Colorimetric Paper-Based Sensors against Cancer Biomarkers

Abstract

Cancer is a major cause of mortality and morbidity worldwide. Detection and quantification of cancer biomarkers plays a critical role in cancer early diagnosis, screening, and treatment. Clinicians, particularly in developing countries, deal with high costs and limited resources for diagnostic systems. Using low-cost substrates to develop sensor devices could be very helpful. The interest in paper-based sensors with colorimetric detection increased exponentially in the last decade as they meet the criteria for point-of-care (PoC) devices. Cellulose and different nanomaterials have been used as substrate and colorimetric probes, respectively, for these types of devices in their different designs as spot tests, lateral-flow assays, dipsticks, and microfluidic paper-based devices (μPADs), offering low-cost and disposable devices. However, the main challenge with these devices is their low sensitivity and lack of efficiency in performing quantitative measurements. This review includes an overview of the use of paper for the development of sensing devices focusing on colorimetric detection and their application to cancer biomarkers. We highlight recent works reporting the use of paper in the development of colorimetric sensors for cancer biomarkers, such as proteins, nucleic acids, and others. Finally, we discuss the main advantages of these types of devices and highlight their major pitfalls.

Keywords: cancer diagnosis; colorimetric detection; paper-based devices.

Figure 1

Examples of: (A) types of samples and biomarkers, (B) types of paper, (C) recognition elements and labels, and (D) signal readouts used in colorimetric paper sensors.

Figure 2

Examples of different types of PADs. Dipsticks (A): urine test strips. Reproduced and adapted with permission from [13]; Spot test (B): photographs (a) and bar charts (b) of the corresponding grey values of the colorimetric readout based on a highly porous poly(L-lactic) acid nanofiber and NC platforms for AFP detection. Reproduced and adapted with permission from [30]; LFA (C): schematic representation of LFA principle for the detection of microRNA-215 (a) and photographs and corresponding optical measurements (b) of the developed LFA in the presence (2.5 nM) and absence (0 nM) of microRNA-215. Reproduced and adapted with permission from [32]; µPAD (D): photograph of the microfluidic sensor for detection of 1000 pM of microRNA-21 based on peroxidase mimetic activity of DNA-templated Ag/Pt nanoclusters. Reproduced and adapted with permission from [26].

Figure 3

Number of published papers by year of publication. Data obtained from ISI WEB OF KNOWLEDGE with the keywords “colorimetric AND paper-based” (purple bar) and “colorimetric AND paper-based AND cancer” (orange bar). Data collected in March 2022.

Figure 4

Scheme of distance-based detection of CEA (A). Results of CEA detection (B). Reproduced and adapted with permission from [15].

Figure 5

Scheme of ring-over device for CEA detection (A). Results of CEA detection (B). Reproduced and adapted with permission from [38].

Figure 6

Scheme of VCP detection (A) without (upper) and with (bottom) magnet. Comparison of detection results of VCP (B) with (left) and without (right) magnet. Reproduced and adapted with permission from [36].

Figure 7

Scheme of IL-6 detection by LFIA. Reproduced with permission from [31].

Figure 8

(A) Pictures of the colorimetric assay for telomerase activity (B) and corresponding graphic with linear relationship between MB and telomerase concentration. Reproduced and adapted with permission from [63].

Figure 9

Scheme of HER2 detection by an adsorption-desorption colorimetric LFA. Reproduced with permission from [35].

Figure 10

Scheme of LFA test strips (A). Scheme of competitive LFA with aptamer as recognition elements for exosome identification (B). Reproduced and adapted with permission from [37].