Liquid-Liquid Separators

Important Features:

• Bench to plant

Our device is well-characterized and directly scalable from lab to pilot to production.

• Separates emulsions with ease

Instead of using agitation to form microdroplets, we improve mixing by using a flow pattern that has a large surface area, thus avoiding emulsions that generally cause separation issues.

• Independent of density

The operating principle behind the technology is based on a liquid’s wettable nature, so it works with any liquid-liquid system regardless of their density difference.

• Excellent chemical compatibility

Machined in materials with excellent chemical resistance, Zaiput separators work with a wide range of organic solvents, in acidic and basic solutions.

• Modular

Plug and play functionality at all scales.

Other Advantages:

• Cost effective

Our devices come at a lower price than competing technologies. Our devices also reduce your operating cost thanks to minimal maintenance and highly efficient performance.

• Minimal internal volume

Our device eliminates the need for moving or coalescing parts, so it has a drastically reduced dead volume.

• Green technology

Our device shows excellent separation performance and high extraction efficiency, reducing solvent consumption. It is suitable for any chemical process, from bulk to high-value chemical industries.

• Pressure rating

The metal shell design allows Zaiput separators to be used inline with a pressurized process (up to 300 psi/ 2 MPa).

If the video does not play properly, click here to see our demo.

Zaiput Flow Technologies' patented separators provide continuous separation of an immiscible phase (liquid-liquid or gas-liquid) by leveraging differences in wetting properties of the liquids onto a porous membrane.

• When a stream composed of two phases (for example: an aqueous liquid and an organic liquid or a gas and a liquid) enters the separator, one phase will have an affinity for the membrane and fill the pores (this is referred to as the “wetting” phase), and the other phase will be repelled and will not fill the pores (this is referred to as the “non-wetting” phase).
• Once the membrane pores are filled with the wetting phase, a pressure differential is applied between the two sides of the membrane. This pressure differential is finely adjusted by Zaiput’s patented internal pressure controller to apply just enough pressure to “push” the wetting phase without forcing the non-wetting phase through the pores (see figure below). The separator is designed to maintain a constant pressure differential across the designated flow rates even when conditions are fluctuating. As a result, the separator can be used as a “plug-and-play”, modular unit.
• A key aspect of the technology is that it exploits differences in wettability and surface forces to accomplish the separation; as a result, the device can separate liquids with the same density and emulsions with continuous operation.

Performance

Examples of liquid-liquid separations that can be used to test the performance of the Zaiput liquid-liquid separator. Note that the applications are not limited to this list.

Liquid 1	Liquid 2
Water NaCl solution HCl solution Brine liquor	Light oil Alkanes (hexane, heptane, octane) Acetate (ethyl acetate, isopropyl acetate) Toluene Long-chain alcohols Diethylene glycols (at 60 ˚C) Methyl ethyl ketone Benzene

Performance under pressure disturbance:
Zaiput's liquid-liquid separator is designed to handle pressure disturbances in the system so that the separation of the liquid phases can be achieved without any manual control. To demonstrate this ability, we carried out the following experiments:

Here, we feed the separator with two immiscible liquids (water-hexane, water-ethyl acetate). The separator has a hydrophobic membrane inside. We simulated downstream operations or disturbances by setting a value of back pressure on the outlet of the organic stream. For successful complete separation, water should exit on one side, while the organic exit on the other side. That being said, there are two modes of incomplete separation:

(1) Retention of organic in the aqueous phase
(2) Breakthrough of water through the membrane with the organic phase
The results of experiments with either water-hexane or water-ethyl acetate are shown here (where R represents % of retention and B the % of breakthrough):

The results show that a simple separation (hexane/water, interfacial tension 50 mN/m) runs with complete separation at all of the tested total flow rates, with different ratios of flow rates, and at different levels of disturbances created in the system (with increasing back pressure on the organic side).

The separator also has excellent performance when challenged with a pair of liquids with very low interfacial tension (ethyl acetate/water, interfacial tension 6.8 mN/m). Under these conditions, the separator provides complete separation at different total flow rates and with different ratios of flow rates but tolerates fewer disturbances to achieve complete separation in a single step.

