1 chemical sensors 報告學生：陳天文授課老師：吳坤憲半導體感測元件報告 2...

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Chemical SensorsChemical Sensors

報告學生：陳天文授課老師：吳坤憲

半導體感測元件報告

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OutlineOutline

І. Introduction

Ⅱ. Electrochemical SensorsⅢ. Biological SensorsⅣ. Discussion and QuestionsDiscussion and QuestionsⅤⅤ. . ReferencesReferences

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化學感測器通常指的是一種體積小、靈敏度高且化學感測器通常指的是一種體積小、靈敏度高且對環境對環境 (( 空氣及水空氣及水 )) 中中特種化合物特種化合物有相當有相當高選擇高選擇性性之感測器。之感測器。

例如例如 : : 葡萄糖生化感測器專門為偵測血液中葡葡萄糖生化感測器專門為偵測血液中葡萄糖而設計。萄糖而設計。化學感測器不僅用在學術研究化學感測器不僅用在學術研究，，且可用在生化樣且可用在生化樣

品偵測以做醫學診斷品偵測以做醫學診斷；；及環境污染現場分析及環境污染現場分析。。

І. 前言

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І. 化學感測器之種類化學感測器之種類

化學感測器依感應元件之種類及目的不同一般分化學感測器依感應元件之種類及目的不同一般分為四大類為四大類 ::

(1)(1) 壓電晶體壓電晶體化學感測器化學感測器 (piezoelectric sensors)(piezoelectric sensors)(2)(2) 電化學電化學感測器感測器 (electrochemical sensors)(electrochemical sensors)(3)(3) 光學光學感測器感測器 (optical sensors)(optical sensors)(4)(4) 生化生化感測器感測器 (biological sensors)(biological sensors)

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І. 化學感測器之應用

臨床及生醫藥物測試，醫療儀器之診斷與治療用研究工業藥廠品管，發酵製程，廢水廢棄物監測農業成熟度、儲藏、農藥與運輸過程之檢測安全防衛毒性物質檢測環保空氣、水質污染機器人自動化檢測應用

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І. 相關重要製造技術之比較相關重要製造技術之比較

半導體製程薄膜製程厚膜印刷製程相對成本高中低可微小化程度次微米 -奈米次微米 -微米微米特殊製程之彈性低高中元件單價不一定低最低再現性與穩定性最高高中

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І. 化學感測器的組成單元感測器的組成單元一般說來，要構成化學感測器（ sensor ）必須要有兩個

基本部分：一是分子辨識單元（ molecular recognition unit ）、二是信號轉換單元（ signal transduction unit ）。

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І. 分子辨識單元

如何得知待測物 (分析物 )? 就要靠「分子辨識」，而推動分子辨識的主要動力是「分子間的作用」；愈多受質(substrate) 與受體 (receptor) 分子間的作用存在，則愈可有效的分子辨識。

用來與待測受質（即分析物）交互作用（ interaction ）的部分。也就是類似一個「陷阱」，可以吸引受質並「捕獲」住；再接著引起後續的信號傳遞（ signal transduction ）。設計分子辨識單元有兩項指標：愈高的選擇性（ selectivity ）及愈強的親和力（ affinity ）愈好。

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І. 信號轉換單元信號轉換單元因我們無法直接看到受質是否被分子辨識單元「辨識」，因此

感測器中需要有告知我們的讀出單元（ readout unit ），即將分子的辨識行為直接（ direct ）轉換為可被讀出的訊號。常用的轉換信號方式有兩種：可轉換成電化學訊號（ electrochemical signal ）或光學信號（ optical signal ）。

分子辨識與信號傳遞兩單元的整合是相當重要的，它直接反應到微觀（ microscopic ）的分子行為是否能有效的被直接巨觀（ macroscopic ）讀出。有極佳的分子辨識單元但無法輕易被觀察，算是設計不良的感測器；有極靈敏的信號傳遞單元但無法辨識特定受質，也是無用。

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Ⅱ. 電化學感測器種類

Potentiometric– Ion Selective Electrode– Redox Electrode– Field Effect Transistor, FET– Gas-sensing electrodes

Amperometric– Oxygen electrode– Glucose electrode

1111

+++++

-----

electrode solution

double layer

OxOx

RedRed

ne-

RΩ

ZwRct

Zf

Cd

Interfacial Phenomenon of Electrochemical SystemInterfacial Phenomenon of Electrochemical System

RΩ is solution resistance

Cdl is capacitance of electro-double layer

Zf is faradaic impedance

Rct is charge transfer resistance

Zw is warburg impedance

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Ⅱ. 化學感測器常用之非金屬薄膜簡介

• 常用的非金屬薄膜包括有 SiO2 、 Si3N4 、 olysilicon 、 silicon oxynitride 、 SiC 、 SiB 、等，而影響薄膜的重要參數包括有鍍膜的溫度、薄膜的內部應力與形變、被覆的邊緣、對蝕刻液的抵抗、及針孔的生成。特別是薄膜的應力與製程有十分的關係，需特別注意。• 有機分子薄膜可用以改善表面的機械特性 (friction) 或形成疏水區域 (hydrophobic region) ，通常可以用 PECVD 生成 .

