Membranes made from Nano-droplets have potential in Medical Research

Membranes made from Nano-droplets have potential in Medical Research

Membranes formed in-lab from nano-droplets could have future use in medicines

For the first time, researchers from the Laboratory of Materials and Interface Chemistry, Eindhoven University of Technology (TUE), with a significant contribution of assistant professor Joe Patterson, have made a comprehensive video of liquid membrane formation using a transmission electron microscope (TEM). They used soap-like nanodroplets submerged in water to create the membrane. Their results are published in Nature, Chemistry and have been highlighted in the Nature, Chemistry News & Views article ‘The molecular Lego movie’.

LPEM Movie of the in-situ self-assembly experiment. Stabilized and cropped. Ianiro, A. et al. Nat. Chem. (2019)

This experiment has continuously recorded the whole process of how the membrane is formed under a microscope. Before this, scientists had to freeze the final membrane and get a snapshot of one or several moments of the membrane forming. This advance is achieved due to a well controlled liquid environment and can be now set in the microscope thanks to the DENSsolutions Ocean system.

Screenshots from the video of the membrane forming on the silicon chip. These were taken using a transmission electron microscope. You can watch the full video here. Ianiro, A. et al. Nat. Chem. (2019)

Membranes are of great interest in research as their selective barriers have potential uses in many fields: drug delivery, water treatment and chemical processes all rely on membrane technology. They are of particular interest in pharmaceutical research as they are the ideal shape to transport a drug through the body and release it only when the membrane finds a specific type of cell, for example, a cancer cell.

The Experiment

The researchers from the Materials and Interface Chemistry group led by Prof. Nico Sommerdijk formed a membrane from soap-like molecules called amphiphilic molecules, which simply means that they interact with both fats and water. Amphiphilic molecules are good building blocks for membranes as they can be lined up with the water-interacting side facing one way and the lipid-interacting parts facing the other way to form larger structures.

The DENSsolutions Ocean In Situ TEM liquid system was essential in this research. The core of the system consists of a dual chip Nano-Cell that sandwiches two chips together to form a microfluidic compartment.

First, the chambers within the tip surrounding the Nano-Cell were flooded with an amphiphilic solvent in order for it to fill the compartment. Then, the solvent was expelled with air, leaving the compartment saturated. Finally, the tip was flooded with water which gradually diffused into the compartment. It was during this stage that the water particles encouraged the solvent particles to organise themselves into a membrane structure.

Step 1. Polymer solvent

Step 2. Air

Step 3. Water

The membrane itself formed in stages. First, the solvent molecules arranged themselves into nanodroplets with a hydrophobic core and a protective hydrophilic shell. The DENSsolutions Nano-Cell created a hotspot of these nanodroplets and they gradually arranged themselves into a hollow membrane.

Diagram of the amphiphilic membrane forming in water. Arash Nikoubashman and Friederike Schmid.

Future Research

Watching how the nanoparticles form and arrange themselves with an electron microscope is a huge step in learning how to manipulate these membranes. The techniques covered in this research will be of interest to scientists working in food science, synthesis chemistry and separation science.

Hanglong Wu, who made a significant contribution to this paper during his PhD period, commented in an interview with DENSsolutions, that the technique “has been extensively used in studying the dynamics and structures of hard materials (for example, metallic nanoparticles) in the aqueous solution in the last decade, but it has been barely employed into soft matter field, mainly due to the inherent high beam sensitivity and low contrast.

“In this Nat. Chem. paper, we actually demonstrate we can probe the soft matter formation with such high contrast. People for sure will start to use the technique in the soft matter field.” – Hanglong Wu

The next stage will be fine-tuning how to manipulate the size and shape of the membrane. This research from Eindhoven is an important step in an exciting field.

If you are interested in the equipment we provided for this research, then contact us to see how we can streamline your experiments.

Membranes formed in-lab from nano-droplets could have future use in medicines

For the first time, researchers from the Laboratory of Materials and Interface Chemistry, Eindhoven University of Technology (TUE), with a significant contribution of assistant professor Joe Patterson, have made a comprehensive video of liquid membrane formation using a transmission electron microscope (TEM). They used soap-like nanodroplets submerged in water to create the membrane. Their results are published in Nature, Chemistry and have been highlighted in the Nature, Chemistry News & Views article ‘The molecular Lego movie’.

LPEM Movie of the in-situ self-assembly experiment. Stabilized and cropped. Ianiro, A. et al. Nat. Chem. (2019)

This experiment has continuously recorded the whole process of how the membrane is formed under a microscope. Before this, scientists had to freeze the final membrane and get a snapshot of one or several moments of the membrane forming. This advance is achieved due to a well controlled liquid environment and can be now set in the microscope thanks to the DENSsolutions Ocean system.

Screenshots from the video of the membrane forming on the silicon chip. These were taken using a transmission electron microscope. You can watch the full video here. Ianiro, A. et al. Nat. Chem. (2019)

Membranes are of great interest in research as their selective barriers have potential uses in many fields: drug delivery, water treatment and chemical processes all rely on membrane technology. They are of particular interest in pharmaceutical research as they are the ideal shape to transport a drug through the body and release it only when the membrane finds a specific type of cell, for example, a cancer cell.

