Abstract
For successful deep space exploration, a vast amount of chemistry-related challenges has to be overcome. In the last two decades, flow chemistry has matured enough to take the lead in performing chemical research in space. This perspective article summarizes the state of the art of space chemistry, analyzes the suitability of flow chemistry in extraterrestrial environment, and discusses some of the challenges and opportunities in space chemistry ranging from establishing an end-to-end microfactory to asteroid mining.
1. Introduction
There is an increasing public and private interest in deep-space explorations. However, there are many challenges associated with long-duration space flights mostly due to the limited resources available during these journeys. For example, the limited storage space means a serious restriction and the possibility of refilling stocks through space launches is expensive and time-consuming. Astronauts suffer from different health problems and illnesses: osteopenia which has been observed during the Project Gemini, sleep disturbances [1], or space motion sickness, just to mention a few [2]. In addition, the short shelf life (typically less than 1 year) of pharmaceuticals in space adds another layer of complexity to the problems [3]. The treatment of these conditions often requires chemical and medical solutions.
Chemistry has had an undeniable role making us capable to reach space. The vast amount of research and development, from the plastic pieces of satellites to high energy rocket propellants, all involved intensive chemical research. However, to date, chemistry has had more of a supporting role than being the discipline of investigation [4]. Nevertheless, some chemical research has been done in space and also in microgravity environment (e.g., synthesis of polymers) [5]. One might rightfully ponder: Why have we done such a limited amount of chemical research in space? Do we need to do chemical research in space at all?
The way how chemical reactions are performed resembles the conditions two hundred years ago, i.e., chemists still use round bottom flasks and stirrers most of the time [6]. Adaptation of the conventional experimental methodology in chemistry to space is far from straightforward. The microgravity (μg) environment affects convection and fluid dynamics, which results in an environment where conventional batch chemistry does not seem evident. In this perspective, we show why flow chemistry shall be the method of choice for space chemistry research.
The content of this perspective can be summarized in the following points: first, we will give a brief overview on the historical and present approaches of space chemistry. In this section, we separately discuss scientific, technological, and industrial results. Next, we will detail why we believe that flow chemistry will have a vital role in the future of space chemistry. Finally, we will describe some intriguing challenges and opportunities. We consider challenges as cases where the problem lies in a problem space with open boundaries. For several millennia, e.g., walking on the Moon was a challenge. In contrast, opportunities are considered as finding solutions in a closed problem space (with rapid development of natural sciences and engineering, walking on the Moon became an opportunity in the early 1960s). While opportunities are constrained by technical problems, challenges are focusing on concepts in a much wider aspect.
2. Previous Achievements and Present Approaches
2.1. Scientific Aspects
Astrochemistry studies the abundance and reaction of chemical elements and molecules in the universe [7]. These properties are typically observed and analyzed in Earth-based laboratories, while scientists also operate Earth- and Sun-orbit satellites in space [8]. Spectroscopic techniques are utilized for analysis serving with unique information on the composition of gaseous envelopes, planetesimals, protoplanets, prestellar, and protostellar cores and the atmosphere of the celestial bodies [7]. Such studies have shown that the occurrence of amino acids, nucleotides, and other organic materials are the results of chemical reactions in the giant clouds around protostars [9]. The large variety of organic molecules translates into a wide variety of reactive events, which are currently investigated by astrochemists. One particular research direction is the photochemical formation of organic molecules in young solar systems [10], where the high ultraviolet (UV) radiation of the protostar and the wide temperature range (10–106 K) affects the surrounding material resulting in the formation of organic molecules in large variety.
Since the reconstruction of astrophysical environment is a challenge on Earth, theoretical methods are particularly important to model astrochemical processes. Different levels of theory are available from high-order quantum chemistry calculations (QM) through DFT-based ab initio molecular dynamics to macroscopic rate equation models which allow for the investigation of reactions in gas phase, on dust-surfaces, and ice-trapped processes [11, 12]. On the experimental side, techniques are available to create an environment on Earth consisting of ultrahigh vacuum, cryogenic temperatures, and strong UV source to investigate the mechanism and kinetics of photochemical processes in interstellar ice [13].