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Ⅱ. 電化學感測器常用之電極方式

1. 雙電極式 2. 三電極式

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Ⅱ. 電化學感測器 - measurement example

General circuitry for measurement of potential at non-ISE(Ion Selective Electrode) type indicating electrode

1. Indicating electrode.

2. Biological material on indicating electrode.

3. Reference electrode.

4. Electrolyte containing material to be

measured.

5. High impedance potentiometer.

6. Display unit.

7. Operational amplifier current follower.

8. Comparator circuit.

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Ⅱ.電化學感測器之 - Ion Selective Electrode & Redox Electrode

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Ⅱ. 電化學感測器 - ion-sensitive

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Ⅱ. 電化學感測器工作原理 - Potentiometric

Ion-sensitive field effect transistor(ISFET) : 1970 first reported by Bergveld 1974 first pH ISFET with Si3N4

by Matsuo and Wise 1980 first enzyme sensor by Caras and Janata (penicillin)diversified microsensor development for multianalytesmeasurement in clinical applications(Glucose, Urea, Blood Gas..)

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Ⅱ. 薄膜平面式電極

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Ⅱ. Potentiometric - FET

Field Effect Transistor :

VG: applied voltage to gateVD: applied voltage to drain

Source and Substrate tied to Ground.

The source and drain allow theconductivity of the inversion layer at thesurface of the p-type substrate to bemeasured. The current that flows from the drain to the source, ID, is measured as a function of VG and VD.

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Ⅱ. Chemical Sensitive FET (CHEMFET)

Unsaturated region :VD < VG -VT (VDsat)ID =μnWC0x(VG -VT -Eref - ?sol-mem VD/2)/L

Satuurated region :VD > VG -VT (VDsat)ID =μnWC0x(VG - VT -Eref - ?sol-mem )²/2L

1. Silicon substrate 2. insulator 3. Chemically sensitive membrane4. Source 5. drain6. Insulating encapsulant

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Ⅱ. Membranes for Ion Selective FET

• Solid-state membranes : mostly for pH sensing Si3N4 SiO2 hydration in aquesous solutions ZrO2

Al2O3 Ta2O5 good pH sensitivity (52-58 mV/pH), fast response (sec) neglible drift, little hysteresis• Polymer membranes :multiple casting for "pin-hole" free membrane PVC + ionophore for specific ions valinomycin K+

tHODPP Ca2+

• Heterogeneous membranes : compatable with semi-conductor processes, using finly divided powder of inorganic salt, immobilized in a polymer matrix. PNF + silver chloride Cl- PNF + silver iodide + silver sulphide I-, CN-

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Ⅱ. Enzyme-based FET (ENFET)

Applying a thin layer of gel whichcontains the enzyme over the ion-selectivemembrane which typically is pH-sensitiveISFET. PenicillinasePenicillin --------> Penicilloate + H+ GODGlucose + O2 ---->Gluconate+H++H2O2

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Ⅱ. Immunochemical FET (IMFET)

The solution-membrane interface acts as a perfect capacitor. Then the HEMFET can measure the adsorption of charged species at the interface. Since antibodies, antigens, and proteins are generally electrically charged molecules, so the polarized CHEMFET could be used to monitor their non-specific adsorption at the solution-membrane interface. Ab + Ag <----> AbAg K = [AbAg]/[Ab][Ag]

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Ⅱ. ENFET酵素電極之製程

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Ⅱ. 電化學感測器之 Amperometric

By applying a potential between areference and indicating electrode cangive rise to a current which may berelated to the concentration of anelectroactive analyte in solution. Therate of the heterogeneous electrontransfer process can be controlled byvariation of the applied potential. Thereaction current is diffusion limited and can be controlled by electrode surface area, temperature, stirring speed,..etc.

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Ⅱ. 電化學感測器工作原理 - Amperometric

Cycle Voltametric and Electron Transfer : In aqueous solution, one can applypotential "window" from about +1.0 to -0.6 V vs. reference electrode to monitorelectroactive analytes. By scanning the"window" potential with different rate,or different waveform, one can determine the adsorption substance and concentration from the recording CV. However, the major problems are electrode fouling by proteins and filming of the electrode by the product or products of the electron transfer reaction.

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Ⅱ. 平面式二電極感測器及放大電路

• 研發方向 : –最小侵入式 –微電流式化學感測 –MEMS 及 CMOS 製程 –可攜式儀表系統 –酵素固定化

• 利用聯電 UMC 0.5uM DPDM 標準 CMOS製程 (die size: 1.0 mm x 1.0 mm , electrode size: 600 u x 800 u)

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Ⅱ. 化學感測器之生醫應用

Microsensor for Glucose Measurement :

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Ⅱ. Blood Gas Sensor (pH, PO2, PCO2)

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Transducers

signal

Sig

nal

pro

cess

or

Electrochemical

Optical

Thermal

Mass-sensitiveSignal display

Ⅲ. Design Principle of BiosensorDesign Principle of Biosensor

reaction

interferent

analyte

product

Recognition layer

analyte

Bio-affinity

bio-element

bio-element

Bio-catalysis

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Biological bindingBiological binding

Cross-linkingCross-linking EntrapmentEntrapment

Covalent bindingCovalent binding

AdsorptionAdsorption

Immobilizationof

Bio-elements

Immobilizationof

Bio-elements

BA

BA

Ⅲ. Immobilization MethodsImmobilization Methods

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Ⅲ. 葡萄糖生化感測器

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System on System on chipchip

Cross-sectional schematic of the subsurface, embedded MEMS integrated technology.

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Nanotube BlocksNanotube Blocks

Carbon Nanotubes

• diameters to ca. 1 nm

• mechanically robust

• chemical stability

• metals & semiconductors w/o control

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Current Nanosensor Devices - Porous SiliconCurrent Nanosensor Devices - Porous Silicon

PropertiesProperties• PorosityPorosity• NanocrystallinityNanocrystallinity• PhotoluminescencePhotoluminescence

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ApplicationsApplications• Capacitive humidity sensors - metal coated (macro)Capacitive humidity sensors - metal coated (macro)• Ion-sensitive Field Effect Transistor (future)Ion-sensitive Field Effect Transistor (future)

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Nanowire Nanosensors

• Binding of chemical or biological species to the

surface of a nanowire will result in depletion or

accumulation of carriers.

• The change in carrier concentration due to binding

can be directly monitored by measuring the

nanowire conductance.

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Nanowire NanosensorsNanowire Nanosensors

• A solid state FET, whose conductance is modulated by an applied gate, is transformed into a nanosensor by modifying the silicon oxide surface.

• The conductance of modified SiNWs increases stepwise with discrete changes in pH from 2 to 9. Hence, changes in the surface charge can chemically-gate the SiNW .

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Ⅳ. Discussion anDiscussion and d Questions Questions

化學感測器為一新興發展的新科技，目前世界化學感測器為一新興發展的新科技，目前世界各國無不積極投入研究各國無不積極投入研究。。結合化學、醫工及半導體技術之智慧型、積體化、結合化學、醫工及半導體技術之智慧型、積體化、

多機能化、微小生物感測器，是相當令人感興趣多機能化、微小生物感測器，是相當令人感興趣的挑戰。的挑戰。

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Ⅴ. References

電化學分析方法與感測器講義電化學分析方法與感測器講義 :: 台灣大學醫工所林啟萬台灣大學醫工所林啟萬晶片載具與製程講義晶片載具與製程講義 :: 台灣大學醫工所林啟萬台灣大學醫工所林啟萬分子辨識與感測器網頁分子辨識與感測器網頁 ::台大化學系四年級王宗興　 Development of Biosensor and Biosensing Technology Presented by: 成功大學 Hsien-Chang Chang (張憲彰 ) Nanostructured Materials, Nanodevices and Nanosyste

ms used as Nanosensors Presented by: Laura Bukkosy Smith 化學感測器整合計畫研究規劃與成果報導師範大學化學研究所施正雄師範大學化學研究所施正雄

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Current Nanosensor Devices - NanoprobesCurrent Nanosensor Devices - NanoprobesNanosensors - Nanoparticles/NanoprobesNanosensors - Nanoparticles/Nanoprobes

