title: A linear dilution microfluidic device for cytotoxicity assays.
abstract: A two-layer polymer microfluidic device is presented which creates nine linear dilutions from two input fluid streams mixed in varying volumetric proportions. The linearity of the nine dilutions is conserved when the flow rate is held constant at 1.0 microl min(-1) (R(2) = 0.9995) and when it is varied from 0.5-16 microl min(-1) (R(2) = 0.9998). An analytical expression is presented for designing microfluidic devices with arbitrary numbers of linear dilutions. To demonstrate the efficacy of this device, primary human epidermal keratinocytes (HEK) were stained with nine dilutions of calcein, resulting in a linear spread of fluorescent intensities (R(2) = 0.94). The operating principles of the device can be scaled up to incorporate any number of linear dilutions. This scalability, coupled with an intrinsic ability to create linear dilutions under a variety of operating conditions, makes the device applicable to high throughput screening applications such as combinatorial chemistry or cytotoxicity assays.
authors.affiliation: Joint Department of Biomedical Engineering at The University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695-7115, USA. gmwalker@ncsu.edu
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Walker
authors.forename: Nancy
authors.initials: N
authors.lastname: Monteiro-Riviere
authors.forename: Jillian
authors.initials: J
authors.lastname: Rouse
authors.forename: Adrian T
authors.initials: AT
authors.lastname: O'Neill
mesh_terms: D002478:Cells, Cultured; D020650:Combinatorial Chemistry Techniques; D004058:Diffusion; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D004563:Electrochemistry / Q000379:methods; D004867:Equipment Design; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects; D008832:Microchemistry; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods*; D044085:Microfluidics; D015233:Models, Statistical; D008962:Models, Theoretical