  In analogy to the development of fluorescent proteins, innovative tools for
screening optoacoustic cell labels could lead to tailored protein labels for
OA, imparting novel ways to visualize biological structure and function.
Optoacoustic imaging emerges towards a highly promising modality for life
sciences and medical practise with advantageous capabilities such as great
accessible depth, and 3D studying of living tissue. The development of novel
labels with molecular specificity could significantly enhance the optoacoustic
contrast, specificity, and sensitivity and allow optoacoustic to interrogate
tissues not amenable to the fluorescence method. We report on an optoacoustic
flow cytometer (OAFC) prototype, developed for screening optoacoustic reporter
genes. The cytometer concurrently records light scattering for referencing
purposes. Since recording light scattering is completely independent from OA,
we believe it to be a more reliable referencing method than e.g. fluorescence
or ultrasound-backscatter. Precise characterization of our OAFC prototype
showcases its ability to optoacoustically characterize objects in-flow that are
in the size range of single cells. We apply the OAFC to distinguish individual
E. coli cells based on optoacoustic properties of their expressed
chromoproteins read in-flow using microfluidic arrangements and achieved
precisions over 90%. We discuss how the light scattering referenced OAFC method
offers a critical step towards routine measurement of optoacoustic properties
of single-cells and could pave the way for identifying genetically encoded
optoacoustic reporters, by transferring working concepts of the fluorescence
field.
