Colorimetric Band-aids for Point-of-Care Sensing and Treating Bacterial Infection

Abstract

Sensing bacterial infections and monitoring drug resistance are very important for the selection of treatment options. However, the common methods of sensing resistance are limited by time-consuming, the requirement for professional personnel, and expensive instruments. Moreover, the abuse of antibiotics causes the accelerated process of bacterial resistance. Herein, we construct a portable paper-based band-aid (PBA) which implements a selective antibacterial strategy after sensing of drug resistance. The colors of PBA indicate bacterial infection (yellow) and drug resistance (red), just like a bacterial resistance colorimetric card. On the basis of color, antibiotic-based chemotherapy and Zr-MOF PCN-224-based photodynamic therapy (PDT) are used on site to treat sensitive and resistant strains, respectively. Eventually, it takes 4 h to sense, and the limit of detection is 10⁴ CFU/mL for drug-resistant E. coli. Compared with traditional PDT-based antibacterial strategies, our design can alleviate off-target side effects, maximize therapeutic efficacy, and track the drug resistance in real time with the naked eye. This work develops a new way for the rational use of antibiotics. Given the low cost and easy operation of this point-of-care device, it can be developed for practical applications.

Scheme 1. (A) Preparation Routes of CP and pH-Responsive Transformation between Contracted State and Swollen State of Chitosan. (B) Schematic Illustration of PBA (“0”, Green) for Sensing Bacterial Infection (“1”, Yellow) and Drug Resistance (“2”, Red), and Implementing Antibiotic-Based Chemotherapy and PCN-224-Based PDT, Respectively

Figure 1

(A) TEM image of CP. (B) Dark-field TEM image of CP and its corresponding TEM elemental mappings of C–K, N–K, O–K, and Zr–L signals. (C) The preparation route of PBA: i, LiCl and NaIO₄; ii, NaCNBH₃ and CP; iii, BTB solution (5% PEG, pH 7.4). SEM graphs of cellulose paper (D) and PBA (E, F).

Figure 2

Use of PBA for sensing drug resistance. (A) The schematic diagram of PBA (green) for sensing bacterial infection (yellow) and drug resistance (red). The typical pictures of (B) PBA_{no nitrocefin} and (C) PBA after incubation with buffer (pH 8.0–6.0), E. coli solution, bacterial secretions, and extracts for 4 h. (D) Quantitative analysis of PBA with different concentrations of β-lactamase ranging from 0.02 to 0.18 U/mL. The inset includes the typical images of PBA after reaction with β-lactamase. (E) Quantitative analysis of PBA with different concentrations of DR E. coli. The color intensity was calibrated by subtracting the mean intensity of DS E. coli group on each side of the DR E. coli group.

Figure 3

Use of PBA for selective treatment on the basis of drug resistance. (A) Schematic illustration of PBA combined with chemotherapy and PDT to kill DR E. coli. (B) Typical SEM images of PBA modified with different amounts of CP. Viability of DS E. coli (C) and DR E. coli (D) incubated on PBA or PBA_{no ampicillin} with or without light irradiation. Statistical analysis was performed using the student’s two-tailed t test (**p < 0.01). (E) L929 cell viability after incubation with different concentrations of CP for 12 h. (F) The typical SEM images of E. coli after incubation with PBA.

Figure 4

Investigation of validity periods. (A) Typical pictures of PBA when adding bacterial solutions. The reaction time is 4 h. Survival percentages of DS E. coli (B) and DR E. coli (C). Bacterial concentration is 10⁷ CFU/mL.

Figure 5

Use of PBA for wound disinfection in mice. (A) Photographs of wounds on the mice. Inset images in the first row revealed the color on PBA. (B) Photomicrographs showing section of skin tissues with H&E staining. (C) Bacteria was separated from wound tissue and then cultured on agar plates. The upper row belongs to DS E. coli, and the lower row belongs to DR E. coli. 1, PBA_{no ampicillin}; 2, PBA; 3, PBA+vis.