Continuous Purification from Flow Chemistry Systems with In-Line Flash Chromatography

Recorded June 15, 2022.

Join Christopher Thomson, Researcher at Heriot-Watt University, as he shares his work expanding the tool kit of automated flow synthesis with the development of in-line flash chromatography purification.

In this webinar, you will learn:

  • An introduction to flow chemistry and in-line purification technologies.
  • An overview of prior continuous chromatography methods, their advantages and limitations.
  • How to interface flow reactors with puriFlash automated chromatography systems.
  • ‘Tips & Tricks’ for performing continuous in-line flash chromatography.
  • Future prospects for developing in-line flash chromatography.

Chris completed his chemistry with biochemistry degree (MChem, 1st Class) at Heriot-Watt University, Edinburgh, in 2018 and was recipient of the ‘William H. Perkin Prize’ for excellence in organic chemistry. He was then awarded a PhD scholarship through the EPSRC funded centre for doctoral training in critical resource catalysis (CRITICAT), under the joint supervision of Dr Filipe Vilela and Dr Ai-Lan Lee.

Chris’ research focuses on the development and implementation of enabling technologies – especially flow chemistry – to enhance heterogeneous photocatalysis for organic synthesis.

He has published several papers on the development of flow systems featuring enabling technologies, such as: in-line NMR spectroscopy, in-line UV-Vis. spectroscopy, static mixing photocatalyst monoliths produced via functional material additive manufacturing, and most recently, reported the first example of continuous in-line flash chromatography – which will be the subject of this webinar.

Complement Flow Synthesis With In-Line Purification Using Flash Chromatography

In this application note, we describe a novel method to perform the continuous isolation of flow synthesis products from residual starting materials, catalysts or by-products to expedite chemical discovery. A promising new approach is highlighted here, featuring the Advion Interchim Scientific puriFlash® 5.250 preparative LC system.

The first results of our cooperation with the VilelaLAB and Continuum Flow Lab at Heriot-Watt University, Edinburgh, on this topic are outlined here and can be read in more detail in the following source: C.G.Thomson et al.: Expanding the Tool Kit of Automated Flow Synthesis: Development of In-line Flash Chromatography Purification, J. Org. Chem. 2021, 86, 20, 14079–14094.

Natural Products Purification – Improved Workflow with Mass Spec

Lab Manager Tech Trends Webinar. Recorded August 11, 2021.

This webinar features the Interchim PuriFlash® flash purification and preparative HPLC system and demonstrates separation of natural products, purification of specific target molecules and the combination of mass spectrometry detection of the same both for product confirmation and mass directed fraction collection using an Advion expression® compact mass spectrometer.

As a viewer, you will learn more about:

  • Natural product separation and analyte isolation from tea and herbs/spices starting from TLC separation
  • Column selection criteria for flash chromatography and preparative reverse phase HPLC
  • Integrating mass spectrometry detection of analytes from TLC plates and collected fractions
  • Mass spectrometry directed fraction collection to simplify the entire workflow and automate purification processes

The Essential Systems & Consumables for Purification, Evaporation & Mass Spectrometry

The Advion Interchim Scientific suite of systems and consumables allows users to harness the power of mass spectrometry, flash chromatography, prep LC and more. Simple and robust, download our brochure to learn more about:

  • The Advion Interchim Scientific expression® compact mass spectrometer (CMS): A fast and easy analytical tool for the organic chemist. Ideal for fast reaction monitoring, the expression® CMS features a single quadrupole that can adapt to multiple ionization sources in seconds, including both ESI and APCI. The expression® CMS offers a variety of novel sampling techniques, including fast assay methods for liquids, solids, gases, and even air-sensitive compounds.
  • Direct mass analysis of TLC plates in 30 seconds at the push of a button with Plate Express
  • One-touch analysis of solids and liquid samples with the ASAP® probe
  • LC/CMS
  • puriFlash® ultra performance flash purification: Ideal for method development and purification of rare and high added value compounds, the Interchim family of puriFlash® systems offer users a wide range of throughput options and the highest recovery rates at >95%.
  • Mass-Guided Purification: the Interchim puriFlash® + Advion CMS offers the ideal solution for Flash-MS, and can provide fraction identification in <30 seconds.

