The water, sanitation, and hygiene (WASH) sector is a key public health issue that is at the very core of the survival of people and is the focus of the first two targets of Sustainable Development Goal 6 (SDG 6) of the UN SDG charter. It not only addresses the issues relating to drinking water, sanitation, and hygiene, but also the quality and sustainability of water resources worldwide. About 3.6 billion people (close to half of the world’s population) are living in areas with a potential water scarcity of one month per year and this scarcity is expected to span almost 4.8−5.7 billion people by 20501,2. Climate change, deforestation, farming with excessive use of fertilizers, urbanization, and the rising population are leading up to the problem of limited freshwater availability causing water-stressed conditions (see Fig. 1). This condition has been further exacerbated during the COVID-19 pandemic3. Alarmed by the need of safety concerns, people during this pandemic have been consuming more and more freshwater to clean themselves to maintain better hygiene. Limited availability of clean water has also resulted in the growth of the bottled water industry globally which has inherently led to a dramatic rise in plastic pollution caused by the mismanaged waste of plastic bottles. In this scenario, it becomes imperative to ensure and augment a sustainable supply of clean water.

Fig. 1: Global trend.
figure 1

Reduced water availability and increasing population85,86.

The current demand for about 4600 km3 per year4 of clean water can only be met by recycling but its acceptance varies as per cultural and safety concerns5. Modern technologies are not reliable in ensuring cost-effective removal of contaminants during treatment and the emergence of various contaminants such as pharmaceuticals, personal care products, pesticides, herbicides, heavy metals as well as anti-microbial resistant bacteria has posed additional concerns6. Estradiol (E2) and Ethinyl estradiol (EE2) in surface water sources originating from consumption and excretion of oral contraceptive pills are few examples that cannot be removed efficiently by regular water treatment processes7,8. The presence of E2 and EE2 in water has been linked to depleting fish populations and intersex phenomena in freshwater fish9. Also, traces of pharmaceuticals including antibiotics, anticonvulsants, mood stabilizers, synthetic hormones, and oestrogens have been detected in drinking water supplies10,11. These and other studies establish that current water treatment facilities are facing serious challenges in tackling emerging contaminants.

Membrane technology is attracting increasing interest as part of water treatment technology. Depending on separation properties, membranes currently used in large-scale applications can be categorized into microfiltration (MF), ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO), and all these are typically made from polymeric and ceramic materials (see Fig. 2).

Fig. 2: Basic features of commonly used water treatment membrane.
figure 2

Membranes are typically made from polymeric and ceramic materials. Reproduced with permission from ref. 87, copyright (Elsevier, 2018).

Membranes are used in various fields including wastewater treatment, desalination, and drinking water treatment as well as in various medical applications such as artificial kidneys and artificial lungs12. However, membrane technology, especially RO is limited by high energy consumption and the need for pre-treatments, resulting in high operational expenses13. Also, despite the high selectivity in RO, the rejection of small nonpolar solutes is typically low14,15.

Prevalent membrane manufacturing technologies are based on a ‘top-down’ macroscopic design approach which poses challenges in molecular selectivity of the material, defined as a measure of the permeability of the relevant compound for the membrane due to the non-uniform pore sizes. To improve this aspect, several ‘bottom-up’ strategies based on molecular designs have recently emerged. These are commonly referred to as biomimetic or bioinspired membranes16. This field is rapidly developing and global events such as the 2018 Artificial Water Channels Faraday Discussions meeting17 have seen extensive discussions covering various fields including biology, physics, and chemistry. To gain more insights into this interesting direction of research, authoritative reviews are readily available18,19,20. Additionally, a review written by the authors of this paper providing clarity on the subtle differences between the terms bioinspiration and biomimetics is also now available21. Separate from these reviews, the scope of this paper is to provide a critical bibliometric analysis of the recent trends and developments in terms of leading researchers/groups and collaboration networks actively working in this direction of research.

