We’ve just had our latest paper published in RSC Digital Discovery! This is the result of Luokun’s brief but very productive internship in the group last year (separate blog post about his experience in the group). Luckily for us, Luokun has been offered a PhD position and will be staying with us, so plenty more cool science to look forward to!

What’s this paper really about?

One of our guiding principles in the group is that realising the full potential of digitisation requires a fresh look not just at what reacts with what, but also where this happens and what else is around. Nature is the master of surrounding reactivity with the right environment: just look at enzymes and how their active sites/prosthetic groups are nestled within a much larger structure; or how hopelessly impossible it seems for cellular processes to continue without the cell’s many membranes and modes of compartmentalising its activities. Containers can be smart — instead of being totally impermeable they can let certain things in/out but keep other from entering or leaving. And they don’t always have to be large like traditional glass containers in chemistry. In fact, for permeable containers being small allows molecules to reach the interior via diffusion (their random jittery movement), do something exciting, and then either leave or accumulate and build up like pearls in an oyster!

Our digital aerosol reactor, built entirely in-house, provides a way to produce millions of tiny chemical droplets and study their reactions. Digitizing our aerosol setup means tiny chemical “packets” can be released according to a computer program with very precise control over when and how much solution is sprayed. Our paper binds this progress with a way to turn these tiny liquid droplets into something more like a primitive cell. For this, we take advantage of gel-formation between alginate — a large molecule derived from seaweed — and calcium ions. This way, not only can we generate tiny hydrogel particles, but use them as tiny reactors by preloading them with reactive compounds.

Interested? Read on to find out more about what’s possible using these microscopic reactors.

What are COFs and MOFs?

Imagine building a miniature city, not with bricks and mortar, but with molecules! This is what we explore in research, using Covalent Organic Frameworks (COFs) and Metal-Organic Frameworks (MOFs). These aren’t just ordinary materials, but super materials that can help clean the environment, store gases, or even deliver drugs precisely where they’re needed in the body.

COFs and MOFs are made by connecting molecules into a repeating 3D pattern, kind of like constructing a giant crystal lattice but on a nanoscale. These materials are super porous, meaning they have lots of tiny holes that can capture or release other molecules. This makes them incredibly useful for a wide range of applications!

So, what is the difference between COFs and MOFs? Although both are composed of molecules connected in a repeating 3D pattern, the main differences lie in their composition and the way they are linked:

COFs : These are made entirely of light elements such as carbon, hydrogen, oxygen, etc., and are interconnected through covalent bonds (strong connections like the ones between hydrogen and oxygen in water molecules). This material is very stable and difficult to break down.

MOFs : These contain metal ions and organic ligands (molecules that help arrange the metal ions), linked via coordination bonds (a more flexible type of connection). This allows MOFs to have many different structures and a broader range of uses.

In short, if you think of them as buildings, COFs are like constructions made with one type of sturdy brick, while MOFs are built with a variety of materials, including some metal components, allowing for more complex structures. This makes MOFs more flexible in adjusting and optimizing their performance.

How do we make these materials?

Creating COFs and MOFs can be tricky. Traditional methods are like slow cooking; they take a lot of time and energy. But under the guidance of my mentor, Dr. Hessam Mehr, we use something called an aerosol reactor. This reactor is like a magic box that allows us to create these materials faster and with less waste, which is great for the environment!

What’s special about an aerosol reactor?

An aerosol reactor works by spraying tiny droplets or particles through a mist, which then transform into COFs or MOFs. Think of it as using a spray paint can to create a detailed mural. Each droplet has all the ingredients needed to form our materials, and when they meet, they stick together in just the right way.

This method is not only quick but also very efficient. It allows us to experiment with different recipes for making COFs and MOFs, tweaking the process until we get the best possible material for a specific job, like finding the best ingredients for a super cake.

Why does this matter?

You might wonder, why should we care about these tiny materials? Well, they could be game-changers in many fields. For example, they could capture harmful gases from the air or help store renewable energy more efficiently. They might even be used in medical treatments to deliver drugs precisely where they are needed, minimizing side effects.

The future is bright!

Research in this field is like being both a magician and a scientist. Every day, we discover more about what these tiny structures can do and how they can help us solve some of the world’s big problems.

I hope this brief introduction to the world of COFs and MOFs has sparked your curiosity. Perhaps one day, you’ll join us in the lab to discover even more materials that can make the world a better place. Until then, keep wondering, asking questions, and exploring the world around you.