Applications

The Zaiput liquid-liquid separator can be used for a wide range of applications. Below are a few examples:

1. Liquid-liquid extraction/In-line workup

• Liquid-liquid extraction is one of the primary purification methods providing high selectivity and low energy consumption.
• Zaiput’s technology provides the ability to perform the extraction in continuous flow with a simple plug-and-play device.
• Zaiput’s separator can be used in conjunction with different chemistries, with applications ranging from pharmaceuticals to polymer synthesis.
• Alternatively, it can be a standalone unit operating in any laboratory or industrial process.

Selected list of publications

Andrea Adamo, Rachel L. Beingessner, Mohsen Behnam, Jie Chen, Timothy F. Jamison, Klavs F. Jensen, Jean-Christophe M. Monbaliu, Allan S. Myerson, Eve M. Revalor, David R. Snead, Torsten Stelzer, Nopphon Weeranoppanant, Shin Yee Wong, Ping Zhang, On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system Science April 2016.

Nicolas Lamborelle, Justine F Simon, Andre LUXEN and Jean-Christophe Monbaliu, Continuous-Flow Thermolysis for the Preparation of Vinylglycine Derivatives Org. Biomol. Chem. Nov 2015.

Irina Sagamanova, Carles Rodríguez-Escrich, István Gábor Molnár, Sonia Sayalero, Ryan Gilmour, and Miquel A. Pericàs, Translating the Enantioselective Michael Reaction to a Continuous Flow Paradigm with an Immobilized, Fluorinated Organocatalyst ACS Catal. Sept 2015.

Leibfarth FA, Johnson JA, and Jamison TF, Scalable synthesis of sequence-defined, unimolecular macromolecules by Flow-IEG Proc. Natl. Acad. Sci. Aug 2015.

2. Biphasic reaction or quenching system

• In liquid-liquid reactions, often the reaction stream needs to be quenched by an immiscible phase.
• Zaiput’s liquid-liquid separator can be used downstream or in-line to separate the biphasic reaction.

Selected list of publications

Baptiste Leforestiera and Markus Vögtle, Safe Generation and Direct Use of Chlorine Azide in Flow Chemistry: 1,2-Azidochlorination of Olefins and Access to Triazoles Synlett. June 2016.

Steffen Glöckner, Duc N. Tran, Richard J. Ingham, Sabine Fenner, Zoe E. Wilson, Claudio Battilocchio and Steven V. Ley, The rapid synthesis of oxazolines and their heterogeneous oxidation to oxazoles under flow conditions Org. Biomol. Mol. Oct 2014.

3. Solvent switch (between reactions)

• Solvent switching is a common step in multistep synthesis. In general, it is done manually and in a batchwise process that
  is slow and tedious.
• Zaiput’s liquid-liquid separator can be inserted between two reactions by simply connecting the streams.

Selected list of publications

Trevor A. Hamlin, Gillian M. L. Lazarus, Christopher B. Kelly, and Nicholas E. Leadbeater, A Continuous-Flow Approach to 3,3,3-Trifluoromethylpropenes: Bringing Together Grignard Addition, Peterson Elimination, Inline Extraction, and Solvent Switching. Org. Process Res. Dev. Aug 2014.

4. Homogeneous catalyst recovery

• A biphasic homogeneous-catalyzed reaction refers to catalysis that takes place at the interface between the two immiscible phases.
• Despite its high selectivity, it is difficult to operate at a large scale because it requires highly active mixing to keep the two liquids in contact.
• Even at small-scale, homogeneous catalysis is rarely used because it poses problems with catalyst recovery via phase separation.
• Zaiput’s separator offers an easy and flexible way to separate the two phases and recover the catalyst.

Selected list of publications

Maryam Peer, Nopphon Weeranoppanant, Andrea Adamo, Yanjie Zhang, and Klavs F. Jensen, Biphasic catalytic hydrogen peroxide oxidation of alcohols in flow: Scale up and extraction Org. Process Res. Dev. Aug 2016.

Javier Guerra, David Cantillo and C Oliver Kappe, Visible-Light Photoredox Catalysis using a Macromolecular Ruthenium Complex: Reactivity and Recovery by Size-Exclusion Nanofiltration in Continuous Flow Catal. Sci. Technol. Feb 2016.

