title: The chemistrode: a droplet-based microfluidic device for stimulation and recording with high temporal, spatial, and chemical resolution.
abstract: Microelectrodes enable localized electrical stimulation and recording, and they have revolutionized our understanding of the spatiotemporal dynamics of systems that generate or respond to electrical signals. However, such comprehensive understanding of systems that rely on molecular signals-e.g., chemical communication in multicellular neural, developmental, or immune systems-remains elusive because of the inability to deliver, capture, and interpret complex chemical information. To overcome this challenge, we developed the "chemistrode," a plug-based microfluidic device that enables stimulation, recording, and analysis of molecular signals with high spatial and temporal resolution. Stimulation with and recording of pulses as short as 50 ms was demonstrated. A pair of chemistrodes fabricated by multilayer soft lithography recorded independent signals from 2 locations separated by 15 mum. Like an electrode, the chemistrode does not need to be built into an experimental system-it is simply brought into contact with a chemical or biological substrate, and, instead of electrical signals, molecular signals are exchanged. Recorded molecular signals can be injected with additional reagents and analyzed off-line by multiple, independent techniques in parallel (e.g., fluorescence correlation spectroscopy, MALDI-MS, and fluorescence microscopy). When recombined, these analyses provide a time-resolved chemical record of a system's response to stimulation. Insulin secretion from a single murine islet of Langerhans was measured at a frequency of 0.67 Hz by using the chemistrode. This article characterizes and tests the physical principles that govern the operation of the chemistrode to enable its application to probing local dynamics of chemically responsive matter in chemistry and biology.
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
authors.forename: Delai
authors.initials: D
authors.lastname: Chen
authors.forename: Wenbin
authors.initials: W
authors.lastname: Du
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Weishan
authors.initials: W
authors.lastname: Liu
authors.forename: Andrey
authors.initials: A
authors.lastname: Kuznetsov
authors.forename: Felipe E
authors.initials: FE
authors.lastname: Mendez
authors.forename: Louis H
authors.initials: LH
authors.lastname: Philipson
authors.forename: Rustem F
authors.initials: RF
authors.lastname: Ismagilov
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004558:Electric Stimulation; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D008839:Microelectrodes; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D008856:Microscopy, Fluorescence
chemical_list: D007328:Insulin; D005947:Glucose; D002118:Calcium