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Urinary tract infections (UTIs) make up a significant proportion of the global burden of disease in vulnerable groups and tend to substantially impair the quality of life of those affected, making timely detection of UTIs a priority for public health. However, economic and societal barriers drastically reduce accessibility of traditional lab-based testing methods for critical patient groups in low-resource areas, negatively affecting their overall healthcare outcomes. As a result, cellulose-based materials such as paper and thread have garnered significant interest among researchers as substrates for so-called frugal analytical devices which leverage the material’s portability and adaptability for facile and reproducible diagnoses of UTIs. Although the field may be only in its infancy, strategies aimed at commercial penetration can appreciably increase access to more healthcare options for at-risk people. In this review, we catalogue recent advances in devices that use cellulose-based materials as the primary housing or medium for UTI detection and chart out trends in the field. We also explore different modalities employed for detection, with particular emphasis on their ability to be ported onto discreet casings such as sanitary products. Graphical abstract

Leukocyte esterase (LE) is a useful marker that can be used in establishing a diagnosis of urinary tract infections (UTIs). The development of a UTI diagnostic method with quantitative determinations of biomarkers across all age groups is becoming more important. In this report, microfluidic resistance sensors based on silver ink (Ag ink) and silver ink mixed with ZnO nanoparticles (Ag-ZnO ink) were synthesized and coated on cellulose paper, namely LE-Ag-μPADs and LE-Ag-ZnO-μPADs, respectively, for the sensitive detection of LE. The microfluidic design increases the precision of data and further allows for quantitative determination and early detection of LE in human urine. The quantification of LE relies on the change in the resistance readout coating with Ag ink as well as Ag-ZnO ink in the detection zone. A mixture of 3-(N-tosyl-l-alaninyloxy)-5-phenylpyrrole (PE) and 1-diazo-2-naphthol-4-sulfonic acid (DAS) was deposited in the sample zone to selectively recognize LE, and the resulting nonconductive products, i.e., azo compounds, further reacted with the Ag ink and Ag-ZnO ink to increase resistance. The quantitative detectable LE concentrations between 2 to 32 (×5.2 U mL-1), i.e. ≈12 to 108 μg L-1, cover the commercial dipstick range of trace, +1 and +2. The minimum detectable concentration of LE in urine was 1 (×5.2 U mL-1). The lower concentrations of LE detectable by LE-Ag-μPADs (1-8 × 5.2 U mL-1) are below the value achieved with the ELISA LE kit. Urine samples from inpatients with indwelling urinary catheters were used, and the LE levels measured by the present device were highly correlated with those determined by a commercial urine analyser.

ATP-driven bioluminescence relying on the D-luciferin-luciferase reaction is widely employed for several biosensing applications where bacterial ATP detection allows to verify microbial contamination for hygiene monitoring in hospitals, food processing and in general for cell viability studies. Several ATP kit assays are already commercially available but an user-friendly ATP biosensor characterized by low-cost, portability, and adequate sensitivity would be highly valuable for rapid and facile on site screening. Thanks to an innovative freeze-drying procedure, we developed a user-friendly, ready-to-use and stable ATP sensing paper biosensor that can be combined with smartphone detection. The ATP sensing paper includes a lyophilized “nano-lantern” with reaction components being rapidly reconstituted by 10 μL sample addition, enabling detection of 10−14 mol of ATP within 10 min. We analysed urinary microbial ATP as a biomarker of urinary tract infection (UTI), confirming the capability of the ATP sensing paper to detect the threshold for positivity corresponding to 105 colony-forming units of bacteria per mL of urin, This research was sponsored in part by PRIN 2015 “Multifunctional nanotools for advanced cancer diagnostics” (Prot. 2015TWP83Z) and the NATO Science for Peace and Security Programme under Grant No. 985042. The ICN2 is funded by the CERCA Programme/Generalitat de Catalunya and also supported by the Severo Ochoa program of the Spanish Ministry of Economy, Industry and Competitiveness (MINECO, grants No. SEV-2017-0706 and MAT2017-87202-P).

Escherichia coli is a generic indicator of fecal contamination, and certain serotypes cause food- and water-borne illness such as O157:H7. In the clinic, detection of bacteriuria, which is often due to E. coli, is critical before certain surgical procedures or in cases of nosocomial infection to prevent further adverse events such as postoperative infection or sepsis. In low- and middle-income countries, where insufficient equipment and facilities preclude modern methods of detection, a simple, low-cost diagnostic device to detect E. coli in water and in the clinic will have significant impact. We have developed a simple paper-based colorimetric platform to detect E. coli contamination in 5h. On this platform, the mean color intensity for samples with 10(5)cells/mL is 0.118±0.002 (n=4), and 0.0145±0.003 (P

In a recent issue of the Journal of Clinical Microbiology, Kunin and Buesching (1) describe a novel technique to diagnose common urinary pathogens in office-collected samples. Using a three-layer circular sandwich with filter paper as the solid-phase dilution device, it was possible to pick up members of the family Enterobacteriaceae and staphylococci from urine specimens. The technology was standardized by monitoring the penetration of microbes through the filter paper onto MacConkey or Trypticase soy medium seeded onto a template. As a control to the sandwich technology, serial 10-fold dilutions of various organisms were cultured on the surfaces of agar plates. The sensitivity and specificity with 487 urine samples for gram-negative bacteria or with 405 samples for gram-positive bacteria were excellent. There is no information on any residual antimicrobial (AM) activity in 892 specimens. However, it would be pertinent to standardize the technology for urine samples with residual AM activity. Bacteriuria and AM activity are often encountered during clinical practice. Recent investigations of AM activity in Taiwan pointed to such an activity in 55.5% of 112 patients on their arrival at an emergency department (2). Furthermore, AM activity was also evident in 25.1% of 203 internal medicine outpatients, 7.6% of 471 high school students, and 7.4% of 202 people at a center for senior citizens. There was no correlation between the bacterial counts and sterility of a specimen and its AM activity. Residual AM activity in urine was likely to interfere in the three-layer sandwich technique during filtration of microbes onto culture medium. Antibacterial substances block the filter paper pores, lowering the number of microbes that filter through. The differently sized AMs may clog the pores in an unspecified manner. Any differential concentration of an antibacterial agent on the culture medium after filtration through the clogged filter paper would adversely affect sensitivity and specificity. Such an effect should be determined by soaking antibacterial agents and microbes onto filter paper. Well-designed experiments to address blockage of filter paper pores or any differential inhibition of bacterial growth are desirable. Such experiments would guarantee that concurrent bacteriuria and AM activity in urine would not interfere with a correct diagnosis, even in areas where AM drugs are freely available and histories of patients tend to be unreliable (2).

Urinary glucose concentration was measured in 96 patients aged 2 months to 12 years, with urinary tract infections, in 78 control subjects, and in 548 apparently healthy girls, aged 5 to 14 years, who were screened for asymptomatic bacteriuria. A spectophotometric method and a paper strip test were comparatively evaluated. The results obtained by the strip paper test closely agreed with those obtained spectrophotometric method and a paper strip test were comparatively evaluated. urinary glucose concentration to subnormal levels in specimens obtained under standardized conditions and in random specimens incubated for 8 hours at 37°C. before testing.