Astrochemistry and the accompanying astrobiology and -physics are rapidly growing, fast-emerging fields. However, we feel the need to emphasize the difference between astrochemistry and space chemistry. By definition, astrochemistry is a passive study which relies on measurements and observation of chemistry in the universe. In contrast, we propose using the term “space chemistry” for the chemical operations/research where mankind performs chemistry in space.
In order to promote development of space chemistry in the above sense, two symposia were organized under the umbrella of the American Chemical Society's Spring and Fall meetings in 2017 [14]. In these meetings, the recent results and new possibilities in polymerization and nanoscale materials synthesis under microgravity conditions and the synthesis of energetic materials, in particular that of fuels and oxidizers used in space rocket propellants and satellite navigation systems, were covered. The opportunities offered by the drug on demand platforms for extended space travel were discussed together with the latest results on selective organic synthesis of complex molecules such as natural products and active pharmaceutical ingredients. The presentations of the Space Chemistry Symposia also included the emerging field of polyimide and polyamide aerogels, high energy photochemical reactions, photoelectrochemical transformation of CO2 to useful products (e.g., oxygen and hydrocarbons), and the electrochemistry of reagentless oxidations and reductions in space. Furthermore, the in-situ Martian chemical and mineralogical analysis with chemical instruments and the elemental concentrations of nearby planetary bodies and utilization of these elements or compounds were presented. Space chemistry has been already featured in Nature Reviews Chemistry [4].
2.2. Technological Aspects
Chemistry has been deeply involved in the design and synthesis of new materials for a wide range of purposes in space technology, such as the production of composite matrix resins, high-temperature adhesives, or more specialized cryogenic fuel tanks and high energy rocket propellants [15, 16].
Microgravity affects the physicochemical processes that are governed by mass transfer. The fluid dynamics in space are strikingly different in contrast to those observed in terrestrial conditions. To this end, fluid dynamics studies have been carried out on the International Space Station (ISS), investigating, for example, the capillary effect. Dreyer and coworkers studied the possibility of exploiting capillary effects instead of using pumps [17, 18].
The effects of microgravity conditions can be used to our advantage. Protein crystallizations have been investigated in detail in microgravity environment [19]. Although the overall benefits of doing crystallizations in space are often debated, numerous examples show improvement in comparison to results acquired under terrestrial conditions. Littke and John have found that the single crystals obtained from the crystallization of β-galactosidase and lysozyme enzymes are significantly larger than those on Earth [20]. In a similar vein, Tanaka and coworkers reported improvement in quality of hematopoietic prostaglandin D synthase crystals obtained in microgravity environment [21]. This research contributed to the development of a drug candidate for the treatment of Duchenne muscular dystrophy [22].
Polymer research in space is a fairly well studied field, it is an area where researchers deliberately seek for microgravity conditions for three major reasons: microgravity greatly reduces buoyancy-driven fluid flow, pressure head effects are virtually eliminated, and the sedimentation is virtually eliminated [5].
Conventional, Earth-based analytical instruments have to face various requirements when applied in space: energy consumption, size and weight, temperature, and radiation resistance are pivotal parameters. A variety of analytical instruments are used on the ISS to ensure the livable environment for the astronauts. Spectrometers for unmanned aircraft vehicles have also been developed [23].
Let us mention here the ISSpresso (Figure 1) which was developed to brew quality espresso coffee on the ISS [24]. If we accept (as we frequently do during the daily work in the laboratory) that extractions are chemical processes, then we can consider the ISSpresso as an archetypal continuous-flow chemistry instrument [25]. In this, the water is fed into the machine from a plastic pouch without headspace. Inside the machine, the aspirated and pressurized water passes through a heater before reaching the coffee capsule. At the end of the process, the freshly brewed espresso is collected into another plastic pouch.
