Prototype Smartphone-Based Device for Flow Cytometry with Immunolabeling via Supra-nanoparticle Assemblies of Quantum Dots.

Zhujun Xiao,Ghinwa H. Darwish,W. Russ Algar,Kimihiro Susumu,Igor L. Medintz

doi:10.1021/acsmeasuresciau.1c00033

Abstract

Methods for the detection, enumeration, and typing of cells are important in many areas of research and healthcare. In this context, flow cytometers are a widely used research and clinical tool but are also an example of a large and expensive instrument that is limited to specialized laboratories. Smartphones have been shown to have excellent potential to serve as portable and lower-cost platforms for analyses that would normally be done in a laboratory. Here, we developed a prototype smartphone-based flow cytometer (FC). This compact 3D-printed device incorporated a laser diode and a microfluidic flow cell and used the built-in camera of a smartphone to track immunofluorescently labeled cells in suspension and measure their color. This capability was enabled by high-brightness supra-nanoparticle assemblies of colloidal semiconductor quantum dots (SiO2@QDs) as well as a support vector machine (SVM) classification algorithm. The smartphone-based FC device detected and enumerated target cells against a background of other cells, simultaneously and selectively counted two different cell types in a mixture, and used multiple colors of SiO2@QD-antibody conjugates to screen for and identify a particular cell type. The potential limits of multicolor detection are discussed alongside ideas for further development. Our results suggest that innovations in materials and engineering should enable eventual smartphone-based FC assays for clinical applications.

Highlights

Smartphones are emerging as a versatile platform for portable bioanalysis and imaging.[1−6] The built-in light sources, cameras, batteries, network connectivity, and computing power of smartphones can enable or support many of the same capabilities as conventional benchtop spectroscopic and imaging instruments
We show that our prototype smartphone-based flow cytometer (FC) device can detect a target cell type against a background of nontarget cells, concurrently and selectively enumerate two different cell types in a mixture, and screen for and identify a cell type based on the PL color of its immunolabeling
To focus on the cells passing through the microfluidic channel, the distance between the doublet lens and the channel was adjustable via screws at all four corners of the chip holder

Summary

■ INTRODUCTION

Smartphones are emerging as a versatile platform for portable bioanalysis and imaging.[1−6] The built-in light sources, cameras, batteries, network connectivity, and computing power of smartphones can enable or support many of the same capabilities as conventional benchtop spectroscopic and imaging instruments. Cellular analyses are an important subset of bioanalysis, with immunophenotyping by flow cytometry being one of the most widely used and powerful tools for this purpose.[15,16] Contemporary flow cytometers (FCs) can measure doubledigit numbers of fluorescently labeled biomarkers per cell and provide morphological information.[17−19] Examples of applications include the detection of leukemias and lymphomas, immune-related disorders, circulating tumor cells, stem cells, fetal cells, and pathogenic bacteria.[20−24] FCs are often large and expensive instruments and often require operators with specialized training They tend to be limited to well-funded research laboratories and shared core. Our results suggest that continued materials development and device engineering should eventually enable smartphone-based FC assays with clinical relevance and utility

■ RESULTS

■ DISCUSSION AND CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES