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Kinetic Requirements for Spatiotemporal Chemical Imaging with Fluorescent Nanosensors
journal contribution
posted on 2017-04-05, 00:00 authored by Daniel Meyer, Annika Hagemann, Sebastian KrussFluorescent
nanosensors are powerful tools for basic research and
bioanalytical applications. Individual nanosensors are able to detect
single molecules, while ensembles of nanosensors can be used to measure
the bulk concentration of an analyte. Collective imaging of multiple
nanosensors could provide both spatial and temporal chemical information
from the nano- to the microscale. This type of chemical imaging with
nanosensors would be very attractive to study processes such as chemical
signaling between cells (e.g., neurons). So far,
it is not understood what processes are resolvable (concentration,
time, space) and how optimal sensors should be designed. Here, we
develop a theoretical framework to simulate the fluorescence image
of arrays of nanosensors in response to a concentration gradient.
For that purpose, binding and unbinding of the analyte is simulated
for each single nanosensor by using a Monte Carlo simulation and varying
rate constants (kon, koff). Multiple nanosensors are arranged on a surface and
exposed to a concentration pattern cA(x,y,t) of an analyte.
We account for the resolution limit of light microscopy (Abbe limit)
and the acquisition speed and resolution of optical setups and determine
the resulting response images ΔI(x,y,t). Consequently, we introduce
terms for the spatial and temporal resolution and simulate phase diagrams
for different rate constants that allow us to predict how a sensor
should be designed to provide a desired spatial and temporal resolution.
Our results show, for example, that imaging of neurotransmitter release
requires rate constants of kon = 106 M–1 s–1and koff = 102 s–1 in many scenarios,
which corresponds to high dissociation constants of Kd > 100 μM. This work predicts if a given fluorescent
nanosensor array (rate constants, size, shape, geometry, density)
is able to resolve fast concentration changes such as neurotransmitter
release from cells. Additionally, we provide rational design principles
to engineer nanosensors for chemical imaging.