The Experiment

The researchers from the Materials and Interface Chemistry group led by Prof. Nico Sommerdijk formed a membrane from soap-like molecules called amphiphilic molecules, which simply means that they interact with both fats and water. Amphiphilic molecules are good building blocks for membranes as they can be lined up with the water-interacting side facing one way and the lipid-interacting parts facing the other way to form larger structures.

The DENSsolutions Ocean In Situ TEM liquid system was essential in this research. The core of the system consists of a dual chip Nano-Cell that sandwiches two chips together to form a microfluidic compartment.

First, the chambers within the tip surrounding the Nano-Cell were flooded with an amphiphilic solvent in order for it to fill the compartment. The solvent was then expelled with air, leaving the compartment saturated. Then, the solvent was expelled with air, leaving the compartment saturated. Finally, the tip was flooded with water which gradually diffused into the compartment. It was during this stage that the water particles encouraged the solvent particles to organise themselves into a membrane structure.

Step 1. Polymer solvent

Step 2. Air

Step 3. Water

The membrane itself formed in stages. First, the solvent molecules arranged themselves into nanodroplets with a hydrophobic core and a protective hydrophilic shell. The DENSsolutions Nano-Cell created a hotspot of these nanodroplets and they gradually arranged themselves into a hollow membrane.

Diagram of the amphiphilic membrane forming in water. Arash Nikoubashman and Friederike Schmid.

Future Research

Watching how the nanoparticles form and arrange themselves with an electron microscope is a huge step in learning how to manipulate these membranes. The techniques covered in this research will be of interest to scientists working in food science, synthesis chemistry and separation science.

Hanglong Wu, who made a significant contribution to this paper during his PhD period, commented in an interview with DENSsolutions, that the technique “has been extensively used in studying the dynamics and structures of hard materials (for example, metallic nanoparticles) in the aqueous solution in the last decade, but it has been barely employed into soft matter field, mainly due to the inherent high beam sensitivity and low contrast.

“In this Nat. Chem. paper, we actually demonstrate we can probe the soft matter formation with such high contrast. People for sure will start to use the technique in the soft matter field.” – Hanglong Wu

The next stage will be fine-tuning how to manipulate the size and shape of the membrane. This research from Eindhoven is an important step in an exciting field.

If you are interested in the equipment we provided for this research, then contact us to see how we can streamline your experiments.

Introducing our newest team member

Introducing our newest team member

You can only be innovative and successful in a high tech field like in-situ TEM if you have a great team. At DENSsolutions we constantly look out for new talent to increase our application expertise. That is why we are very happy that Dr. Dan Zhou, who did her PhD study and second postdoctoral research at the Stuttgart Center for Electron Microscopy (StEM) in Max-Planck Institute for Solid State Research in Stuttgart, Germany, decided to join us.

We interviewed her to learn more about her history, her drive and passion for electron microscopy, and her choice of DENSsolutions.

When did you fall in love with TEM (transmission electron microscopy)?

It started from the last year of my undergraduate study when I was working with SEM (scanning electron microscopy). At that time, the more profound information with much higher spatial resolution from TEM gradually attracted more and more of my interest.

How did you get to know more about TEM?

I started my graduate studies with the basics of electron optics and general TEM techniques at Trinity College Dublin in Ireland. I did some research on different nanomaterials with the basic TEM techniques I had learned, and there I realized I wanted to pursue more in-depth TEM techniques with a specific target/direction.

So, my next decision was to go to the Stuttgart Center for Electron Microscopy (StEM) in Germany to work on quantitative TEM imaging and spectroscopy. And there, my passion in quantification with better accuracy, precision and efficiency drove me to join Prof. Paul Voyles’ group at the University of Wisconsin-Madison to work on a project that had collaborations with researchers from different professional backgrounds. And so on.

What exactly do you mean when you say that you wanted quantitative and profound knowledge?

We say quantitative in comparison to qualitative. For example, in a HAADF STEM image, if we see a higher intensity at one atom column position than the others, we know qualitatively that there are more atoms or heavier elements there. But quantitatively, how many more? Which heavier elements? We need to learn and develop techniques to answer with ultimate accuracy and precision.

Besides, modern TEM instruments have enabled the integration of various TEM techniques, and synchronized material processes. They provide the possibility of providing profound information, including structure, chemical bonding, chemical or physical processes, properties and so on, which is far beyond former possibilities.

What drives you to achieve accuracy and precision?

Well, accuracy and precision are very important in scientific research. They directly determine the reliability of our scientific data. Meanwhile, personally, I’m a person with strong curiosity and am easily self-motivated by challenges. The target of knowing quantitative information from TEM data is not as easy as it might seem. It has a lot of challenges. To complete it, I need to learn from, and collaborate with, a lot of scientists from different backgrounds, such as data scientists, material scientists etc, and, of course, professional microscopists.

