Flow-S: A Field-Deployable Device with Minimal Hands-On Effort to Concentrate and Quantify Schistosoma Circulating Anodic Antigen (CAA) from Large Urine Volumes

Diagnostics, vol. 14, pp. 820

Abstract

A laboratory-based lateral flow (LF) test that utilizes up-converting reporter particles (UCP) for ultrasensitive quantification of Schistosoma circulating anodic antigen (CAA) in urine is a well-accepted test to identify active infection. However, this UCP-LF CAA test requires sample pre-treatment steps not compatible with field applications. Flow, a new low-cost disposable, allows integration of large-volume pre-concentration of urine analytes and LF detection into a single field-deployable device. We assessed a prototype Flow-Schistosoma (Flow-S) device with an integrated UCP-LF CAA test strip, omitting all laboratory-based steps, to enable diagnosis of active Schistosoma infection in the field using urine. Flow-S is designed for large-volume (5–20 mL) urine, applying passive paper-based filtration and antibody-based CAA concentration. Samples tested for schistosome infection were collected from women of reproductive age living in a Tanzania region where S. haematobium infection is endemic. Fifteen negative and fifteen positive urine samples, selected based on CAA levels quantified in paired serum, were analyzed with the prototype Flow-S. The current Flow-S prototype, with an analytical lower detection limit of 1 pg CAA/mL, produced results correlated with the laboratory-based UCP-LF CAA test. Urine precipitates occurred in frozen banked samples and affected accurate quantification; however, this should not occur in fresh urine. Based on the findings of this study, Flow-S appears suitable to replace the urine pre-treatment required for the laboratory-based UCP-LF CAA test, thus allowing true field-based applications with fresh urine samples. The urine precipitates observed with frozen samples, though less important given the goal of testing fresh urines, warrant additional investigation to evaluate methods for mitigation. Flow-S devices permit testing of pooled urine samples with applications for population stratified testing. A field test with fresh urine samples, a further optimized Flow-S device, and larger statistical power has been scheduled.

Authors 13

1. Daniëlle de Jong Aachen Department of Cell and Chemical Biology

   Leiden University Medical Center

   Affiliation as printed

   Department of Cell and Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands

2. Cody S. Carrell

   Salus (United States)

   Affiliation as printed

   Salus Discovery LLC, Madison, WI 53703, USA

3. Jane K. Maganga

   Mwanza Intervention Trials Unit · National Institute for Medical Research

   Affiliation as printed

   Mwanza Intervention Trials Unit/National Institute for Medical Research, Mwanza, Tanzania

4. Loyce Mhango

   Mwanza Intervention Trials Unit · National Institute for Medical Research

   Affiliation as printed

   Mwanza Intervention Trials Unit/National Institute for Medical Research, Mwanza, Tanzania

5. Peter Shigella

   Mwanza Intervention Trials Unit · National Institute for Medical Research

   Affiliation as printed

   Mwanza Intervention Trials Unit/National Institute for Medical Research, Mwanza, Tanzania

6. Maddy Gill

   Salus (United States)

   Affiliation as printed

   Salus Discovery LLC, Madison, WI 53703, USA

7. Ryan Shogren

   Salus (United States)

   Affiliation as printed

   Salus Discovery LLC, Madison, WI 53703, USA

8. Brianna Mullins

   Salus (United States)

   Affiliation as printed

   Salus Discovery LLC, Madison, WI 53703, USA

9. Jay W. Warrick

   Salus (United States)

   Affiliation as printed

   Salus Discovery LLC, Madison, WI 53703, USA

10. John M. Changalucha

    Mwanza Intervention Trials Unit · National Institute for Medical Research

    Affiliation as printed

    Mwanza Intervention Trials Unit/National Institute for Medical Research, Mwanza, Tanzania

11. Govert J. van Dam Aachen Department of Parasitology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Parasitology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands

12. Jennifer A. Downs

    Catholic University of Health and Allied Sciences · Mwanza Intervention Trials Unit · National Institute for Medical Research · Weill Cornell Medicine

    Affiliation as printed

    Center for Global Health, Weill Cornell Medicine, New York, NY 10065, USA

    Department of Medicine, Weill Bugando School of Medicine, Mwanza, Tanzania

    Mwanza Intervention Trials Unit/National Institute for Medical Research, Mwanza, Tanzania

13. Paul L. A. M. Corstjens corresponding Aachen Department of Cell and Chemical Biology

    Leiden University Medical Center

    Affiliation as printed

    Department of Cell and Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands