Bioactive paper provides a low-cost platform for diagnostics

Abstract

Bioactive paper includes a range of potential paper-based materials that can perform analytical functions normally reserved for multi-well plates in the laboratory or for portable electronic devices. Pathogen detection is the most compelling application. Simple paper-based detection, not requiring hardware, has the potential to have impacts in society, ranging from the kitchen to disasters in the developing world. Bioactive-paper research is an emerging field with significant efforts in Canada, USA (Harvard), Finland and Australia. Following a brief introduction to the material and surface properties of paper, I review the literature. Some of the early work exploits the porosity of paper to generate paper-based microfluidics ("paperfluidics") devices. I exclude from this review printed electronic devices and plastics-supported devices.

Keywords: Antibody; Antimicrobial paper; Bacteriophage; Bioactive paper; Biosensor; DNA aptamer; Lateral flow; Paper-supported assay; Paperfluidics; Pathogen detection.

Figure 1

The chemical structures of polyamide-epichlorohydrin (PAE) and glyoxal-modified polyacrylamide (GPAM) wet-strength resins. PAE gives permanent wet strength whereas GPAM cross-links hydrolyze with exposure time to water.

Figure 2

Alkyl ketene dimer (AKD) and alkyl succinic anhydride “size” react with fibers to lower surface energy and water-penetration rates.

Figure 3

Killing bacteria with filter paper impregnated with wild T4 phage (left), and filter paper with genetically-engineered T4 phage with cellulose-binding module (CBM) (right) giving spontaneous adhesion of the phage head to cellulose. The CBM-immobilized phage infects and kills the bacteria giving transparent regions in the media .

Figure 4

Coupling a DNA aptamer to oxidized cellulose.

Figure 5

The influence of PAE wet-strength resin on paper-supported ELISA. AR-Ab is a conventional anti-mouse antibody (Ab) immobilized by non-specific adsorption. CBD-Ab is complex structure with 5 Abs fused to 5 cellulose-binding modules (CBMs) (Adapted from [77]).

Figure 6

Cellulose-binding-module protein used to attach TiO₂ to cellulose (Adapted from [30]).

Figure 7

Coupling antibodies or DNA aptamers to carboxylated microgels (Adapted from [17]).

Figure 8

Chromatographic elution of filter paper spotted with fluorescently-labeled microgel (Adapted from [17]).

Figure 9

Bodenhamer’s displacement assay for pathogen detection on transparent films. Initially a dye-conjugated antibody is bound to an immobilized facsimile antigen, giving a colored √. Antigen exposure strips the antibody-dye conjugate from the surface, giving a color change , .

Figure 10

Enzyme-linked immunosorbent assay (ELISA) scheme for detection and reporting.

Figure 11

DNA aptamer with built-in fluorescent reporting. In the initial duplex, the fluorescent aptamer is quenched. Upon exposure to the target, the duplex dissociates, giving a fluorescent signal (Adapted from [101]).

Figure 12

Gold-nanoparticle reporting with a DNA-aptamer biosensor. Initially the aptamers prevent the nanoparticles from aggregating (Adapted from [10]). Exposure to target strips the aptamers from the particles causing aggregation and color change.

Figure 13

A paper-supported sensor measuring the presence of DNase. Decomposition of the stabilizing chains on the nanoparticles causes them to aggregate, giving a color change (Adapted from [23]).

Figure 14

Antigen displaces facsimile antibody-quencher from quantum dot, producing fluorescence .