(4kn) Membranes with Functional Intrinsic Cavity for Isomer Separations

1.0 Background

Climate change is identified by the IPCC Synthesis Report 2023 as a key global challenge. A major contributor to carbon emissions are separation processes in oil and gas, chemical, and pharmaceutical industries, which account for 10–15% of energy consumption in the United States. This is primarily attributed to liquid-to-gas phase changes in classical unit operations such as evaporation and distillation. Membrane-based techniques can separate molecules based on their molecular size and/or chemical affinity, without any phase change, which could potentially cut down the carbon emissions by 90%. This is illustrated by the success of membrane reverse osmosis that uses 50% less energy than conventional multi-effect evaporation for desalination.

By contrast, there is little development of using membrane technique in isomer separations, although their market size is 40 times larger compared to reverse osmosis. The identical formula but distinct atom arrangement in isomer molecules leads to the similarities in their sizes, boiling points, and chemical affinities, which makes the separation highly challenging. The current state of the art relies on crystallization, chromatography, distillation, and adsorption. These processes are energy intensive, expensive, and some are limited to batch scale.

2.0 Vision

The key challenge of membrane-based isomer separation is the accurate manipulation over the size and functionality of the membrane pores, so that they can differentiate isomer molecules of close dimensions and/or affinities. Until now this goal has not yet been achieved. Macrocycles and porous organic cages are small crystalline materials with intrinsic cavities which can be tailored at angstrom-level precision. They have demonstrated encouraging performance for separating isomers via adsorption, but not in the form of membranes. This is due to the difficulty of connecting these porous crystals into robust membranes without cracks or defects. The vision of my research is to create a new family of functional intrinsic cavities (FICs) incorporating a variety of moieties, which can be crosslinked into continuous, large scale, and defect-free membranes for isomer separations.

2.1 World-leading research

Isomer separations is the grand challenge for the membrane community. Until now, there is a lack of platform strategy that can precisely tune the pore structures and functionalities to separate a wide range of isomers. The key advancement of FIC membranes is the tailorable pore size to angstrom precision by varying the cavity identities. I believe my research would establish the impact of FIC membranes through publications in world-leading multidisciplinary journals, which would make significant contributions to porous materials and membrane research communities.

2.2 Societal and economic impact

Isomer separations are strategically important to society and economy. A slight difference in isomer structure results in completely distinct chemical products. For example, xylenes usually appear in the mixture of isomers including para-xylene (p-xylene), ortho-xylene (o-xylene), and meta-xylene (m-xylene). Among them, p-xylene is the key constituent for manufacturing polyethylene terephthalate, with a global market of 66.9 billion USD in 2022. If my research plan is successful, FIC membranes can enhance selectivity of xylene isomers while facilitating fast liquid transport, enabling a sustainable manufacturing of p-xylene with lower energy consumption and cost.

2.3 National importance

Chiral drugs are a special class of isomers that are mirror-image twins sharing one chiral center. Whilst one chiral drug is effective in treating diseases, the other can be extremely toxic. Therefore, chiral separation is significant for the development of pharmaceuticals, and reaches a market size of 53.9 billion USD in 2022. To this end, the Nobel Prize in Chemistry 2001 has been awarded to the production of single chiral drugs through chirally catalyzed reactions. Since then, there has been a rising prevalence of chiral separations in pharma pipelines through projects supported by National Science Foundation, across chemistry (CHE-0809776, CHE-2203506, CHE-1609778), molecular modelling (TI-1621012), and chemical engineering (CBET- 1546589). I believe that FIC membranes enriched with chiral groups could lead to continuous manufacture of chiral drugs, which can benefit a large proportion of the population.

3.0 Aims and objectives

The objectives of my research are:

1. To synthesize new FICs from macrocycles and cages with crosslinkable “arms”;
2. To fabricate membranes from FICs at both batch scale and pilot scale via a roll-to-roll process;
3. To explore performance of FIC membranes in a variety of isomer separations such as differentiation of xylenes and separation of chiral drugs.

