title: Acoustofluidic chemical waveform generator and switch.
abstract: Eliciting a cellular response to a changing chemical microenvironment is central to many biological processes including gene expression, cell migration, differentiation, apoptosis, and intercellular signaling. The nature and scope of the response is highly dependent upon the spatiotemporal characteristics of the stimulus. To date, studies that investigate this phenomenon have been limited to digital (or step) chemical stimulation with little control over the temporal counterparts. Here, we demonstrate an acoustofluidic (i.e., fusion of acoustics and microfluidics) approach for generating programmable chemical waveforms that permits continuous modulation of the signal characteristics including the amplitude (i.e., sample concentration), shape, frequency, and duty cycle, with frequencies reaching up to 30 Hz. Furthermore, we show fast switching between multiple distinct stimuli, wherein the waveform of each stimulus is independently controlled. Using our device, we characterized the frequency-dependent activation and internalization of the β2-adrenergic receptor (β2-AR), a prototypic G-protein coupled receptor (GPCR), using epinephrine. The acoustofluidic-based programmable chemical waveform generation and switching method presented herein is expected to be a powerful tool for the investigation and characterization of the kinetics and other dynamic properties of many biological and biochemical processes.
authors.affiliation: Department of Engineering Science and Mechanics, ‡Biomedical Engineering, §Department of Chemistry, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ahmed
authors.forename: Hari S
authors.initials: HS
authors.lastname: Muddana
authors.forename: Mengqian
authors.initials: M
authors.lastname: Lu
authors.forename: Jarrod B
authors.initials: JB
authors.lastname: French
authors.forename: Adem
authors.initials: A
authors.lastname: Ozcelik
authors.forename: Ye
authors.initials: Y
authors.lastname: Fang
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Butler
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Benkovic
authors.forename: Andreas
authors.initials: A
authors.lastname: Manz
authors.forename: Tony Jun
authors.initials: TJ
authors.lastname: Huang
mesh_terms: D000162:Acoustics / Q000295:instrumentation; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation