Journal ArticleA thorough investigation of the design considerations for microscale thermal field-flow fractionation and characterization of a 25 μm thin microscale thermal field-flow fractionation system is reported. A 4-50 times volume reduction from mesoscale and macroscale systems warrants customized design and operational conditions for microscale separation systems. Theoretical calculations are done to illustrate the importance of the increased dispersion due to extra-column tubing, off-chip detection and sample injection volume with reduced channel dimensions. An optimized microscale thermal field-flow fractionation (ThFFF) channel is fabricated using rapid and cost effective manufacturing and assembly processes. Specifically, improvements in material selection and arrangement are implemented to achieve higher particle retentions. The new instrument arrangement includes high conductivity silicon as the cold wall and a thin polymer layer with low thermal conductivity as the hot wall which results in high temperature gradients (~ 106 ºC/m) across the microchannel and subsequently high retention. Single particle retention separations are carried out with polystyrene nanoparticle samples in an aqueous carrier to characterize the device and demonstrate the improvements
