Development of an IoT-integrated multiplexed digital PCR system for quantitative detection of infectious diseases

Ji Wook Choi, Won Ho Seo, Young Suh Lee, So Young Kim, Bong Suk Kim, Kyoung G. Lee, Seok Jae Lee and Bong Geun Chung

Lab Chip, 2022, 22, 3933
DOI: 10.1039/D2LC00726F

A sample-to-answer DNA detection microfluidic system integrating sample pretreatment and smartphone-readable gradient plasmonic photothermal continuous-flow PCR

Zengming Zhang, Shuhao Zhao, Lei Jiang, Junjun Wu, Wenhan Zhao, Xiaoniu Guo, Niancai Peng and Fei Hu

Analyst, 2022, 147, 4876
DOI: 10.1039/D2AN00908K

A lab-on-chip device for the sample-in-result-out detection of viable Salmonella using loop-mediated isothermal amplification and real-time turbidity monitoring

Siyuan Wang, Ning Liu, Lingyan Zheng, Gaozhe Cai and Jianhan Lin

Lab Chip, 2020, 20, 2296
DOI: 10.1039/D0LC00290A

A rapid nucleic acid concentration measurement system with large field of view for a droplet digital PCR microfluidic chip

Jinrong Shen, Jihong Zheng, Zhenqing Li, Yourong Liu, Fengxiang Jing, Xinjun Wan, Yoshinori Yamaguchi and Songlin Zhuang

Lab Chip, 2021, 21, 3742
DOI: 10.1039/D1LC00532D

Micro-PCR chip-based multifunctional ultrafast SARS-CoV-2 detection platform

Hao Yin, Zhaoduo Tong, Chuanjie Shen, Xin Xu, Hui Ma, Zhenhua Wu, Yong Qi and Hongju Mao

Lab Chip, 2022, 22, 2671
DOI: 10.1039/D2LC00101B

Multiplex amplification of target genes of periodontal pathogens in continuous flow PCR microfluidic chip

Zhenqing Li, Jiahui Liu, Ping Wang, Chunxian Tao, Lulu Zheng, Shinichi Sekine, Songlin Zhuang, Dawei Zhang and Yoshinori Yamaguchi

Lab Chip, 2021, 21, 3159
DOI: 10.1039/D1LC00457C

A digital microfluidic platform coupled with colorimetric loop-mediated isothermal amplification for on-site visual diagnosis of multiple diseases

Mei Xie, Tianlan Chen, Zongwei Cai, Bo Lei and Cheng Dong

Lab Chip, 2023, 23, 2778
DOI: 10.1039/D2LC01156E

A microfluidic chip for rapid analysis of DNA melting curves for BRCA2 mutation screening

Xuyan Lin and Stefan Nagl

Lab Chip, 2020, 20, 3824
DOI: 10.1039/D0LC00624F

A continuous flow PCR array microfluidic chip applied for simultaneous amplification of target genes of periodontal pathogens

Bo Yang, Ping Wang, Zhenqing Li, Chunxian Tao, Qingxiang You, Shinichi Sekine, Songlin Zhuang, Dawei Zhang and Yoshinori Yamaguchi

Lab Chip, 2022, 22, 733
DOI: 10.1039/D1LC00814E

Point-of-care diagnostic devices for periodontitis – current trends and urgent need

Alexandra Griffith, Charmi Chande, Sahitya Kulkarni, Josuel Morel, Yu-Hsuan Cheng, Emi Shimizu, Carla Cugini, Sagnik Basuray and Vivek Kumar

Sens. Diagn., 2024, 3, 1119
DOI: 10.1039/D3SD00317E

Achievement of 15-Minute Adaptive PCR Benchmark with 1370 nm Laser Heating

Nicholas Spurlock, Rosana Alfaro, William E. Gabella, Kunal Chugh, Megan E. Pask, Franz Baudenbacher and Frederick R. Haselton

Biosensors, 2025, 15, 258
DOI: 10.3390/bios15040258

A Systematic Review of In Vitro Studies Using Microchip Platforms for Identifying Periodontopathogens from the Red Complex

Carlos M. Ardila, Gustavo A. Jiménez-Arbeláez and Annie Marcela Vivares-Builes

Dentistry Journal, 2023, 11, 245
DOI: 10.3390/dj11110245

Exploring the potential of microfluidics for next-generation drug delivery systems