Fill out the form to download the full Advion Interchim Scientific brochure now.

Monitoring, Modelling and Optimisation of Continuous Flow Reactions Using On-line Mass Spectrometry

Horbaczewskyj, Christopher Stefan (2019) Monitoring, Modelling and Optimisation of Continuous Flow Reactions Using On-line Mass Spectrometry. PhD thesis, University of Leeds.


An on-line mass spectrometry method has been developed to monitor, model and optimise continuous flow reactions. This method makes use of dual-piston pumps, tubular reactor block, Vici sample actuator, an Advion expression Compact Mass Spectrometer (CMS) and other analytical systems to investigate a variety of chemical systems based on their need for process improvement. Full reaction automation employed MATLAB, the Snobfit algorithm, along with Modde DoE software. On-line mass spectrometry has advantages over other analytical techniques as it has shorter acquisition times (2-60 s), low chemical sensitivity (~108 mol%) and chemical identity as well as the potential to provide quantitative information. In this work, reaction quantitation has been explored using four chemical systems, where each of them was monitored by a variety of analytical techniques, with the overall aim being to examine if on-line mass spectrometry can be used for quantitative analysis. For all cases investigated, process improvements were made whilst also determining optimal operating conditions to improve conversions, yields or selectivities as well as looking at reaction waste reduction. Flow chemistry and the work conducted has shown how waste can be reduced for certain reactions when compared to more traditional approaches. This method relies on machine learning, full process automation and quick process analytical technology to determine optimum conditions as well as build large reaction data sets. Large data sets were created using a hybrid DoE-kinetic composite circumscribed orthogonal design. Mass spectrometry provided valuable reaction information and has the potential for reaction quantitation depending on the required application, reaction system and ionisation settings. Compound thermal stability can be problematic in APCI+ mode whilst ion suppression is problematic in ESI+ mode. Still a versatile analytical tool, on-line mass spectrometry was found to be inherently quantitative. The continuous-flow-on-line-MS-self-optimisation platform was used to investigate a variety of different reactions to show versatility of the MS system. These reactions are summarized below. 1) An N-Boc deprotection of AZD5634 for optimisation and process scale-up, with achieved conversions >95% and scale-up to pilot and commercial scale using on-line mass spectrometry). 2) An N-Boc deprotection reaction using a hybrid DoE-kinetic model for optimisation and large data set generation, with achieved conversion >90%. 3) An SNAr reaction of AZD4547 for product selectivity and yield improvement, with achieved conversion of ~38% and DP yield of ~30%. 4) The synthesis and optimisation of Fe-N-heterocyclic carbene complexes using an electrochemical method for use in a C-H hydroxylation reaction. Optimum electrochemical conditions of either 7 V and 4 minutes residence time, or 2.5 V and 15 minutes residence were achieved.

University of Leeds Webinar: Self-Optimizing Continuous Flow Reactors

Chemical processes can be performed in two ways; in batch or in flow, each method having set advantages and disadvantages associated with them.

Flow chemistry has gathered increasing attention over the past decade and is being readily adopted into academia to help improve synthetic routes, which maybe undesirable in batch, where outputs such as yield, productivity, E-factor or selectivity maybe improved via various methods of optimisation. On-line analytics within continuous flow chemistry allow reactions to be monitored in real-time ultimately allowing immediate characterisation and the ability to optimise in the easiest possible way.

Hosted by Jack Henion, Advion’s Chief Scientific Founder, Chris Horbaczewskyj of the University of Leeds outlines the work carried out within the Bourne group for process development applications:

  • Use of flow chemistry with online HPLC in the self-optimisation of reactions,
  • Use of online mass spectrometry for the optimisation of continuous flow reactions using an experimental design approach,
  • The development of new algorithms for multiple variable optimisation in chemical systems.