The ISSpresso brewer and brew chamber. The image is courtesy of Argotec and Lavazza
Citation: Journal of Flow Chemistry JFChem 7, 3-4; 10.1556/1846.2017.00033
2.3. Industrial Aspects
Very recently, SpacePharma [26], a private company specialized in providing microgravity services, launched a nanosatellite in cooperation with India's national space agency, ISRO [27]. The nanosatellite is equipped with a microfluidic reactor and some analytical facility. The laboratory is remotely controlled from the ground [28]. The laboratory is able to carry out four different experiments which are automated and repeatable: biochemical experiment, organic crystallization, self-assembly of nano-blocks, and fluid physics. According to the University of Glasgow's press release, the Cronin group is part of the same project line [29]. They describe a one-pot three step assembly and aim to produce a drug candidate in crystalline form. The microfluidic device is equipped with an onboard microscope.
3. What Makes Flow Chemistry Suitable for Space?
We strongly believe that in order to perform fundamental chemistry research in space, the design and creation of a standardized, automated, and flexible space laboratory are vital. Such laboratory would perform a wide range of chemical operations in a safe isolated and reproducible manner without the requirement of human intervention, possibly even in outer space, under extreme conditions (strong UV radiation, low temperature, vacuum, radiation). Once the operation of this space-laboratory is safe and sound, it will allow us to explore the advantages of the extreme conditions of space for chemical reactions. As a result, production lines might be developed and the synthesis of molecules, otherwise impossible to obtain, would potentially become achievable in outer space through the exploitation of unusual binding situations [30] or the application of the quantum mechanical tunneling effect [31].
Flow chemistry is often mentioned in the context of “novel process window” [32] and “harsh reaction conditions” [33, 34]. It is due to the same underlying advantageous properties that flow chemistry is suitable for space applications (Table 1). Most importantly, there is no headspace in micro- and mesofluidic flow reactors in which chemicals can float to make results irreproducible. In addition to that, the flow rate and the pressure can be controlled using a pump and a back-pressure regulator, respectively. Exploitation of these properties brings about a situation where reactions can be carried out under exactly the same conditions as on Earth. Another important advantage of flow chemistry is its inherent safety which originates from the small reaction scale and the precise parameter control. Furthermore, flow chemistry is amenable to combining multiple reactions and purification steps (telescoping) to create complex molecules from simple building blocks in one continuous stream.
Advantageous properties of flow reactors for space laboratories
| Property | Advantage in space |
|---|---|
| No headspace | Operation in microgravity |
| Closed reaction zone | Safety, no contamination |
| Precise control of parameters | Safety, reproducible |
| High level automation and remote control | User-friendly |
| In-line analytical instruments | Compatibility |
| Wide range of chemical reactions | Advanced research |
| Often high conversion reactions | Less waste generation |
Finally, the ease of automation, remote control, and the feasibility of in-line analytics are all beneficial for space chemistry applications.
4. Opportunities
4.1. Design, Safety, and Testing
The environment, the launch process, and the structure of the spacecraft itself impose stringent constraints on the equipment designated for space usage. The lifecycle of space instruments is depicted in Figure 2. The instrument is required to sustain rapid pressure changes during the course of launch and deployment, and this necessitates thorough testing. Besides striving for a low-weight, low-power compact design, the selection of materials, components, and technologies, as well as safety hazards, especially structural failure and material risks, require special attention. Starting materials, products, and waste shall be stored in closed, separated containers, and the frequency of on-board maintenance activities shall also be minimized or eliminated. Potential reactions must be selected based on trade-off analysis between scientific demands and technological constraints. Additionally, the lack of gravity does not help cooling by convection (i.e., hot air does not rise as on the ground). Liquid spills do not behave as expected. The above considerations originate from safety requirements, but it makes sense to design space flow chemistry instruments in a way that those will remain operational even if complications arise.
The lifecycle of space-deployed instruments
Citation: Journal of Flow Chemistry JFChem 7, 3-4; 10.1556/1846.2017.00033
A number of platforms are available to test an equipment in microgravity environment. The choice of the appropriate platform depends on the properties of the experiment and the device. Drop towers, ground simulation facilities, sounding rockets, and airplanes owned by space agencies and private companies provide opportunity for microgravity experiments from a few seconds to several minutes. In case of long-term experiments, one can use satellites or on-board testing on the ISS is possible.
4.2. CO2 Conversion and Continuous-Flow Photochemistry
The availability of sufficient and renewable energy supply is crucial to support long-term space exploration and to sustain our society on Earth. Carbon dioxide is one of the potential energy sources that can be utilized either on Mars or on Earth. The Martian atmosphere consists of ca. 96% CO2 [35].
Carbon dioxide is a greenhouse gas, and even though the amount of CO2 in Earth's atmosphere is below 0.05%, it has a significant contribution to climate change [36]. Actions have been undertaken to decrease CO2 emission and also to utilize it as a renewable energy source and for the production of raw materials (Figure 3a). The methanol economy, proposed by George Olah, is a future economy model in which methanol is the main source of energy (Figure 3b) [37]. Methanol can be directly produced from CO2 through reduction with H2 or via electrochemical methods utilizing water. Other hydrocarbons, such as longer alcohols (ethanol, propanol), formates, or carbonates, can potentially be produced too.
(a) CO2 as a green carbon resource. (b) Methanol, a potential building block of the future
Citation: Journal of Flow Chemistry JFChem 7, 3-4; 10.1556/1846.2017.00033
The task of establishing a CO2 based economy is however not easy. The reduction of CO2 is energetically challenging and requires an appropriate catalyst and energy input [38]. The capture of CO2 from the atmosphere mimics nature's photosynthesis but requires the development of high efficiency technologies. Even if all these issues are solved, the other side of the chemical equation has to be balanced; therefore, reliable source of hydrogen (either in the form of dihydrogen, water, or protons) is necessary.
As a sustainable energy input, the high UV component of sunlight could be exploited for the photocatalytic reduction of CO2 [39]. Recently, Rajeshwar and coworkers developed a method for the solar photoelectrosynthesis of methanol using a copper-based catalyst [40]. The continuous-flow electroreduction of carbon dioxide is an emerging area [41]. It does not require much imagination to conceptualize a light powered continuous-flow electrosynthesis system for methanol production. It is important to note that most often O2 is produced on the anode as a byproduct and could potentially be used to maintain the atmosphere of a spaceship or a Martian colony. Finally, and going beyond the reduction of CO2, continuous-flow photochemistry has demonstrated its applicability in a wide range of fields from organic synthesis to material science and waste water treatment [42].
4.3. Flow Nanonization
Flow nanonization on Earth is getting more and more important due to the better control of the parameters of nanoformulation and easier scalability [43]. Nanonization of drugs and pharmaceuticals can lead to increased bioavailability both on Earth and in space [44]. Furthermore, the enhanced absorption of nanonized nutrients might be a key for the future of space farming [45].
4.4. Communal Waste Recycling
The culminating waste in industrialized regions brings up the necessity to develop commercially benefiting, technologically efficient, and environmentally benign methods to collect, transform, and reuse waste, which is in fact an essential need during space travel too. A proposed space technology for organic waste treatment comprises a technology which treats the organic waste in a batch process involving waste collection, decomposition with anaerobic and heterotrophic bacteria, and production of the recycled biomass. A waste conversion technology in flow can be conceptualized using immobilized bacteria [46].
4.5. Quantum Mechanical Tunneling
The one-dimensional barrier penetration of particles, the so-called quantum mechanical tunneling (QMT) is a quantum mechanical effect which may lead to very unusual, unexpected chemical transformations [31]. It bears high scrutiny under low-energy conditions, where conventional kinetic reaction rates are negligible. Quantum tunneling has been rationalized by theoretical and experimental studies in charge, proton [47], carbon [48], and light heteroatom [49] transfer reactions. In outer space, the reactants have to face conditions suitable for QMT. Furthering our understanding of QMT might allow us to synthesize unusual chemical structures.