Gargi Bhattacharjee, Nisarg Gohil, Malvika Shukla, Swati Sharma, Indra Mani, Alok Pandya, Dinh-Toi Chu, Nhat Le Bui, Yen-Vy Nguyen Thi, Khushal Khambhati, Rupesh Maurya, Suresh Ramakrishna and Vijai Singh

OpenNano, 2023, 12, 100150
DOI: 10.1016/j.onano.2023.100150

Detection of Periodontal Pathogens Based on an Integrated Continuous Flow PCR and Capillary Electrophoresis Microfluidic Chip

Bo Yang, Jiaxin Huang, Chunxian Tao, Zhenqing Li, Dawei Zhang and Yoshinori Yamaguchi

Separations, 2023, 10, 271
DOI: 10.3390/separations10040271

Recent advances of oral fluids-based point-of-care testing platforms for oral disease diagnosis

Zhen Chai, Yiru Yu, Peilin Cheng, Lei Zhao, Bojan Petrovic, Ang Li, Feng Xu, Ye Li and Minli You

Translational Dental Research, 2025, 1, 100003
DOI: 10.1016/j.tdr.2024.100003

A low-cost and hand-hold PCR microdevice based on water-cooling technology

Kaixin sun, Ben Whiteside, Michael Hebda, Yiqiang Fan, Yajun Zhang, Yumeng Xie and KunMing Liang

Biomed Microdevices, 2023, 25
DOI: 10.1007/s10544-023-00652-4

Point-of-Care Strategies for Detection of Waterborne Pathogens

Sandeep Kumar, Monika Nehra, Jyotsana Mehta, Neeraj Dilbaghi, Giovanna Marrazza and Ajeet Kaushik

Sensors, 2019, 19, 4476
DOI: 10.3390/s19204476

Electrokinetic microdevices for biological sample processing

Gloria Porro, Till Ryser, Pierre-Emmanuel Thiriet, Micaela Siria Cristofori and Carlotta Guiducci

Nat Rev Electr Eng, 2024, 1, 768
DOI: 10.1038/s44287-024-00099-6

Research progress of All-in-One PCR tube biosensors based on functional modification and intelligent fabrication

Yanhui Wang, Longjiao Zhu, Peijin Guo, Yangzi Zhang, Xinyue Lan and Wentao Xu

Biosensors and Bioelectronics, 2024, 246, 115824
DOI: 10.1016/j.bios.2023.115824

Making Molecular Diagnostics Faster

Carl T. Wittwer, Luming Zhou, Felix Ye, Adam Millington, Adrian de Cola and Noriko Kusukawa

Int J Lab Hematology, 2025
DOI: 10.1111/ijlh.14487

Advances in Nucleic Acid Amplification-Based Microfluidic Devices for Clinical Microbial Detection

Thi Ngoc Diep Trinh and Nae Yoon Lee

Chemosensors, 2022, 10, 123
DOI: 10.3390/chemosensors10040123

Nanotechnology for ultrafast nucleic acid amplification

Yiru Wang, Yan Fei, Tao Yang, Zisheng Luo, Yanqun Xu, Bin Su and Xingyu Lin

Nano Today, 2023, 48, 101749
DOI: 10.1016/j.nantod.2022.101749

Integrated Microfluidic-Based Platforms for On-Site Detection and Quantification of Infectious Pathogens: Towards On-Site Medical Translation of SARS-CoV-2 Diagnostic Platforms

Andres Escobar, Phyllis Chiu, Jianxi Qu, Yushan Zhang and Chang-qing Xu

Micromachines, 2021, 12, 1079
DOI: 10.3390/mi12091079

An Integrated, Real-Time Convective PCR System for Isolation, Amplification, and Detection of Nucleic Acids

Guijun Miao, Meng Guo, Ke Li, Xiangzhong Ye, Michael G. Mauk, Shengxiang Ge, Ningshao Xia, Duli Yu and Xianbo Qiu

Chemosensors, 2022, 10, 271
DOI: 10.3390/chemosensors10070271

Simulation of Rapid Thermal Cycle for Ultra-Fast PCR

Zhuo Yang, Jiali Zhang, Xin Tong, Wenbing Li, Lijuan Liang, Bo Liu and Chang Chen

