Introduction
For over 75 years, analytical ultracentrifugation (AUC) has proven to be a powerful method for characterizing solutions of macromolecules, and an indispensable tool for the quantitative analysis of macromolecular interactions. There are approximately 400 XLI analytical ultracentrifuges in use worldwide. These instruments are distributed almost evenly between industrial settings, primarily in pharmaceutical, biopharmaceutical, and polymer companies, and academic research facilities associated with biochemistry, biophysics, molecular biology, and material science programs. AUC provides core information for over 350 scientific publications a year (source: SciFinder 2008, using “AUC” as the search term) with usage increasing steadily (436 references in 2008).
From 1950 to 1992, advances in AUC were developed largely by academic labs and commercialized by Beckman Instruments (now Beckman Coulter Inc.). The current analytical ultracentrifuge, the XLI, was developed in the mid-1980s by retro-fitting an existing high-speed preparative centrifuge with absorbance and interference optics (Giebeler 1992; Yphantis et al. 1994). Since 1992, only one new optical system, the fluorescence optics (Schmidt and Riesner 1992; MacGregor et al. 2004; MacGregor 2000; Kroe and Laue 2009) has been commercialized and no improvements to the existing optical systems have been commercialized. Alternative base instruments have been commercially available that are less versatile than the XLI due to their lower maximum rotor speeds (LumiSizer by LUM GmbH: 6,000 rpm; BI XDC by Brookhaven Instruments: 10,000 rpm; DC24000 by CPS instruments: 24,000 rpm) and unconventional sample holders (monosector cells or discs instead of multisector cells). While these machines marginally qualify as analytical centrifuges, they clearly demonstrate the expansion potential for innovative AUC designs, such as one-shot detection of concentration profiles (LumiSizer) or non-optical detection by X-ray absorption (XDC).
The utility and feasibility of new optical systems for AUC has been demonstrated by the user community for turbidity (Cantow 1964; Scholtan and Lange 1972; Müller 1989; Mächtle 1992, 1999a), low angle laser light scattering (Bhattacharyya 2006; Mächtle and Börger 2006), Raman scattering (Bhattacharyya 2006), the Tsvetkov optics (Lavrenko et al. 1999), and Schlieren detection (Lloyd 1974; Cölfen and Borchard 1994; Mächtle 1999b; Börger et al. 2004). Even though compromised by the XLI geometry, each of these optical systems provides useful, even unique ways to monitor sedimenting particles. However, they cannot be made available commercially due to the legal restrictions on the XLI.
The Open AUC Project will remedy this situation by providing a new, alternative analytical ultracentrifuge platform, open source software drivers to operate the instrument, open source data analysis and data management tools, and open hardware and software standards that will encourage innovation. The current status of these advances is described here.