側向流體免疫分析法(Lateral Flow Immunoassay, LFIA) 的快篩試紙針對特殊疾病
或病癥的反應會在測試線上呈色，根據先前研究已知呈色現象是奈米金粒子在與蛋
白質交互反應後會產生肉眼可見的淡紅色至深紅色，可以依照濃度深淺給予個別病
兆輕度、中度、重度等量表的定義。目前LFIA 快篩試紙以肉眼目測為主，常受到判
定者主觀認知影響結果，若要更進一步精準的判定結果則需要仰賴醫療系統中心內
的傳統醫療用檢測儀，傳統的醫療用檢測儀器非常昂貴，所以要做到低成本又不失
精準的檢測方法十分困難。於此，本文設計一套超緊湊光學系統來給予LFIA 試紙的
定量化分析，旨在開發一套系統能維持LFIA 成本低、操作容易的優勢；媲美院方昂
貴儀器的精準度。
在這次研究中開發一套可偵測波長400∼1000nm、光譜解析度5∼8nm、狹縫
20μm、光柵間距3μm、整體尺寸20 × 10.5 × 10 mm 的光譜模組，光譜模組搭載於電
路板與其他光學機構，成為光譜檢測平台。光譜檢測平台可透過指令對LFIA 試紙進
行單點式掃描取得光譜，由大量光譜數據進行分析。建構好的光譜量測平台經由實
驗室校正完成之後，偕同醫療機關執行臨床檢驗並與食藥署核可的測定方法比對。
藉由兩個臨床案例實驗做大規模的功能確校，其一是新冠肺炎染疫初期的早期判定，
光譜檢測平台協助LFIA 檢測可得12 筆陽性檢體100% 檢出且IgG 及IgM 的偵測極
限個別可達11.67ng 及10.17ng；其二是新冠疫苗施打後抗體保護力判定，光譜檢測
平台與食藥署核可的檢定法cPass assay 測得抑制率作比對，其線性回歸關聯係數達
0.864、雙尾T 測試p<0.001 有極高的顯著區別判定有無疫苗保護力及Bland-Altman
分析法信賴區間高達94.2%，證實本研究架構的光學平台於臨床檢驗是可行的。

The lateral flow immunoassay (LFIA) is a paper-based platform with extensive application in point-of-care (POC) testing and many fields. However, its clinical application is severely limited due to the lack of quantitative ability of standard LFIA tests, whose color intensity of the test line varies depending on the concentration of the target analyte tested. Our proposed ultra-compact optical system can significantly reduce misinterpretations of LFIA results. It can be used to conduct an LFIA without having any expert around, thereby minimizing the waste of healthcare resources and making it easier for researchers in academia and industry to perform LFIA-related experiments.
Our proposed optical system had a detectable wavelength range of 400∼1000nm, a spectral resolution of 5∼8nm, and an entrance slit of 20 μm, the chip was made of SU-8 thick film photoresists and the size is 20 x 10.5 x 10mm. Two clinical research were conducted for largescale functional validation via our system,one of which was the early detection in COVID-19 pandemic. Our developed platform assisted LFIA to achieve 100% sensitivity of 12 positive serums and the limit of detection IgG and IgM was 11.67ng and 10.17ng. Secondly, aiming to detect COVID-19 vaccines efficacy through neutralizing antibodies, the linear regression correlation coefficient of 0.864 and the p<0.001 of the two-tailed T-test were compared with the cPass assay approved by the FDA, and the confidence interval of the Bland-Altman assay was 94.2%, confirming that the optical platform of this study is feasible for clinical testing.

[1] R. Maboudian, “Surface processes in mems technology,” Surface Science Reports,
vol. 30, no. 6-8, pp. 207–269, 1998.
[2] M. J. Madou, Fundamentals of microfabrication: the science of miniaturization. CRC press, 2002.
[3] K. Gupta, N. K. Jain, and R. Laubscher, “Chapter 4 - advances in gear manufacturing,” in Advanced Gear Manufacturing and Finishing, K. Gupta, N. K. Jain, and R. Laubscher, Eds. Academic Press, 2017, pp. 67–125.
[4] M. Neviere and W. R. Hunter, “Analysis of the changes in efficiency across the ruled area of a concave diffraction grating,” Applied Optics, vol. 19, no. 12, pp. 2059–2065, 1980.
[5] M. C. Hettrick, “Varied line-space gratings: past, present and future,” in Diffraction Phenomena in Optical Engineering Applications, vol. 560. SPIE, 1986, pp. 96–108.
[6] A. Mudcharoen and S. S. Makhanov, “Optimization of rotations for six-axis machining,” The International Journal of Advanced Manufacturing Technology, vol. 53, no. 5, pp. 435–451, 2011.
[7] Y. Liu, X. Tan, X. Xu, Y. Hong, and S. Fu, “Design and fabrication of soft x-ray blazed diffraction gratings,” in ICO20: Optical Devices and Instruments, vol. 6024. SPIE, 2005, pp. 650–656.
[8] Y. Liu, X. Tan, Z. Liu, X. Xu, Y. Hong, and S. Fu, “Soft x-ray holographic grating beam splitter including a double frequency grating for interferometer pre-alignment,”Optics Express, vol. 16, no. 19, pp. 14 761–14 770, 2008.
[9] P. Mouroulis, D. W. Wilson, P. D. Maker, and R. E. Muller, “Convex grating types for concentric imaging spectrometers,” Applied Optics, vol. 37, no. 31, pp. 7200–7208, 1998.
[10] J. P. Backlund, D. W. Wilson, and R. E. Muller, “Structured-groove phase gratings for control and optimization of the spectral efficiency,” in Diffractive Optics and Micro-Optics. Optical Society of America, 2004, p. 6.
[11] M. Okano, H. Kikuta, Y. Hirai, K. Yamamoto, and T. Yotsuya, “Optimization of
diffraction grating profiles in fabrication by electron-beam lithography,” Applied optics, vol. 43, no. 27, pp. 5137–5142, 2004.
[12] C. T. DeRoo, R. L. McEntaffer, D. M. Miles, T. J. Peterson, H. R. Marlowe, J. H.
Tutt, B. D. Donovan, B. Menz, V. Burwitz, G. Hartner et al., “Line spread functions of blazed off-plane gratings operated in the littrow mounting,” Journal of Astronomical Telescopes, Instruments, and Systems, vol. 2, no. 2, p. 025001, 2016.
[13] H. Ju, P. Zhang, J. Liang, S. Wang, and Y. Wu, “Blazed silicon gratings fabricated by deflecting crystal orientation (111) silicon wafer,” Journal of Micro/Nanolithography, MEMS, and MOEMS, vol. 4, no. 1, p. 019701, 2005.
[14] S.-C. Lo, E.-H. Lin, K.-L. Lee, T.-T. Liang, J.-C. Liu, P.-K. Wei, and W.-S. Tsai,“A concave blazed-grating-based smartphone spectrometer for multichannel sensing,” IEEE Sensors Journal, vol. 19, no. 23, pp. 11 134–11 141, 2019.
[15] J. A. McCoy, R. L. McEntaffer, and D. M. Miles, “Extreme ultraviolet and soft x-ray diffraction efficiency of a blazed reflection grating fabricated by thermally activated selective topography equilibration,” The Astrophysical Journal, vol. 891, no. 2, p. 114, 2020.
[16] P. Mouroulis, F. T. Hartley, D. W. Wilson, V. E. White, A. Shori, S. Nguyen, M. Zhang, and M. Feldman, “Blazed grating fabrication through gray-scale x-ray lithography,”Optics Express, vol. 11, no. 3, pp. 270–281, 2003.
[17] P. I. Hagouel, “Blazed diffraction gratings fabricated using x-ray lithography: fabrication, modeling and simulation,” Microelectronics Reliability, vol. 43, no. 2, pp.249–258, 2003.
[18] C.-H. Ko and M.-F. R. Lee, “Design and fabrication of a microspectrometer based on silicon concave micrograting,” Optical Engineering, vol. 50, no. 8, p. 084401, 2011.
[19] R. W. Wood, “Lxxxv. the echelette grating for the infra-red,” The London, Edinburgh,and Dublin Philosophical Magazine and Journal of Science, vol. 20, no. 118, pp. 770–778, 1910.
[20] M. B. Fleming and M. Hutley, “Blazed diffractive optics,” Applied optics, vol. 36,no. 20, pp. 4635–4643, 1997.
[21] C. Palmer and E. G. Loewen, “Diffraction grating handbook,” 2005.
[22] Z. Li, J. Gao, H. Yang, T. Wang, and X. Wang, “Roughness reduction of large-area
high-quality thick al films for echelle gratings by multi-step deposition method,” Optics express, vol. 23, no. 18, pp. 23 738–23 747, 2015.
[23] B. Zhang, Q. Wang, N. Shen, and H. Ding, “Experimental investigation and numerical analysis of mechanical ruling for an aluminum-coated diffraction grating,” Journal of Manufacturing Science and Engineering, vol. 139, no. 2, 2017.
[24] R. Montesanti, S. Little, P. Kuzmenko, J. Bixler, J. Jackson, J. Lown, R. Priest, and B. Yoxall, “Strategies for single-point diamond machining a large format germanium blazed immersion grating,” in Advances in Optical and Mechanical Technologies for Telescopes and Instrumentation II, vol. 9912. SPIE, 2016, pp. 971–981.
