Time-domain signal averaging to improve microparticles detection and
enumeration accuracy in a microfluidic impedance cytometer
Abstract
Microfluidic impedance cytometry is a powerful system to measure micro
and nano-sized particles and is routinely used in point-of-care settings
disease diagnostics and other biomedical applications. However, small
objects near a sensor’s detection limit are plagued with relatively
significant background noise and are difficult to identify for every
case. While many data processing techniques can be utilized to reduce
noise and improve signal quality, frequently they are still inadequate
to push sensor detection limits. Here, we report the first demonstration
of a novel signal averaging algorithm effective in noise reduction of
microfluidic impedance cytometry data, improving enumeration accuracy
and reducing detection limits. Our device uses a 22 μm tall microchannel
and gold coplanar microelectrodes that generates an electric field,
recording bipolar pulses from polystyrene microparticles flowing through
the channel. In addition to outlining a modified moving signal averaging
technique theoretically and with a model dataset, we also performed a
compendium of characterization experiments including variations in flow
rate, input voltage, and particle size. Multi-variate metrics from each
experiment are compared including signal amplitude, pulse width,
background noise, and signal-to-noise ratio (SNR). Incorporating our
technique resulted in improved SNR and counting accuracy across all
experiments conducted, and the limit of detection improved from 5 μm to
1 μm particles without modifying microchannel dimensions. Succeeding
this, we envision implementing our modified moving average technique to
develop next generation microfluidic impedance cytometry devices with an
expanded dynamic range and improved enumeration accuracy. This can be
exceedingly useful for many biomedical applications, such as infectious
disease diagnostics where devices may enumerate larger-scale immune
cells alongside sub-micron bacterium in the same sample.