Sensors, 2022, 22, 9990
DOI: 10.3390/s22249990

Electrophoretic techniques for rapid detection of bacterial pneumonia: Current status and future perspectives

Aiqin Zhong, Zhijun Li and Yiqun Song

International Journal of Electrochemical Science, 2025, 20, 100928
DOI: 10.1016/j.ijoes.2025.100928

Sub-5-Minute Ultrafast PCR using Digital Microfluidics

Liang Wan, Mingzhong Li, Man-Kay Law, Pui-In Mak, Rui P. Martins and Yanwei Jia

Biosensors and Bioelectronics, 2023, 242, 115711
DOI: 10.1016/j.bios.2023.115711

A Rubik’s microfluidic cube

Xiaochen Lai, Zhi Shi, Zhihua Pu, Penghao Zhang, Xingguo Zhang, Haixia Yu and Dachao Li

Microsyst Nanoeng, 2020, 6
DOI: 10.1038/s41378-020-0136-4

A fully integrated rapid on-chip antibiotic susceptibility test – A case study for Mycobacterium smegmatis

Hamed Ghorbanpoor, Araz Norouz Dizaji, Iremnur Akcakoca, Ewen O. Blair, Yasin Ozturk, Paul Hoskisson, Tanil Kocagoz, Huseyin Avci, Damion K. Corrigan and Fatma Dogan Guzel

Sensors and Actuators A: Physical, 2022, 339, 113515
DOI: 10.1016/j.sna.2022.113515

A systematic implementation of padlock probing-based rolling circle amplification in an integrated microfluidic device for quantitative biomolecular analyses

Catarina R.F. Caneira, Rafaela R. Rosa, Virginia Chu, Mats Nilsson, Narayanan Madaboosi, Ruben R.G. Soares and João P. Conde

Analytica Chimica Acta, 2025, 1351, 343834
DOI: 10.1016/j.aca.2025.343834

Microchip Electrophoresis for Fluorescence-Based Measurement of Polynucleic Acids: Recent Developments

Renna L. Nouwairi, Killian C. O’Connell, Leah M. Gunnoe and James P. Landers

Anal. Chem., 2021, 93, 367
DOI: 10.1021/acs.analchem.0c04596

Emerging optofluidic technologies for biodiagnostic applications

Jiandong Wu, Bo Dai, Zhenqing Li, Tingrui Pan, Dawei Zhang and Francis Lin

VIEW, 2021, 2
DOI: 10.1002/VIW.20200035

Impact of Microfluidic Chip Electrophoresis in Modern Analysis: An Update on Recent Trends

Sumit Pasricha, Rohit Bhatia, Preeti Patel and Bhupinder Kumar

CAC, 2023, 19, 358
DOI: 10.2174/1573411019666230526163826

A novel method of droplet generation based on the self-propelling of water phase and its potential application in multiplexing continuous flow PCR

Xiaoguang Lu, Qianyue Jia, Yaning Zheng, Zishan Qin, Yong Li, Chao Shi and Cuiping Ma

Biosensors and Bioelectronics, 2025, 279, 117400
DOI: 10.1016/j.bios.2025.117400

Advancements and Trends in Electrochemical Biosensors for Saliva-Based Diagnosis of Oral Diseases: A Bibliometric Analysis (2000–2023)

Qian Tang, Fushen Zhang, Weiye Xu, Zejun Deng, Zhangui Tang and Jufang Huang

International Dental Journal, 2025, 75, 100840
DOI: 10.1016/j.identj.2025.100840

Rapid PCR powered by microfluidics: A quick review under the background of COVID-19 pandemic

Xiaobin Dong, Luyao Liu, Yunping Tu, Jing Zhang, Guijun Miao, Lulu Zhang, Shengxiang Ge, Ningshao Xia, Duli Yu and Xianbo Qiu

TrAC Trends in Analytical Chemistry, 2021, 143, 116377
DOI: 10.1016/j.trac.2021.116377

The Effect of Molecular Mass of Hydroxyethyl Cellulose on the Performance of Capillary Electrophoretic Separation of Proteins

Jiaxin Huang, Chunxian Tao, Zhenqing Li, Erika Miyake, Qingxiang You, Wen Xiao, Dawei Zhang and Yoshinori Yamaguchi

