Sample preparation: a crucial factor for the analytical performance of rationally designed MALDI matrices

Evidence is presented that the performance of the rationally designed MALDI matrix 4-chloro-α-cyanocinnamic acid (ClCCA) in comparison to its well-established predecessor α-cyano-4-hydroxycinnamic acid (CHCA) is significantly dependent on the sample preparation, such as the choice of the target plate. In this context, it becomes clear that any rational designs of MALDI matrices and their successful employment have to consider a larger set of physicochemical parameters, including sample crystallization and morphology/topology, in addition to parameters of basic (solution and/or gas-phase) chemistry

Unity between God and mind? A study on the relationship between panpsychism and pantheism

The author thanks the John Templeton Foundation and The Pantheism and Panentheism Project for sponsoring this paperA number of contemporary philosophers have suggested that the recent revival of interest in panpsychism within philosophy of mind could reinvigorate a pantheistic philosophy of religion. This project explores whether the combination and individuation problems, which have dominated recent scholarship within panpsychism, can aid the pantheist’s articulation a God/Universe Unity. Constitutive holistic panpsychism is seen to be the only type of panpsychism suited to aid pantheism in articulating this type of unity. There are currently no well-developed solutions to the individuation problem for this type of panpsychism. Moreover, the gestures towards a solution appear costly to the religious significance of pantheism. This article concludes that any hope that the contemporary panpsychism might aid pantheists in articulating Unity is premature and possibly misplaced.Publisher PDFPeer reviewe

Enhanced MALDI MS sensitivity by weak base additives and glycerol sample coating

The concept of rationally designing MALDI matrices has been extended to the next “whole sample” level. These studies have revealed some unexpected and exploitable insights in improving MALDI sensitivity. It is shown that (i) additives which only provide additional laser energy absorption are best to be avoided; (ii) the addition of proton donors in the form of protonated weak bases can be highly beneficial; (iii) the addition of glycerol for coating crystalline samples is highly recommended. Overall, analytical sensitivity has been significantly increased compared to the current “gold” standards in MALDI MS, and new insights into the mechanisms and processes of MALDI have been gained

4-Chloro-α-cyanocinnamic acid is an advanced, rationally designed MALDI matrix

Matrix-assisted laser desorption ionization (MALDI) has become an enabling technology for the fields of protein mass spectrometry (MS) and proteomics. Despite its widespread use, for example, in protein identification via peptide mass fingerprinting, a comprehensive model for the generation of free gas-phase ions has not yet been developed. All matrices in use today, such as α-cyano-4-hydroxycinnamic acid (CHCA), have been found empirically and stem from the early days of MALDI. By systematic and targeted variation of the functional groups of the α-cyanocinnamic acid core unit, 4-chloro-α-cyanocinnamic acid (Cl-CCA) was selected and synthesized, and it exhibited outstanding matrix properties. Key features are a substantial increase in sensitivity and a considerably enhanced peptide recovery in proteomic analyses because of a much more uniform response to peptides of different basicity. Using Cl-CCA as a matrix for a 1 fmol bovine serum albumin (BSA) in-solution digest, the sequence coverage is raised to 48%, compared with 4% for CHCA. For a gel band containing 25 fmol of BSA, unambiguous protein identification becomes possible with Cl-CCA. These findings also imply ion formation via a chemical ionization mechanism with proton transfer from a reactive protonated matrix species to the peptide analytes. The considerable increase in performance promises to have a strong impact on future analytical applications of MALDI, because current sensitivity limits are overcome and more comprehensive analyses come into reach