Bioinspired bottom-up design strategies

Proteins and peptide-based structures can facilitate highly selective transport of water and ions across biological membranes, and this has inspired their use in allied technologies concerning separation principles and translating into new materials (see Fig. 3). Pioneering studies include transport in planar lipid bilayers22 and the effect of ionophores (e.g., valinomycin, gramicidin, and nonactin)23,24. Also, biomimetic energy conversion, using rhodopsin proteins, has been studied since the 1970s25,26,27,28. However, a breakthrough came through the discovery of ‘nature’s water channel’, the aquaporin protein29, which led to the award of the Nobel Prize to Peter Agre in 200330,31. At present, most developments and research on biomimetic membrane technology are based on the use of aquaporin proteins18,32,33. The terms biomimetic membranes and aquaporin membranes have become almost synonymous and the technology is now gradually being commercialized34. Besides water treatment and energy conversion, biomimetic membranes are also being explored for use in biomedicine, biosensor, and carbon capture technologies35,36.

Fig. 3: Examples of biomimetic and bioinspired membrane.
figure 3

Membrane materials as water selective building blocks in form of (left) aquaporin proteins (AQPs), (centre) carbon nanotubes (CNTs), and (right) molecular pore-forming assemblies. Reproduced with permission from ref. 15, copyright (Springer Nature, 2016).

Membrane protein-mediated separation

Aquaporin proteins (or aquaporins) are transmembrane-spanning proteins capable of facilitating water transport across cellular membranes. Certain aquaporin isoforms are highly selective to water and are also referred to as orthodox aquaporins. They have remarkably high-water permeability (up to 109 H2O molecules s−1) reflecting the low (~5 kcal mol−1) energy barrier to transport35. Aquaporin proteins can be seen as building blocks for membrane design35,37,38 and, in principle, one gram of aquaporin protein can filter up to 700 L of water per second. Compared to traditional polymeric membranes this translates into a 10−100 fold higher productivity (m s−1 bar−1)39.

In particular, the E. coli bacterial isoform AqpZ is a comparably stable orthodox aquaporin40,41 and is mostly explored in the development of biomimetic water purification technology. The AqpZ water channel is narrow (~2.3 Å) which allows for single-file transport of water molecules while preventing passage of other solutes42. The selectivity mechanism is based on size exclusion, electrostatic repulsion, and water molecule dipole reorientation43. The fast transport of water through aquaporin channels can be described as a “frictionless” non-Poiseuille flow (slip flow) via a smooth narrow hydrophobic channel44 as opposed to the friction-induced flow through carbon nanotubes (CNTs)45.

Due to the obvious potentials of the aquaporin technology, NASA (USA) is actively investigating the possibility of using biomimetic membranes in space missions46,47. Also, biomimetic membranes are now being used commercially in applications ranging from food and beverage processing, wastewater treatment, and industrial water reuse34. However, full-scale implementation of biomimetic aquaporin membranes is still in its infancy48,49. Recently, the fabrication of two-dimensional crystalline sheets with a high packing density of β-barrel structure channels has been demonstrated which may pave the way for increasing the membrane performance in terms of flux and rejection32.

De novo design of water selective materials

The development of artificial water channels as building blocks for separation membranes was initiated by the seminal molecular dynamics (MD) simulations paper by Hummer et al.50 revealing water transport through sub-nm diameter carbon nanotubes (CNTs). Five years later, the first experimental realization of a CNT-based membrane was published, albeit, not with sub-nm tubes51. Recently, highly permeable (up to 6-fold higher than in the mammalian orthodox AQP1) 0.8 nm diameter CNTs embedded in a lipid membrane matrix were reported where the transport mechanism is based on a single-file water molecule transport52. However, these CNTs are also permeable to cations (K+ and H+). A good discussion on CNT water permeation and ionic selectivity can be found in a paper by Corry53.

In parallel to the focus on CNTs, several research groups have worked with multi-molecular self-assembled structures. For instance, helical hydrophobic pores built from self-assembly of dendritic dipeptides are seen capable of water and proton transport with the rejection of other cations and anions54. Also, the so-called imidazole (I) quartets stabilized by inner dipolar water wires can form chiral self-assembled narrow (<0.3 nm) channel structures with high water permeability55,56. Recently, hybrid polyamide membranes with embedded I-quartets have shown highly selective transport of water with 99.5% screening of NaCl and 91.4% screening of boron, with a water flux of 75 l m−2 h−1 at 65 bar using a feed solution representative of seawater57. Self-assembling water-permeable channels can also be built from stacks of m-oligophenylethynyl (OPE) macrocycles stabilized by H-bonding networks and aromatic backbone stacking between the macrocyclic. These channels have significant water permeability, albeit, five-fold lower than AQP1. They also have finite ionic permeability (<6 pS) for K+ but are impermeable to Na+58. The latest study has demonstrated 2.5 times water permeability than that of AQP1 with foldamer-based artificial water channels59.

