KEYWORDS: Particles, Modulation, Signal detection, Signal to noise ratio, Interference (communication), Electronic filtering, Spatial resolution, Luminescence, Signal generators, Particle systems
Flow cytometry relies on the detection of cells selectively stained with fluorescence markers. Optically they can be detected as fluorescence particles. The use of microuidics offers a wide range of benefits over traditional flow cytometer designs but when replacing expensive components with inexpensive counterparts the sensitivity of the instrument suffers. To increase the sensitivity of the detection system, spatial modulation has been proposed. Spatial modulation is implemented via _ne pitched shadow masks close to the microuidic channel which generate a signal pattern when a fluorescent particle passes by. Using a _ne pitch and long total length for the pattern a high spatial resolution and long total exposure time are combined. Particle detection from local maxima is not directly possible with spatially modulated signals due to the jagged pulse shape. We compare the performance of different approaches for particle detection from local maxima. Matched filtering and the derivative of the correlation signal provide either a good peak-signal-to-noise ratio (PSNR) or a high spatial resolution. But both approaches suffer from low dynamic range due to side maxima. We derive the solution for a minimum- mean-square-error (MMSE) filter which transforms the modulated pulse shape into a target pulse shape with a single strong maximum. We investigate the performance of the MMSE filter and find that it provides tunable suppression of noise and side maxima along with a high spatial resolution. The use of the MMSE filter therefore is an ideal choice for particle detection from spatially modulated signals.
Detection of fluorescent particles is an integral part of flow cytometry for analysis of selectively stained cells. Established flow cytometer designs achieve great sensitivity and throughput but require bulky and expensive components which prohibit mass production of small single-use point-of-care devices. The use of a combination of innovative technologies such as roll-to-roll printed microuidics with integrated optoelectronic components such as printed organic light emitting diodes and printed organic photodiodes enables tremendous opportunities in cost reduction, miniaturization and new application areas. In order to harvest these benefits, the optical setup requires a redesign to eliminate the need for lenses, dichroic mirrors and lasers. We investigate the influence of geometric parameters on the performance of a thin planar design which uses a high power LED as planar light source and a PIN-photodiode as planar detector. Due to the lack of focusing optics and inferior optical filters, the device sensitivity is not yet on par with commercial state of the art flow cytometer setups. From noise measurements, electronic and optical considerations we deduce possible pathways of improving the device performance. We identify that the sensitivity is either limited by dark noise for very short apertures or by noise from background light for long apertures. We calculate the corresponding crossover length. For the device design we conclude that a low device thickness, low particle velocity and short aperture length are necessary to obtain optimal sensitivity.
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