Editing Microfluidics (section)

=== Particle detection microfluidics ===
One potential application area involves particle detection in fluids. Particle detection of small fluid-borne particles down to about 1 μm in diameter is typically achieved using a [[Coulter counter]], in which electrical signals are generated when a weakly-conducting fluid such as in [[saline water]] is passed through a small (~100 μm diameter) pore, so that an electrical signal is generated that is directly proportional to the ratio of the particle volume to the pore volume. The physics behind this is relatively simple, described in a classic paper by DeBlois and Bean,<ref>{{cite journal| vauthors = DeBlois RW, Bean CP |title=Counting and sizing of submicron particles by the resistive pulse technique|journal=Rev. Sci. Instrum.|date=1970|volume=41|issue=7|pages=909–916|doi=10.1063/1.1684724|bibcode=1970RScI...41..909D }}</ref> and the implementation first described in Coulter's original patent.<ref>{{cite patent|country=US|number=2656508|status=|title=Means for counting particles suspended in a fluid|pubdate=Oct. 20, 1953|inventor=Wallace H. Coulter}}</ref> This is the method used to e.g. size and count erythrocytes ([[red blood cells]]) as well as leukocytes ([[white blood cell]]s) for standard blood analysis. The generic term for this method is [[resistive pulse sensing]] (RPS); Coulter counting is a trademark term. However, the RPS method does not work well for particles below 1 μm diameter, as the [[signal-to-noise ratio]] falls below the reliably detectable limit, set mostly by the size of the pore in which the analyte passes and the input noise of the first-stage [[amplifier]].{{citation needed|date=June 2023}}

The limit on the pore size in traditional RPS Coulter counters is set by the method used to make the pores, which while a trade secret, most likely{{according to whom|date=October 2020}} uses traditional mechanical methods. This is where microfluidics can have an impact: The [[lithography]]-based production of microfluidic devices, or more likely the production of reusable molds for making microfluidic devices using a [[Molding (process)|molding]] process, is limited to sizes much smaller than traditional [[machining]]. Critical dimensions down to 1 μm are easily fabricated, and with a bit more effort and expense, feature sizes below 100&nbsp;nm can be patterned reliably as well. This enables the inexpensive production of pores integrated in a microfluidic circuit where the pore diameters can reach sizes of order 100&nbsp;nm, with a concomitant reduction in the minimum particle diameters by several orders of magnitude.

As a result, there has been some university-based development of microfluidic particle counting and sizing<ref>{{cite journal | vauthors = Lewpiriyawong N, Yang C | title = AC-dielectrophoretic characterization and separation of submicron and micron particles using sidewall AgPDMS electrodes | journal = Biomicrofluidics | volume = 6 | issue = 1 | pages = 12807–128079 | date = March 2012 | pmid = 22662074 | pmc = 3365326 | doi = 10.1063/1.3682049 }}</ref><ref>{{cite journal | vauthors = Gnyawali V, Strohm EM, Wang JZ, Tsai SS, Kolios MC | title = Simultaneous acoustic and photoacoustic microfluidic flow cytometry for label-free analysis | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 1585 | date = February 2019 | pmid = 30733497 | pmc = 6367457 | doi = 10.1038/s41598-018-37771-5 | bibcode = 2019NatSR...9.1585G }}</ref><ref>{{cite journal | vauthors = Weiss AC, Krüger K, Besford QA, Schlenk M, Kempe K, Förster S, Caruso F | title = In Situ Characterization of Protein Corona Formation on Silica Microparticles Using Confocal Laser Scanning Microscopy Combined with Microfluidics | journal = ACS Applied Materials & Interfaces | volume = 11 | issue = 2 | pages = 2459–2469 | date = January 2019 | pmid = 30600987 | doi = 10.1021/acsami.8b14307 | hdl = 11343/219876 | s2cid = 58555221 | hdl-access = free }}</ref> with the accompanying commercialization of this technology. This method has been termed microfluidic [[resistive pulse sensing]] (MRPS).