High-Throughput Automation in Chemical Process Development

Selekman, Joshua A.; Qiu, Jun; Tran, Kristy; Stevens, Jason M.; Rosso, Victor W.; Simmons, Eric M.; Yi, Xiao; Janey, Jacob M.

doi:10.1146/annurev-chembioeng-060816-101411

Cited by 105 publications

(94 citation statements)

References 93 publications

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“…Many automated strategies for screening and optimization in flow, for both discrete (solvents, catalysts, ligands) and continuous (temperature, loading, time) reaction variables, can now be found in the literature. Similar automated systems can be employed for reaction discovery (by combining stocks of different reactants) and for the rapid synthesis of compound libraries, amply demonstrating the rapidity and versatility of flow systems for such purposes [68][69][70][71]. Inline analytics allow immediate evaluation of the reaction's outcome and combination with smart algorithms [machine learning, artificial intelligence, and design of experiments (DoE)] enables self-optimization protocols [72,73], reducing the number of experiments necessary to optimize complex systems.…”

Section: Automated Screening Platforms For Flow Photochemistrymentioning

confidence: 99%

Flow Photochemistry: Shine Some Light on Those Tubes!

Sambiagio

Noël

2020

Trends in Chemistry

313

223

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Continuous-flow chemistry has recently attracted significant interest from chemists in both academia and industry working in different disciplines and from different backgrounds. Flow methods are now being used in reaction discovery/methodology, in scale-up and production, and for rapid screening and optimization. Photochemical processes are currently an important research field in the scientific community and the recent exploitation of flow methods for these methodologies has made clear the advantages of flow chemistry and its importance in modern chemistry and technology worldwide. This review highlights the most important features of continuous-flow technology applied to photochemical processes and provides a general perspective on this rapidly evolving research field. Microflow Technology and Photochemistry: A Perfect MatchThe use of light to promote chemical reactions has been exploited since the 18th century, but only recently a resurgence has been observed in synthetic organic chemistry, in particular due to the development of visible-light photoredox catalysis [1-5]. All transformations involving light (e.g., Figure 1A-D) must consider, besides classical chemical parameters (i.e., reaction conditions), the photophysical aspects of the sensitizer (see Glossary)/photocatalyst (when used), and the reactor design. The latter, although often neglected by chemists, is a critical aspect for the outcome of the studied chemical transformation. This includes, for example, the size, shape, and material of the reaction vessel, the characteristics and positioning of the light source(s), and heat-transfer properties, particularly when high-intensity lamps are used [6,7]. The engineering and technological aspects of photochemical processes are often at the basis of the irreproducibility and non-scalability of such transformations.According to the Beer-Lambert law, light transmittance decreases exponentially with the distance from the light source ( Figure 1F). For a standard batch reactor (diameter at least in the centimeter range), light intensity decreases considerably from the flask walls to the middle of the reaction mixture, resulting in slow reactions and nonhomogeneous irradiation of the reaction mixture. Performing photochemical reactions in microchannels (ID < 1 mm) allows a higher and more homogeneous photon flux, resulting in shorter reaction times and consequently less side-product formation due to over-irradiation, often observed in batch [8,9]. Another advantage of microflow chemistry, correlated with the large surface:volume ratio, is improved heat and mass transfer, with the possibility to perform mass-transfer-limited multiphasic reactions efficiently [10]. Reactive chemicals and intermediates can be handled more safely in flow than in batch, as no accumulation of dangerous components occurs within the confined reactor volume due to the continuous nature of the process. Together, these result in often faster, safer, and higher-yielding reactions, with the possibility to perform reactions under condition...

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Section: Automated Screening Platforms For Flow Photochemistrymentioning

confidence: 99%

Flow Photochemistry: Shine Some Light on Those Tubes!

Sambiagio

Noël

2020

Trends in Chemistry

313

223

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“…If this phase can be shortened, it can significantly reduce the iteration time of a DMTA cycle. Laboratory automation has and will continue to play a decisive role in this context 135,136,137,138 . Fast compound synthesis using robust reactions in batch or flow with automated analytics and purification will help speed-up the Make phase.…”

Section: Challenge 4: Reducing Cycle Timesmentioning

confidence: 99%

Rethinking drug design in the artificial intelligence era

Schneider

Walters

Plowright

et al. 2019

Nat Rev Drug Discov

566

349

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Perspective │2 Artificial intelligence (AI) tools are increasingly being applied in drug discovery. Whilst some protagonists point to vast opportunities potentially offered by such tools, others remain skeptical, waiting for a clear impact to be shown in drug discovery projects. The truth is probably somewhere between these extremes, but it is clear that AI is providing new challenges not only for the scientists involved but also for the biopharma industry and its established processes for discovering and developing new medicines. This article presents the views of a diverse group of international experts on the 'grand challenges' for small-molecule drug discovery with AI and approaches to address them.

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“…Measurement science has also played a central role in enabling the rise of high throughput experimentation, which has become an important feature of modern pharmaceutical discovery and development. [1][2][3][4][5] High throughput experimentation is now a large, complex and rapidly evolving branch of chemistry and an important focus for academic research. [6][7][8][9][10][11][12][13][14] In addition, high throughput experimentation is now routinely employed by a number of other industries beyond pharma.…”

Section: Introductionmentioning

confidence: 99%