[25] Y. Ikeda, N. Kobayashi, P. Kuzmenko, S. L. Little, P. B. Mirkarimi, J. B. Alameda,S. Kaji, Y. Sarugaku, C. Yasui, S. Kondo et al., “Znse immersion grating in the short nir region,” in Advances in Optical and Mechanical Technologies for Telescopes and Instrumentation, vol. 9151. SPIE, 2014, pp. 1401–1412.
[26] T. Kita and T. Harada, “Ruling engine using a piezoelectric device for large and highgroove density gratings,” Applied optics, vol. 31, no. 10, pp. 1399–1406, 1992.
[27] P. G. Glöersen, “Ion- beam etching,” Journal of Vacuum Science and Technology,
vol. 12, no. 1, pp. 28–35, 1975.
[28] Q. Liu, Y. Cheng, F. Gao, Y. Zhou, and J. Wu, “Fabrication of the blazed convex grating by holographic ion beam etching,” in AOPC 2015: Advanced Display Technology; and Micro/Nano Optical Imaging Technologies and Applications, vol. 9672. SPIE, 2015,
pp. 153–158.
[29] Y. Aoyagi and S. Namba, “Blazed ion-etched holographic gratings,” Optica Acta: International Journal of Optics, vol. 23, no. 9, pp. 701–707, 1976.
[30] Y. Aoyagi, K. Sano, and S. Namba, “High spectroscopic qualities in blazed ion-etched holographic gratings,” Optics Communications, vol. 29, no. 3, pp. 253–255, 1979.
[31] S. Matsui, T. Yamato, H. Aritome, and S. Namba, “Fabrication of sio2 blazed
holographic gratings by reactive ion-etching,” Japanese Journal of Applied Physics,
vol. 19, no. 3, p. L126, 1980.
[32] J. Seely, R. Cruddace, M. Kowalski, W. Hunter, T. Barbee, J. Rife, R. Eby, and K. Stolt,“Polarization and efficiency of a concave multilayer grating in the 135–250-å region and in normal-incidence and seya–namioka mounts,” Applied optics, vol. 34, no. 31, pp. 7347–7354, 1995.
[33] M. Kowalski, T. Barbee, R. Cruddace, J. Seely, J. Rife, and W. Hunter, “Efficiency and long-term stability of a multilayer-coated, ion-etched blazed holographic grating in the 125–133-å wavelength region,” Applied optics, vol. 34, no. 31, pp. 7338–7346, 1995.
[34] M. Ekberg, F. Nikolajeff, M. Larsson, and S. Hård, “Proximity-compensated blazed
transmission grating manufacture with direct-writing, electron-beam lithography,” Applied optics, vol. 33, no. 1, pp. 103–107, 1994.
[35] D. W. Wilson, P. D. Maker, R. E. Muller, P. Z. Mouroulis, and J. Backlund, “Recent advances in blazed grating fabrication by electron-beam lithography,” Current Developments in Lens Design and Optical Engineering IV, vol. 5173, pp. 115–126, 2003.
[36] M. Oliva, D. Michaelis, T. Benkenstein, J. Dunkel, T. Harzendorf, A. Matthes, and U. D. Zeitner, “Highly efficient three-level blazed grating in the resonance domain,”Optics letters, vol. 35, no. 16, pp. 2774–2776, 2010.
[37] A. Franke, M. Schattenburg, E. M. Gullikson, J. Cottam, S. Kahn, and A. Rasmussen,“Super-smooth x-ray reflection grating fabrication,” Journal of Vacuum Science & Technology B: Microelectronics and Nanometer Structures Processing, Measurement, and Phenomena, vol. 15, no. 6, pp. 2940–2945, 1997.
[38] C.-H. Chang, J. Montoya, M. Akilian, A. Lapsa, R. Heilmann, M. Schattenburg, M. Li,K. Flanagan, A. Rasmussen, J. Seely et al., “High fidelity blazed grating replication using nanoimprint lithography,” Journal of Vacuum Science & Technology B: Microelectronics and Nanometer Structures Processing, Measurement, and Phenomena, vol. 22,no. 6, pp. 3260–3264, 2004.
[39] C.-H. Chang, R. Heilmann, R. Fleming, J. Carter, E. Murphy, M. Schattenburg, T. Bailey,J. Ekerdt, R. Frankel, and R. Voisin, “Fabrication of sawtooth diffraction gratings using nanoimprint lithography,” Journal of Vacuum Science & Technology B:
Microelectronics and Nanometer Structures Processing, Measurement, and Phenomena,
vol. 21, no. 6, pp. 2755–2759, 2003.
[40] D. M. Miles, J. A. McCoy, R. L. McEntaffer, C. M. Eichfeld, G. Lavallee, M. Labella, W. Drawl, B. Liu, C. T. DeRoo, and T. Steiner, “Fabrication and diffraction efficiency of a large-format, replicated x-ray reflection grating,” The Astrophysical Journal, vol.869, no. 2, p. 95, 2018.
