Wave-shaped microfluidic chip assisted point-of-care testing for accurate and rapid diagnosis of infections

Bin-Feng Yin; Xin-Hua Wan; Ming-Zhu Yang; Chang-Cheng Qian; A. S. M. Muhtasim Fuad Sohan

doi:10.1186/s40779-022-00368-1

Your Location：

Home >

Browse articles >

Wave-shaped microfluidic chip assisted point-of-care testing for accurate and rapid diagnosis of infections

RESEARCH | Updated：2023-02-28

- Wave-shaped microfluidic chip assisted point-of-care testing for accurate and rapid diagnosis of infections
- Wave-shaped microfluidic chip assisted point-of-care testing for accurate and rapid diagnosis of infections
- 解放军医学杂志（英文版） 2022年9卷第5期页码：553-564
- Affiliations：
  
  1.School of Mechanical Engineering, Yangzhou University, Yangzhou 225127, Jiangsu, China
  2.Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College, Beijing 100005, China
- Author bio：
  
  * binfengyin@yzu.edu.cn
- Funds：
  
  the National Natural Science Foundation of China(81902167;52075138);the Natural Science Foundation of Jiangsu Province(BK20190872)
- DOI：10.1186/s40779-022-00368-1
  中图分类号：
- 纸质出版：2022-10
- Accepted：
Scan QR Code
Wave-shaped microfluidic chip assisted point-of-care testing for accurate and rapid diagnosis of infections[J]. 解放军医学杂志（英文版）, 2022,9(5):553-564.

Yin BF, Wan XH, Yang MZ, Qian CC, Sohan ASMMF. Wave-shaped microfluidic chip assisted point-of-care testing for accurate and rapid diagnosis of infections. Mil Med Res. 2022;9(1):8.
Wave-shaped microfluidic chip assisted point-of-care testing for accurate and rapid diagnosis of infections[J]. 解放军医学杂志（英文版）, 2022,9(5):553-564. DOI： 10.1186/s40779-022-00368-1.

Yin BF, Wan XH, Yang MZ, Qian CC, Sohan ASMMF. Wave-shaped microfluidic chip assisted point-of-care testing for accurate and rapid diagnosis of infections. Mil Med Res. 2022;9(1):8. DOI： 10.1186/s40779-022-00368-1.

摘要

Abstract

Background:

Early diagnosis and classification of infections increase the cure rate while decreasing complications

which is significant for severe infections

especially for war surgery. However

traditional methods rely on laborious operations and bulky devices. On the other hand

point-of-care (POC) methods suffer from limited robustness and accuracy. Therefore

it is of urgent demand to develop POC devices for rapid and accurate diagnosis of infections to fulfill on-site militarized requirements.

Methods:

We developed a wave-shaped microfluidic chip (WMC) assisted multiplexed detection platform (WMC-MDP). WMC-MDP reduces detection time and improves repeatability through premixing of the samples and reaction of the reagents. We further combined the detection platform with the streptavidin–biotin (SA-B) amplified system to enhance the sensitivity while using chemiluminescence (CL) intensity as signal readout. We realized simultaneous detection of C-reactive protein (CRP)

procalcitonin (PCT)

and interleukin-6 (IL-6) on the detection platform and evaluated the sensitivity

linear range

selectivity

and repeatability. Finally

we finished detecting 15 samples from volunteers and compared the results with commercial ELISA kits.

Results:

Detection of CRP

PCT

and IL-6 exhibited good linear relationships between CL intensities and concentrations in the range of 1.25–40 μg/ml

0.4–12.8 ng/ml

and 50–1600 pg/ml

respectively. The limit of detection of CRP

PCT

and IL-6 were 0.54 μg/ml

0.11 ng/ml

and 16.25 pg/ml

respectively. WMC-MDP is capable of good adequate selectivity and repeatability. The whole detection procedure takes only 22 min that meets the requirements of a POC device. Results of 15 samples from volunteers were consistent with the results detected by commercial ELISA kits.

Conclusions:

WMC-MDP allows simultaneous

rapid

and sensitive detection of CRP

PCT

and IL-6 with satisfactory selectivity and repeatability

requiring minimal manipulation. However

WMC-MDP takes advantage of being a microfluidic device showing the coefficients of variation less than 10% enabling WMC-MDP to be a type of point-of-care testing (POCT). Therefore

WMC-MDP provides a promising alternative to POCT of multiple biomarkers. We believe the practical application of WMC-MDP in militarized fields will revolutionize infection diagnosis for soldiers.

关键词

Keywords

references

Delano MJ , Ward PA . The immune system’s role in sepsis progression, resolution, and long-term outcome . Immunol Rev . 2016 ; 274 ( 1 ): 330 - 53 .

van der Poll T , van de Veerdonk FL , Scicluna BP , Netea MG . The immunopathology of sepsis and potential therapeutic targets . Nat Rev Immunol . 2017 ; 17 ( 7 ): 407 - 20 .

