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Residence Time Distribution Across Coflore Systems

Residence time distribution (RTD) is the probability distribution function that a solid or fluid element will exit a continuous flow system with respect to time, used as a measure of plug flow.⁠

RTD is often displayed as a bell-shaped curve, with a more narrow curve indicating better residence time uniformity across all of the molecules within a flow reactor - showing that the reactor exhibits good "plug flow", i.e. reaction uniformity across your flow process.

A narrow RTD is essential for process uniformity and is one of the key requirements of any flow reactor.

AMT chemical engineers, Josh Trenchard and Andrew Karras, are continually testing and evaluating our Coflore systems, generating technical content and case studies to demonstrate their versatility and modularity. Several investigations have looked to determine RTDs for the ACR, ATR and RTR with respect to variables such as residence time and agitation frequency. In this post, a sample of RTD testing for each system has been summarised below:

Coflore ACR

The Coflore ACR is a modular cellular flow reactor with 10 reaction cells linked together with interconnecting channels. The reactor volume can be adjusted by inserting different sizes of agitator into the reactor block.

The Coflore ACR

For the ACR, RTDs have been experimentally determined at a fixed residence time of 30 minutes and using 50% volume agitators (V50), with a bottom up flow direction, whilst varying agitation frequency. The "CSTRs in series" model was applied to the distribution curves to assess the number of theoretical stages.

⁠The RTD curves were found through the cumulative distribution, experimentally, a step change in process media from water to a low concentration sodium chloride solution, data was recorded for at least 3 residence times using a conductivity sensor.

Run #

Agitation Frequency (Hz)

Number of CSTRs in Series













Table 1: Summary of Results of the ACR RTD Testing.

The result of this testing is summarised in Table 1. Overall, the 50% volume agitators (V50) show good performance. In the table, it can be seen that the ACR has at least 10 distinct reaction stages, with agitation frequency having a noticeable impact.

Coflore ATR

The Coflore ATR is a modular tubular flow reactor where the reactor volume can be adjusted by connecting multiple reactor tubes of either 0.35 L and 1.25 L. Up to 8 reactor tubes can be configured in two banks of 4 providing volumes up to 10L.

The Coflore ATR

For the ATR, residence time distributions were experimentally determined for an incremental increase in ATR tubes from 1 to 4 at a fixed residence time per reactor tube. For the ATR 1.25 L reactor tubes, the flowrate of process media was set at 312.5 mL/min. for the ATR 0.35 L reactor tubes, the flowrate of process media was set at 87.5 mL/min. This inherently means that the total reactor residence time varies for each test, but each individual tube is subject to identical conditions.

A proportional volume of saturated brine was injected into the process feed line and data was recorded for at least 3 residence times using a conductivity sensor.

For 0.35 L reactor tubes, it was determined that the total number of stages increases logarithmically with an increasing number of tubes whereas for 1.25 L reactor tubes, the increase was found to be exponential as summarised in Graphs 1 and 2:

Graph 1: Results of the 0.35 L ATR RTD Testing.

Graph 2: Results of the 1.25 L ATR RTD Testing.

Extrapolation of the testing carried out allows us to estimate that for a 10 L ATR, and for a 30 minute reactor residence time, the number of stages would be >500, demonstrating the high degree of plug flow in the Coflore ATR system.

Coflore RTR

The Coflore RTR is a production-scale tubular reactor suitable for use in fine chemical and pharmaceutical API manufacturing. The RTR reactor has a 100 L internal volume and houses a free-moving agitator that separates the reactor tube into 10 distinct stages via baffles located along the agitator.

Two Coflore RTR Reactors

To determine the nature of plug flow in the RTR, water was continuously fed to the RTR at a flowrate of 9.5 Litres per minute, equating to a residence time of 10.5 minutes. 60 mL of saturated brine solution was injected into the water feed line and data was recorded for at least 2 residence times using a conductivity sensor at the outlet. For this test, the agitation speed of the RTR was set at 25 cycles per minute. Through monitoring the change in conductivity vs time, the RTD can be calculated as summarised in Graph 3.

The Coflore RTR was determined to have consistent orderly flow behaviour. At the tested agitation speed of 25 cycles per minute, 11 ± 1 CSTRs in series were observed.

Closing Remarks

For all three Coflore systems, a high degree of plug flow is observed. Whilst a snapshot of the RTD testing carried out has been presented above, we are always more than happy to share any relevant technical information with customers and so if you have a specific application and would like to find out whether the Coflore systems may be suitable, please don't hesitate to contact a member of the team and we will be happy to help. Our team can be reached at or you can contact our business development manager, Dr Mike Kenny,


“One of today's most important tools for modernizing the pharmaceutical industry is a process known as continuous manufacturing”

Director of the FDA’s Centre for Drug Evaluation and Research,

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