New faces in materials innovation

Luokun Zhang, former group intern returned to the group, along with two new faces, Zehua Li and Junyi Chen to complete their practical post-graduate project in advanced functional materials. Always the patient and methodical experimenter, Luokun trialled quite a few project ideas in his first couple of weeks before finally settling on generation of composite materials. Along the way, we had to build our own microscope, for which Luokun designed 3D-printed a sample stage. We both learned a lot about optics, thanks to Abhishek Sharma and Ilya Starshynov who held our hand in the process. Zehua and Junyi both explored Schiff bases this summer, using them to assemble large molecules and new materials inside our prototype aerosol reactor.

Antimicrobial resistance

For the first time, this year we hosted a Chemical Biology post-graduate student. Zixi Wu took a brave leap aboard an ambitious project where we looked into the feasibility of generating a diverse range potential new antimicrobials by exposing existing antibiotics to reactive conditions within our aerosol system. Zixi deserves extra kudos for keeping his cool on a project with many layers of unknowns. His early results pave the way for future students taking on this challenge.

From Georgia to Scotland

Mariam Kalathil visited us from warm Georgia, US as part of the Arcadia summer exchange programme. Despite never having taken courses in organic chemistry or electronics, she excelled in her project, building a one-of-a-kind experimental setup to answer a fundamental chemistry question. The goal of Mariam’s project was to find out whether the messiest chemical mixtures also produced the largest number of new chemical compounds.

Building in the workshop

Talented and extremely keen Nuffield placement student Saad Azad was busy building a motorised XY stage out of old CD/DVD drives! Saad had to pull these drives out of dead computers in electronics recycling, and control the motor moving the laser back and forth using an Arduino program. These types of stages are useful in microscopy, where they are used to scan different parts of a sample automatically.

Invisible hands

UpnaLab Phd student Josu Irisarri spent this summer in Glasgow looking at ways to control chemical droplets using sound. We tried too many mad experiments to list here but one nice Friday found a quick zap of sonic energy could extract little droplets off the surface of a petri dish of water, bringing us a step closer to the tantalising future of contact-free chemistry.

Prototypes galore

Our brilliant intern Basia Jarzabek had just finished the 3rd year of her undergraduate course in Chemistry but this summer her days were mostly spent 3D printing, laser cutting, soldering and programming. She went from never having touched CAD software to helping everyone with their parts. Aerosols particles are very sensitive to their environment, so Basia’s goal was to prototype a temperature- and humidity-controlled environment for them.

Learning from each other

Group meetings and lab time were great opportunities to learn from each other. A personal highlight was getting a fresh appreciation of how video rather than raw data can be the perfect medium for documenting experiments.

Thank you

A heartfelt thank you to every one of our brilliant students. Their curiosity, energy and positive vibes have fuelled me all summer and inspired many that they interacted with. A big thank you to everyone in the ARC who facilitated their project as well. I will miss some names, but these projects would not have been possible without the help of Maria Diana Castro Spencer, Jennifer Mathieson, Jim McIver, Mary Wong, Phil Kitson, and Lee Cronin.

During my undergraduate studies, I developed a strong interest in organic chemistry. My main focus was on alkali metal catalysis and photo-induced phase change energy storage dyes, primarily using solvent-based methods to synthesize reactants and explore their reaction mechanisms— a process that was quite “traditional”. When I joined Hessam’s lab, I encountered parallel aerosol reactors for the first time. I was amazed by this novel method of synthesis and decided to experiment with synthesizing known compounds using the aerosol reactor to test its potential in compound synthesis.

Due to the exceptionally high surface area to volume ratio of droplets in aerosols, substances can more rapidly interact with the heat source or reaction environment, thereby accelerating heat transfer and reaction rates. This means that chemical reactions can be effectively promoted even at lower temperatures. In addition, the evaporation of the solvent is an endothermic process, which allows the aerosol droplets to locally increase their temperature during evaporation without the need for an external heat source. These properties make aerosol methods particularly suitable for synthesis reactions that require mild heating or low thermal initiation.For instance, in the synthesis of macrocyclic Schiff bases from aldehydes/ketones and amines, the dehydration step involved not only stabilizes the product by forming double bonds but also releases heat, providing the necessary activation energy for the reaction. This is beneficial for synthesizing longer chains or even [3+3] type macrocyclic Schiff bases. Consequently, we chose macrocyclic Schiff bases as our target products for synthesis.

