Pathways and Challenges for Biomimetic Desalination Membranes with Sub-Nanometer Channels – The Future of Desalination?

The authors acknowledge the support received from the National Science Foundation through the Engineering Research Center for Nanotechnology-Enabled Water Treatment (EEC1449500) and via Grant CBET 1437630. The authors also acknowledge funding from the National Science Foundation Graduate Research Fellowship Program under grant no. DGE-1752134, awarded to C.J.P. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.


Transmembrane protein channels, including ion channels and aquaporins that are responsible for fast and selective transport of water, have inspired membrane scientists to exploit and mimic their performance in membrane technologies. These biomimetic membranes comprise discrete nanochannels aligned within amphiphilic matrices on a robust support. While biological components have been used directly, extensive work has also been conducted to produce stable synthetic mimics of protein channels and lipid bilayers.

However, the experimental performance of biomimetic membranes remains far below that of biological membranes. In this review, we critically assess the status and potential of biomimetic desalination membranes. We first review channel chemistries and their transport behavior, identifying key characteristics to optimize water permeability and salt rejection.

We compare various channel types within an industrial context, considering transport performance, processability, and stability. Through a re-examination of previous vesicular stopped-flow studies, we demonstrate that incorrect permeability equations result in an overestimation of the water permeability of nanochannels. We find in particular that the most optimized aquaporin-bearing bilayer had a pure water permeability of 2.1 L m–2 h–1 bar–1, which is comparable to that of current state-of-the-art polymeric desalination membranes.

Through a quantitative assessment of biomimetic membrane formats, we analytically show that formats incorporating intact vesicles offer minimal benefit, whereas planar biomimetic selective layers could allow for dramatically improved salt rejections. We then show that the persistence of nanoscale defects explains observed subpar performance. We conclude with a discussion on optimal strategies for minimizing these defects, which could enable breakthrough performance.

Biomimetic Desalination Membranes

As stressors like population growth, industrialization, and climate change threaten to deplete and contaminate our freshwater resources, larger bodies of saline water could provide a vast supply of water for drinking, agricultural, and industrial use.(1) However, desalination of these waters requires more energy and financial resources than traditional freshwater purification methods.(2) Currently, the state-of-the-art technology for desalination is reverse osmosis (RO) using thin-film-composite (TFC) polyamide membranes.(3,4) Fully aromatic TFC-RO membranes are readily produced at industrial scale through interfacial polymerization, whereby a rapid reaction occurs at the interface of immiscible organic and aqueous phases to form a highly cross-linked polyamide selective layer on a porous support(5) (Figure 1). With the advent of the TFC-RO membrane and energy recovery devices, seawater desalination energy requirements for the RO stage have drastically reduced from ∼15 kWh m–3 using the original cellulose acetate membranes of the 1970s down to only ∼2 kWh m–3, only ∼25% above the practical minimum energy.(2)

Figure 1. Transition in desalination research from focusing on dense polymers that reject salt by a solution-diffusion mechanism to considering sub-nanometer channels capable of molecularly sieving ions. In the solution-diffusion panel (left), common reactants for TFC-RO membranes are represented, which rapidly react at an organic–aqueous interface during interfacial polymerization to form a cross-linked, fully aromatic polyamide selective layer with characteristic ridge-valley morphology. Salt rejection determined by a solution-diffusion mechanism results from the higher partitioning and/or diffusion rates of water over ions. In the ion sieving panel (right), common molecular sieves that have been considered for desalination are shown, with ideal water pathways illustrated. In pores similar in size to water, single-file water transport is induced. Nanotubes and nanochannels can be synthetic (e.g., carbon nanotubes) or biological (e.g., aquaporins). To produce nanoporous sheets, sub-nanometer pores where only a few atoms are vacant have been etched in single-layer graphene using chemical oxidation, electron beam irradiation, doping, and ion bombardment.(12) For 2D laminates, the water pathway is through interlayer spaces between sheets. Studies so far have primarily considered graphene oxide nanosheets for 2D laminates.(13,14) The molecular sieving mechanism for ion rejection is by size exclusion, where highly uniform pores exclude larger solutes and ideally transport only molecules similar in size to water.