An Easy-to-Machine Electrochemical Flow Microreactor: Efficient Synthesis of Isoindolinone and Flow Functionalization

Ana A. Folgueiras-Amador, Kai Philipps, Sébastien Guilbaud, Jarno Polacker, Prof. Dr. Thomas Wirth

Flow electrochemistry is an efficient methodology to generate radical intermediates. An electrochemical flow microreactor has been designed and manufactured to improve the efficiency of electrochemical flow reactions. With this device only little or no supporting electrolytes are needed, making processes less costly and enabling easier purification. This is demonstrated by the facile synthesis of amidyl radicals used in intramolecular hydroaminations to produce isoindolinones. The combination with inline mass spectrometry facilitates a much easier combination of chemical steps in a single flow process.

The in-line MS analysis was carried out using Advion Expression® CMS (Atmospheric Pressure Ionisation Techniques (APCI)) and an MRA® valve.

To learn more about the Wirth Research Group, visit the University of Cardiff online at

Mass Spectrometry for Chemists: Direct Analysis of TLC Plates, Solids and Gases

TLC/CMS, the atmospheric liquids and solids probe (ASAP), and the volatile APCI source provide direct analysis without sample preparation – even for air-sensitive compounds.

With the daily need to analyze a variety of samples, these techniques are indispensable in a busy lab.

Learn how a single instrument can be adapted to each of these sample requirements and rapidly changed to accommodate back-to-back assays. Listen to users in the field speak about the innovative sample inlets that have cut down on sample prep and streamlined their everyday work flow.

During this webinar you will:

  • Learn how the CMS offers real-time results and decision making right at the bench. This allows chemists to optimize reactions, know when to quench, and know when they have failed and to move on
  • Learn several novel sample techniques that can streamline workflow in your lab
  • Find fast analysis methods for liquids, solids and vapor-phase compounds

Hear from leaders in mass spectrometry including:

  • Dr. Jack Henion, Advion Scientific Founder
  • Matthew Turner, Experimental Officer in Mass Spectrometry, Department of Chemistry, Loughborough University
  • Tao Yongfeng, Post Doctorate, The Romo Group, Baylor University
  • Sean M. Kerwin, PhD, Associate Professor, Department of Chemistry & Biochemistry, Texas State University

University of Cambridge, Ley Group

A: One of the focus points for Ley Group research is the development of continuous flow synthesis methods. We aim to include new enabling techniques into our work to facilitate the collection of data relevant to the reactions we conduct. We work across the early synthesis spectrum – from discovery to scale-up and process development.


A: Standard detectors we use in our work can be problematic when trying to discern what is in a product mixture leaving a flow reactor. For example, UV detectors are useful only in very restricted flow-based situations and don’t give compositional information. IR is a step up from this, but suffers from issues when peaks in starting materials, products and by-products overlap. Some transformations may also lead to undetectable changes in an IR spectrum. While flow-based NMR can be good when it’s usable, its expense and lack of resolution at a bench-top level hinder its utility.


A: The expression® CMS struck the perfect balance between cost, ease-of-use and detection capabilities that we needed for our research. We’re able to get large amounts of relevant information about reaction mixtures, in real-time, without worrying in most cases about overlapping peaks or detection signals. This information is used by our control systems to make decisions about product stream composition, allowing us to automate procedures such as reaction telescoping, process start up and self-optimization. The expression® CMS software is fantastic also – everything is recorded, letting us go back over the raw data to gain even more insights into how product compositions change over time in our processes.


A: I would recommend the system to any group that works with continuous flow chemistry, especially those that need real-time analysis of stream compositions. The ease at which the unit can be integrated into any process makes it an extremely attractive unit to use. It’s also very easy to switch the expression® CMS into a standalone MS unit for independent sample analysis, making it versatile in any organic chemistry laboratory.


A: Org. Process Res. Dev., 2016, 20, 386–394