What is a Schiff base？

Schiff bases are a type of chemical compound that often come up in organic chemistry. They’re made when an amine (that’s a molecule containing nitrogen bonded to three different organic groups) reacts with an aldehyde or ketone (these are types of compounds that have a carbonyl (C=O) group, which includes a carbon atom double-bonded to an oxygen atom). When they react, they form a new compound called an imine or Schiff base featuring a double bond between a nitrogen and a carbon atom. This reaction is pretty simple but super important because Schiff bases can be used in lots of different ways, like in dyes, pigments, and even some medicines.

Macrocyclic Schiff bases are like the bigger, more complex cousins of regular Schiff bases. The “macro” part of the name means large, and “cyclic” means ring-shaped, so these are large ring-shaped molecules. They also have the characteristic nitrogen-to-carbon double bond, just like regular Schiff bases. What makes them special is their size and structure, which allow them to form very stable complexes with metals. This makes them useful in more advanced applications, like catalysis (which helps speed up chemical reactions), or in creating materials that can grab and hold onto specific molecules, a bit like how a lock holds a key. This can be really handy in areas like environmental science, where you might want to capture pollutants, or in medicine, for delivering drugs to specific parts of the body.

What are aerosols and why use them in our experiments?

Aerosol synthesis is an innovative chemical synthesis technique that suspends reactants as extremely fine particles in a gas, with the goal of enhancing reaction efficiency and product quality. This method stands out compared to traditional solution-based approaches for several reasons. First, the reactants in aerosol form have a much larger surface area, which may speeds up reactions and increases their progress towards completion. This makes aerosol synthesis particularly suitable for chemical reactions that require fast reactivity and high yield.

Another major advantage of aerosol synthesis is its environmental friendliness. Traditional chemical synthesis often involves large amounts of organic solvents, which are not only costly but also pose significant environmental risks. Aerosol technology can significantly reduce or even eliminate the use of solvents, thereby lowering environmental impact and reducing energy consumption. For instance, in the production of nanomaterials, aerosol methods can avoid the use of organic solvents at high temperatures, reducing the emission of harmful substances.

Despite its many benefits, aerosol synthesis does have some limitations. For example, it requires specialized equipment to generate and control aerosol particles, which means higher technical requirements and initial investments. Additionally, maintaining the stability of aerosols and precisely controlling particle size are technical challenges that need to be addressed in experiments. However, with ongoing technological advancements and further research, aerosol synthesis is showing tremendous potential in fields like pharmaceuticals, catalyst fabrication, and high-performance materials synthesis. As technology continues to advance, it is expected that aerosol synthesis will play an increasingly important role in chemical manufacturing, especially in an era that emphasizes green and sustainable chemical processes.

How did we approach the problem?

We started by searching for reaction formulas related to the synthesis of macrocyclic Schiff bases using the traditional bulk solution method, selecting reaction systems that are mild, with temperatures slightly above or equal to room temperature. Next, we replicate these reactions using the original published protocol to make sure they are reproducible. Once verified successfully, we then attempt to synthesize the macrocyclic Schiff bases using aerosol synthesis in our aerosol reactor.

To create macrocyclic Schiff bases using an aerosol reactor, we prepared two reagent vials. In one, we dissolved the amine in solvent; in the other, we dissolved aldehyde also in solvent. We also added a small amount of acid to the aldehyde mixture because acid can speed up or catalyze Schiff base formation.

Next, we fitted each reagent vial with a piezoelectric element, whose role is to convert the solution into a mist of aerosol particles, and placed the vial assembly inside the aerosol reactor. Finally, we connected the reactor to a computer which is programmed to control the emission aerosol by activating the piezoelectric elements.

What is a piezoelectric actuator?

A piezoelectric atomizer is a small device that uses quick vibrations to turn liquids into a fine mist. It works by using a special material that vibrates rapidly when electricity is applied, creating pressure waves that break the liquid into tiny droplets. You can find these atomizers in everyday items like humidifiers, which add moisture to the air, aroma diffusers, which spread essential oils, and medical devices like nebulizers, which help people inhale medicine. They’re popular because they can create a fine mist without using heat, making them efficient and safe for delicate liquids.

By positioning the vials at a slight angle relative to each other, we encouraged microdroplets from each source to collide with each other to form the Schiff base. We collected the products of aerosol reaction on two glass slides within the reactor, one at the top and one at the bottom. This setup allowed us to capture and analyze the products separated afterwards.