In particular, QMT is applied in combination with flow chemistry using the flash vacuum pyrolysis (FVP) technique [50]. Following the rapid, intense heating of the reactants (>1000 K) under low pressure, highly reactive substances, e.g., carbenes, are generated. These substances can be captured by solid noble elements under cryogenic conditions (10–15 K) (matrix isolation). At this temperature, the reaction is frozen in the classic kinetic sense; however, product formation can occur via QMT.
5. Challenges
5.1. Synthesis on Demand, the End-to-end Microfactory
We have already mentioned the illnesses and the reduced drug lifetime which might hamper a deep-space exploration. How can we ensure the access to the needed pharmaceuticals? Not only in space, but also on Earth “the lab of the future” (LOTF) is a place where one can potentially “dial-a-molecule” on a computer screen and the fully automated laboratory will synthesize, purify, and analyze it [51]. Flow chemistry is prognosticated to take a vital role in LOTF. Chemists are not yet at the stage where this can be done for any molecule, but the automated synthesis of specific compound libraries [52], active pharmaceutical ingredients [53], or even the end-to-end continuous manufacturing of certain pharmaceuticals is indeed possible [54]. Furthermore, Fitzpatrick and Ley created a cloud-based reactor system which can be monitored and remote-controlled through an internet browser [55]. Once our technology is able to produce drugs on demand, the concept could be readily extended to other useful materials.
5.2. Asteroid Mining
Although the optimal methods to mine an asteroid has been studied and debated for decades and several technical challenges need to be solved, there is no question asteroid mining could one day become a booming part of the global (or universal) economy.
Hydraulic fracturing or hydrofracking is a good stimulation technique when fissured rocks are fractured by pressurized liquid, especially water, often containing sand. This method is applied to excavate natural gas, petroleum, or brine from deep-rock formations. Although this application is quite controversial in many countries on Earth, this procedure might be of great help to mine the invaluable materials from dwarf planets, asteroids, and other near-Earth objects (NEOs). The loosely bound ores of rare-earth elements and expensive transition metals might be mined by this flow technique and utilized on the spot. Moreover, rocket fuel could be produced from carbonaceous chondrites, which are rich in water.
6. Conclusion, Outlook: Collaboration is the Key
In 2014, researchers realized the importance of the emerging field of space chemistry. To tackle the challenges and opportunities mentioned in this article, the Flow Chemistry Society established the Space Chemistry Project [56], a consortium for academic experts, industry innovators, and decision-makers from the top pharma and other chemistry and life-science firms. The worldwide network is constantly growing as space opens new routes for chemistry (Table 2). The consortium envisions to enable the routine practice of chemical synthesis in outer space to benefit humanity.
Members of the Space Chemistry Consortium
| University | Industry |
|---|---|
| Boston University (US) | AbbVie (CH) |
| Case Western University (US) | ComZat (UK) |
| California State University, Fullerton (US) | InnoStudio (HU) |
| Eindhoven University of Technology (NL) | Novartis (CH) |
| Imperial College London (UK) | SpacePharma (CH, IL, US) |
| James Cook University (AU) | ThalesNano (HU) |
| Kyoto University (JP) | Zaiput (US) |
| Massachusetts Institute of Technology (US) | |
| Nelson Mandela University (RSA) | |
| University of Cambridge (UK) | Governmental and other research organizations |
| University of Cardiff (UK) | Fraunhofer Institute (GE) |
| University of Lyon (FR) | Flow Chemistry Society (CH) |
| University of Mainz (GE) | Max Planck Institute (GE) |
| University of Southern California (US) | Scripps Institute (US) |
| University of Szeged (HU) | |
| University of Tokyo (JP) | |
| University Wisconsin–Madison (US) | |
| Virginia Commonwealth University (US) |
There is a vast amount of research associated with space research, yet space chemistry is still in its infancy. Nevertheless, we can expect remarkable development in the next couple of years, thanks to the new directions marked out by the members of the Space Chemistry Consortium and SpacePharma. We strongly believe that flow chemistry is not just “an option” but it is “the way” to tackle the difficulties associated with space chemistry. Flow chemistry can now open the door to study organic chemistry in space for the first time.
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