TY - JOUR
T1 - Acoustofluidic chemical waveform generator and switch
AU - Ahmed, Daniel
AU - Muddana, Hari S.
AU - Lu, Mengqian
AU - French, Jarrod B.
AU - Ozcelik, Adem
AU - Fang, Ye
AU - Butler, Peter J.
AU - Benkovic, Stephen J.
AU - Manz, Andreas
AU - Huang, Tony Jun
N1 - Publisher Copyright:
© 2014 American Chemical Society.
PY - 2014/12/2
Y1 - 2014/12/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84915820010&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84915820010&partnerID=8YFLogxK
U2 - 10.1021/ac5033676
DO - 10.1021/ac5033676
M3 - Article
C2 - 25405550
AN - SCOPUS:84915820010
SN - 0003-2700
VL - 86
SP - 11803
EP - 11810
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 23
ER -