Single and bimolecular molecular water (and OH) channels can be formed from Pillar[5]arene derivatives with attached oligohydrazide chains stabilized by intramolecular H-bonds in a bilayer membrane60. These channels have no apparent H+ transport which may be explained via alternative hydrophobic/hydrophilic lumen regions disrupting water wires formation akin to the mechanism found in orthodox aquaporins (e.g., AqpZ and AQP1) although they can sustain transport of cations to some degree. Most recent studies on this have shown improved selectivity61,62,63.

In summary, the research field of artificial water channels is still a fertile area of research and despite numerous advances made during the last two decades; there are major outstanding challenges where stabilization of the molecular complexes and ensuring efficient selectivity properties are among the pertinent challenges. Recent reviews may be referred for further details64,65.

Bibliometric analysis

To the best of our knowledge, there are no bibliometric studies on biomimetic membrane development. This study aims to survey the publications and research trends in biomimetic membranes based on the publicly available scientific literature database using scientometric analysis.

Bibliometric analysis is a strong tool for understanding the growth and prospects of a research area. Bibliometric strategies have been utilized to examine the evolution of research fields, recognize associations between logical development and strategy changes and identify the growing interdisciplinary collaborations66. The bibliometric analysis offers in-depth quantitative and statistical scientific insights into the methods for making decisions about policy matters. For example, the British government initiated a pilot project to make bibliometric analysis a part of the research excellence framework (REF) to decide the university funding strategies67. An early example is the study of Pritchard68 and over the last three decades, bibliometric analyses have benefitted from the advent of the world wide web. Now comprehensive analyses can be performed using various online databases (e.g., Scopus, Google Scholar, and Web of Science). In addition, various software tools such as Citespace, Bibexcel, Publish or Perish, Ucinet, Gephi, Pajek, VOSviewer, and Science of Science (Sci2) can provide illustrative data representation and mapping69.

Scopus, a database containing > 70 million entries from more than 5000 publishers with records dating back to 1788 is the most reliable database for bibliometric investigations especially because each record is labelled with key data such as author’s name, source, referred-to references, catchphrases, publisher, publication date and research area. Furthermore, clients can download the total metadata for entries in a particular research field based on a given inquiry term. Visualization of similarity (VOS) mapping is a topical-based procedure that permits representative and clear conception of progressively research fields70. Also, VOS mapping can outline clusters and collaboration networks with vortices connected by edges66,71. Edges in the graph are based on direct citations. Vortices are assigned based on weight (e.g., number of publications) and score (e.g., citations per journal or country) with equal weightage assigned to these factors. Clusters are defined from bibliographic coupling (i.e., if paper A is cited by papers B, C and D then the respective paper pairs (B and C, B and D, and C and D) form a cluster relationship72.

Here we combine network, cluster, and bibliometric analyses of scientific literature metadata within the area of biomimetic and bioinspired membranes. Specifically, we address eight key questions: (i) How many peer-reviewed publications are available on the topic of biomimetic membranes and artificial water channels for membranes and what is their growth trend? (ii) What are the major scientific and technological areas covered within this research? (iii) Which are the most cited publications? (iv) Which journals are the most active outlets for this type of research? (v) Which scientific institutions are leading this area of research? (vi) Which countries are focused on supporting growth in this area? (vii) Who are the leading authors and who is collaborating with who? and (viii) What sort of developments have shaped the advances in this area?

Data gathering and methods

In this investigation, comprehensive research was carried out by analyzing the literature available from Scopus from January 1962 to March 2021. To identify the patterns, both bibliometric investigations and structural approaches were used. The total metadata of all scientific publications was collated in MS Excel format. The query keywords used for this topical analysis were biomimetic membranes water and artificial water channels. In selecting search keywords, a certain degree of overlap is unavoidable i.e., a particular publication can overlap both in the biomimetic membrane water and artificial water channels keyword search, but the overlap was less than 2%. Also, some of the biomimetic membranes may contain records that do not per se address water purification. Nevertheless, we believe that we capture the overall pattern using the selected keywords.

We used VOSviewer (version 1.6.15) to construct and visualize bibliometric networks in terms of publication networks and collaboration networks quantified as publications citing other publications73. The Bibliometrix (version 3.0) R package was used for bibliometric analysis of metadata from Scopus for calculating the overall collaboration index74.

Trends in scientific studies on biomimetic membranes

A total of 2865 entries were found most relevant after the screening of the entire data based on the papers published in the English language. The record distributions were divided into five classes: original research papers (2133; 75%), review papers (267; 9%), conference papers (170; 6%), book chapters (43; 2%), and others such as book, letter, erratum etc. (252; 8%). 398 of these entries were ‘open access’ (14%) and the remaining were available through subscription. The average number of citations per paper was 11.25 and the average number of authors per paper was 3.68 with (75; 3%) being single-author papers. The overall collaboration index calculated as the total number of authors of multi-authored articles divided by the total number of multi-authored articles was 3.8.

Number of publications on biomimetic membranes since 2000

Figure 4 shows the growth trend in biomimetic membranes over the last two decades. Prior to 2000, very few papers were published in this area. More than 76% of the publications were published after 2009. The entire period (1962−2021) can roughly be divided into two periods: an early explorative phase until 2002 and a developmental phase from 2003 onwards.

Fig. 4: Number of publications per year from January 2000 to March 2021.
figure 4

Publications for biomimetic membranes and artificial water channels.

During the early phase, biomimetic membrane development was mainly focused on ionophore-based ion-selective electrodes, and efforts were directed towards energy harvesting (e.g., artificial photosynthesis). The developmental phase started after the first crystal structure of aquaporin was reported in 200075. This and subsequent structures reported in the following years enabled a detailed molecular understanding of the transport mechanisms which in turn spurred a growing interest in the biomimetic membrane research area.

From 2003 to 2012, the number of scientific publications showed an average annual growth rate of 7%. During this period, more crystal structures of aquaporins became available, and more atomistic simulations appeared elucidating transport mechanisms in narrow conduits. In 2004−2005, the first aquaporin membrane patent application was filed76,77 and in 2007, it was demonstrated how aquaporin proteins can be incorporated into polymeric vesicles39. Still, the challenge was to create large-scale synthetic biomimetic membranes78,79. During this time, forward osmosis (FO) became a commercial technology pioneered by Hydration Technology Innovations (HTI)66,80. Companies such as Oasys Water, Modern Water, Porifera, Trevi Systems, Applied Biomimetic, and Aquaporin A/S also emerged in the FO market48. FO may be considered as a biomimetic process (as biological water transport is partly mediated by aquaporins) but not a biomimetic product as such—still FO as a technology may indeed have spurred interest in the scientific understanding of the molecular basis for selective efficient water transport.

From 2012 onwards, the average annual percentage growth of the number of publications rose to 15% and from 2018, an average of 500 publications are being published annually consolidating the field as an established research area. In parallel, technological developments are ongoing as exemplified by the Danish company Aquaporin A/S which from 2012 began commercializing biomimetic aquaporin FO and RO membranes based on joint research collaboration with Singapore Membrane Technology Centre81. Aquaporin now makes products for various industrial applications82,83,84.

Figure 4 also highlights increasing research in artificial water channels measured by the number of publications. Interest in this area grew from 2000 and peaked around 2010 with a subsequent stabilization in the publication activity. Despite the concomitant commercial realization of aquaporin biomimetic membranes, it is clear that protein-based membrane designs are still facing significant challenges such as ensuring a sufficiently high density of aquaporins in the membrane material to make full use of the water transport potential. These challenges are likely to continue to spur interest in artificial water channel research.

