Noncommunicable diseases (NCDs) or chronic diseases are responsible for 36 million deaths per year, and the majority of these deaths have been reported in low- and middle-income countries.

The four major causes of NCD deaths include: cardiovascular diseases (17.3 million annual deaths), cancers (7.6 million), chronic respiratory diseases (4.2 million) and diabetes (1.3 million). There is a growing need for the development of low-cost, fast, noninvasive methodologies to diagnose and treat these classes of disease.

Although polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) are among widely routine diagnostic formats in laboratories, their usage in diagnostic resource-limited settings is limited due to multiple factors. Therefore, there is great potential for point-of-care (POC) diagnostics in resource-limited settings.

Paper has recently received a lot of attention as an ubiquitous and nonexpensive material that is easily storable and easy to use. Furthermore, it is compatible with diverse biochemical and biomedical applications.

Paper-based diagnostics are one of the many formats of POC that could be manufactured in multiple formats, including dipstick assay and lateral flow assay (LFA). Microfluidic paper-based analytical devices (uPAD) are normally used to read these paper-based assays.

There have been many advances in this field, where scientists have focused on improving the detection sensitivity, accuracy and read-out quantification, simplifying the procedures, and multifunctionalizing the technology.

Furthermore, many researchers have focused on improving the fabrication techniques, sample preparation procedures and associated analytical techniques. Finally, there have been efforts to manufacture miniaturized and integrated paper-based diagnostic devices with the sample-in-answer-out capability.

On the other hand, there is a lack of naturally-occurring predictive markers that could be limiting for the paper-based POC applicability. Warren et al. reported the design of exogenous agents in a mouse model that could serve as synthetic biomarkers for NCDs through production of signals that could be detected and quantified in the urine by paper tests.

Basically, nanoparticles were conjugated to the ligand-coded reporters via protease-sensitive peptide substrates. These nanoparticles were delivered into the body, where they passively targeted the problem sites (tumors or blood clots).

Since the proteases were upregulated in these diseased sites, they cleaned the peptide substrates, which caused the reporters to be released and cleared into urine to be detected by sandwich immunoassays (ELISA on paper lateral flow assay). This format could allow for multiplexed probes in vivo and their simultaneous qualification.

In brief, LFA and injectable synthetic biomarkers can be modified as a potential diagnostic method for multiple diseases. This has the capability to form a general NCD diagnostic platform applicable to all settings without a need for advanced, highly-priced equipment of highly-trained medical staff.