5. Separation of hazardous materials after in-situ generation

• Flow synthesis becomes very useful for handling hazardous intermediates. This is because the compounds can be consumed directly into another flow synthesis without isolation.
• An example (e.g., Lehman, Dec 2016) includes the safe and scalable preparation of diazomethane, which involves the generation of a N-methyl-N-nitrosourea intermediate. At the end of diazomethane synthesis, Zaiput’s SEP is used to separate the desired product and waste.
• Alternatively, Zaiput’s SEP can be used for inline extraction of the hazardous intermediate in order to avoid a potentially unsafe off-line/batch-wise workup (e.g., Cantillo D et al, 2016).

Selected list of publications

Hansjoerg Lehmann, A scalable and safe continuous flow procedure for in-line generation of diazomethane and its precursor MNU. Green Chemistry. Dec 2016.

David Cantillo, Bernd Wolf, Roland Goetz, and C. Oliver Kappe, Continuous Flow Synthesis of a Key 1,4-Benzoxazinone Intermediate via a Nitration/Hydrogenation/Cyclization Sequence Org. Process Res. Dev. Dec 2016.

6. Counter Current Extraction

• Complex extraction requiring multistage operation can be quickly accomplished. The scalability of the technology allows seamless processing from the laboratory to the production scale.
• At the laboratory scale we provide an integrated, ready to use platform.

7. Analytical Process Monitoring

• In-line analytical tools are typically designed for single phases.
• Zaiput devices allows a biphasic stream to be separated making it possible to quickly deploy in-line analytical tools.
• Works with both liquid-liquid and gas-liquid streams.

8. Continuous Product Isolation after Chromatographic Purification

• Aqueous work-up for product isolation is tedious and cumbersome, especially in preparative chromatography.
• In-line single or multistage extraction with a Zaiput device streamlines operation, simplifying solvent recovery.

Membranes

A variety of membranes for your Zaiput separator are available to optimize separation performance and throughput. Membranes are available in both hydrophobic and hydrophilic, they are low cost and easy to replace.

Membrane selection process:

The key parameters for identifying a suitable membrane for separation are the interfacial tension between the two phases and the viscosity of the permeating phase (this has an effect on throughput of the device).

In general, the lower the interfacial tension, the smaller the pore size needs to be. However, smaller pore size reduces the maximum viscosity that can be accommodated by the membrane.

For general applications, we recommend reviewing the information in the Membrane Selection Guide.

If you have any questions, contact us at support@zaiput.com

Scientific research articles using our separator:

Liquid-Liquid Separation
Gas-Liquid Separation

Liquid-Liquid Separation

Koichiro Masuda, Tomhohiro Ichitsuka, Nagatoshi Koumura, Kazuhito Sato, Shu Kobayashi, Flow fine synthesis with heterogeneous catalysts Tetrahedron Feb 2018.

Gemoets, H. P. L. (2018). Enabling and accelerating C-H functionalization through continuous-flow chemistry Eindhoven: Technische Universiteit Eindhoven

Jatuporn Salaklang, Veronique Maes, Matthias Conradi, Rudy Damsb and Tanja Junkers, Direct synthesis of acrylate monomers in heterogeneous continuous flow processes Reaction Chemistry and Engineering Dec 2017.

Joshua Britton and Timothy F Jamison, The assembly and use of continuous flow systems for chemical synthesis Nature Protocols Oct 2017.

Dr. Martina L. Contente, Federica Dall'Oglio, Dr. Lucia Tamborini, Prof. Francesco Molinari, Prof. Francesca Paradisi, Highly Efficient Oxidation of Amines to Aldehydes with Flow-based Biocatalysis ChemCatChem Sep 2017.

Gabriel Glotz, Rene Lebl, Doris Dallinger, C. Oliver Kappe, Integration of Bromine and Cyanogen Bromide Generators for the Telescoped Continuous Synthesis of Cyclic Guanidines Angew. Chem. Int. Ed. Sep 2017.

Amanda C. Wicker, Frank A. Leibfarth and Timothy F. Jamison, Flow-IEG enables programmable thermodynamic properties in sequence-defined unimolecular macromolecules Polym. Chem. Sep 2017.

Valerio De Vitis, Federica Dall'Oglio, Andrea Pinto, Carlo De Micheli, Francesco Molinari, Paola Conti, Diego Romano, Lucia Tamborini, Chemoenzymatic Synthesis in Flow Reactors: A Rapid and Convenient Preparation of Captopril Chemistry Open July 2017.

