Hierarchically structured microchip for point-of-care immunoassays with dynamic detection ranges.

Point-of-care (POC) medical assays provide critical information to guide clinical therapy for a broad range of medical scenarios, such as resource-poor settings and specialty departments in hospitals. Even though many types of POC assays can be done in automated devices, these POC assays typically cannot well accommodate the multiplexed detection of biomarkers where a large dynamic range is needed. Here, we report a POC assay, which is both automated and suitable for detecting multiple biomarkers with dynamic detection ranges. We call it a dynamic multiplexed immunoassay (DMI). We control the concentrations of capture antibodies and the intensity of the readout signal to dynamically modulate the detection range of immunoassays (pg mL-1 to μg mL-1), leading to the multiplexed detection of C-reactive protein (CRP), procalcitonin (PCT), and interleukin 6 (IL-6) simultaneously in undiluted human serum samples. The POC assay allows the rapid and accurate detection of infection in patients.

[1]  S. Kingsmore,et al.  Discriminative value of inflammatory biomarkers for suspected sepsis. , 2012, The Journal of emergency medicine.

[2]  K. Faulds,et al.  Multiplex in vitro detection using SERS. , 2016, Chemical Society reviews.

[3]  Xingyu Jiang,et al.  A miniaturized, parallel, serially diluted immunoassay for analyzing multiple antigens. , 2003, Journal of the American Chemical Society.

[4]  Peter Schlattmann,et al.  Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. , 2013, The Lancet. Infectious diseases.

[5]  A prospective, multi-centre US clinical trial to determine accuracy of FebriDx point-of-care testing for acute upper respiratory infections with and without a confirmed fever , 2018, Annals of medicine.

[6]  Ashitha L. Vijayan,et al.  Procalcitonin: a promising diagnostic marker for sepsis and antibiotic therapy , 2017, Journal of Intensive Care.

[7]  Y. K. Cheung,et al.  1 Supplementary Information for : Microfluidics-based diagnostics of infectious diseases in the developing world , 2011 .

[8]  Xingyu Jiang,et al.  Controllable Assembly of Enzymes for Multiplexed Lab-on-a-Chip Bioassays with a Tunable Detection Range. , 2018, Angewandte Chemie.

[9]  Xingyu Jiang,et al.  A microfluidic indirect competitive immunoassay for multiple and sensitive detection of testosterone in serum and urine. , 2016, The Analyst.

[10]  J. Bienvenu,et al.  Procalcitonin as an Acute Phase Marker , 2001, Annals of clinical biochemistry.

[11]  Nicola Bizzaro,et al.  Current state of diagnostic technologies in the autoimmunology laboratory , 2012, Clinical chemistry and laboratory medicine.

[12]  J. Y. Kim,et al.  Diagnosis and evaluation of severity of sepsis via the use of biomarkers and profiles of 13 cytokines: a multiplex analysis , 2015, Clinical chemistry and laboratory medicine.

[13]  Xingyu Jiang,et al.  Chemiluminescence immunoassay based on microfluidic chips for α-fetoprotein. , 2014, Clinica chimica acta; international journal of clinical chemistry.

[14]  M. Nijsten,et al.  Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. , 2018, The Lancet. Infectious diseases.

[15]  Zhi Zhu,et al.  Au@Pt nanoparticle encapsulated target-responsive hydrogel with volumetric bar-chart chip readout for quantitative point-of-care testing. , 2014, Angewandte Chemie.

[16]  Patrick Garidel,et al.  Stability of buffer-free freeze-dried formulations: A feasibility study of a monoclonal antibody at high protein concentrations. , 2015, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[17]  Yadollah Omidi,et al.  Recent advances in simultaneous electrochemical multi-analyte sensing platforms , 2017 .

[18]  James F Rusling,et al.  Multiplexed electrochemical protein detection and translation to personalized cancer diagnostics. , 2013, Analytical chemistry.

[19]  Yonggoo Kim,et al.  Procalcitonin as a diagnostic marker and IL-6 as a prognostic marker for sepsis. , 2013, Diagnostic microbiology and infectious disease.

[20]  Juan Li,et al.  A nanozyme tag enabled chemiluminescence imaging immunoassay for multiplexed cytokine monitoring. , 2018, Chemical communications.

[21]  Yiping Chen,et al.  Skiving stacked sheets of paper into test paper for rapid and multiplexed assay , 2017, Science Advances.

[22]  Toshio Tanaka,et al.  IL-6 in inflammation, immunity, and disease. , 2014, Cold Spring Harbor perspectives in biology.

[23]  Xingyu Jiang,et al.  Materials for Microfluidic Immunoassays: A Review , 2017, Advanced healthcare materials.

[24]  C. Seymour,et al.  Point-of-care sensors for the management of sepsis , 2018, Nature Biomedical Engineering.

[25]  J. Kasperski,et al.  Analysis of procalcitonin and CRP concentrations in serum of patients with chronic spontaneous urticaria , 2012, Inflammation Research.

[26]  Y. Liu,et al.  An automated and portable microfluidic chemiluminescence immunoassay for quantitative detection of biomarkers. , 2017, Lab on a chip.

[27]  Yujun Song,et al.  Nanoporous Glass Integrated in Volumetric Bar-Chart Chip for Point-of-Care Diagnostics of Non-Small Cell Lung Cancer. , 2016, ACS nano.

[28]  Ian Todd,et al.  ELISA in the multiplex era: Potentials and pitfalls , 2015, Proteomics. Clinical applications.

[29]  Mark B Pepys,et al.  C-reactive protein: a critical update. , 2003, The Journal of clinical investigation.

[30]  Jinghua Yu,et al.  Multiplexed sandwich immunoassays using flow-injection electrochemiluminescence with designed substrate spatial-resolved technique for detection of tumor markers. , 2013, Biosensors & bioelectronics.

[31]  T. Robak,et al.  Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis. , 1998, Mediators of inflammation.

[32]  Dan Wu,et al.  Improvement of enzyme-linked immunosorbent assay for the multicolor detection of biomarkers , 2016, Chemical science.

[33]  David T. Huang,et al.  Procalcitonin‐Guided Use of Antibiotics for Lower Respiratory Tract Infection , 2018, The New England journal of medicine.

[34]  R. Hotchkiss,et al.  Sepsis: Preventing organ failure in sepsis — the search continues , 2017, Nature Reviews Nephrology.

[35]  Yang Wang,et al.  Electrospun Nanofibrous Membranes: A Novel Solid Substrate for Microfluidic Immunoassays for HIV , 2008 .