After the Schiff base reaction is completed, the amine (-NH2) and aldehyde (-C=O) groups undergo a condensation reaction to form an imine bond (-C=N-). Therefore, we can use infrared spectroscopy to detect functional groups in the product and look for the (-C=N-) absorption peak, which indicates the presence of the imine bond. After calculating the theoretical molecular weight of the target product, we also used mass spectrometry to measure the mass-to-charge ratio of the reaction product, from which we can infer the actual mass of the product. By comparing the measured mass with the calculated mass, we can verify whether the molecule obtained is the target product. These steps help us to get a better idea of which product molecules have formed.

What is infrared spectroscopy?

Infrared spectroscopy (IR) is a practical chemical analysis technique that identifies and studies chemical substances by measuring specific frequencies at which compounds absorb infrared light. Each chemical has its unique “molecular fingerprint,” consisting of a series of specific absorption peaks that reflect the vibrations of chemical bonds within the molecule. This technique allows us to quickly determine the type and molecular structure of substances and is widely used in research, quality control, and environmental monitoring. The advantages of IR spectroscopy include its speed and non-destructive nature, providing accurate chemical information without damaging the sample.

What is Mass spectroscopy?

Mass spectrometry (MS) is an analytical technique used to identify compounds and measure their abundance by analyzing the mass-to-charge ratio (m/z) of sample molecules. In this process, the sample is first ionized to create charged particles, which are then accelerated in an electromagnetic field and separated based on their mass-to-charge ratios. A mass spectrometer generates a spectrum by detecting these separated ions, showing the distribution of ions with different m/z values, which helps to identify the chemical substances and their structures within the sample.

The applications of mass spectrometry are vast and include drug development, biological research, environmental science, and forensic science. The main advantages of this technique are its high sensitivity and the ability to detect trace amounts of substances, providing precise molecular mass information. Mass spectrometry can also analyze multiple components in complex samples, making it an indispensable tool in modern analytical science.

Future plan

This study primarily showcases an innovative synthesis technique—using aerosol chemistry to manufacture macrocyclic Schiff bases. Although macrocyclic Schiff bases themselves have been extensively studied, the highlight of this research is the development of a brand new method of preparation. This method, which synthesizes through the collision of micron-sized aerosol droplets, not only enhances synthesis efficiency but also reduces environmental impact, offering a sustainable and efficient option for the field of chemical manufacturing.

In the future, we can focus on further refining this technology by introducing electrodes to enhance interactions between aerosol droplets using electrostatic forces to improve the success rate of reactions. Additionally, adjusting the boiling point of solvents and precisely controlling reaction temperatures will enhance reactivity and reduce unwanted side reactions, increasing the quality and yield of products.

These improvements will not only provide an opportunity to deeply understand the mechanisms of aerosol chemical reactions but also suggest that this new method could transform the future of chemical manufacturing. With this innovative synthesis approach, we look forward to opening a new chapter in chemical synthesis, especially in terms of efficient and environmentally friendly synthesis strategies.

Over the past three months, I have had the privilege of being guided by Dr. Hessam Mehr, which has allowed me to rediscover the field of organic synthesis from an aerosol perspective. Without his guidance, I would not have been able to complete this complex project. Dr. Mehr’s extensive knowledge in organic chemistry, supramolecular chemistry, and software programming has been immensely beneficial to me. His expertise not only helped me address various challenges in the laboratory but also greatly broadened my academic horizon. Working with him has been a highly enjoyable and fruitful experience, deepening my understanding of chemical research.

I sincerely thank Dr. Hessam Mehr for his meticulous guidance and selfless assistance, and I hope to have the opportunity to collaborate with him again in the future. I would also like to express my gratitude to the other members of the Hessam group. I am particularly thankful to Zhang Luokun for his significant help with modeling the vial holder, Ms. Mariam Kalathil for her support in carrying out the experiments, and fellow student Chen Junyi for his valuable writing advice. Their assistance has been crucial to my research work.

More about Josu

¡Hola!

My name is Josu Irisarri and I came from Spain as a visiting researcher to learn about sound chemistry and aerosols within my 3rd PhD year. I’m really grateful for having the opportunity of sharing science, time and passion in Mehr research group at the Advance Research Center (ARC) of the University of Glasgow. I got in touch with Hessam Mehr after he came to Pamplona to visit our laboratory (UPNALAB). I was later invited to an acoustic chemistry workshop at Glasgow where I could present my research work of the past years. After that, I got on board into this lovely journey.