Gotts JE , Matthay MA . Sepsis: pathophysiology and clinical management . BMJ . 2016 ; 353 : i1585 .

Bao GQ , He L , Lee D , D’angelo J , Wang HC . An ongoing search for potential targets and therapies for lethal sepsis . Mil Med Res . 2015 ; 2 : 20 .

Kumar S , Tripathy S , Jyoti A , Singh SG . Recent advances in biosensors for diagnosis and detection of sepsis: a comprehensive review . Biosens Bioelectron . 2019 ; 124–125 : 205 - 15 .

Ma XY , Tian LX , Liang HP . Early prevention of trauma-related infection/sepsis . Mil Med Res . 2016 ; 3 : 33 .

Molinero-Fernández Á , Arruza L , López MÁ , Escarpa A . On-the-fly rapid immunoassay for neonatal sepsis diagnosis: C-reactive protein accurate determination using magnetic graphene-based micromotors . Biosens Bioelectron . 2020 ; 158 : 112 .

Lam SW , Bauer SR , Fowler R , Duggal A . Systematic review and meta-analysis of procalcitonin-guidance versus usual care for antimicrobial management in critically ill patients: focus on subgroups based on antibiotic initiation, cessation, or mixed strategies . Crit Care Med . 2018 ; 46 ( 5 ): 684 - 90 .

Rose-John S , Winthrop K , Calabrese L . The role of IL-6 in host defence against infections: immunobiology and clinical implications . Nat Rev Rheumatol . 2017 ; 13 ( 7 ): 399 - 409 .

Belushkin A , Yesilkoy F , González-López JJ , Ruiz-Rodrígue JC , Ferrer R , Fàbrega A , et al . Rapid and digital detection of inflammatory biomarkers enabled by a novel portable nanoplasmonic imager . Small . 2020 ; 16 ( 3 ): 1906108 .

Vashist SK , Venkatesh AG , Schneider EM , Beaudoin C , Luppa PB , Luong JHT . Bioanalytical advances in assays for C-reactive protein . Biotechnol Adv . 2016 ; 34 ( 3 ): 272 - 90 .

Chen NS , Zhou M , Dong X , Qu JM , Gong FY , Han Y , et al . Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study . Lancet . 2020 ; 395 ( 10223 ): 507 - 13 .

Yoo H , Shin J , Sim J , Cho H , Hong S . Reusable surface plasmon resonance biosensor chip for the detection of H1N1 influenza virus . Biosens Bioelectron . 2020 ; 168 : 112561 .

Smilowitz NR , Kunichoff D , Garshick M , Shah B , Pillinger M , Hochman JS , et al . C-reactive protein and clinical outcomes in patients with COVID-19 . Eur Heart J . 2021 ; 42 ( 23 ): 2270 - 9 .

Lloyd-Jones DM , Liu K , Tian L , Greenland P . Narrative review: Assessment of C-reactive protein in risk prediction for cardiovascular disease . Ann Intern Med . 2006 ; 145 ( 1 ): 35 - 42 .

Lv XX , Wang HD . Pathophysiology of sepsis-induced myocardial dysfunction . Mil Med Res . 2016 ; 3 : 30 .

Erlinger TP , Platz EA , Rifai N , Helzlsouer KJ . C-reactive protein and the risk of incident colorectal cancer . JAMA . 2004 ; 291 ( 5 ): 585 - 90 .

Baron JA , Cole BF , Sandler RS , Haile RW , Ahnen D , Bresalier R , et al . A randomized trial of aspirin to prevent colorectal adenomas . N Engl J Med . 2003 ; 348 ( 10 ): 891 - 9 .

Ji TX , Xu XQ , Wang XD , Cao N , Han XR , Wang MH , et al . Background-free chromatographic detection of sepsis biomarker in clinical human serum through near-infrared to near-infrared upconversion immunolabeling . ACS Nano . https://doi.org/10.1021/acsnano.0c05700 https://doi.org/10.1021/acsnano.0c05700 . Epub ahead of print .

Gaini S , Koldkjaer OG , Pedersen C , Pedersen SS . Procalcitonin, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in community-acquired infections and sepsis: a prospective study . Crit Care . 2006 ; 10 ( 2 ): R53 .

Liu LB , Han ZY , An F , Gong XN , Zhao CG , Zheng WP , et al . Aptamer-based biosensors for the diagnosis of sepsis . J Nanobiotechnol . 2021 ; 19 ( 1 ): 216 .

Wang P , Kricka LJ . Current and emerging trends in point-of-care technology and strategies for clinical validation and implementation . Clin Chem . 2018 ; 64 ( 10 ): 1439 - 52 .

Shrivastava S , Trung TQ , Lee NE . Recent progress, challenges, and prospects of fully integrated mobile and wearable point-of-care testing systems for self-testing . Chem Soc Rev . 2020 ; 49 ( 6 ): 1812 - 66 .

