近年來電化學感測器應用在穿戴式裝置相當盛行，其中透過非侵入式感測器檢測人體汗液中乳酸濃度，將有助於進行健康診斷進而了解身體狀況，及早發現疾病將可進一步治療以防止病情惡化。然而，作為穿戴式裝置，酵素型感測器上修飾的酶長期於常溫下使用容易造成失活，且有高生產成本的缺點。為了克服這些問題，開發基於電催化反應的觸媒應用於非酵素型電化學乳酸感測器有了其必要性。
為了開發出合適的電催化材料應用於非酵素型電化學乳酸感測器，在第四章本研究提出使用層狀雙氫氧化物(Layered double hydroxide, LDH)作為電催化材料，並引入電催化乳酸之氧化反應，開發出非酵素型電化學乳酸感測器。Ni LDH修飾之網印刷碳電極對於乳酸已有著不錯的感測能力，在0.55 V (vs. Ag/AgCl KCl Sat’d)的施加電位下具有23.51 μA mM-1 cm-2的感測靈敏度，而乳酸檢測的濃度線性範圍則為5~25 mM。本研究嘗試摻入第二元金屬合成NiFe LDH以及NiCo LDH，探討導入第二元金屬的LDH對於乳酸感測能力的影響，結果顯示NiCo LDH修飾之網印刷碳電極在0.55 V (vs. Ag/AgCl KCl Sat’d)的施加電位下具有30.59 μA mM-1 cm-2的感測靈敏度。為了實踐應用於檢測汗液的穿戴式電化學乳酸感測器，本研究進行了人體汗液中常見的物質來進行干擾測試，結果顯示NiCo LDH修飾之電極對於乳酸具有優異的選擇性。NiCo LDH修飾之電極擁有0.533 mM的偵測極限，而對於人體內汗液成分來說，正常的乳酸濃度一般大約是5~20 mM，因此這樣的偵測極限是足夠使用的。為了臨摹人體使用環境，NiCo LDH修飾之電極在攝氏35度以及濕度為70%的環境下進行保存，在經過28天之後電極擁有98.72%的回覆率，相較於酵素修飾電極的49.24%的回覆率，結果顯示非酵素型電化學乳酸感測器應用於穿戴式裝置將更具優勢。
NiCo LDH修飾之電極擁有較高乳酸感測靈敏度的結論下，在第五章改變水熱法的合成方式，使用沸石咪唑骨架材料(Zeolitic imidazolate framework-67, ZIF-67)為Co的前驅物，進而轉換成NiCo LDH。使用此合成方法衍生之NiCo LDH，除了能保有ZIF-67原先立體結構的形貌提供更大的比表面積，透過轉換能在材料表面產生LDH的結構。這樣的合成方式相較於第四章使用水熱法合成之NiCo LDH，有效的提升了材料對於乳酸的電催化活性，乳酸感測靈敏度從30.59 μA mM-1 cm-2提升至83.98 μA mM-1 cm-2。另外在前驅物ZIF-67的合成過中藉由加入不同濃度的CTAB能夠控制粒徑大小，進而轉換出不同尺度之NiCo LDH，結果顯示在中型尺度下之NiCo LDH對於乳酸有著較佳的感測能力。為了實踐應用於人體汗液非侵入式檢測，本研究使用了二極式元件型的量測系統，樣品取自真實人體的汗液並使用0.1 M NaOH進行稀釋，結果顯示此系統能夠分辨有氧運動與無氧運動下乳酸濃度的差異。

The availability of a simple electrochemical sensor for monitoring lactate concentration in biological fluids can minimize the disease risks and facilitate the health diagnostics. To improve the reliability and stability of wearable sensors, how to inhibit the biological degradation of the expensive enzyme was important. To solve the above issue, non-enzymatic lactate detection with proper electrocatalysts was proposed and developed. In this study, layered double hydroxide (LDH) based electrocatalysts were synthesized and further introduced to electrocatalyze lactate oxidation reaction. The results revealed that Ni-based LDH exhibited good electrocatalytic activity for oxidizing lactate molecule. After decorating with secondary metal ion into the structure of LDH, a sensitivity of NiCo LDH was reached to 30.59±0.34 μA mM-1 cm-2 (R2=0.9993 within the linear ranges of 5~25 mM) at an applied potential of 0.55 V (vs. Ag/AgCl KCl Sat’d) without any signal of interferents, such as ascorbic acid, glucose, and other ions. To further improve the sensitivity of NiCo LDH, ZIF-67 derived NiCo LDH with various particle sizes for non-enzymatic lactate sensors were synthesized and discussed. After optimization of the particle size of ZIF-67, the sensitivity of ZIF-67 derived NiCo LDH for lactate was approached to 83.98 μA mM-1 cm-2 at an applied potential of 0.55 V (vs. Ag/AgCl KCl Sat’d), which was attributed to its intrinsic 3D structure and high porosity. In the final part, the concentration of lactate in the real human sweat was examined by our proposed electrochemical sensors. This work provides potential electrocatalytic materials for utilizing in enzyme-free electrochemical lactate sensor with reliable and stable performance to further introduce in wearable electronics.