Reduced Operational Costs, Improved Reliability and Efficiency and Enhanced Product Water Quality

Despite the substantial reduction in energy consumption and overall cost, seawater RO still has room for improvement. While current water permeabilities enable near-optimal performance, increased water-solute selectivity would allow for reduced operational costs, improved reliability and efficiency, and enhanced product water quality.(4) For example, TFC-RO membranes inadequately retain chloride and some small neutral solutes, such as boron in seawater desalination and trace organic contaminants in wastewater reuse, necessitating extra purification steps which increase the cost of desalination.(4)Transport through the polyamide layer is well described by the solution-diffusion model, in which permeants (i.e., water and solutes) partition into the dense polyamide layer and diffuse through it (Figure 1).(6) 

The resultant permselectivity of the membrane is attributed to differences in abilities and rates of species to dissolve into and diffuse through the polyamide membrane material.(7) Although intrinsic water permeability can far exceed salt permeability during solution diffusion, as it does for polyamide, historical data suggest that it will be difficult to significantly advance performance with polymeric systems. Commercial desalination and water purification membranes typically exhibit a permeability–selectivity trade-off, similar to the Robeson plot for polymeric gas separations.(8−11) 

Furthermore, despite many decades of extensive research, no polymeric material has yet surpassed the desalination performance (i.e., water permeability, water-salt selectivity, and cost-effectiveness) of fully aromatic polyamide.

To overcome the limitations of the solution-diffusion-based polyamide membranes, research focus has shifted toward the development of desalination membranes that remove solutes via molecular sieving. In this mechanism of ion rejection, highly uniform, rigid pores that are smaller than the diameter of hydrated salt ions transport water and nearly completely reject ions by size exclusion (Figure 1). Recent formats of molecular sieves considered for desalination include nanotubes and nanochannels, two-dimensional (2D) laminates, and nanoporous sheets (Figure 1).(14) 

However, these top-down efforts have failed so far to achieve adequate salt rejection due to the persistence of defects coupled with the daunting challenges of tuning interlayer spacing or pore size.(12,13,15) 

Biomimetic membranes, or composites comprising an amphiphilic matrix with discrete, aligned nanochannels on a robust support, may provide a platform for industrial-scale molecular sieves that overcome the limitations of solution-diffusion-based polyamide membranes.

After over 3.5 billion years of evolution,(16,17) the cell membranes of modern organisms can perform an array of highly complicated functions, which rely on a system of complex transmembrane proteins aligned within the amphiphilic lipid bilayer. In this system, water and only select ions pass through channel pores and pumps, depending on the energy and nutrient needs of the cell.(18,19) In pioneering work, Preston et al. determined that an integral membrane protein formed a biological channel that selectively transports water in and out of many types of cells. This protein was the CHannel-forming Integral Protein of 28 kDa (CHIP28),(20,21) later called the aquaporin. For these discoveries, Peter Agre and Roderick MacKinnon shared the 2003 Nobel Prize in Chemistry. Through additional biophysical studies, ion channels also showed impressive selectivity, inspiring the design of synthetic ion channels.(22−25) 

Eventually, researchers realized the potential implications of these channels for industrial-scale water purification, especially aquaporin in the use of desalination, and attempted to produce biomimetic membranes, or materials that mimic the structure and performance of biological membranes.(26−35) 

While much of the work has focused on water-solute separations, the biomimetic membrane format also presents opportunities to develop membranes with tunable selectivity based on a chosen channel type.However, translating biological mechanisms into industrial-scale technology necessitates scale-up by orders of magnitude—from the microscopic size of a cell membrane to tens of square meters.(36) For industrial relevance, the synthesis of a biomimetic membrane would need to be cost-effective and simple. Simultaneously, such a membrane would need to be mechanically stable under RO pressures exceeding 70 bar and chemically stable during repeated membrane cleaning and usage.(37) Notably, even at the lab scale, sufficiently high-salt rejection has not yet been achieved for biomimetic desalination membranes after over a decade of research.(37,38) 

Therefore, channels, selective layer formats, synthesis strategies, and support layer types must be carefully considered to attain the capabilities of this technology. While certain aspects of biomimetic desalination membranes have been reviewed recently,(37−42) a critical analysis of their performance and their potential application in water-treatment processes remains necessary.In this critical review, we examine efforts toward biomimetic desalination membranes for water purification in order to identify the best strategies to realize their full potential for both desalination and solute–solute selectivity. We first examine molecular transport, contrasting solution-diffusion with molecular sieving and assessing transport through the mixed matrix of biomimetic selective layers. We next identify the key characteristics of the aquaporin that explain its ultraselectivity and fast water transport, comparing this biological channel to several synthetic channels and placing each in industrial context. Using corrected analysis of reported permeability measurements, we then show that the water permeabilities of many channels have been overestimated. Subsequently, we predict best-case-scenario outcomes for common biomimetic formats, including membranes with intact vesicles and membranes with planar biomimetic layers. For the more promising planar format, the biggest challenge is the presence of nanoscale defects. Through mathematical models, we estimate the defect density for several reported biomimetic membranes. We then discuss synthesis pathways that could limit both the presence of defects and the effect of defects on transport performance.