This experience will be crucial not only for my personal career but also for developing my transversal skills, such as, multicultural communication or networking. Here in the ARC there are researcher from many different countries all around the world with whom I’m always enjoying good conversations.  My current main interests are in human computer interaction and contactless haptics and I’m willing to spread my maker and technical knowledge among this laboratory family.

Taking black coffee with hot milk in a glass with ice cubes is my favourite activity when sited on a terrace surrounded by friends and sunny nice day. You can find me hiking the highest mountains of Scotland or visiting the mysterious lakes and islands around. Sometime I like to stop for local beer and food or trying to pronounce right the Scottish accent with words like “Hiya”, “Awright”, “Wee”, “Hapnin” or “Edinbruh”. The climate isn’t the best, although since I’m here it is mainly sunny. They say that I have brought the good weather somehow.

¡Hasta la vista!

Last summer I was faced with the decision of what subfield of Chemistry my final year project was going to revolve around. Following a six-week summer internship in the Complex Chemistry labs of the University’s Advanced Research Centre (ARC), I was particularly keen about the possibility of tackling areas that deviated a bit more from our base curriculum or areas that one may initially associate with the field of Chemistry. I was eager to witness and understand more about the ever-evolving incorporation of automation and digitisation into the field, and learn some new, relevant skills along the way. As such, I selected “Complex Chemistry” as my top preference for my Honours project and was fortunate enough to join Dr. Hessam Mehr’s research group as a result.

Brief project background

My seven weeks in the Mehr Group revolved around the exploration of aerosol microdroplets as a reaction medium for chemical synthesis. The idea behind this stems in part from the successful applications of other departures from traditional “flask-based” synthetic approaches, such as flow chemistry and microfluidics, with their own sets of advantages. The two main incentives for performing chemistry in the aerosol medium, i.e. in “spray” form are:

1. The potential of different chemical pathways/reactivity as a result of substantially confined volumes — reaction acceleration in microdroplets has been a prominent observation in literature.
2. Performing chemistry within this medium is inherently “stochastic”. Is there potential for novel pathways for a given set of chemical building blocks based on the probabilistic nature of droplet interactions within an aerosol cloud?

My experience

More specifically, my experience in the lab was very much focused on demonstrating the feasibility of some known organic reactions via an ultrasonic atomiser-based apparatus for droplet generation. The “reactor” (photographed below) was connected to a computer via a MicroPython circuit, and any chosen reaction was controlled and tuned via a Python program. One thing I very much appreciated and enjoyed was getting to assemble a physical circuit from scratch, coupling it with a script and seeing it all come to life when testing out the spraying of a solvent of choice. Hessam was very helpful and keen to demonstrate processes such as soldering and laser-cutting (for the assembly of the acrylic box, as seen in the photograph), as well as explaining the unfamiliar features of the algorithm and circuitry.

The biggest challenge within the project certainly had to do with my choice to explore organic reactivity in the medium, coupled with our primary method of droplet detection — microscopy. The droplets generated during a given aerosol reaction were allowed to settle onto a glass slide for visualisation under a Raspberry Pi-based RGB microscope. A reaction is deemed to have proceeded if distinct reagent and product droplets can be identified. This distinction is typically attributed to a significant difference in colour between the two — something that organic chemistry is not particularly known for. As such, my resilience was certainly tested when scouring the lands for an organic reaction that would undergo a distinct colour change in a reasonable timeframe under mild conditions. What this meant was that the eventual sight of a beautiful contrast between distinct red/orange and colourless droplets following an ado-dye synthesis in the aerosol medium put a big smile of excitement and relief on my face.

Nearing the end of my project, with the help of Dr. Mehr’s programming expertise, I had the opportunity to witness the seemingly simple, yet promising potential of changing up the algorithm loop to facilitate multi-step reactivity involving an unstable intermediate, i.e. stoichiometric spraying in a sequential manner, as opposed to the simultaneous spraying of two atomisers as per a simple binary reaction. Starting to see the extent of how such an affordable apparatus could be tailored and fine-tuned through the power of code to facilitate a truly hands-off approach to performing mainstream chemistry in an atypical medium was, needless to say, a very rewarding way to wrap up my project.

Final thoughts; what next?