[41] S. Grabarnik, A. Emadi, H. Wu, G. de Graaf, and R. Wolffenbuttel, “Microspectrometer with a concave grating fabricated in a mems technology,” Procedia Chemistry, vol. 1, no. 1, pp. 401–404, 2009.
[42] Y.-P. Chen, Y.-P. Lee, J.-H. Chang, and L. A. Wang, “Fabrication of concave gratings by curved surface uv-nanoimprint lithography,” Journal of Vacuum Science & Technology B: Microelectronics and Nanometer Structures Processing, Measurement, and
Phenomena, vol. 26, no. 5, pp. 1690–1695, 2008.
[43] J. Chen, C. Gu, H. Lin, and S.-C. Chen, “Soft mold-based hot embossing process for precision imprinting of optical components on non-planar surfaces,” Optics Express, vol. 23, no. 16, pp. 20 977–20 985, 2015.
[44] A. F. Coskun, J. Wong, D. Khodadadi, R. Nagi, A. Tey, and A. Ozcan, “A personalized food allergen testing platform on a cellphone,” Lab on a Chip, vol. 13, no. 4, pp. 636–640, 2013.
[45] W. Gao, H. Huang, Y. Zhang, P. Zhu, X. Yan, J. Fan, and X. Chen, “Recombinase
polymerase amplification-based assay for rapid detection of listeria monocytogenes in
food samples,” Food Analytical Methods, vol. 10, no. 6, pp. 1972–1981, 2017.
[46] N. Lopez-Ruiz, V. F. Curto, M. M. Erenas, F. Benito-Lopez, D. Diamond, A. J. Palma, and L. F. Capitan-Vallvey, “Smartphone-based simultaneous ph and nitrite colorimetric determination for paper microfluidic devices,” Analytical chemistry, vol. 86, no. 19, pp. 9554–9562, 2014.
[47] K.-H. Wu, W.-C. Huang, S.-C. Chang, C.-H. Kao, and R.-H. Shyu, “Colloidal silverbased lateral flow immunoassay for rapid detection of melamine in milk and animal feed,” Materials Chemistry and Physics, vol. 231, pp. 121–130, 2019.
[48] B. H. Park, S. J. Oh, J. H. Jung, G. Choi, J. H. Seo, E. Y. Lee, T. S. Seo et al., “An integrated rotary microfluidic system with dna extraction, loop-mediated isothermal amplification, and lateral flow strip based detection for point-of-care pathogen diagnostics,”Biosensors and Bioelectronics, vol. 91, pp. 334–340, 2017.
[49] B. Zhang, W. Ma, F. Li, W. Gao, Q. Zhao, W. Peng, J. Piao, X. Wu, H. Wang, X. Gong et al., “Fluorescence quenching-based signal amplification on immunochromatography test strips for dual-mode sensing of two biomarkers of breast cancer,” Nanoscale, vol. 9, no. 47, pp. 18 711–18 722, 2017.
[50] I. Denisov, K. Lukyanenko, A. Yakimov, I. Kukhtevich, E. Esimbekova, and P. Belobrov, “Disposable luciferase-based microfluidic chip for rapid assay of water pollution,” Luminescence, vol. 33, no. 6, pp. 1054–1061, 2018.
[51] J. H. Leuvering, P. Thal, M. v. d. Waart, and A. Schuurs, “Sol particle immunoassay (spia),” Journal of immunoassay, vol. 1, no. 1, pp. 77–91, 1980.
[52] L. Chunduri, M. K. Haleyurgirisetty, S. Patnaik, P. E. Bulagonda, A. Kurdekar, J. Liu, I. K. Hewlett, and V. Kamisetti, “Development of carbon dot based microplate and microfluidic chip immunoassay for rapid and sensitive detection of hiv-1 p24 antigen,”Microfluidics and Nanofluidics, vol. 20, no. 12, pp. 1–10, 2016.
[53] Y. Ji, M. Ren, Y. Li, Z. Huang, M. Shu, H. Yang, Y. Xiong, and Y. Xu, “Detection
of aflatoxin b1 with immunochromatographic test strips: Enhanced signal sensitivity
using gold nanoflowers,” Talanta, vol. 142, pp. 206–212, 2015.
[54] C. Li, W. Luo, H. Xu, Q. Zhang, H. Xu, Z. P. Aguilar, W. Lai, H. Wei, and Y. Xiong, “Development of an immunochromatographic assay for rapid and quantitative detection of clenbuterol in swine urine,” Food Control, vol. 34, no. 2, pp. 725–732, 2013.
[55] H. Xu, J. Chen, J. Birrenkott, J. X. Zhao, S. Takalkar, K. Baryeh, and G. Liu, “Goldnanoparticle-
decorated silica nanorods for sensitive visual detection of proteins,” Analytical
chemistry, vol. 86, no. 15, pp. 7351–7359, 2014.