Separations, 2022, 9, 284
DOI: 10.3390/separations9100284

Advances in continuous-flow based microfluidic PCR devices—a review

Madhusudan B Kulkarni and Sanket Goel

Eng. Res. Express, 2020, 2, 042001
DOI: 10.1088/2631-8695/abd287

Rapid Detection of Streptococcus mutans Using an Integrated Microfluidic System with Loop-Mediated Isothermal Amplification

Jingfu Wang, Jingyi Wang, Xin Chang, Jin Shang, Yuehui Wang, Qin Ma and Liangliang Shen

J. Microbiol. Biotechnol., 2023, 33, 1101
DOI: 10.4014/jmb.2304.04026

Optical Technologies for Single-Cell Analysis on Microchips

Xiaowen Ou, Peng Chen and Bi-Feng Liu

Chemosensors, 2023, 11, 40
DOI: 10.3390/chemosensors11010040

A rapid and label-free platform for virus enrichment based on electrostatic microfluidics

Xiaoxiang Zhou, Zhanping Li, Zhen Zhang, Libo Zhu and Quanjun Liu

Talanta, 2022, 242, 122989
DOI: 10.1016/j.talanta.2021.122989

Development of a portable multi-step microfluidic device for point-of-care nucleic acid diagnostics

Lulu Shi, Zirui Pang, Jianghao Yu, Jiaming Zhu, Xiaohong Xie, Shiling Xie, Lichuan Gu, Wei Hu, Hai Xu, Ling Li, Jifang Tao and Mingyu Wang

Analytica Chimica Acta, 2025, 1336, 343518
DOI: 10.1016/j.aca.2024.343518

The point-of-care-testing of nucleic acids by chip, cartridge and paper sensors

Yuyue Xu, Tao Wang, Zhu Chen, Lian Jin, Zuozhong Wu, Jinqu Yan, Xiaoni Zhao, Lei Cai, Yan Deng, Yuan Guo, Song Li and Nongyue He

Chinese Chemical Letters, 2021, 32, 3675
DOI: 10.1016/j.cclet.2021.06.025

A digital PCR system based on the thermal cycled chip with multi helix winding capillary

Bin Li, Yuanming Li, Yangyang Jiang, Andreas Manz and Wenming Wu

Sci Rep, 2020, 10
DOI: 10.1038/s41598-020-74711-8

A multiplexed electrochemical quantitative polymerase chain reaction platform for single-base mutation analysis

Yang Wang, Hong Sun, Gaolian Xu, Mengdi Guan, Qingyang Zhang, Zhiying Wang, Zaizai Dong, Wenhui Chen, Xiaoxiao Yang, Anbang Qiao, Yubo Fan, Xinxia Cai, Zhou Chen, Lingqian Chang and Bo Wei

Biosensors and Bioelectronics, 2022, 214, 114496
DOI: 10.1016/j.bios.2022.114496

Closed-Loop Microreactor on PCB for Ultra-Fast DNA Amplification: Design and Thermal Validation

Panagiotis Skaltsounis, George Kokkoris, Theodoros G. Papaioannou and Angeliki Tserepi

Micromachines, 2023, 14, 172
DOI: 10.3390/mi14010172

Recent advancements in nucleic acid detection with microfluidic chip for molecular diagnostics

Zheng Li, Xiaojian Xu, Dou Wang and Xingyu Jiang

TrAC Trends in Analytical Chemistry, 2023, 158, 116871
DOI: 10.1016/j.trac.2022.116871

Recent advancements in microfluidic-based biosensors for detection of genes and proteins: Applications and techniques

Saeed Siavashy, M. Soltani, Shayan Rahimi, Mehraveh Hosseinali, Zahra Guilandokht and Kaamran Raahemifar

Biosensors and Bioelectronics: X, 2024, 19, 100489
DOI: 10.1016/j.biosx.2024.100489

Design and fabrication of portable continuous flow PCR microfluidic chip for DNA replication

Zhenqing Li, Yadong Li, Shinichi Sekine, Heqi Xi, Atsuo Amano, Dawei Zhang and Yoshinori Yamaguchi

Biomed Microdevices, 2020, 22
DOI: 10.1007/s10544-019-0457-y

Continuous polymerase chain reaction microfluidics integrated with a gold-capped nanoslit sensing chip for Epstein-Barr virus detection