It is an understatement to say that I am incredibly grateful to Dr. Hessam Mehr for all the patience and guidance throughout my time here. The group provided me with a refreshing look at a different side of Chemistry that aims to take full advantage of where the world is heading technologically — and it’s doing so with accessibility and ease-of-communication in mind. While my time in the group is now over, with the prospect of exploring various other yet-unclear endeavours, the experience I have gained working in Mehr Research is nothing short of invaluable, and the skills I’ve developed will undoubtedly aid me in any facet of Chemistry, or many other potential career path for that matter.

At the time of writing this post I’m preparing for my final degree exams coming up in just under three weeks, so fingers crossed! What keeps me going are some great destress socials with friends; playing some great games and talking for hours about Japanese animation and graphic novels! Following graduation I hope to take some time to enjoy some lovely (hopefully!) sun with my family in Poland, as well as take my partner around some places she’s not seen there yet!

That’s all, folks!

Two years ago, I came to Glasgow after finishing my undergraduate studies in China. For my program, I learnt the synthesis technology and characterisation (such as atomic force microscope, transmission electron microscope, etc.) of some popular advanced materials (such as quantum dots, perovskite batteries, etc.), which will be the basis of my research work in the future.

When Hessam pitched the idea of using microdroplets as reactors, I was attracted by this crazy idea, and so embarked on a project to create micron-sized soft materials out of seaweed. This blog post is to share with you why these materials are so interesting and how we hope to use them to make the next generation of chemical containers.

What really is a chemical container?

When it comes to chemical reactions, many people think of two solutions mixed in a beaker or test tube, changing from one colour to another. The function of beakers or test tubes is to isolate the reaction from the environment. As a traditional reaction container, they have the advantages of low price and easy operation, but the disadvantages of only carrying out one kind of reaction at the same time are also obvious. If I need to do four chemical reactions and try five reactant ratios for each reaction, assuming I need 5 mL of reactant for each reaction, then I need 20 beakers or test tubes and 100 mL of reactant solution. This soon starts to become impractical when we need to examine a larger number of reactions and conditions.

Perhaps you can say that, under the premise of constant total volume, if the interior of a container is divided into several smaller partitions, the above problem can be solved. This is true and indeed it’s the design idea behind more modern reaction vessels like 96 well plates.

You can even go above 96 wells and well plates with 384, 1536, and even 12,000 wells are available commercially. However, this idea soon runs into limitations. Not only would tinier wells become prohibitively expensive to manufacture, manually using them would be cumbersome and time consuming, even with the help of automation, such as robotic pipetting machines.

This is where our idea of using aerosols comes in: if we are able to turn individual aerosol particles (each just a few microns in size) into chemical containers, it would provide a fast and easy way to make millions of tiny containers that we would never be able to create manually.

Why calcium alginate?

Let’s look more closely at how exactly we are planning to create our next-generation reaction vessels. In order to build a container around an aerosol particle, the easiest way is to form it within the medium where the reaction will take place, called in situ in chemistry. Can this strategy address the challenge of building microscopic isolated chemical environments?

This puts forward new requirements for the chemistry used to form our reaction vessels: the reaction generating the container needs to be robust and reliable (not easily affected by the reaction conditions such as temperature, pH, etc.), and it should be possible for small molecules to enter and leave the container.

In my project, we focused on alginate-based materials to meet this challenge. Alginate is a natural polysaccharide derived from brown seaweed. Due to its unique properties such as biocompatibility, biodegradability, and the ability to form gels in the presence of divalent cations like calcium, alginate is widely used in various industries, including food, pharmaceuticals, and biomedical applications.

Calcium alginate happens to meet all of the above conditions. It is produced by cross-linking alginate using calcium ions, which works under a wide range of conditions. As a bonus, the soft structure generated this way can be rapidly dismantled in the presence of compounds like ethylenediaminetetraacetic acid (EDTA), so that we can easily release the contents of our container.

What does cross-linking mean?

In chemistry and biology a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. Cross-linking leads to gel formation, which improves the mechanical strength and stability conpared to uncross-linking solution. The cross-linking is widely applied in drug delivery, tissue engineering, food encapsulation, etc.

How did we do it?

Usually, calcium alginate is produced by reacting sodium alginate solution with calcium chloride solution. In order to obtain micron-scale calcium alginate, though, we needed to create tiny sodium alginate droplets (smaller than the diameter of a human hair). Obviously, these droplets wouldn’t be practical to make manually, so we turned to a somewhat unusual method instead: using an ultrasonic atomiser.

What is an ultrasonic atomiser?

