Engineering a Point-of-Care Paper-Microfluidic Electrochemical Device Applied to the Multiplexed Quantitative Detection of Biomarkers in Sputum

Abstract

Health initiatives worldwide demand affordable point-of-care devices to aid in the reduction of morbidity and mortality rates of high-incidence infectious and noncommunicable diseases. However, the production of robust and reliable easy-to-use diagnostic platforms showing the ability to quantitatively measure several biomarkers in physiological fluids and that could in turn be decentralized to reach any relevant environment remains a challenge. Here, we show the particular combination of paper-microfluidic technology, electrochemical transduction, and magnetic nanoparticle-based immunoassay approaches to produce a unique, compact, and easily deployable multiplex device to simultaneously measure interleukin-8, tumor necrosis factor-α, and myeloperoxidase biomarkers in sputum, developed with the aim of facilitating the timely detection of acute exacerbations of chronic obstructive pulmonary disease. The device incorporates an on-chip electrochemical cell array and a multichannel paper component, engineered to be easily aligned into a polymeric cartridge and exchanged if necessary. Calibration curves at clinically relevant biomarker concentration ranges are produced in buffer and artificial sputum. The analysis of sputum samples of healthy individuals and acutely exacerbated patients produces statistically significant biomarker concentration differences between the two studied groups. The device can be mass-produced at a low cost, being an easily adaptable platform for measuring other disease-related target biomarkers.

Classification and applications of nanomaterials in vitro diagnosis

“…When the temperature approaches the material's Curie temperature, its ferromagnetism and superparamagnetism disappear, and it shows paramagnetic activity [ 45 ]. MNPs have been used in a range of applications, including biomarkers and biosensors, MRI, positron emission tomography (PET), fluorescence imaging, tissue healing, drug carriers, disease detection and treatment [ [46] , [47] , [48] , [49] , [50] ]. Yu et al discovered that oligomalic acid-modified MNPs can be used as bioprobes to specifically recognize and capture complementary nucleotide strands, as well as isolate and purify them in the presence of a magnetic field [ 51 ].…”

Sustainable Sensing with Paper Microfluidics: Applications in Health, Environment, and Food Safety

“…The prototype's performance was successfully validated in field conditions. Moreover, paper-based devices have been employed to diagnose other diseases and analytes, including influenza virus H5N1 [138], Neisseria meningitides [139], nucleic acid detection [140,141], noncommunicable diseases [142], cancer diagnosis [57,143,144], chronic obstructive pulmonary disease (COPD) biomarkers [145], HIV [146,147], pregnancy, infertility [148,149], and bioanalytes (uric acid, glucose, H 2 O 2 , and cholesterol) [150][151][152], etc. In a recent study, Bezdekova et al [153] introduced a proof-of-concept paper-based device for diagnosing prostate cancer (CaP) from urine samples.…”

Sustainable Sensing with Paper Microfluidics: Applications in Health, Environment, and Food Safety

“…Moreover, paper-based devices have been employed to diagnose other diseases and analytes, including influenza virus H5N1 [135], Neisseria meningitides [136], nucleic acid detection [137,138], non-communicable diseases [139], cancer diagnosis [57,140,141], chronic obstructive pulmonary disease (COPD) biomarkers [142], HIV [143,144], pregnancy, infertility [145,146], and bioanalytes (uric acid, glucose, H 2 O 2 , Cholesterol) [147][148][149], etc. In a recent study, Bezdekova et al [150] introduced a proof-of-concept paper-based device for diagnosing prostate cancer (CaP) from urine samples.…”