Han-Yun Hsieh, Ray Chang, Yung-Yu Huang, Po-Han Juan, Hidetoshi Tahara, Kuan-Yi Lee, Di Ngoc Kha Vo, Ming-Han Tsai, Pei-Kuen Wei, Horn-Jiunn Sheen and Yu-Jui Fan

Biosensors and Bioelectronics, 2022, 195, 113672
DOI: 10.1016/j.bios.2021.113672

Advances in Electrochemical Biosensors for the Detection of Common Oral Diseases

Chaoran Liu, Changjun Guan, Yanan Li, Ze Li, Yanchun Wang and Guanghong Han

Critical Reviews in Analytical Chemistry, 2025, 55, 775
DOI: 10.1080/10408347.2024.2315112

Rapid visualized isothermal nucleic acid testing of Vibrio parahaemolyticus by polymerase spiral reaction

Shiyu He, Hongbo Jang, Chao Zhao, Kun Xu, Juan Wang, Bo Pang, Xiaoxue Si, Minghua Jin, Xiuling Song and Juan Li

Anal Bioanal Chem, 2020, 412, 93
DOI: 10.1007/s00216-019-02209-y

High throughput DNA concentration determination system based on fluorescence technology

Zhenqing Li, Pengbo Zhang, Bo Yang, Jiahui Liu, Heqi Xi, Dawei Zhang and Yoshinori Yamaguchi

Sensors and Actuators B: Chemical, 2021, 328, 128904
DOI: 10.1016/j.snb.2020.128904

The application of microfluidic technology in allergen detection: A review

Dandan Luo, Peng Wang, Huifei Lu, Xianhai Zeng, Hailiang Zhao and Jiangqi Liu

Medicine, 2025, 104, e42645
DOI: 10.1097/MD.0000000000042645

Point-of-care diagnostics for infectious diseases: From methods to devices

Chao Wang, Mei Liu, Zhifei Wang, Song Li, Yan Deng and Nongyue He

Nano Today, 2021, 37, 101092
DOI: 10.1016/j.nantod.2021.101092

COVID-19 Diagnostic Strategies. Part I: Nucleic Acid-Based Technologies

Tina Shaffaf and Ebrahim Ghafar-Zadeh

Bioengineering, 2021, 8, 49
DOI: 10.3390/bioengineering8040049

Current status, advances, challenges and perspectives on biosensors for COVID-19 diagnosis in resource-limited settings

Yu Shen, Touhid Bin Anwar and Ashok Mulchandani

Sensors and Actuators Reports, 2021, 3, 100025
DOI: 10.1016/j.snr.2021.100025

A rapid and low-cost platform for detection of bacterial based on microchamber PCR microfluidic chip

Zhenqing Li, Xiaolu Ma, Zhen Zhang, Xiaoyang Wang, Bo Yang, Jing Yang, Yuan Zeng, Xujun Yuan, Dawei Zhang and Yoshinori Yamaguchi

Biomed Microdevices, 2024, 26
DOI: 10.1007/s10544-024-00699-x

Portable biosensor-based oral pathogenic bacteria detection for community and family applications

Jieyu Ming, Xin Zeng and Ronghui Zhou

Anal Bioanal Chem, 2023, 415, 5221
DOI: 10.1007/s00216-023-04809-1

Miniaturized Thermal Monitoring Module With CO₂ Laser Ablated Microfluidic Device for Electrochemically Validated DNA Amplification

Madhusudan B. Kulkarni, Mary Salve and Sanket Goel

IEEE Trans. Instrum. Meas., 2021, 70, 1
DOI: 10.1109/TIM.2021.3097861

Salivary Biomarkers in Periodontal Disease: Revolutionizing Early Detection and Precision Dentistry

Seyed Ebrahim Alavi, Lavanya A. Sharma, Ajay Sharma and Hasan Ebrahimi Shahmabadi

Mol Diagn Ther, 2025
DOI: 10.1007/s40291-025-00799-1

How does the Internet of Things (IoT) help in microalgae biorefinery?

