Lab-on-chip technology for chronic disease diagnosis

Abstract

Various types of chronic diseases (CD) are the leading causes of disability and death worldwide. While those diseases are chronic in nature, accurate and timely clinical decision making is critically required. Current diagnosis procedures are often lengthy and costly, which present a major bottleneck for effective CD healthcare. Rapid, reliable and low-cost diagnostic tools at point-of-care (PoC) are therefore on high demand. Owing to miniaturization, lab-on-chip (LoC) technology has high potential to enable improved biomedical applications in terms of low-cost, high-throughput, ease-of-operation and analysis. In this direction, research toward developing new LoC-based PoC systems for CD diagnosis is fast growing into an emerging area. Some studies in this area began to incorporate digital and mobile technologies. Here we review the recent developments of this area with the focus on chronic respiratory diseases (CRD), diabetes, and chronic kidney diseases (CKD). We conclude by discussing the challenges, opportunities and future perspectives of this field.

Keywords: Biomedical engineering; Diagnosis; Diagnostic markers.

Fig. 1

Summary of conventional and LoC-based diagnostic methods for CRD, diabetes and CKD, and future directions

Fig. 2

Examples of LoC-based diagnostic applications for chronic respiratory diseases. a A label-free microfluidic electrochemical sensor based on carbon nanotubes/ferrocene for DNA detection of Mycobacterium tuberculosis. The device integrates three channels for negative control, DNA detection, and mismatch DNA detection; b An automated and integrated LoC platform for detection of multiple CRD protein biomarkers in human saliva. Left: a photograph demonstration of the chip; Right: signal image of the microsphere array; c A microfluidic chip for studying the chemotactic function of neutrophils from asthma patients. The top image shows neutrophil capture from one drop of blood. The bottom image shows the diffusion-based gradient generation in a microfluidic device; d A microfluidic platform for evaluating neutrophil chemotaxis to the sputum samples from COPD patients. The left image illustrates the flow-based gradient generation in a PDMS device. The right image shows neutrophil migration to a sputum gradient. The figures are adapted from refs. ^,,, with permission from AIP Publishing for a, Royal Society of Chemistry for b, National Academy of Sciences for c and PLOS for d, respectively

Fig. 3

Examples of LoC-based diagnostic applications for diabetes. a (Left) Illustration of a µPAD to test glucose with (left bottom) and without (left top) SiO₂ nanoparticles modification; (Right) Illustration of the proposed μPAD showing the analysis of an artificial urine sample spiked with lactate, glucose, and glutamate; b An easy and low-cost three-dimensional microfluidic paper device for glucose assay. The right image shows the flow pattern of the device; c A microfluidic biosensor for the detection of amino acids using enzymatic reactions coupled with spectrophotometric detection; d A simple microfluidic tool for erythrocyte fragility study by analyzing osmotic lysis kinetics under hydrodynamic focusing. The inset images (a–d) show the cell images at various locations. The figures are adapted from refs. ^,,, with permission from Royal Society of Chemistry for a, d, American Chemical Society for b, and Springer for c, respectively

Fig. 4

Examples of LoC-based diagnostic applications for chronic kidney disease. a A PoC device to measure the elevated creatinine level in blood based on electrophoretic separation and conductivity detection. The different functional units include: [1] sample opening; [2] evaporation reservoir; [3] Cations injection channel by moving boundary electrophoresis; [4] double-T injector; [5] reservoir with gas bubble for liquid expansion control; [6] conductivity detection electrodes; [A, B] high-voltage injection anode and cathode; [C, D] high-voltage separation anode and cathode; [E] electrodes to measure sample conductivity; b A microfluidic device integrated with 3D printed movable components and a smartphone imaging platform for colorimetric urinary protein quantification; c A microfluidic chip integrated with the capillary–gravitational valves for urinary creatinine measurement. Left: Scheme of the rectangular hand-assist kit and its operation processes. Right: The sequential functions of chip for creatinine assay as the angle of the chip was changed; The figures are adapted from refs. ^,, from Royal Society of Chemistry for a, American Chemical Society for b, and Elsevier for c, respectively