3.1 Synthesis of new FICs

My recent work published in Nature has reported FIC membranes comprising macrocycles with 0.61 nm cavity size, which are attractive for differentiating p-xylene (0.58 nm) over o- and m-xylenes (0.68 nm) by molecular sieving. However, these membranes are too hydrophilic to facilitate hydrophobic xylene molecules. This research plan aims to synthesize macrocycle-based new FIC with hydrophobic alkane “arms”. I hypothesize that the affinity and hence the transport of hydrophobic liquids would be enhanced through these hydrophobic “arms”, so that the xylene molecules can be directed into the macrocycle cavities where the separation is enabled.

In addition, our work in Nature Materials has reported the fabrication of continuous cage membranes, but they are still packed via weak Van der Waals forces between cage crystals and cannot withstand the shear stress of tangential flow in real operating conditions. My future research aims to synthesize cage-based FIC with alkene “arms”. I hypothesize that the alkene groups can be crosslinked under ultraviolet (UV) light to enhance the mechanical stability of the resulting FIC membranes, enabling continuous operation under high pressures and tangential flows. Moreover, the chiral amines in FIC can provide selective separation of chiral drugs.

3.2 Fabrication of FIC membranes

At laboratory scale, macrocycle-based FIC membranes will be fabricated through controlled interfacial polymerization method that we have developed in Science since 2015, and cage-based FIC membranes will be fabricated via self-assembly followed by UV crosslinking.

To upscale the manufacturing, a roll-to-roll process could be developed through a collaboration with my current industry host Exactmer Limited, which recently opened a £2M Advanced Membrane Manufacturing Suite. Free-standing nanofilms will be created at an aqueous-organic interface with the individual monomers in each solution, and then be deposited on the porous support to form composite FIC membranes. A vacuum roller and heating chambers will be used in-line to remove excess liquids. UV will be applied to crosslink cage-based FIC membranes. The aim is to produce spiral wound membrane modules at pilot scale (30cm width, 100cm length) for the test in isomer separations.

3.3 Evaluation of membrane performance

The fabricated FIC membranes will be tested for isomer separation performance with synthetic mixtures of xylenes or chiral drugs. Permeance and rejections/selectivities will be collected to analyze the membrane performance. These results will loop back to guide the chemistry design and experimental conditions for optimizing the performance. I am also keen to test the FIC membranes in real-world applications. If the concept is successfully proved in laboratory, I will seek industrial collaborations to challenge these membranes in the real feedstock under manufacturing conditions.

Teaching Interest

1.0 Undergraduate teaching

As Head of Membrane Research at a life sciences company Exactmer Limited, I was invited to be a Visiting Lecturer for the 2^nd Year Chemical Engineering Course at Queen Mary University of London. During the academic year 2022-2023, I taught 78 undergraduate students and contributed to:

• Design the Separation Processes module scheme;
• Prepare teaching materials, problem set sheets, and exam questions;
• Lecture membrane separation processes on ultrafiltration, nanofiltration, and reverse osmosis;
• Teach the problem set tutorial and provide frequent office hours to answer students’ questions;
• Provide industrial perspective on the real-world separation challenges using experience with my business host Exactmer;
• Arrange the lab tour for students to enhance their understanding on membrane techniques;

2.0 Postgraduate supervision

I started the supervision of master students from 2017 and Ph.D students from 2018 when I was a Research Associate at Imperial College. After beginning my current role as a business-based Future Leaders Fellow in 2022, I am head of a team, leading postdoctoral researchers, which carries out membrane research in the company. At the same time, I co-supervise Ph.D students and postdoctoral researchers as an industrial advisor through the collaboration with universities in EPSRC Programme grant (EP/V047078/1). Until now, I have supervised 4 master students, 6 Ph.D students, and 6 postdoctoral researchers in total. Through this journey, I have contributed to:

• Conceive research plans and ideas on the target scientific challenges, the chemistry design, and the new methodology;
• Lead n the recruitment process, ensuring that EDI has been followed during the entire process;
• Write and secure £1.5M grant funding through Future Leaders Fellowships (Ref: MR/W009382/1);
• Draft and file patent globally (PCT/GB2021/050781, 2021);
• Coordinate the collaborations and report to industrial funders (ExxonMobil, Evonik);

3.0 Potential Teaching Courses

I have experience in teaching membrane separation processes, and would be enthusiastic to teach Separation Processes.

With my research experience in interfacial polymerization and membrane separation, I would like to contribute to teach Laboratory courses.

Further, as my current role is a research leader at a life sciences industry, I am willing to design a new course and share my experience on the knowledge transfer from academia to industry.