Major disciplines and leading journals for biomimetic membranes research

The major disciplines reporting research on biomimetic membranes are shown in Fig. 5. From a Scopus search, 21 disciplines were identified and the top six disciplines each having more than 500 publications are shown here. Publications on artificial water channels for the same categories selected are also shown. Some of these publications may have happened in several disciplines because of the topic and shared co-authorship.

Fig. 5: Publications within the top six disciplines.
figure 5

Publications on the topic of biomimetic membranes (red colour) and on artificial water channels (blue colour).

For papers classified as biomimetic membranes, most were published within the materials science category with the lowest number of publications in the environmental science category. For papers classified as artificial water channels, this pattern reverses with most papers published within the environmental science category and the lowest number in the materials science category. This may reflect the earlier onset of interest in biomimetic membranes with a strong focus on creating a new membrane material per se. The annual publications reached 25 by 2003 for biomimetic membranes and this occurred five years later for artificial water channel papers. This reflects on a transition from an earlier technology-driven focus to a more challenge-driven focus in applications within environmental science.

This trend is also seen in the choice of journals for the two topics (see Table 1). For the biomimetic membrane publications, a significant body is published in journals with a biological/biophysical scope reflecting the focus on biological proteins within the topic. For artificial channels journals, scopes generally fall within a broader technology focus. The analysis also shows that the top ten journals account for only 15% of publications reflecting a high diversity in the choice of journal. The Scopus CiteScore values (i.e., the average citations received by the publications in that particular journal) fall within a wide range for both topic classes.

Table 1 Top 10 journals for publications.

To analyze the citations, mapping plots were made for the top 25 journals in terms of papers published using VOSviewer (see Fig. 6). Network connections were derived based on the citations of a given paper in a particular journal by papers published in other journals. Before 2010, the choice of main journals for biomimetic membranes was characterized by ‘biology’-type journals with strong network connections. Later, more recently broader scoped journals emerged, and the maturity of the field is evident from papers published in the leading technology journal Journal of Membrane Science over the years. For artificial water channels papers, the analysis revealed a more distributed network but with the Journal of Membrane Science appearing as the main choice.

Fig. 6: Publication network for the top 25 journals.
figure 6

Publications for papers on (a) biomimetic membranes and for (b) artificial water channel publications.

Highly cited reviews and research papers

Tables 2 and 3 show the top 10 highly cited research papers in biomimetic membranes and artificial water channels respectively during the considered period. A list of the top 20 cited review papers for both classes is presented in Table 4. These review papers cover a wide spectrum of ideas and processes related to biomimetic membranes synthesis and applications. Initially, the main focus was on applications in biomedicine, biosensors, and energy conversion. However medical applications, sensor sensitivity, and energy conversion remain a biomimetic challenge in terms of up-scaling and efficiency. A spike occurred after 2010 with focus leaning towards separation applications paving the way for full-scale disruptive technologies and applications. Table 5 provide details of review papers published after 2019. The fact that 14 papers were published in such a short time testified growing interest in separation processes.

Table 2 Top 10 highly cited papers on biomimetic membranes.
Table 3 Top 10 highly cited papers on artificial water channels.
Table 4 Top 20 cited review papers on biomimetic membrane and artificial water channels.
Table 5 Recent review papers from 2019 on biomimetic membrane and artificial water channels.

Leading countries and organizations

The leading countries in biomimetic membranes and artificial water channels research are shown in Fig. 7 respectively. More than 99% of the papers are multi-authored; hence multiple countries may get registered for a given entry.

Fig. 7: Leading countries for publications in terms of the number of publications.
figure 7

Publications in terms of the number of publications (black) and normalized share (blue) a biomimetic membranes and b artificial water channels.

For the biomimetic membrane topic, the USA and China are leading the list in terms of the number of publications. The top 10 countries account for more than 80% of the publications in this area. When analyzing the normalized share of publications calculated as the ratio between the number of publications and population of the country, Singapore and Denmark stand out in terms of research intensity on biomimetic membranes. For Singapore, this reflects a strong governmental focus in terms of research funding (e.g., to Nanyang Technological University and the National University of Singapore) and for Denmark, this reflects the commercial activities driven by the Danish company Aquaporin A/S and engineering activities led primarily at the Technical University of Denmark. For artificial water channels again the USA and China are leading in terms of the number of publications. The top 10 countries account for more than 74% of publications in this area. In terms of the normalized share of publications, Australia is leading followed by Canada, and several European countries including France, the United Kingdom, and Germany.

