  Diffractometric biosensing is a promising technology to overcome critical
limitations of refractometric biosensors, the dominant class of label-free
optical transducers. These limitations manifest themselves by higher noise and
drifts due to insufficient rejection of refractive index fluctuations caused by
variation in temperature, solvent concentration, and most prominently,
non-specific binding. Diffractometric biosensors overcome these limitations
with inherent self-referencing on the submicron scale with no compromise on
resolution. Despite this highly promising attribute, the field of
diffractometric biosensors has only received limited recognition. A major
reason is the lack of a general quantitative analysis. This hinders comparison
to other techniques and amongst different diffractometric biosensors. For
refractometric biosensors, on the other hand, such a comparison is possible by
means of the refractive index unit (RIU). In this publication, we suggest the
coherent surface mass density, $\Gamma_{\rm{coh}}$, as a quantity for
label-free diffractometric biosensors with the same purpose as RIU in
refractometric sensors. It is easy to translate $\Gamma_{\rm{coh}}$ to the
total surface mass density $\Gamma_{\rm{tot}}$, which is an important parameter
for many assays. We provide a generalized framework to determine
$\Gamma_{\rm{coh}}$ for various diffractometric biosensing arrangements which
enables quantitative comparison. Additionally, the formalism can be used to
estimate background scattering in order to further optimize sensor
configurations. Finally, a practical guide with important experimental
considerations is given to enable readers of any background to apply the
theory. Therefore, this paper provides a powerful tool for the development of
diffractometric biosensors and will help the field to mature and unveil its
full potential.