[1] J.Kim ,A.S. Campbell and J. Wang, Wearable non-invasive epidermal glucose sensors: A review, Talanta, 2018, 177, 163-170.
[2] L.Rassaei, O. Wouter , T. Seiya, J.R.Ernst, Lactate biosensors: current status and outlook, Analytical and Bioanalytical Chemistry, 2014, 406, 123-137.
[3] S.O.Garcia, Y. V. Ulyanova, R. Figuero, K. H. Bhatt, S. Singhal, P. Atanassov, Wearable Sensor System Powered by a Biofuel Cell for Detection of Lactate Levels in Sweat, ECS Journal of Solid State Science and Technology, 2016, 5, 3075-3081.
[4] L.J.Currano, F. C. Sage, M. Hagedon, L. Hamilton, J. Patrone, Wearable Sensor System for Detection of Lactate in Sweat, Surface Science Reports, 2018, 8, 15890.
[5] P.Manivel, S. Vembu, N.Noel, V. David, M. Kanagaraj and K.Murugavel, A novel electrochemical sensor based on a nickel-metal organic framework for efficient electrocatalytic oxidation and rapid detection of lactate, New Journal of Chemistry, 2018, 42, 11839-11846.
[6] S.Kim, K.Kim, H.J.Kim, H.N.Lee, T.J.Park and Y. M. Park, Non-enzymatic electrochemical lactate sensing by NiO and Ni(OH)2 electrodes: A mechanistic investigation, Electrochimica Acta, 2018, 276, 240-246.
[7] J.Pena-Bahamonde, H. N. Nguyen, S. K. Fanourakis and D. F. Rodrigues, Recent advances in graphene-based biosensor technology with applications in life sciences, Journal of Nanobiotechnology, 2018, 16, 75.
[8] J.Kim, A.S.Camppbell, Wearable biosensors for healthcare monitoring, Nature Biotechnology, 2019, 37, 389-406.
[9] http:// onlinelibrary.wiley.com/doi/abs/10.1002
[10] I.I.K.Steineck, Z. Mahmoudi, A. Ranjan, S.Schmidt, J. Bagterp, K. gard , Comparison of Continuous Glucose Monitoring Accuracy Between Abdominal and Upper Arm Insertion Sites, Diabetes Technology and Therapeutics, 2019, 21, 295-302.
[11] S.K.Vashist, D. Zheng and H.T. Luong, Technology behind commercial devices for blood glucose monitoring in diabetes management: a review, Analytica Chimica Acta, 2011, 703, 124-136.
[12] N.J.Forrow and S.J. Walters, Transition metal half-sandwich complexes as redox mediators to glucose oxidase, Biosens Bioelectron, 2004, 19, 763-770.
[13] http. ://www.dovepress.com/physicochemical-and-biological-comparison
[14] A.Kubiak and M.Biesaga, Porphyrins in analytical chemistry. A review, Talanta, 2000, 51, 209-224
[15] W.S. Wang, W.T. Kuo,H.Y. Huang and C.H. Luo, Wide dynamic range CMOS potentiostat for amperometric chemical sensor, Sensors-Basel, 2010, 10, 1782-1797.
[16] J.M.Peake, G. Kerr and J.P. Sullivan, A Critical Review of Consumer Wearables, Mobile Applications, and Equipment for Providing Biofeedback, Monitoring Stress, and Sleep in Physically Active Populations, Frontiers in Physiology, 2018, 9, 743.
[17] M.Ha, S. Lim and H.Ko, Wearable and flexible sensors for user-interactive health-monitoring devices, Journal of Materials Chemistry B, 2018, 6, 4043-4064.
[18] S.Sharma, Z.Huang , M. Rogers and M. Boutelle, Evaluation of a minimally invasive glucose biosensor for continuous tissue monitoring, Analytical and Bioanalytical Chemistry, 2016, 408, 8427-8435.