We conclude with a discussion on the practicality of biomimetic desalination membranes and how to best exploit the strengths of discrete nanochannels as molecular sieves in other applications beyond desalination.

Figure 2. Channel types for biomimetic membranes, including biological as well as bioinspired and bioderived. (a) Single channel water permeability versus pore interior diameter. The pore interior diameter here is defined as the inner diameter of the most constricted region. For PAH[4], the pore diameter shown refers to the average width of dynamic voids that formed in channel clusters.

Channel permeabilities from stopped-flow data and simulations were adjusted to 25 °C and corrected for any previous errors in permeability calculation (see SI, Section S1 for details). (b) (left) Overhead view of AqpZ tetramer and (right) side view of single AqpZ channel with characteristic hourglass shape. (c) GramA dimer as it exists in biological and vesicular environments. In organic solvents, the monomers can intertwine to form a parallel or antiparallel helix. AqpZ and GramA diagrams were drawn using PyMOL(69) with protein sequences from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB-PDB,, PDB-ID codes 1RC2(70) and 1NRM.(71) (d) Dependence of water diffusivity through pores on the number of interior hydrogen-bond points.

Data extracted from ref (56). (e) Cyclic peptide nanotubes. (left) Hydrogen-bonding pattern of pore-forming, stacked cyclic peptides. A polyglycine structure is shown for simplicity; side residues would typically be present. (right) Modified cyclic peptide with interior peptide-mimicking functional groups. The analogous unmodified cyclic peptide is radially symmetrical with a fourth primary amine side chain (cyclo[(d-Ala-Lys)4]).(72) (f) Single-walled carbon nanotube porins (wide and narrow) with armchair pattern. Number of carbons approximate those of wCNTP and nCNTP. (g) (left) PAP[5] and (right) PAH[4] nanochannels with peptide appendages that form interarm hydrogen bonds. (h) (left) Aquafoldamer subunits with “sticky” ends. Differences in end groups that comprise Aqf1 and Aqf2 subunits are illustrated. (right) Weak hydrogen-bonding pattern of pore-forming, stacked aquafoldamers. Six subunits are needed to cross a DOPC membrane. (i) Pure water permeability versus total channel areal coverage in a DOPC bilayer. Single channel permeabilities from (a) were divided by channel cross-sectional area and converted into channel water permeability (A) coefficients using eq 3. Overall biomimetic layer A coefficients were calculated for various densities of channels within a DOPC bilayer using eq 7. DOPC bilayer hydraulic permeability was taken as 0.15 L m–2 h–1 bar–1.(73) The shaded region indicates the water permeability of current commercial TFC-RO membranes, an adequate range for desalination performance. Permeabilities are listed in Table S1.

** Read the Complete Paper and Conclusions from AZ Nano by Following the Link Below


  • Cassandra J. Porter: Department of Chemical and Environmental Engineering, Yale University, New Haven, Connecticut 
  • Jay R. Werber: Department of Chemical and Environmental Engineering, Yale University, New Haven, Connecticut and Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 
  • Mingjiang Zhong: Department of Chemical and Environmental Engineering, Yale University, New Haven, Connecticut 
  • Corey J. Wilson: School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
  • Menachem Elimelech: Department of Chemical and Environmental Engineering, Yale University, New Haven, Connecticut 

One comment on “Pathways and Challenges for Biomimetic Desalination Membranes with Sub-Nanometer Channels – The Future of Desalination?

  1. […] Pathways and Challenges for Biomimetic Desalination Membranes with Sub-Nanometer Channels – The Future of Desalination? – Genesis Nanotechnology — Read on… […]


Please leave us your comments and any suggestions. Thanks! Administrator at GNT

Please log in using one of these methods to post your comment: Logo

You are commenting using your account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.