Biomarker detection for disease diagnosis using cost-effective microfluidic platforms

Abstract

Early and timely detection of disease biomarkers can prevent the spread of infectious diseases, and drastically decrease the death rate of people suffering from different diseases such as cancer and infectious diseases. Because conventional diagnostic methods have limited application in low-resource settings due to the use of bulky and expensive instrumentation, simple and low-cost point-of-care diagnostic devices for timely and early biomarker diagnosis is the need of the hour, especially in rural areas and developing nations. The microfluidics technology possesses remarkable features for simple, low-cost, and rapid disease diagnosis. There have been significant advances in the development of microfluidic platforms for biomarker detection of diseases. This article reviews recent advances in biomarker detection using cost-effective microfluidic devices for disease diagnosis, with the emphasis on infectious disease and cancer diagnosis in low-resource settings. This review first introduces different microfluidic platforms (e.g. polymer and paper-based microfluidics) used for disease diagnosis, with a brief description of their common fabrication techniques. Then, it highlights various detection strategies for disease biomarker detection using microfluidic platforms, including colorimetric, fluorescence, chemiluminescence, electrochemiluminescence (ECL), and electrochemical detection. Finally, it discusses the current limitations of microfluidic devices for disease biomarker detection and future prospects.

Figure 1

Fabrication schematic of 3D high aspect ratio PDMS microfluidic networks using a plastic plate embedded hybrid stamp. Reproduced with permission from Royal Society of Chemistry.

Figure 2

Paper-based and its hybrid microfluidic platforms. (A) FLASH fabrication for paper-based microfluidic devices. (1) Schematic of the method. (2)–(5) FLASH fabrication procedures. Reproduced with permission from Royal Society of Chemistry. (B) A PDMS/paper hybrid chip for instrument-free diagnosis of infectious diseases using a UV light pen. Reproduced with permission from American Chemical Society.

Figure 3

Biomarker detection using integrated nano-sensors on the chip. (A) Schematic of the working principle of the colorimetric assays for detection of glucose with cerium oxide nanoparticles using a paper-based microfluidic device. Reproduced with permission from American Chemical Society. (B) Schematic of a PDMS/paper hybrid chip for multiplexed one-step pathogen detection using graphene oxide (GO) nanosensors. (1) The hybrid microfluidic biochip layout. (2) and (3) One step turn-on detection based on interaction among GO, aptamers and pathogens. (4) Cross-reaction investigation of Staphylococcus aureus and Salmonella enterica with their corresponding and non-corresponding aptamers. Reproduced with permission Royal Society of Chemistry.

Figure 4

A paper-based microfluidic platform with electrochemical detection for multiplexed cancer biomarker detection. (A) Device fabrication procedures. (B) Schematic representation of the electrochemical immunoassay procedures using CEA as an example. Reproduced with permission from Elsevier.

Figure 5

Biomarker detection on microfluidic platforms with chemiluminescence and electrochemiluminescence detection. (A) Schematic representation of rare cell capture and detection using aptamers and chemiluminescence. Reproduced with permission from Elsevier. (B) Microfluidic electrochemiluminescence array for cancer biomarker detection. 1) syringe pump; 2) injector valve; 3) switch valve; 4) tubing for inlet; 5) outlet; 6) PMMA plate; 7) Pt counter wire; 8) Ag/AgCl reference wire; 9) PDMS channels; 10) pyrolytic graphite chip; 11) Immunoassay complex on RuBPY-silica nanoparticles. Reproduced with permission from Springer.