Michael R Chapman, Maria H. Kwan, Georgina King, Katherine E Jolley, Mariam Hussain, Shahed Hussain, Ibrahim E Salama, Carlos González Nino, Lisa A Thompson, Mary E Bayana, Adam Clayton, Bao N. Nguyen, Nicholas J Turner, Nikil Kapur, and A. John Blacker, A Simple and Versatile Laboratory Scale CSTR for Multiphasic Continuous-Flow Chemistry and Long Residence Times Org. Process Res. Dev. June 2017.

Jinu Joseph John, SimonKuhn, Leen Braeken, and Tom Van Gerven, Temperature controlled interval contact design for ultrasound assisted liquid-liquid extraction Chem. Eng. Res. Des. June 2017.

Hannes P. L. Gemoets, Gabriele Laudadio, Kirsten Verstraete, Prof. Dr. Volker Hessel, and Dr. Timothy Noël, A Modular Flow Design for the meta-Selective C−H Arylation of Anilines Angew. Chem. Int. Ed. May 2017.

Nopphon Weeranoppanant, Andrea Adamo, Galym Saparbaiuly, Eleanor Rose, Christian Fleury, Berthold Schenkel, and Klavs F. Jensen, Design of Multistage Counter-Current Liquid–Liquid Extraction for Small-Scale Applications Ind. Eng. Chem. Res. Apr 2017.

Yi Shen, Nopphon Weeranoppanant, Lisi Xie, Yue Chen, Marcella R. Lusardi, Joseph Imbrogno, Moungi G. Bawendi and Klavs F. Jensen, Multistage extraction platform for highly efficient and fully continuous purification of nanoparticles Nanoscale Mar 2017.

C. Battilocchio, G. Iannucci, S. Wang, E. Godineau, A. Kolleth, A. De Mesmaeker and S. V. Ley Flow synthesis of cyclobutanones via [2 + 2] cycloaddition of keteneiminium salts and ethylene gas React. Chem. Eng. Mar 2017.

Joshua Britton and Colin L. Raston, Multi-step continuous-flow synthesis Chem. Soc. Rev. Jan 2017.

David Cantillo, Bernd Wolf, Roland Goetz, and C. Oliver Kappe, Continuous Flow Synthesis of a Key 1,4-Benzoxazinone Intermediate via a Nitration/Hydrogenation/Cyclization Sequence Org. Process Res. Dev. Dec 2016.

Hansjoerg Lehmann, A scalable and safe continuous flow procedure for in-line generation of diazomethane and its precursor MNU. Green Chemistry. Dec 2016.

Maryam Peer, Nopphon Weeranoppanant, Andrea Adamo, Yanjie Zhang, and Klavs F. Jensen, Biphasic catalytic hydrogen peroxide oxidation of alcohols in flow: Scale up and extraction Org. Process Res. Dev. Aug 2016.

Franz J. Strauss, David Cantillo, Javier Guerrac and C. Oliver Kappe, A laboratory-scale continuous flow chlorine generator for organic synthesis React. Chem. Eng. Aug 2016.

Baptiste Leforestiera and Markus Vögtle, Safe Generation and Direct Use of Chlorine Azide in Flow Chemistry: 1,2-Azidochlorination of Olefins and Access to Triazoles Synlett. June 2016.

Andrea Adamo, Rachel L. Beingessner, Mohsen Behnam, Jie Chen, Timothy F. Jamison, Klavs F. Jensen, Jean-Christophe M. Monbaliu, Allan S. Myerson, Eve M. Revalor, David R. Snead, Torsten Stelzer, Nopphon Weeranoppanant, Shin Yee Wong, Ping Zhang, On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system Science April 2016.

L Osorio-Planes, C Rodríguez-Escrich, MA Pericas, Removing the superfluous: a supported squaramide catalyst with a minimalistic linker applied to the enantioselective flow synthesis of pyranonaphthoquinones Catalysis Science & Technology Mar 2016.

Lorenzo Di Marco, Dr. Morgan Hans, Prof. Lionel Delaude and Dr. Jean-Christophe M. Monbaliu, Continuous-Flow N-Heterocyclic Carbene Generation and Organocatalysis Chem. Eur. J. Feb 2016.

Javier Guerra, David Cantillo and C Oliver Kappe, Visible-Light Photoredox Catalysis using a Macromolecular Ruthenium Complex: Reactivity and Recovery by Size-Exclusion Nanofiltration in Continuous Flow Catal. Sci. Technol. Feb 2016.