Ultrasonic atomisers are devices that using ultrasonic vibrations to create a fine mist or spray of liquid. They are commonly used in various applications such as humidifiers, medical nebulisers, spray-coating systems, and even in certain types of fuel injectors used in cars.

Here is how our atomiser setup works. First, we have a very cool electronic component called a piezoelectric actuator. What does the actuator do? It moves in response to an electric potential (aka voltage). If we change the voltage very rapidly (say a few hundred thousand times a second), the actuator starts to vibrate fast enough that any liquid that comes into contact with it is smashed into microscopic droplets. Second, we need a way to bring the solution in the bottle to the actuator. For this we use a wick made of cotton. One end of the wick is in contact with the liquid in the bottle and the other end touches the piezoelectric element at the mouth of the bottle. The solution is diffused through the cotton wick to the top. To summarise, when sodium alginate solution is poured into the vial the cotton wick draws it up and brings it into contact with the actuator.

Next, we energise the piezoelectric element. We can control exactly when this happens using a computer program that can be customised according to our experiment. When activated, the actuator undergoes periodic deformation, producing sound wave. But these sound waves are very high in frequency, so we cannot hear them; that’s why they are called ultrasonic pulses. The overall result is that our sodium alginate solution is broken up into microscopic droplets and ejected upward.

In our experiments, we tried two different methods of preparing calcium alginate. One was to make sodium alginate and calcium chloride solution form droplet, which reacted after collision in the air and collected by glass sheet; The other is to allow a solution of sodium alginate to form droplets, which are collected in a petri dish or beaker containing a solution of calcium chloride. We found that the second method works better when there is no intervention (such as using an electromagnetic field to control the movement of the droplets). This is probably because the likelihood of alginate and calcium droplets colliding in the air is not very large in the first method.

We didn’t only use sodium alginate and calcium solutions in our experiments. The table below shows some of the other combinations that we tried (there were many many more!). Some of these combinations gave us very interesting results that you can see in the microscopy pictures at the bottom.

Then, we tried to introduce the reaction of iron ions into the formation of calcium alginate reaction vessel to verify that the calcium alginate generated in situ can serve as the reaction vessel. When sodium ferrocyanate solution is mixed with ferric chloride solution, the mixed solution will change from light yellow to blue. We added sodium ferrocyanate solution to sodium alginate solution so that the resulting droplets were a mixture of sodium alginate and sodium ferrocyanate, and a mixture of calcium chloride and ferric chloride was added to the petri dish. At the end of the reaction, the blue droplets can be clearly observed under the light microscope at 5.6 times magnification. This means that the reaction can be carried out in calcium alginate reaction vessels.

The next question that came to our mind was whether we could put anything, such as solid particles, inside our microscopic containers. To see if this was possible, we added iron oxide powder to the above solution of sodium ferrocyanide and sodium alginate. After the reaction, the solid particles can be clearly observed under the optical microscope (see picture c below).

Finally, we added EDTA (Ethylene Diamine Tetraacetic Acid) to the petri dish after the reaction was completed, and after a few seconds, all the blue products previously appeared disappeared, which means that the cross-linked structure of calcium alginate can be destroyed in a short time.

Looking to the future

Many thanks to Dr. Hessam Mehr for his unwavering support and patient guidance, which enabled me to complete this project. Making tiny chemical containers is a very exciting area of research and we think that we have only begun to scratch the surface in the short period working on this project. We need to try more types of reactions to understand what other unique materials can be made using our aerosol-powered and computer-controlled techniques.

We had to tackle many challenges in this project. For example, when forming sodium alginate droplets, we found that different components of the solution require adjusting parameters such as voltage and frequency, and finding the optimal values seems to be tricky, which is also the challenge of this technology.

These days, I spent the weekends visiting some small towns around Glasgow, and enjoying the beautiful scenery, which always gives me the energy to continue my experiment with the complete enthusiasm when back in the lab.

At the same time, this project has allowed me to face everything that happens in scientific experiments with peace of mind. Not all experiments are a success but you can always learn something from each one, and there are always new challenges when you least expect them. I regard this period as a gentle prelude to my future academic life.

Fellow scientist will be familiar with the perks of our job, the moments of learning, discovery, and sharing that keep us going. Somewhat paradoxically, though, one aspect of academic life that I rarely look forward to is going to conferences.