Optical biochemical sensors for near field opticsOptical biochemical sensors for near field opticsSingle molecule localizationSingle molecule localizationIntracellular applications - pH, Ca, Na, K, Cl, O, MgIntracellular applications - pH, Ca, Na, K, Cl, O, Mg

glucose, glutamateglucose, glutamate

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Enabling Nanotechnology for Sensor SystemsEnabling Nanotechnology for Sensor Systems• Cantilevers as resonant/oscillating sensorsCantilevers as resonant/oscillating sensors• Biomolecular Motors for a new class of sensorsBiomolecular Motors for a new class of sensors• Self-assembling nanostructures/new nanomaterials for muSelf-assembling nanostructures/new nanomaterials for multi-analyte sensorslti-analyte sensors• Redox-switchable nanoelectronic devicesRedox-switchable nanoelectronic devices• Nanowires for efficient diodes, lasers, parallel sensors, optNanowires for efficient diodes, lasers, parallel sensors, optical interconnectsical interconnects• Technologies to integrate nanodevices at the nano and maTechnologies to integrate nanodevices at the nano and macro sensing levelscro sensing levels• Nanoscale power sourcesNanoscale power sources

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Enabling Nanotechnology for Sensor SystemsEnabling Nanotechnology for Sensor SystemsNanodevices - Cantilevers as Sensors Nanodevices - Cantilevers as Sensors

• AFM sensor tipsAFM sensor tips• Probes for Specific Probes for Specific

DNA SequencesDNA Sequences

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Definition of NanosensorsDefinition of Nanosensors

Three categories of nanosensors:Three categories of nanosensors:Nanostructured materials - e.g. porous silicon:Nanostructured materials - e.g. porous silicon:

Micro - (features < 2nm)Micro - (features < 2nm)Meso - (features 2nm - 100nm)Meso - (features 2nm - 100nm)Macro - (features > 100nm)Macro - (features > 100nm)

Nanoparticles/NanoprobesNanoparticles/NanoprobesSpherical nanosize materialSpherical nanosize material

Nanodevices/NanosystemsNanodevices/NanosystemsCantilevers, NEMS, mostly theoreticalCantilevers, NEMS, mostly theoretical

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Applications for NanosensorsApplications for Nanosensors

Biomedical Biomedical In vivo - within the body, intracellularIn vivo - within the body, intracellularIn vitro - exterior to the body, test tubeIn vitro - exterior to the body, test tubeDisease detection, cellular repair, drug deliveryDisease detection, cellular repair, drug deliveryMeasurement of pH, calcium, sodium, potassium, Measurement of pH, calcium, sodium, potassium,

chloride, oxygen, glucose, glutamate, magnesiumchloride, oxygen, glucose, glutamate, magnesium

Environmental- methanol, ethanol, 2-propanol, acetone, Environmental- methanol, ethanol, 2-propanol, acetone,

toluene, airborne chemical/biological agentstoluene, airborne chemical/biological agents

Smart MaterialsSmart MaterialsCommunicationsCommunications

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Description: Description: Porous silicon is identical to the silicon used in many Porous silicon is identical to the silicon used in many technological applications today, but its surface contains tiny pores rantechnological applications today, but its surface contains tiny pores ranging from < 2nm to microns, that can absorb and emit light.ging from < 2nm to microns, that can absorb and emit light.

History: History: • Material first reported in 1956 by Uhlir as an effect from electroMaterial first reported in 1956 by Uhlir as an effect from electrochemical polishing studies using a low current density. chemical polishing studies using a low current density. • Chemical etching with HF/HNO3 also produced porous silicon.Chemical etching with HF/HNO3 also produced porous silicon.• Crystalline etch channels found in early 1970’s by Theunissen.Crystalline etch channels found in early 1970’s by Theunissen.• Pickering et. al. first noted photoluminescence at room temperatPickering et. al. first noted photoluminescence at room temperature.ure.• Canham observed room temperature fluorescence in 1990 and suCanham observed room temperature fluorescence in 1990 and suggested Quantum Confinement as origin of fluorescence.ggested Quantum Confinement as origin of fluorescence.

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Manufacturing MethodsManufacturing Methods• Electrochemical EtchingElectrochemical Etching

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Manufacturing MethodsManufacturing Methods• Chemical EtchingChemical Etching

• Spark ErosionSpark Erosion• Chemical Vapor DepositionChemical Vapor Deposition

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PropertiesProperties• PorosityPorosity• NanocrystallinityNanocrystallinity• PhotoluminescencePhotoluminescence

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PropertiesProperties• ElectroluminescenceElectroluminescence• ReflectivityReflectivity• ConductionConduction

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Current Nanosensor Devices - Porous SiliconCurrent Nanosensor Devices - Porous SiliconApplicationsApplications

• Reversible Microcavity Chemical SensorReversible Microcavity Chemical Sensor• MethanolMethanol• EthanolEthanol• 2-Propanol2-Propanol• AcetoneAcetone• TolueneToluene

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• DNA Microcavity BiosensorDNA Microcavity Biosensor• DNA / c-DNA bindingDNA / c-DNA binding

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• Hot wire anemomemeter to measure fluid flowHot wire anemomemeter to measure fluid flow• Thin film bolometers for IR radiation detectionThin film bolometers for IR radiation detection• PhotodetectorsPhotodetectors

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• Capacitive humidity sensors - metal coated (macro)Capacitive humidity sensors - metal coated (macro)• Ion-sensitive Field Effect Transistor (future)Ion-sensitive Field Effect Transistor (future)

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Current Nanosensor Devices - Other Current Nanosensor Devices - Other Nanostructured MatNanostructured Mat

erialserialsMicro Pen Lithography (MPL) and Ink Jet Printing (IJP) ofMicro Pen Lithography (MPL) and Ink Jet Printing (IJP) ofsurfactant-templated mesophase silica - by evaporationsurfactant-templated mesophase silica - by evaporation

• pH sensor arrays (fluorescence)pH sensor arrays (fluorescence)

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Current Nanosensor Devices - NanoparticlesCurrent Nanosensor Devices - NanoparticlesNanosensors - Nanoparticles/NanoprobesNanosensors - Nanoparticles/Nanoprobes

North Western University - Mirkin GroupNorth Western University - Mirkin Group• New Nanostructured Materials and NanosensorsNew Nanostructured Materials and Nanosensors

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Current Nanosensor Devices - NanoparticlesCurrent Nanosensor Devices - NanoparticlesNanosensors - Nanoparticles/NanoprobesNanosensors - Nanoparticles/Nanoprobes

CdSe Nanocrystals as biological sensors/labelsCdSe Nanocrystals as biological sensors/labels

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Current Nanosensor Devices - NanoprobesCurrent Nanosensor Devices - NanoprobesNanosensors - Nanoparticles/NanoprobesNanosensors - Nanoparticles/Nanoprobes

Optical biochemical sensors for near field opticsOptical biochemical sensors for near field opticsSingle molecule localizationSingle molecule localizationIntracellular applications - pH, Ca, Na, K, Cl, O, MgIntracellular applications - pH, Ca, Na, K, Cl, O, Mg

glucose, glutamateglucose, glutamate

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Future NanosensorsFuture NanosensorsNanodevices - Nano Electro Mechanical Systems (NEMS) Nanodevices - Nano Electro Mechanical Systems (NEMS)

• NEMS oscillators (resonant sensors) used to detectNEMS oscillators (resonant sensors) used to detect• Magnetic forces of a single spinMagnetic forces of a single spin• Biomechanical forcesBiomechanical forces• Adsorbed massAdsorbed mass

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Future Nanosensors - NanoparticlesFuture Nanosensors - NanoparticlesNanosensors - Nanoparticles/NanoprobesNanosensors - Nanoparticles/Nanoprobes

• Magnetite - dextran nanoparticles for MRI diagnosis of Magnetite - dextran nanoparticles for MRI diagnosis of liver, lymph node, vascular diseases liver, lymph node, vascular diseases• Iodinated nanoparticles-indirect computed tomography Iodinated nanoparticles-indirect computed tomography lymphography detection of cancerous lymph nodeslymphography detection of cancerous lymph nodes• Magnetically responsive spheres to eliminate target cellMagnetically responsive spheres to eliminate target cells such as erthrocytes, neuroblastoma cells, Burkitt lymphs such as erthrocytes, neuroblastoma cells, Burkitt lymphoma cellsoma cells• Improving activity of neuropeptidesImproving activity of neuropeptides• Gene therapyGene therapy• Oral vaccinationsOral vaccinations

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ConclusionsConclusions• Existing nanosensors have realistic applicationsExisting nanosensors have realistic applications• Current envisioned nanosensors are still based on macroseCurrent envisioned nanosensors are still based on macrosensing techniques that are enhanced or miniaturizednsing techniques that are enhanced or miniaturized• Future nanosensors will create paradigm shiftsFuture nanosensors will create paradigm shifts• Enabling nanotechnology and future nanosensors - in vivo Enabling nanotechnology and future nanosensors - in vivo nanorobots, sensory and repair systems - will be possible witnanorobots, sensory and repair systems - will be possible with the development of nanoelectronics, and integratable nanoh the development of nanoelectronics, and integratable nanodevicesdevices• Fine line between what is science fiction and science factFine line between what is science fiction and science fact

1 chemical sensors 報告學生：陳天文 授課老師：吳坤憲 半導體感測元件 報告 2...

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1 chemical sensors 報告學生：陳天文授課老師：吳坤憲半導體感測元件報告 2...