Small-angle X-ray scattering (SAXS) offers various ways to characterize drug-delivery systems and large molecules. Understanding the structure of drug-delivery systems and large molecules at a molecular level is a crucial step in designing drugs and drug-delivery systems alike.
The SAXS technique can provide insights into structures in the 1–100 nm range. SAXS requires little or no sample preparation and enables scientists to run experiments at or close to in vivo conditions.
Historical perspectiveRöntgen discovered X-rays in 1895. In 1912, Laue discovered the diffraction of X-rays by crystals (1). Guinier's work in late 1939 led to the main principles of SAXS (2). In the 1940s and 1950s, Otto Kratky investigated X-ray diffraction at small angles as a technique for the structural analysis of macromolecules. He developed the SAXS method into a powerful tool for structural research, particularly in the field of polymers and molecular biology (3). Considered one of the fathers of SAXS, Kratky founded the Institute for Physical Chemistry in Graz, Austria, which became an early center for this technique. The institute led to many advances in SAXS such as the first commercial instrument for SAXS.
Early SAXS experiments took place in laboratories. In the 1970s, the availability of synchrotrons and high-intensity synchrotron radiation helped bring the technique to prominence. In recent years, technical advances have made laboratory-based SAXS instruments attractive again.
The pair-distance distribution function p(r) in Equation 2 is the geometrical representation of the object in the beam. p(r) maps the distances of all electron pairs inside the particle. The scattering intensity I and the geometrical representation p(r) are related by Fourier transform.
However, representing a three-dimensional (3D) object with a one-dimensional distribution function necessarily omits some information. Converting p(r) into a three-dimensional object becomes difficult and requires additional constraints by the scientist such as connectedness or compactness.