Open Access

Benchtop NMR instruments in combination with flow cells are well suited for real-time process and reaction monitoring applications. In this study, a benchtop NMR spectrometer was demonstrated as a process analytical technology (PAT) tool for screening and optimization of the solvent extraction step in downstream processing of polyhydroxyalkanoate (PHA) biopolymers. This polymer class is one of the few thermoplastic materials synthesized 100 % via biotechnological routes which fully biodegrade in common natural environments. This makes them excellent candidate materials for sustainable replacement of conventional plastic materials. Online NMR experiments were conducted in a fully automated laboratory setup, employing commercially available 5x4 mm PTFE tubing as a low-cost flow-cell assembly. The extraction process of the PHA copolymer poly-(hydroxybutyrate-co-hydroxyhexanoate) obtained from Ralstonia eutropha biomass was performed in a thermostated stirred batch reactor. Extraction performance was monitored in two different solvents, chloroform and acetone, in a range of ground lyophilized cell loadings from 20 to 120 g/L. The study shows the versatility of benchtop NMR spectroscopy for process monitoring, facilitating endpoint determination and extraction efficiency by optimizing process parameters.

The feasibility of using a high repetition rate (up to 4 MHz), pulsed master oscillator power amplifier (MOPA) fiber laser source for double- and multi-pulse laser-induced breakdown spectroscopy (DP- or MP-LIBS) was investigated on silicon and steel samples. A thorough investigation of laser parameters was carried out to assess the effects of the duration, delays and energies of the applied pulses, the varying of which was found to be all possible by tuning the operating parameters of the laser. It was established that from the point of view of signal enhancement, the most important parameter by far is the energy of follow-up laser pulses in a burst. It was also demonstrated, that even when using up to 100 μs interpulse delays, the second pulse always generates a significantly stronger emission than the single-pulse case. Upwards from the second pulse, the signals generated by consecutive laser pulses showed similar emission intensities, up until the fourth laser pulse. The integration of the emission signal across several consecutive laser pulses can be also beneficial, which is possible because the low energy (a few mJ), relatively long laser pulses (several hundreds of ns) do not generate high background emission. We also demonstrate the improvement of analytical performance of DP-LIBS using this fiber laser source in a quantitative application on standard steel samples for Cu, Ni and Cr elements.

Chemical industry is currently in a rapidly changing environment, e.g., due to variability of raw material quality, high energy costs and demand for improving efficiency. Process optimization and new process concepts become more and more important. Flexible chemical plants can produce various high-quality products using multi-purpose equipment with short downtimes between campaigns and reduce time to market for new products. Intensified continuous production plants allow for difficult to produce compounds like exothermic reactions with high heat dissipation. Highly automated chemical process monitoring along with real-time quality control are prerequisites to such concepts and, thus, should be based on “real-time” chemical information. A commercially available benchtop NMR spectrometer was integrated to the full requirements of an automated chemical production environment such as explosion safety, field communication, and robust evaluation of sensor data. Field studies in modular and conventional production plant setups show promising results gaining process knowledge for further optimization. NMR spectroscopy appeared as powerful online analytical method and allows using a modular data analysis approach, which can even serve as reliable reference method for further calibration-dependent PAT applications (e.g., NIR or Raman spectroscopy). Based on experiences from earlier field studies an enhanced field enclosure setup was developed and built, including the option of a secondary analytical method (e.g., optical spectroscopy). Integrated control systems allow for a flexible implementation based on the available automation infrastructure at the chemical plant or pilot plant setup. In the future, modular interconnecting “smart” PAT systems and process equipment have the potential speed up the setup of production equipment for chemicals and pharma-ceuticals and therefore help to reduce the time-to-market.

Fatty acid esters of 3-monochloropropane-1,2-diol (3-MCPD) are heat-induced contaminants formed from fats and sodium chloride. The mode of action for the 3-MCPD mediated induction of renal tubule neoplasms in rats is still unclear, which is in part due to lacking metabolism data. In the current study, urinary metabolites were identified by one- and two-dimensional 13C nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry following oral administration of 3-MCPD or [13C3]3-MCPD in rats. In addition to 3-MCPD itself, nine metabolites were identified. Four of those, N-acetyl-S-(2,3-dihydroxypropyl)cysteine (DHPMA), 3-MCPD sulfate, β-chlorolactic acid (β-ClLA) and oxalic acid have been reported before. Five novel metabolites in rat urine were thiodiglycolic acid (TDGA), thionyldiglycolic acid (TNDGA), 3-MCPD glucuronide (at least three isomers), 3-carboxy-2-hydroxypropyl mercapturic acid (CHPMA), and 3-(S-carboxymethyl)mercaptolactic acid (CMMLA). Only three metabolites were excreted at mean dose ratios > 1% (after treatment with 50 mg 3-MCPD/kg body weight in male and female rats), i.e. 3-MCPD (7.3%, 9.7%), DHPMA (3.5%, 1.7%) and TDGA (1.1%, 4.0%). The overall mean dose excretion in urine samples (males: 12.2%, females: 16.3%) supported hypotheses on formation of conjugates/adducts of reactive metabolites and the possibility that dechlorination leads to suitable building blocks for amino acid and fatty acid synthesis. The identification of TDGA indicated the interim formation 2-chloroacetaldehyde, previously identified to mediate specific nephrotoxic effects of the cytostatic ifosfamide in rats.

The development of laser sources plays a very important role in the quick advancements in the field of LIBS. However, the development of fiber lasers went mostly unnoticed by the wider LIBS community. These laser sources, traditionally used in industrial cutting and welding processes, despite their high-power output (hundreds of watts) and are very robust nature, were neglected, because they used to work only in continuous mode. Modern fiber lasers however, offer pulsed output with a couple of mJ-s pulse energy, which can be adequate for certain tasks [1,2]. Furthermore, the pulse duration and the pulse repetition rate can be varied in a reasonably wide range, while their price is a fraction of the ones traditionally used in research. In the recent years, our groups made experiences with modern fiber lasers to evaluate the feasibility of their usage in LIBS. The initial experiments proved that they are not just suitable for standard analytical tasks such as quantitative or qualitative analysis, but their unique set of features makes them capable for fundamental research, like no other laser sources currently on the market. The relatively low energy and elongated profile of the pulses are very efficient in ablation and in the generation of low temperature plasmas [3], which means the ionic lines are less numerous, while the emission is mostly free from the background emission typical for the early stages of the plasma lifetime. It can make spectrometer gating and signal integration much simpler and robust. A thorough set of investigations of single pulse, double pulse and even continuous irradiation experiments was performed. The effects of various parameters, such as energy, duration and shape of the pulse as well as inter pulse delay were investigated on the generated signal focusing mainly the signal intensity, the self-absorption and the width of the peaks as well as the plasma properties.