It may be my short attention span or introverted character, but I’ve found it difficult to enjoy the prevalent maximalist approach to conferences: hundreds of participants often in cliques, countless hour-long talks across multiple tracks, and sessions fuelled by coffee and stretching into the late evening. I often end up coming back confused and exhausted, only remembering the first keynote perhaps and a couple of awkward nods at coffee break.

When the Royal Society of Edinburgh (RSE) funded my proposal for an interdisciplinary research workshop, it seemed like the perfect opportunity to channel these conference gripes into a new more minimalist format focusing on a different set of goals:

• Small, interdisciplinary crowd: We wanted to avoid the idea of most participants being nameless strangers to each other. Not only would everyone get to meet each other regardless of their career stage, they would also get a chance to share their unique trajectory.
• Interactivity: No keynotes; everyone given 10 minutes to introduce themselves, with another 10 minutes to pitch an interesting research challenge to the audience or vice versa.

• Trust: Having your ideas-in-progress “scooped” at conferences is not an unfamiliar experience. Can overlap in research interests be channeled towards collaboration rather than competition?
• Looking forward: Rather than showcasing achievements, we wanted everyone to share just enough of their background and areas of interest to catalyse forging new collaborations and sketching joint projects.
• Challenging comfort zones: Everyone should feel slightly outside the comfort zone of their expertise so the discussion is not dominated by one group or field, and ideas can flow freely.
• Removing financial barriers: Registration, travel and accommodation expenses often stop students and early career academics from attending. Generous RSE funding allowed us to subsidise their participation resulting in a more even mix of career stages.

Who participated?

Researchers from 5 European universities came to Glasgow. We also had a good spread of disciplines, including human computer interaction, non-destructive testing, microfluidics, complex systems, physical acoustics, and various flavours of chemistry.

Organisation details

A quick rundown that might be useful for anyone planning a small interdisciplinary academic event:

• RSE Research Workshop application was submitted 28th March 2023 and awarded 8th June 2023.
• Before submitting, I spoke to collaborators in Bristol and Pamplona, who kindly agreed to be core participants.
• With their input, I made a shortlist of UK and Europe labs that may interface with or be interested in the workshop theme
• Initial dates and draft list of participants: October 2023
• November and December were busy months, so I only got round to booking rooms in the ARC building in January. It was almost too late but we managed to find rooms/times that worked. Note to self: Don’t underestimate the level of activity in the ARC.
• A month before the event, I booked catering via the University. We also booked everyone’s hotel rooms, which was painless once we had final confirmation from participants.

How did it go?

To summarise my point of view, this was one of the most fun events that I have ever taken part in. Beyond preparing a brief draft agenda (available here), there was very little organisation to do, with just enough structure to set things in motion initially. From the beginning, discussions flowed naturally and everyone seemed bond quickly. The programme was spontaneous and dynamic, without ever feeling chaotic.

Verbal feedback from participants during the workshop was very encouraging, and our online feedback form was filled with positive comments.

Acknowledgements

This workshop would not have been possible without the Royal Society of Edinburgh’s Research Workshop grant. Without the RSE’s reputation and generous financial backing to support us, it is difficult to imagine bring such a diverse crowd of interdisciplinary research leaders to Glasgow.

I would like to thank Prof Bruce Drinkwater and Dr Asier Marzo for their support and advice. Their contributions predate the grant application that made this workshop possible.

Optimisation is a big part of what chemists spend their time and energy on, in research as well as industry, so accelerating and automating it is of course quite useful. Extending the XDL chemical programming language for optimisation — in addition to synthesis, which was its initial focus — is another highlight and a development that unlocks new directions for digital chemistry. I want to highlight a third achievement, though: mapping out a path between discovery and optimisation.

If you’ve ever seen an odd trace signal in your crude NMR or a curious m/z in the mass spectrum of your reaction mixture and felt tempted to pick up a magnifying glass and dig deeper, amplify that blip in your spectrum and find out what it really is then you know exactly what I am talking about. If only we knew the right conditions to make enough of the trace impurity and isolate it! The unexpected compound could lead us to a whole new reaction or at least a new compound, and especially because you didn’t expect to see your impurity in the first place this compound is more likely to be interesting than something you did expect.

It was a great pleasure to be part of the team working on this project between 2020 and 2021. One interesting technical challenge was to automate our Agilent HPLC system so separations could run round the clock without wasting lots of solvent and we came up with a fun hack that I may write about in the future. Conceptually though, building a bridge between discovery and optimisation stands out as the paper’s most enduring contribution to me.