Smartphone-based point-of-care (POC) technologies have emerged as ideal next-generation point-of-care devices (POCD) for in vitro diagnostics (IVD). The ideal POC test should have the following characteristics: cost-effective, sensitive and specific, rapid, simple, and standalone. Numerous low-cost and compact SP-based readers could be deployed at POC settings for several bioanalytical applications. Various prospective SP-based lateral flow assay (LFA) readers for several analytes based on LFA. Flow cytometry has undergone drastic transitions from a routine clinical technique to a multipurpose diagnostic system when interfacing Microfluidics and smartphone-based devices, for example, a smartphone-based POC flow cytometer employs optofluidic fluorescent imaging for the analysis of large sample volumes of more than 0.1 mL.

Configuration of a conventional fluorescence-based flow cytometer. Fig.1 Configuration of a conventional fluorescence-based flow cytometer. (Cho, 2010)

Application of Smartphone-based Cytometry

  • Blood cell imaging and counting

Clinically known as complete blood count (CBC), counting blood cells is a fundamental test in blood sample analysis. Many diseases can be diagnosed by the infor- mation given by blood cell counts. Scientists reported a smartphone-based cytometry working in blood cell counting where a portable optofluidic imaging cytometry platform was developed by combining a Microfluidic chamber with smartphone-based fluores- cence imaging. The device consists of an LED-based imaging unit, a Microfluidic chamber, and a syringe pump for flow control. The WBCs in the fresh blood sample were fluorescently labeled with nucleic acid stain and diluted before delivered into the Microfluidic chamber by a syringe pump. By capturing and analyzing the videos of cell movement in the chamber, the concentration of labeled WBC was calculated.

  • Cancer cell imaging and counting

A smartphone-based imaging and magnetophoretic cytometry device was developed for density-based cell sorting and cancer cell detection. The device uses two permanent magnets and employs fluorescence microscopic imaging for multiplex detection. Fluorescence images of suspended cancer cells were taken and cell counts were obtained subsequently. In addition, ovarian cancer cells were mixed with red blood cells, and they were successfully separated with magnetic levitation because of the difference in density, which was verified with both smartphone bright-field and fluorescence imaging.

Smartphone cytometry using magnetic levitation and fluorescence microscopy for counting and separation of tumor cells. Fig.2 Smartphone cytometry using magnetic levitation and fluorescence microscopy for counting and separation of tumor cells. (Knowlton, 2017)

  • Pathogen, parasite, and microswimmer imaging and counting

Rapid detection and quantification of parasites from human or environmental samples is important in parasitic disease control, screening and prevention in the developing countries. Increasing examples of using smartphones for pathogen, parasite, and microswimmer detection and counting have been demonstrated. For example, blood-borne filarial parasites Loa loa has been detected and quantified on a smart- phone video microscope recently. Moreover, mobile phone-based imaging and counting single virus particle was made possible recently. Fluorescent labeled human cytomegalovirus particles were imaged on a smartphone with single virus sensitivity confirmed by SEM images. As a step toward nanosensing and imaging, this technique show potential in high-sensitivity virus detection and quantification in the field settings.

POC semen analysis platform on a smartphone. Fig.3 POC semen analysis platform on a smartphone. (Kanakasabapathy, 2017)

Advantages of Smartphone-based Cytometry

Various lens-based or lensfree imaging technologies have been implemented on smartphones, making it possible for the generation of multiparametric profiles of a large cell population for both disease detection and health condition monitoring at the POC. Cytometry running on mobile phones can focus on multimodality and compatibility with real biomedical applications including cell counting, sorting, and characterization of particular disease models.

References

  1. Cho, S.H.; et al. Review Article: recent advancements in optofluidic flow cytometer. BioMicrofluidics. 2010, 4(4):43001.
  2. Knowlton, S.; et al. 3D-printed smartphone-based point of care tool for fluorescence- and magnetophoresis-based cytometry. Lab Chip. 2017, 17(16):2839e51.
  3. Kanakasabapathy, M.K.; et al. An automated smartphone-based diagnostic assay for point-of-care semen analysis. Sci Transl Med. 2017, 9(382):eaai7863.

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