[19] N.I.Khan, and E.Song, Lab-on-a-Chip Systems for Aptamer-Based Biosensing. Micromachines-Basel, 2020, 11, 220
[20] http://www.yole.fr/BIOMEMS_MarketUpdate.aspx
[21] M.Bariya, H.Y.Y. Nyein and A.Javey, Wearable sweat sensors, Nature Electronics, 2018, 1,160-171.
[22] https://academic.oup.com/jnci/article/89/23/1763/2526545
[23] J.Weber, A. Kumar and S. Bhansali, Novel lactate and pH biosensor for skin and sweat analysis based on single walled carbon nanotubes, Sensors and Actuators B: Chemical, 2006, 117, 308-313.
[24] H.Zheng, S. Zhang, X. Liu, Y. Zhou and S. Alwarappan, Synthesis of a PEDOT-TiO2 heterostructure as a dual biosensing platform operating via photoelectrochemical and electrochemical transduction mode, Biosens Bioelectron, 2020, 162, 112234.
[25] M.M.Hussain, A.M.Asiri and M.M.Rahman, A non-enzymatic electrochemical approach for l-lactic acid sensor development based on CuO·MWCNT nanocomposites modified with a Nafion matrix, New Journal of Chemistry, 2020, 44, 9775-9787.
[26] Z.Cai, X. Bu, Pi. Wang, J.C. Ho, J. Yangac and X.Wang, Recent advances in layered double hydroxide electrocatalysts for the oxygen evolution reaction, Journal of Materials Chemistry A, 2019, 7, 5069-5089.
[27] J.M.Lee, T.H. Gu, N. H. Kwon, S. M. Oh, and S.-J. Hwang, Rapid Synthetic Route to Nanocrystalline Carbon-Mixed Metal Oxide Nanocomposites with Enhanced Electrode Functionality. The Journal of Physical Chemistry C, 2016, 120, 8451-8460.
[28] T.Wang, S. Zhang, X.Y.Orcid, M. Lyu, L. Wang, J. Bell, and H. Wang 2-Methylimidazole-Derived Ni-Co Layered Double Hydroxide Nanosheets as High Rate Capability and High Energy Density Storage Material in Hybrid Supercapacitors, ACS Applied Materials & Interfaces, 2017, 9, 15510-15524.
[29] https://www.capterra.com/p/187000/Reviso/
[30] M.Gong, Y. Li, H. Wang, Y. Liang, J. Z. Wu, J. Zhou, J. Wang, T. Regier, F. Wei, and H. Dai, An advanced Ni-Fe layered double hydroxide electrocatalyst for water oxidation, Journal of the American Chemical Society, 2013, 135, 8452-8455.
[31] S.Samuei, J. Fakkar, Z. Rezvani and B.Habibi, Synthesis and characterization of graphene quantum dots/CoNiAl-layered double-hydroxide nanocomposite: Application as a glucose sensor. Analytical Biochemistry, 2017, 521, 31-39.
[32] F.M.Mulder, D. Theo, H.Schimmel and G.Kearley, Hydrogen adsorption strength and sites in the metal organic framework MOF5: Comparing experiment and model calculations, Chemical Physics, 2008, 351, 72-76.
[33] J.Liu, Z. Guo, J. Kaltbeitzel, H. Zhang, Z. Cao and M. Lord, Metal-organic frameworks as protective matrices for peptide therapeutics, Journal of Colloid and Interface Science, 2020, 576, 356-363.
[34] J.L.Mendoza-Cortes, S.S. Han and W.A. Goddard, High H2 uptake in Li-, Na-, K-metalated covalent organic frameworks and metal organic frameworks at 298 K, Journal of Physical Chemistry A, 2012, 116, 1621-1631.
[35] H.Furukawa, K.E. Cordova, M.O.Keeffe and O. M. Yaghi, The chemistry and applications of metal-organic frameworks, Science, 2013, 341, 1230444.
[36] L.E.Kreno, K. Leong, O. K. Farha, M. Allendorf, R. P. Van, and J.T. Hup, Metal-organic framework materials as chemical sensors, Chemical Reviews, 2012, 112,1105-1125.
[37] https://pubs.acs.org/doi/abs/10.1021/ja8057953
[38] P.Horcajada, R. Gref, T.Baati, P. K. Allan, G. Maurin, P. Couvreur,G. Ferey, R.E. Morris and C. Serre, Metal-organic frameworks in biomedicine. Chemical Reviews, 2012, 112, 1232-1268.