Kexin Wang, Kuan Shiong Khoo, Hui Yi Leong, Dillirani Nagarajan, Kit Wayne Chew, Huong Yong Ting, Anurita Selvarajoo, Jo-Shu Chang and Pau Loke Show

Biotechnology Advances, 2022, 54, 107819
DOI: 10.1016/j.biotechadv.2021.107819

Application of Microfluidics for Bacterial Identification

Fraser Daniel, Delaney Kesterson, Kevin Lei, Catherine Hord, Aarti Patel, Anastasia Kaffenes, Harrshavasan Congivaram and Shaurya Prakash

Pharmaceuticals, 2022, 15, 1531
DOI: 10.3390/ph15121531

Advances in Simple, Rapid, and Contamination-Free Instantaneous Nucleic Acid Devices for Pathogen Detection

Yue Wang, Chengming Wang, Zepeng Zhou, Jiajia Si, Song Li, Yezhan Zeng, Yan Deng and Zhu Chen

Biosensors, 2023, 13, 732
DOI: 10.3390/bios13070732

Visualization and Measurements of Blood Cells Flowing in Microfluidic Systems and Blood Rheology: A Personalized Medicine Perspective

Diana Pinho, Violeta Carvalho, Inês M. Gonçalves, Senhorinha Teixeira and Rui Lima

JPM, 2020, 10, 249
DOI: 10.3390/jpm10040249

Recent Advances in Digital Biosensing Technology

Kathrine Curtin, Bethany J. Fike, Brandi Binkley, Toktam Godary and Peng Li

Biosensors, 2022, 12, 673
DOI: 10.3390/bios12090673

Bottom‐up DNA nanostructure‐based paper as point‐of‐care diagnostic: From method to device

Xueping Gao, Liu Feng, Ruijia Deng, Binpan Wang, Yuan He, Ligai Zhang, Dan Luo, Ming Chen and Kai Chang

Interdisciplinary Medicine, 2024, 2
DOI: 10.1002/INMD.20230033

Lower fluidic resistance of double-layer droplet continuous flow PCR microfluidic chip for rapid detection of bacteria

Zhenqing Li, Yifei Wang, Zehang Gao, Shinichi Sekine, Qingxiang You, Songlin Zhuang, Dawei Zhang, Shilun Feng and Yoshinori Yamaguchi

Analytica Chimica Acta, 2023, 1251, 340995
DOI: 10.1016/j.aca.2023.340995

Early Predictor Tool of Disease Using Label-Free Liquid Biopsy-Based Platforms for Patient-Centric Healthcare

Wei Li, Yunlan Zhou, Yanlin Deng and Bee Luan Khoo

Cancers, 2022, 14, 818
DOI: 10.3390/cancers14030818

Pathogen detection on microfluidic platforms: Recent advances, challenges, and prospects

Akshaya Jagannath, Hengji Cong, Jaythoon Hassan, Gabriel Gonzalez, Michael D. Gilchrist and Nan Zhang

Biosensors and Bioelectronics: X, 2022, 10, 100134
DOI: 10.1016/j.biosx.2022.100134

Rapid on-site nucleic acid testing: On-chip sample preparation, amplification, and detection, and their integration into all-in-one systems

Jingwen Wang, Han Jiang, Leiming Pan, Xiuying Gu, Chaogeng Xiao, Pengpeng Liu, Yulong Tang, Jiehong Fang, Xiaoqian Li and Chenze Lu

Front. Bioeng. Biotechnol., 2023, 11
DOI: 10.3389/fbioe.2023.1020430

Exploring the potential of paper-based electrokinetic phenomena in PoC biosensing

Amadeo Sena-Torralba, Yulieth D. Banguera-Ordoñez, Laia Mira-Pascual, Ángel Maquieira and Sergi Morais

Trends in Biotechnology, 2023, 41, 1299
DOI: 10.1016/j.tibtech.2023.04.004

Recent Advances and Applications of Microfluidic Capillary Electrophoresis: A Comprehensive Review (2017–Mid 2019)

Marwa A. A. Ragab and Eman I. El-Kimary

Critical Reviews in Analytical Chemistry, 2020, 1
DOI: 10.1080/10408347.2020.1765729

Separation of proteins by square-wave pulsed field and inversion field capillary electrophoresis

Jiaxin Huang, Yatian Zhang, Chunxian Tao, Shanni Li, Qingxiang You, Dawei Zhang, Zhenqing Li and Yoshinori Yamaguchi

Journal of the Taiwan Institute of Chemical Engineers, 2022, 132, 104145
DOI: 10.1016/j.jtice.2021.11.012