Nicolas Lamborelle, Justine F Simon, Andre LUXEN and Jean-Christophe Monbaliu, Continuous-Flow Thermolysis for the Preparation of Vinylglycine Derivatives Org. Biomol. Chem. Nov 2015.

Irina Sagamanova, Carles Rodríguez-Escrich, István Gábor Molnár, Sonia Sayalero, Ryan Gilmour, and Miquel A. Pericàs, Translating the Enantioselective Michael Reaction to a Continuous Flow Paradigm with an Immobilized, Fluorinated Organocatalyst ACS Catal. Sept 2015.

Leibfarth FA, Johnson JA, and Jamison TF, Scalable synthesis of sequence-defined, unimolecular macromolecules by Flow-IEG Proc. Natl. Acad. Sci. Aug 2015.

Chunhui Dai, David R. Snead, Ping Zhang, and Timothy F. Jamison, Continuous-Flow Syn and Purification of Atropine with Sequential In-Line Separations of Structurally Similar Impurities J. Flow Chem. July 2015.

Steffen Glöckner, Duc N. Tran, Richard J. Ingham, Sabine Fenner, Zoe E. Wilson, Claudio Battilocchio and Steven V. Ley, The rapid synthesis of oxazolines and their heterogeneous oxidation to oxazoles under flow conditions Org. Biomol. Mol. Oct 2014.

Trevor A. Hamlin, Gillian M. L. Lazarus, Christopher B. Kelly, and Nicholas E. Leadbeater, A Continuous-Flow Approach to 3,3,3-Trifluoromethylpropenes: Bringing Together Grignard Addition, Peterson Elimination, Inline Extraction, and Solvent Switching. Org. Process Res. Dev. Aug 2014.

Andrea Adamo, Patrick L Heider, Nopphon Weeranoppanant, and Klavs F. Jensen, Membrane-Based, Liquid-Liquid Separator with Integrated Pressure Control. Ind. Eng. Chem. Res. July 2013.

Gas-Liquid Separation

Jisong Zhang, Andrew R. Teixeira, Lars Thilo Kögl, Lu Yang, and Klavs F. Jensen Hydrodynamics of gas–liquid flow in micropacked beds: Pressure drop, liquid holdup, and two-phase model AIChE Journal June 2017.

Everett J. O’Neal, Chang Ho Lee, Julian Brathwaite, and Klavs F. Jensen, Continuous Nanofiltration and Recycle of an Asymmetric Ketone Hydrogenation Catalyst ACS Catal. March 2015.

Reference to separator’s theory:

Kralj, J. G.; Sahoo, H. R.; Jensen, K. F., Integrated continuous microfluidic liquid-liquid extraction. Lab Chip.2007, 7, (2), 256-263.

Reference to examples of use of liquid–liquid separators:

Sahoo, H. R.; Kralj, J. G.; Jensen, K. F., Multistep Continuous-Flow Microchemical Synthesis Involving Multiple Reactions and Separations. Angew. Chem. Int. Ed. 2007, 46, (30), 5704-5708.

Cervera-Padrell, A. E.; Morthensen, S. T.; Lewandowski, D. J.; Skovby, T.; Kiil, S.; Gernaey, K. V., Continuous Hydrolysis and Liquid–Liquid Phase Separation of an Active Pharmaceutical Ingredient Intermediate Using a Miniscale Hydrophobic Membrane Separator. Org. Process Res. Dev. 2012, 16, (5), 888-900.

Product	Image	Total Flow Rate (ml/min)	Wetted Parts	Max Operating Pressure (MPa)	Dead Volume	Dimensions (mm)
SEP-10		0-12	Perfluorinated polymers (ETFE, PFA, FEP, PTFE)	2 (300 psi)	400μl	77 x 71 x 29
SEP-200-SS		20-200	SS 316 L and FFKM, PTFE, PFA	2 (300 psi)	30ml	206 x 196 x 26
SEP-200-HS			Hastelloy C 276 and FFKM, PTFE, PFA
SEP-3000-SS		200-3000	SS 316 L and FFKM, PTFE, PFA	2 (300 psi)		450 x 607 x 150
SEP-3000-HS			Hastelloy C 276 and FFKM, PTFE, PFA