Design of Experiments for Matrix-Assisted Laser Desorption/Ionization of Amphiphilic Poly(Ethylene Oxide)-b-Polystyrene Block Copolymers

Matrix-assisted laser/desorption ionization (MALDI) has become a very popular ionization technique for mass spectrometry of synthetic polymers because it allows high throughput analysis of low amounts of sample while avoiding the complexity introduced by extensive multiple charging of electrospray ionization. Yet, fundamental mechanisms underlying this ionization process are not fully understood, so development of sample preparation methods remains empirical. Reliable prediction for the optimal matrix/analyte/salt system is indeed still not possible for homopolymers and it becomes even more challenging in the case of amphiphilic block copolymers where conditions dictated by one block are not compatible with MALDI requirements of the second block. In order to perform MALDI of copolymers composed of poly (ethylene oxide) (PEO) and polystyrene (PS) blocks, it was postulated here that experimental conditions suitable for both species would also be successful for PEO-b-PS. Accordingly, designs of experiments based on Quantitative Structure Activity Relationship (QSAR) analysis were first implemented, studying the influence of 19 matrices and 26 salts on the laser fluence requested for successful MALDI. This analysis first permitted to highlight correlations between the investigated 10 descriptors of matrices and salts and the analytical response, and then to construct models that permits reliable predictions of matrix/salt couples to be used for one or the other homopolymer. Selected couples were then used for MALDI of a PEO-b-PS copolymer but no general trend was observed: experimental conditions expected to work often failed whereas ionic adducts of the copolymer were clearly detected with some matrix/salt systems that were shown to badly perform for constituting homopolymers. Overall, this rules out the working assumption stating that the MALDI behavior of chains composed of PEO and PS segments should combine the behavior of the two polymeric species. Yet, although requiring a dedicated design of experiments, MALDI of the amphiphilic PEO-b-PS copolymer was achieved for the first time.