Min J , Nothing M , Coble B , Zheng H , Park J , Im H , et al . Integrated biosensor for rapid and point-of-care-sepsis diagnosis . ACS Nano . 2018 ; 12 ( 4 ): 3378 - 84 .

Yang MZ , Liu Y , Jiang XY . Barcoded point-of-care bioassays . Chem Soc Rev . 2019 ; 48 ( 3 ): 850 - 84 .

Yin BF , Wang Y , Dong ML , Wu J , Ran B , Xie MX , et al . One-step multiplexed detection of foodborne pathogens: combining a quantum dot-mediated reverse assaying strategy and magnetic separation . Biosens Bioelectron . 2016 ; 86 : 996 - 1002 .

Yin BF , Zheng WS , Dong ML , Yu WB , Chen YP , Joo SW , et al . An enzymemediated competitive colorimetric sensor based on Au@Ag bimetallic nanoparticles for highly sensitive detection of disease biomarkers . Analyst . 2017 ; 142 ( 16 ): 2954 - 60 .

Yin BF , Qian CC , Wang SB , Wan XH , Zhou T . A microfluidic chip-based MRS immunosensor for biomarker detection via enzyme-mediated nanoparticle assembly . Front Chem . 2021 ; 9 : 688442 .

Timilsina SS , Jolly P , Durr N , Yafia M , Ingber DE . Enabling multiplexed electrochemical detection of biomarkers with high sensitivity in complex biological samples . Accounts Chem Res . 2021 ; 54 ( 18 ): 3529 - 39 .

Mou L , Dong R , Hu B , Li Z , Zhang J , Jian X . Hierarchically structured microchip for point-of-care immunoassays with dynamic detection ranges . Lab Chip . 2019 ; 19 ( 16 ): 2750 - 7 .

Russell C , Ward AC , Vezza V , Hoskisson P , Alcorn D , Steenson DP , et al . Development of a needle shaped microelectrode for electrochemical detection of the sepsis biomarker interleukin-6 (IL-6) in real time . Biosens Bioelectron . 2019 ; 126 : 806 - 14 .

Zupančič U , Jolly P , Estrela P , Moschou D , Ingber DE . Electrochemical biosensors: Graphene enabled low-noise surface chemistry for multiplexed sepsis biomarker detection in whole blood . Adv Funct Mater . 2021 ; 31 ( 16 ): 2010638 .

Waheed S , Cabot JM , Macdonald NP , Lewis T , Guijt RM , Paull B , et al . 3D printed microfluidic devices: enablers and barriers . Lab Chip . 2016 ; 16 ( 11 ): 1993 - 2013 .

Yin BF , Wan XH , Qian CC , Sohan A , Wang SB , Zhou T . Point-of-care testing for multiple cardiac markers based on a snail-shaped microfluidic chip . Front Chem . 2021 ; 9 : 741058 .

Lee CY , Fu LM . Recent advances and applications of micromixers . Sens Actuators B Chem . 2018 ; 259 : 677 - 702 .

Viktorov V , Mahmud MR , Visconte C . Numerical study of fluid mixing at different inlet flow-rate ratios in tear-drop and chain micromixers compared to a new H-C passive micromixer . Eng Appl Comp Fluid Mech . 2016 ; 10 ( 1 ): 183 - 93 .

Raza W , Hossain S , Kim KY . Effective mixing in a short serpentine split-andrecombination micromixer . Sens Actuators B Chem . 2018 ; 258 : 381 - 92 .

Chan HN , Tan MJA , Wu HK . Point-of-care testing: applications of 3D printing . Lab Chip . 2017 ; 17 ( 16 ): 2713 - 39 .

Zhou ZM , Yu Y , Zhang MZ , Chen J , Ren QQ , Song JT , et al . Chemiluminescence detection of lead (II) using “8-17” DNAzyme and hemin/Gquadruplex with high sensitivity and selectivity . Sensor Actuat B Chem . 2014 ; 201 : 496 - 502 .

Mou L , Li Z , Qi J , Jiang X . Point-of-care immunoassays with tunable detection range for detecting infection in intensive care unit . CCS Chem . 2021 ; 3 ( 5 ): 1562 - 72 .

Ruppert C , Kaiser L , Jacob LJ , Laufer S , Kohl M , Deigner HP . Duplex Shiny app quantification of the sepsis biomarkers C-reactive protein and interleukin-6 in a fast quantum dot labeled lateral flow assay . J Nanobiotechnol . 2020 ; 18 ( 1 ): 130 .

Li T , Yang M . Electrochemical sensor utilizing ferrocene loaded porous polyelectrolyte nanoparticles as label for the detection of protein biomarker IL-6 . Sens Actuators B Chem . 2011 ; 158 ( 1 ): 361 - 5 .

浏览量

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

Microfluidics-based strategies for molecular diagnostics of infectious diseases

钢拱桥极限承载力的综合三因素检算方法

芜湖长江大桥裕溪河桥车桥耦合振动分析

长大货物列车空气管系3维充气模型的数值仿真

架悬机车驱动装置悬挂参数及结构的研究