[56] S. W. Radhi, “Interaction of colloidal gold nanoparticles with protein,” Nano Biomed. Eng, vol. 9, no. 4, pp. 298–305, 2017.
[57] C. Li, F. Xia, K. Wang, C. Wang, P. Xu, H. Zhang, J. Wang, A. Toru, J. Ni, and D. Cui,“Dendrimer-modified gold nanorods as high efficient controlled gene delivery release system under near-infrared light irradiation.” Nano Biomedicine & Engineering, vol. 9, no. 1, 2017.
[58] C. Suárez-Pantaleón, J. Wichers, A. Abad-Somovilla, A. Van Amerongen, and
A. Abad-Fuentes, “Development of an immunochromatographic assay based on
carbon nanoparticles for the determination of the phytoregulator forchlorfenuron,”
Biosensors and Bioelectronics, vol. 42, pp. 170–176, 2013.
[59] P. S. Noguera, G. A. Posthuma-Trumpie, M. van Tuil, F. J. van der Wal, A. d. Boer,
A. P. Moers, and A. van Amerongen, “Carbon nanoparticles as detection labels in
antibody microarrays. detection of genes encoding virulence factors in shiga toxinproducing escherichia coli,” Analytical chemistry, vol. 83, no. 22, pp. 8531–8536, 2011.
[60] G. A. Posthuma-Trumpie, J. H. Wichers, M. Koets, L. B. Berendsen, and A. van
Amerongen, “Amorphous carbon nanoparticles: a versatile label for rapid diagnostic
(immuno) assays,” Analytical and bioanalytical chemistry, vol. 402, no. 2, pp. 593–
600, 2012.
[61] W. Qiu, H. Xu, S. Takalkar, A. S. Gurung, B. Liu, Y. Zheng, Z. Guo, M. Baloda,
K. Baryeh, and G. Liu, “Carbon nanotube-based lateral flow biosensor for sensitive
and rapid detection of dna sequence,” Biosensors and Bioelectronics, vol. 64, pp. 367–372, 2015.
[62] X. Zhang, X. Yu, K. Wen, C. Li, G. Mujtaba Mari, H. Jiang, W. Shi, J. Shen, and
Z. Wang, “Multiplex lateral flow immunoassays based on amorphous carbon nanoparticles
for detecting three fusarium mycotoxins in maize,” Journal of agricultural and
food chemistry, vol. 65, no. 36, pp. 8063–8071, 2017.
[63] Z. Wang, D. Zhi, Y. Zhao, H. Zhang, X. Wang, Y. Ru, and H. Li, “Lateral flow test strip based on colloidal selenium immunoassay for rapid detection of melamine in
milk, milk powder, and animal feed,” International Journal of Nanomedicine, vol. 9,
p. 1699, 2014.
[64] S. C. Lou, C. Patel, S. Ching, and J. Gordon, “One-step competitive immunochromatographic assay for semiquantitative determination of lipoprotein (a) in plasma,”Clinical Chemistry, vol. 39, no. 4, pp. 619–624, 1993.
[65] G. Osikowicz, M. Beggs, P. Brookhart, D. Caplan, S. Ching, P. Eck, J. Gordon,
R. Richerson, S. Sampedro, and D. Stimpson, “One-step chromatographic immunoassay
for qualitative determination of choriogonadotropin in urine,” Clinical chemistry,
vol. 36, no. 9, pp. 1586–1586, 1990.
[66] Z. Wang, J. Jing, Y. Ren, Y. Guo, N. Tao, Q. Zhou, H. Zhang, Y. Ma, and Y. Wang,
“Preparation and application of selenium nanoparticles in a lateral flow immunoassay
for clenbuterol detection,” Materials Letters, vol. 234, pp. 212–215, 2019.
[67] S. Kim and J.-K. Park, “Development of a test strip reader for a lateral flow membranebased immunochromatographic assay,” Biotechnology and Bioprocess Engineering,
vol. 9, no. 2, pp. 127–131, 2004.
[68] M. Jianchun, Y. Qing, Z. Wenyuan, H. Wangwei, and T. Jianguo, “Development and
study of lateral flow test strip reader based on embedded system,” in IEEE 2011 10th
International Conference on Electronic Measurement & Instruments, vol. 1. IEEE,
2011, pp. 201–204.
[69] Y. Yang, M. Ozsoz, and G. Liu, “Gold nanocage-based lateral flow immunoassay for
immunoglobulin g,” Microchimica Acta, vol. 184, no. 7, pp. 2023–2029, 2017.
[70] X. Mao, W. Wang, and T. E. Du, “Dry-reagent nucleic acid biosensor based on blue
dye doped latex beads and lateral flow strip,” Talanta, vol. 114, pp. 248–253, 2013.
[71] C. S. Jørgensen, S. A. Uldum, J. F. Sørensen, I. C. Skovsted, S. Otte, and P. L. Elverdal, “Evaluation of a new lateral flow test for detection of streptococcus pneumoniae and
legionella pneumophila urinary antigen,” Journal of microbiological methods, vol.