[39] A.S.Chang, N.N. Memon, S. Amin, F. Chang, U. Aftab, M.I. Abro, A. Chandio and A. Ahmed Sha Facile Non‐enzymatic Lactic Acid Sensor Based on Cobalt Oxide Nanostructures, Electroanalysis, 2019, 31,1296-1303.
[40] Z.Wang, T.Liu, M. Asif, Y. Yu, W. Wang, H. Wang, F. Xiao and H. Liu, Rimelike Structure-Inspired Approach toward in Situ-Oriented Self-Assembly of Hierarchical Porous MOF Films as a Sweat Biosensor, ACS Applied Materials & Interfaces, 2018, 10, 27936-27946.
[41] O.D.Morales, I.L.Yanez, M.T.M. Koper and F.C.Vallejo, Guidelines for the Rational Design of Ni-Based Double Hydroxide Electrocatalysts for the Oxygen Evolution Reaction, ACS Catalysis, 2015, 5, 5380-5387.
[42] J.Jiang, A. Zhang, L. Li and Lunhong Ai, Nickel–cobalt layered double hydroxide nanosheets as high-performance electrocatalyst for oxygen evolution reaction, Journal of Power Sources, 2015, 278, 445-451.
[43] J.Zhou, M. Min, Y. Liu, Jian Tang and W. Tang, Layered assembly of NiMn-layered double hydroxide on graphene oxide for enhanced non-enzymatic sugars and hydrogen peroxide detection. Sensors and Actuators B: Chemical, 2018, 260, 408-417.
[44] C.Wang, Facile Synthesis of Ni-Co LDH Nanocages with Improved Electrocatalytic Activity for Water Oxidation Reaction, International Journal of Electrochemical Science, 2017, 10003-10014.
[45] E.Asadian, S. Shahrokhian and A.I.Zad, Highly sensitive nonenzymetic glucose sensing platform based on MOF-derived NiCo LDH nanosheets/graphene nanoribbons composite, Journal of Electroanalytical Chemistry, 2018, 808, 114-123.
[46] Z.Lu, H.Xing, R. Sun, J. Bai, B. Zheng and Y. Li, Water Stable Metal–Organic Framework Evolutionally Formed from a Flexible Multidentate Ligand with Acylamide Groups for Selective CO2 Adsorption, Crystal Growth & Design, 2012, 12, 1081-1084.
[47] K.S.Park, Z.Ni, and A.P.Cote, Exceptional chemical and thermal stability of zeolitic imidazolate frameworks, Proceedings of the National Academy of Sciences of the United States of America, 2006, 103, 10186-10191
[48] H.Hu, B.Y.Gua and W.Lou, Construction of Complex CoS Hollow Structures with Enhanced Electrochemical Properties for Hybrid Supercapacitors, Chemical Science, 2016, 1,102-113.
[49] J.Goldstein, D.E.Echlin, J.Charles, L. Eric, Scanning Electron Microscopy and X-ray Microanalysis, Springer Nature, 2000, 6, 1-20.
[50] http:// www.sppic.ntust.edu.tw/files/15-1105-51522,c5703-1.php?Lang
[51] https://en.wikipedia.org/wiki/X-ray_photoelectron_spectroscopy.
[52] https://www.ssi.shimadzu.com/products/uv-vis-spectrophotometers
[53] M.Shakeel, M.Arif, G.Yasin and B.Li, Layered by layered Ni-Mn-LDH/g-C3N4 nanohybrid for multi-purpose photo/electrocatalysis: Morphology controlled strategy for effective charge carriers separation, Applied Catalysis B: Environmental, 2019, 242, 485-498.
[54] W.Zheng, L.Hu and K.Y.Wong, Copper nanoparticles /polyaniline /graphene composite as a highly sensitive electrochemical glucose sensor. Journal of Electroanalytical Chemistry, 2016, 781, 155-160.
[55] B.Egan and J.R. Zierath, Exercise metabolism and the molecular regulation of skeletal muscle adaptation, Cell Metabolism, 2013, 17, 162-184.
[56] Y.Yang, L.D.Melinda, J. Shearer, H. Sheng, W. Li, J.Chen, P. Xiao and Y. Zhang, Highly Active Trimetallic NiFeCr Layered Double Hydroxide Electrocatalysts for Oxygen Evolution Reaction, Advanced Energy Materials, 2018, 8, 1703189
[57] Z.Wang, M. Gui, M. Asif, Y. Yu, S. Dong, H. Wang, W. Wang, F.Wang, F.Xiao and H. Liu, A facile modular approach to the 2D oriented assembly MOF electrode for non-enzymatic sweat biosensors, Nanoscale, 2018, 10, 6629-6638.