Abstract
Cell identification and enumeration are essential procedures within clinical and research laboratories. For over 150 years, quantitative investigation of body fluids such as counts of various blood cells has been an important tool for diagnostic analysis. With the current evolution of point-of-care diagnostics and precision medicine, cheap and precise cell counting technologies are in demand. This article reviews the timeline and recent notable advancements in cell counting that have occurred as a result of improvements in sensing including optical and electrical technology, enhancements in image processing capabilities, and contributions of micro and nanotechnologies. Cell enumeration methods have evolved from the use of manual counting using a hemocytometer to automated cell counters capable of providing reliable counts with high precision and throughput. These developments have been enabled by the use of precision engineering, micro and nanotechnology approaches, automation and multivariate data analysis. Commercially available automated cell counters can be broadly classified into three categories based on the principle of detection namely, electrical impedance, optical analysis and image analysis. These technologies have many common scientific uses, such as hematological analysis, urine analysis and bacterial enumeration. In addition to commercially available technologies, future technological trends using lab-on-a-chip devices have been discussed in detail. Lab-on-a-chip platforms utilize the existing three detection technologies with innovative design changes utilizing advanced nano/microfabrication to produce customized devices suited to specific applications.
Highlights
Precise determination of cells in a sample is important for a broad field of applications, such as tissue culture studies by microbiologists and disease progression in medical laboratories (OYAMA and EAGLE, 1956; Houwen, 2001)
The results showed that coulter counter had great inter-laboratory reproducibility and correlated with the colony counts (Eng and Valensteini, 1989)
Tremendous progress has been made in each paradigm of cell enumeration
Summary
Precise determination of cells in a sample is important for a broad field of applications, such as tissue culture studies by microbiologists and disease progression in medical laboratories (OYAMA and EAGLE, 1956; Houwen, 2001). Flow cytometers and Coulter counters have earned a place in research and clinical laboratories despite their bulky size and costs, which is explained due to the rise in demand for precision high-end cell counters for high throughput counts These devices can cost up to tens of thousands of dollars, which makes them unfeasible for developing countries or for portable point-of-care diagnostics. The third most common type of device utilizes digital image analysis using a photo-microscope (O’Brien et al, 2016) These devices, readily available from established manufacturers like ThermoFischer scientific (i.e., Countess II automated cell counter) and BioRad (TC20 automated cell counter), contain an optical system with autofocus, capable of detecting cells using integrated software to characterize particles in terms of their fluorescent intensity and size while having a processing time of few seconds (Goldberg, 2008; Gupta et al, 2018). SKC,Inc, C-ChipTM Disposable Hemacytometers Scepter 2.0- Sigma-Aldrich Multisizer 4 COULTER COUNTER ACCURI c6- BD
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