116, pp. 33–36, 2015.
[72] F. Stumpf, F. Schwemmer, T. Hutzenlaub, D. Baumann, O. Strohmeier, G. Dingemanns,G. Simons, C. Sager, L. Plobner, F. Von Stetten et al., “Labdisk with complete reagent prestorage for sample-to-answer nucleic acid based detection of respiratory pathogens verified with influenza a h3n2 virus,” Lab on a Chip, vol. 16, no. 1, pp.199–207, 2016.
[73] K. Basile, J. Kok, and D. E. Dwyer, “Point-of-care diagnostics for respiratory viral infections,” Expert review of molecular diagnostics, vol. 18, no. 1, pp. 75–83, 2018.
[74] S. Feng, R. Caire, B. Cortazar, M. Turan, A. Wong, and A. Ozcan, “Immunochromatographic diagnostic test analysis using google glass,” ACS nano, vol. 8, no. 3, pp.3069–3079, 2014.
[75] K.-F. Hung, C.-H. Hung, C. Hong, S.-C. Chen, Y.-C. Sun, J.-W. Wen, C.-H. Kuo, C.-H.Ko, and C.-M. Cheng, “Quantitative spectrochip-coupled lateral flow immunoassay
demonstrates clinical potential for overcoming coronavirus disease 2019 pandemic
screening challenges,” Micromachines, vol. 12, no. 3, p. 321, 2021.
[76] P.-Y. Chen, C.-H. Ko, C. J. Wang, C.-W. Chen, W.-H. Chiu, C. Hong, H.-M. Cheng,
and I.-J. Wang, “The early detection of immunoglobulins via optical-based lateral flow immunoassay platform in covid-19 pandemic,” Plos one, vol. 16, no. 7, p. e0254486,2021.
[77] Y.-C. Wang, S.-W. Lin, I.-J. Wang, C.-Y. Yang, C. Hong, J.-R. Sun, P.-H. Feng, M.-H.Lee, C.-F. Shen, Y.-T. Lee et al., “Interleukin-6 test strip combined with a spectrumbased optical reader for early recognition of covid-19 patients with risk of respiratory failure,” Frontiers in bioengineering and biotechnology, vol. 10, 2022.
[78] W.-C. Chen, Y.-P. Lin, C.-M. Cheng, C.-F. Shen, C.-W. Li, Y.-K. Wang, T.-Y. Shih, C. Hong, T.-C. Chang, and C.-J. Shen, “Detection of sars-cov-2 neutralizing antibodies in vaccinated pregnant women and neonates by using a lateral flow immunoassay coupled with a spectrum-based reader,” Biosensors, vol. 12, no. 10, p. 891, 2022.
[79] 蘇育代, “自動化光譜晶片波長校正及晶片性能量化之演算法研究與開發,”
Master’s thesis, 國立台灣科技大學自動化及控制研究所, 2021.
[80] 陳宜松, “光譜晶片之自動光學瑕疵檢測系統研究與開發,” Master’s thesis, 國立
台灣科技大學自動化及控制研究所, 2022.
[81] 李宜運, “微機電光譜晶片之自動校正系統開發暨非監督品質分類研究,”
Master’s thesis, 國立台灣科技大學自動化及控制研究所, 2021.
[82] M. Bolcato, M. T. Aurilio, A. Aprile, G. Di Mizio, B. Della Pietra, and A. Feola, “Take-home messages from the covid-19 pandemic: Strengths and pitfalls of the italian national health service from a medico-legal point of view,” Healthcare, vol. 9, no. 1, p. 17, 2020.
[83] C. H. GeurtsvanKessel, N. Okba, Z. Igloi, S. Bogers, C. W. Embregts, B. M. Laksono, L. Leijten, C. Rokx, B. Rijnders, J. Rahamat-Langendoen et al., “An evaluation of covid-19 serological assays informs future diagnostics and exposure assessment,” Nature communications, vol. 11, no. 1, pp. 1–5, 2020.
[84] A. H. Al-Rohaimi and F. Al Otaibi, “Novel sars-cov-2 outbreak and covid19 disease; a systemic review on the global pandemic,” Genes & Diseases, vol. 7, no. 4, pp. 491–501, 2020.
[85] A. C. Walls, Y.-J. Park, M. A. Tortorici, A. Wall, A. T. McGuire, and D. Veesler,“Structure, function, and antigenicity of the sars-cov-2 spike glycoprotein,” Cell, vol.181, no. 2, pp. 281–292, 2020.
[86] J. Shang, G. Ye, K. Shi, Y. Wan, H. Aihara, and F. Li, “Structure of 2019-ncov chimeric receptor-binding domain complexed with its receptor human ace2,” Worldw. Protein Data Bank, 2020.
[87] H. Hou, T. Wang, B. Zhang, Y. Luo, L. Mao, F. Wang, S. Wu, and Z. Sun, “Detection of igm and igg antibodies in patients with coronavirus disease 2019,” Clinical & translational immunology, vol. 9, no. 5, p. e1136, 2020.
[88] Q.-L. Jing, M.-J. Liu, Z.-B. Zhang, L.-Q. Fang, J. Yuan, A.-R. Zhang, N. E. Dean,L. Luo, M.-M. Ma, I. Longini et al., “Household secondary attack rate of covid-19 and associated determinants in guangzhou, china: a retrospective cohort study,” The Lancet Infectious Diseases, vol. 20, no. 10, pp. 1141–1150, 2020.
[89] F. F. Diehl, T. P. Miettinen, R. Elbashir, C. S. Nabel, S. R. Manalis, C. A. Lewis, and M. G. Vander Heiden, “Nucleotide imbalance decouples cell growth from cell
proliferation,” bioRxiv, 2021.
[90] P. C. Woo, S. K. Lau, Y. Huang, and K.-Y. Yuen, “Coronavirus diversity, phylogeny and interspecies jumping,” Experimental Biology and medicine, vol. 234, no. 10, pp.1117–1127, 2009.
[91] D. Sterlin, A. Malaussena, and G. Gorochov, “Iga dominates the early neutralizing antibody response to sars-cov-2 virus,” Medecine sciences: M/S, vol. 37, no. 11, pp.968–970, 2021.
[92] R. W. Rosenstein and T. G. Bloomster, “Solid phase assay employing capillary flow,”Aug. 8 1989, uS Patent 4,855,240.
[93] B. O＇Farrell, “Evolution in lateral flow–based immunoassay systems,” in Lateral flow immunoassay. Springer, 2009, pp. 1–33.
[94] J. M. Singer and C. M. Plotz, “The latex fixation test: I. application to the serologic diagnosis of rheumatoid arthritis,” The American journal of medicine, vol. 21, no. 6,pp. 888–892, 1956.
[95] R. L. Campbell, D. B. Wagner, and J. P. O’connell, “Solid phase assay with visual readout,” Oct. 27 1987, uS Patent 4,703,017.
[96] C. Song, A. Zhi, Q. Liu, J. Yang, G. Jia, J. Shervin, L. Tang, X. Hu, R. Deng, C. Xu et al., “Rapid and sensitive detection of β-agonists using a portable fluorescence biosensor based on fluorescent nanosilica and a lateral flow test strip,” Biosensors and Bioelectronics, vol. 50, pp. 62–65, 2013.
[97] A. T. Cruz, A. C. Cazacu, L. J. McBride, J. M. Greer, and G. J. Demmler, “Performance characteristics of a rapid immunochromatographic assay for detection of influenza virus in children during the 2003 to 2004 influenza season,” Annals of emergency medicine, vol. 47, no. 3, pp. 250–254, 2006.
[98] M. Sajid, A.-N. Kawde, and M. Daud, “Designs, formats and applications of lateral flow assay: A literature review,” Journal of Saudi Chemical Society, vol. 19, no. 6, pp. 689–705, 2015.
[99] D. E. Harrison, C. Jordan, R. Zhong, and C. Astle, “Primitive hemopoietic stem cells: direct assay of most productive populations by competitive repopulation with simple binomial, correlation and covariance calculations.” Experimental hematology, vol. 21,no. 2, pp. 206–219, 1993.
[100] H. Bao, M. Yuan, C. Xiao, D. Liu, and W. Lai, “Development of a signal-enhanced lfia based on tyramine-induced aunps aggregation for sensitive detection of danofloxacin,”Food Chemistry, vol. 375, p. 131875, 2022.
[101] J. G. Walker, “Optical imaging with resolution exceeding the rayleigh criterion,” Optica Acta: International Journal of Optics, vol. 30, no. 9, pp. 1197–1202, 1983.
[102] C.-H. Ko, S.-Y. Tsai, Y.-H. Wu, J.-R. Tsai, B.-J. Wang, S.-F. Lin, and C.-D. Hsiao, “Design and verification of a flat-field aberration-corrected concave blaze grating for hyperspectral imaging,” in Conference on Lasers and Electro-Optics/Pacific Rim. Optical Society of America, 2017, p. 987.
[103] W. R. Tompkin, R. Staub, A. Schilling, and H.-P. Herzig, “Diffraction from metallic gratings with locally varying profile forms,” Optics letters, vol. 24, no. 2, pp. 71–73,1999.
[104] G. R. Grimsley and C. N. Pace, “Spectrophotometric determination of protein concentration,”Current protocols in protein science, vol. 33, no. 1, pp. 3–1, 2003.
[105] J. E. Noble, “Quantification of protein concentration using uv absorbance and
coomassie dyes,” in Methods in enzymology. Elsevier, 2014, vol. 536, pp. 17–26.
[106] F. Scholkmann, S. Kleiser, A. J. Metz, R. Zimmermann, J. M. Pavia, U. Wolf, and
M. Wolf, “A review on continuous wave functional near-infrared spectroscopy and
imaging instrumentation and methodology,” Neuroimage, vol. 85, pp. 6–27, 2014.
[107] E. Patterson, C. Shelden, and B. Stockton, “Kubelka-munk optical properties of a barium sulfate white reflectance standard,” Applied optics, vol. 16, no. 3, pp. 729–732, 1977.
[108] B. Brinkworth, “Interpretation of the kubelka-munk coefficients in reflection theory,”Applied Optics, vol. 11, no. 6, pp. 1434–1435, 1972.
[109] W.-H. Chiu, W.-Y. Kong, Y.-H. Chueh, J.-W. Wen, C.-M. Tsai, C. Hong, P.-Y. Chen,and C.-H. Ko, “Using an ultra-compact optical system to improve lateral flow immunoassay results quantitatively,” Heliyon, p. 1, 2022.
[110] H. G. Schulze, R. B. Foist, A. Ivanov, and R. F. Turner, “Fully automated highperformance signal-to-noise ratio enhancement based on an iterative three-point zeroorder savitzky–golay filter,” Applied spectroscopy, vol. 62, no. 10, pp. 1160–1166,2008.
[111] R. Gautam, S. Vanga, F. Ariese, and S. Umapathy, “Review of multidimensional data processing approaches for raman and infrared spectroscopy,” EPJ Techniques and Instrumentation, vol. 2, no. 1, pp. 1–38, 2015.
[112] Z.-M. Zhang, S. Chen, and Y.-Z. Liang, “Baseline correction using adaptive iteratively reweighted penalized least squares,” Analyst, vol. 135, no. 5, pp. 1138–1146, 2010.
[113] F. Qian, Y. Wu, and P. Hao, “A fully automated algorithm of baseline correction based on wavelet feature points and segment interpolation,” Optics & Laser Technology, vol. 96, pp. 202–207, 2017.
[114] J. Fraunhofer, “Uber die brechbarkeit des electrishen lichts,” K. Acad. d. Wiss. zu Munchen, pp. 61–62, 1824.
[115] A. Cotton, “Réseaux obtenus par la photographie des ordres stationaires,” Seances Soc. Fran. Phys, pp. 70–73, 1901.
[116] J. Gao, P. Chen, L. Wu, B. Yu, and L. Qian, “A review on fabrication of blazed gratings,”Journal of Physics D: Applied Physics, vol. 54, no. 31, p. 313001, 2021.
[117] K. Jung, S. Shin, M. Nam, Y. J. Hong, E. Y. Roh, K. U. Park, and E. Y. Song, “Performance evaluation of three automated quantitative immunoassays and their correlation with a surrogate virus neutralization test in coronavirus disease 19 patients and prepandemic controls,” Journal of clinical laboratory analysis, vol. 35, no. 9, p. e23921,2021.
[118] J. Jung, D. Rajapakshe, C. Julien, and S. Devaraj, “Analytical and clinical performance of cpass neutralizing antibodies assay,” Clinical biochemistry, vol. 98, pp. 70–73, 2021.
[119] R. W. Frenck Jr, N. P. Klein, N. Kitchin, A. Gurtman, J. Absalon, S. Lockhart, J. L.Perez, E. B. Walter, S. Senders, R. Bailey et al., “Safety, immunogenicity, and efficacy of the bnt162b2 covid-19 vaccine in adolescents,” New England Journal of Medicine, vol. 385, no. 3, pp. 239–250, 2021.
[120] K. R. Bewley, N. S. Coombes, L. Gagnon, L. McInroy, N. Baker, I. Shaik, J. R. St-Jean, N. St-Amant, K. R. Buttigieg, H. E. Humphries et al., “Quantification of sarscov-2 neutralizing antibody by wild-type plaque reduction neutralization, microneu-tralization and pseudotyped virus neutralization assays,” Nature protocols, vol. 16,no. 6, pp. 3114–3140, 2021.
[121] X. Xie, M. C. Nielsen, A. E. Muruato, C. R. Fontes-Garfias, and P. Ren, “Evaluation of a sars-cov-2 lateral flow assay using the plaque reduction neutralization test,”Diagnostic microbiology and infectious disease, vol. 99, no. 2, p. 115248, 2021.
[122] S. C. Taylor, B. Hurst, C. L. Charlton, A. Bailey, J. N. Kanji, M. K. McCarthy, T. E.Morrison, L. Huey, K. Annen, M. G. DomBourian et al., “A new sars-cov-2 dualpurpose serology test: highly accurate infection tracing and neutralizing antibody response detection,” Journal of clinical microbiology, vol. 59, no. 4, pp. e02 438–20,2021.