attenuated. To overcome this difficulty, we developed an innovative optoelectronic biosensor, which is able to detect targeted biomarkers in high concentrated buffers, like 10× phosphate buffered saline (PBS) with a Debye length of ~0.23 nm and 10× N-methyl-d-glucamine (NMG) buffer with a Debye length of ~0.7 nm. The working principle of this newly designed optoelectronic FET biosensor is based on the fact that the FETs are excited by light rather than by electric field in traditional FETs. Since the penetration of light in a concentrated electrolytic environment is not strictly impeded, the signals of photo-induced currents in the optoelectronic FETs can be well detected.
Our optoelectronic biosensor is composed of a 2D layered semiconductor crystal (tin disulfide, SnS2)-fabricated FET in conjunction with upconverting nanoparticles (UCNPs) via aptamer linkers (referred to as UCNP/SnS2-FET). In a UCNP/SnS2-FET biosensor, the aptamer also acts as a receptor for detecting a specific target. When binding with the target, the aptamer is entangled to shorten the distance between UCNPs and the SnS2-FET; consequently, the upconverted green emission (~530 nm) from 980 nm-excited UCNPs irradiates more intensively on the SnS2-FET (with a bandgap of 2.2 eV ~ 560 nm), resulting in a signal change. By recording the signal change in the SnS2-FET, targeted biomarkers can be detected and quantified.
The aim of this research is to investigate the feasibility, sensitivity, and detection limit of a UCNP/SnS2-FET biosensor by detecting two targeted biomolecules: dopamine and potassium ion. The experimental results demonstrate that we can successfully detect 1 pM of dopamine and 10 pM of potassium ions in 1× PBS and 10× NMG buffer, respectively.

口試委員會審定書 #
謝誌 i
中文摘要 ii
ABSTRACT iv
目錄 vi
圖目錄 ix
簡稱用語對照表 xvi
Chapter 1 導論 1
1.1 二硫化錫簡介 1
1.2 上轉換奈米粒子簡介 2
1.3 場效電晶體生物感測器及其限制 3
1.4 研究動機與設計 7
Chapter 2 文獻回顧 9
2.1 層狀二硫化錫的材料結構與特性 9
2.2 二硫化錫之製備 11
2.2.1 機械剝離法 11
2.2.2 液相剝離法 12
2.2.3 物理氣相沉積法 13
2.2.4 化學氣相沉積法 14
2.3 二硫化錫場效電晶體(SnS2-FET) 15
2.4 上轉換奈米粒子介紹 19
2.4.1 組成與功能 19
2.4.2 能量上轉換的機制 23
2.5 上轉換奈米粒子之製程方法 27
2.5.1 共沉澱法(coprecipitation method) 27
2.5.2 熱裂解法(thermal decomposition method) 28
2.5.3 水熱法(Hydrothermal/solvothermal method) 29
2.6 鉀離子 30
2.7 多巴胺 32
Chapter 3 材料與方法 34
3.1 二硫化錫場效電晶體元件製作 34
3.1.1 基板準備 34
3.1.2 機械剝離法製備二硫化錫之二維奈米材料 34
3.1.3 熱蒸鍍金屬電極 35
3.2 上轉換奈米粒子的合成與官能基修飾 36
3.2.1 UCNP外殼層結構之合成(α-NaYF4) 36
3.2.2 UCNP核心結構之合成(β-NaYF4:Yb, Er) 36
3.2.3 UCNP內核-外殼雙層結構之結合(NaYF4:Yb, Er@NaYF4) 37
3.2.4 UCNP表面之二氧化矽塗佈(Silica-NaYF4:Yb, Er@NaYF4) 37
3.2.5 UCNP表面之胺基修飾(NH2-NaYF4:Yb,Er@NaYF4) 38
3.2.6 UCNP表面之醛基修飾(OHC-NaYF4:Yb, Er@NaYF4) 39
3.3 DNA適體和上轉換奈米粒子修飾於元件表面 40
3.3.1 介電層之表面塗佈 40
3.3.2 DNA適體之修飾 40
3.3.3 UCNP與DNA適體之鍵結 41
3.4 光電生物感測 42
3.4.1 微流道系統 42
3.4.2 生物感測裝置架設 43
Chapter 4 結果與討論 46
4.1 二維奈米材料-二硫化錫之厚度鑑定 46
4.2 上轉換奈米粒子性質鑑定 47
4.3 二硫化錫場效電晶體之量測 48
4.3.1 電性量測 48
4.3.2 光電特性量測 51
4.4 螢光共振能量轉移-適體結構的變化確認 53
4.5 表面修飾證明 56
4.5.1 螢光影像檢測 56
4.5.2 液相閘極電壓檢測 57
4.6 光電檢測機制之確認 58
4.7 鉀離子之光電生物量測 60
4.8 多巴胺之光電生物量測 63
4.9 光電生物量測之控制組 67
Chapter 5 結論 69
參考文獻 71

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