Focus Area Definition
The problem considered is the rapid generation of both qualitative and quantitative data on the products from experiments designed to explore and/or optimise reactions. It is envisaged that the generation, validation and reporting of such data does not cause any perturbations, give rise to unnecessary experimental delays or otherwise compromise the experiments. It is further envisaged that the data can be used as the basis of an automatic feedback system whereby the experimental conditions and/or the reagents used are tuned. The time taken to perform the measurements (i.e. from “sampling” to reporting) is in the range of seconds to minutes with this time generally decreasing in the longer term. The required fidelity of the measurement (i.e. limit of detection, limit of quantitation, degree of structural/conformational proof) is an important consideration that affects the viability of the various Rapid Reaction Analysis approaches. Although the ultimate aim is clear – full automatic identification and quantification of all components in a reaction mixture – it is important this does not detract from work directed towards immensely important advances that can be made with much reduced requirements (e.g. for reaction optimisation identification of components may not be needed).
Challenges and Goals
The major challenges were defined as (click to read more about each individual challenge):
- Equipment development
- Software development
- Equipping academia with analytical equipment needed for reaction analysis
- Automatic identification of components of reactions
The challenges, current state-of-the-art, goals and pathways to achieving these goals are summarised in the roadmap below.
Modern experimental practises can incorporate close coupled analytics, for example open access UPLC/MS or NMR instruments and in situ spectroscopy for reaction monitoring. Therefore, several aspects of this particular challenge are commercially available. However, the following elements are cause for general concern:
- Method Development Time: For measurement approaches that are dependent upon an initial chromatographic separation then definition of the method conditions should be minimised or generic methodologies put in place.
- Response Time: This is defined as the time delay between “sampling” (i.e. the taking of a physical sample or the illumination of the chemistry stream by an optical method for example and the reporting of the data). Generally, the response time should be minimised and any method through which this can be reduced are considered to be in scope for this challenge.
- Dynamic Range: Of particular interest to this challenge are analytical methods that can analyse samples that contain components which span a very large dynamic range e.g. from 10’s of percent to ppm of an individual sample.
- Costs: Currently, the (capital and maintenance) costs associated with RRA can be prohibitively large. This is a significant concern and is the likely to be limiting implementation.
- Integration / Physical Size: There are some examples of technique integration / hyphenation but they tend to be bespoke and generic / multi-vendor capabilities offer advantages. Also, the footprints of sophisticated analytical techniques are very large compared to the size of the experimental equipment generally used for synthesis. A significant reduction in the size of the analytical equipment would help with its integration with the experimental equipment required for the chemistry.
- Sample Heterogeneity: Analytical techniques that are able to cope with mixed phase (e.g. solid/liquid and liquid/liquid) samples, and are able to analyse each phase are required for some chemistries.