The author’s collaboration networks indicate the development taking place in a multi-institutional and multinational manner taking advantage of infrastructures available in author institutions and countries, see Fig. 8. For biomimetic membranes three clusters appear, a leading cluster (blue) dominated by the USA and China with contributions from Australia, Japan, and South Korea; a cluster (red) dominated by Germany, France, and the UK with contributions; and a cluster (green) with Singapore, Denmark, Sweden, India, and Slovenia. For artificial water channels, five clusters appear where the clusters are more equal in strength as compared to the area of the biomimetic membrane: a cluster with the USA and Brazil; a cluster (green) consisting of China, France, Japan, and Romania; a cluster (red) including Singapore and the UK. Russia, India, Canada, Iran, and Turkey; a cluster (blue) including Germany and Netherlands, Australia and Saudi Arabia and a cluster (yellow) with South Korea, Italy, and Sweden.

Fig. 8: Collaboration network between top 20 productive countries.
figure 8

Collaboration network in terms of the number of biomimetic membrane publications (a), and the number of artificial water channel publications (b).

Table 6 shows the top 10 leading research institutions in terms of the number of publications where resources have been dedicated to research biomimetic membranes and artificial water channels. Three leading organizations are from China which indicates a strong research focus in these two areas. Although the USA is leading in terms of the number of biomimetic membrane publications (Fig. 7), only one institution: University of California, San Diego is featured in Table 6 (entry 4 in Table 6) reflecting that research in the area is distributed among many institutions. Similarly, for artificial water channels, only Pennsylvania State University from the USA is featured in Table 6.

Table 6 Top 10 institution affiliations for publications.

Leading authors and their networks

The leading authors who have contributed to biomimetic membranes and artificial water channels are listed in Tables 7 and 8 respectively. For biomimetic membranes, these author’s main research topics as judged from their publications fall primarily within biochemistry and biophysics and to a lesser extent within environmental science. This reflects the findings in Fig. 5b, where materials science, biochemistry, and chemistry are prominent categories. The underlying reason behind this pattern is likely linked to the long history of research in biological membranes focusing on physiological and physical−chemical properties. The discovery of aquaporins originated from this research and led to the subsequent translation into technology development. For artificial water channels, the focus areas are dominated by biophysics, materials science, and research in separation technology and water treatment consistent with the findings in Fig. 5b.

Table 7 Top 10 leading authors of biomimetic membranes publications.
Table 8 Top 10 leading authors of artificial water channels publications.

Conclusions and outlook

The last two decades have witnessed tumultuous interest in developing new membrane materials for use in water separation and purification technologies. Previous developments of water treatment membranes have been dominated by a top-down approach exemplified by the thin-film composite membrane design where separation properties originate from meso- and macro-scale bulk material properties. With an improved understanding of how water and solutes interact at the nanoscale, membranes can now be designed with a bottom-up strategy by employing naturally occurring or synthesized sub-nanometre porous structures. The bibliometric analysis presented in this paper shows that the biomimetic bottom-up approach has accelerated since 2003, with the average annual number of publications on this topic now exceeding 200. The bottom-up approach based on synthetic nano-scale materials took off around 2007 with a lower volume in terms of the number of publications. Concerning journals, the biomimetic membrane area is dominated by ‘biology scope’ journals whereas, for artificial water channels, the journal list is broader. Research within the biomimetic membrane and artificial water channels can be characterized by strong international collaborations. In terms of the absolute number of publications, the USA and China are currently leading. Normalized by the country population size, Singapore and Denmark have significant activities in the biomimetic membrane area and Australia, Canada, France, and the UK have significant activities in the artificial water channel area. Recent reviews suggest that future research and development on biomimetic membranes based on the use of proteins will focus on our ability to synthesize and stabilize proteins (or peptides) in sufficient quantities to achieve high membrane density while achieving scalability. For the artificial water channels, optimizing selectivity, self-assembly properties, and stability will constitute the main challenges to be addressed.