Why do you think collaboration between scientists from different fields is so important?

I think it brings us opportunities now and then. We can’t be experts in all areas. Technology advances so fast. If we work together, then other experts could solve the problem you stumbled upon without striking a blow. Beyond that, you can also see more possibilities through the collaborations. Such collaborative research challenges, helps and inspires me from time to time.

When did you first come into contact with DENSsolutions?

It was during an in-situ workshop in Hamburg in 2014 where I met the VP of Business Development, Dr. Qiang Xu. He introduced me to the Wildfire heating system and DENSsolutions’ visions and ambitions in the in-situ world. I read a lot of literature about in-situ TEM starting from my master time and had done some heating/cooling experiments using the old traditional copper grids before I met Qiang. So, the low drift and precise control of  DENSsolutions’ Wildfire system really blew me away at that time. It was a very impressive and inspiring discussion.

How did you decide to switch from academia to a company and why did you choose DENSsolutions?

I actually wanted to step further into in-situ for some years. This feeling grows as my expertise in quantitative TEM improves. This might sound weird because a lot of people will tell you it is difficult/impossible to be precise/quantitative in in-situ worlds. But I really got depressed when coming to collaborators with quantitative TEM data and being told it was difficult to correlate it with their interests. I know it is not easy for the lab world to replicate the real world, which makes direct correlation between these two worlds less convincing or just impossible.

So I believe any effort in narrowing these two worlds makes sense for lab work to really contribute to real-world science and, eventually, applications. I want to see how these points improve as technology advances. In short, I want to bridge the lab world and real world with the pursuit of accuracy, precision and, ideally, also quantifications to make my devotion to scientific research more meaningful to human society.

For me, the visions and expectations of DENSsolutions’ vacant position in in-situ science attracted me to DENSsolutions, and then the switch from academia to industry happened as it came.  DENSsolutions has impressed me a lot in the past few years. It’s not only because of the overall capability of their products, but more importantly, the detailed features, parameters, and high level of scientific support to customers they keep pursuing. From my talks with people inside and outside the company, I got the idea that DENSsolutions has an excellent grasp of its area. The solutions they provide really touch the key concerns of scientific researchers. In short, the consensus in in-situ science with DENSsolutions and the belief in my own scientific curiosities and pursuits led me to join DENSsolutions.

I believe that by working at DENSsolutions I can benefit in seeing more possibilities of my former expertise and extend my scientific vision and possibilities. I would also be happy to communicate with the wider community to share each other’s knowledge, experiences and expertise.

You can only be innovative and successful in a high tech field like in-situ TEM if you have a great team. At DENSsolutions we constantly look out for new talent to increase our application expertise. That is why we are very happy that Dr. Dan Zhou, who did her PhD study and second postdoctoral research at the Stuttgart Center for Electron Microscopy (StEM) in Max-Planck Institute for Solid State Research in Stuttgart, Germany, decided to join us.

We interviewed her to learn more about her history, her drive and passion for electron microscopy, and her choice of DENSsolutions.

When did you fall in love with TEM (transmission electron microscopy)?

It started from the last year of my undergraduate study when I was working with SEM (scanning electron microscopy). At that time, the more profound information with much higher spatial resolution from TEM gradually attracted more and more of my interest.

How did you get to know more about TEM?

I started my graduate studies with the basics of electron optics and general TEM techniques at Trinity College Dublin in Ireland. I did some research on different nanomaterials with the basic TEM techniques I had learned, and there I realized I wanted to pursue more in-depth TEM techniques with a specific target/direction.

So, my next decision was to go to the Stuttgart Center for Electron Microscopy (StEM) in Germany to work on quantitative TEM imaging and spectroscopy. And there, my passion in quantification with better accuracy, precision and efficiency drove me to join Prof. Paul Voyles’ group at the University of Wisconsin-Madison to work on a project that had collaborations with researchers from different professional backgrounds. And so on.

What exactly do you mean when you say that you wanted quantitative and profound knowledge?

We say quantitative in comparison to qualitative. For example, in a HAADF STEM image, if we see a higher intensity at one atom column position than the others, we know qualitatively that there are more atoms or heavier elements there. But quantitatively, how many more? Which heavier elements? We need to learn and develop techniques to answer with ultimate accuracy and precision.

Besides, modern TEM instruments have enabled the integration of various TEM techniques, and synchronized material processes. They provide the possibility of providing profound information, including structure, chemical bonding, chemical or physical processes, properties and so on, which is far beyond former possibilities.

What drives you to achieve accuracy and precision?

Well, accuracy and precision are very important in scientific research. They directly determine the reliability of our scientific data. Meanwhile, personally, I’m a person with strong curiosity and am easily self-motivated by challenges. The target of knowing quantitative information from TEM data is not as easy as it might seem. It has a lot of challenges. To complete it, I need to learn from, and collaborate with, a lot of scientists from different backgrounds, such as data scientists, material scientists etc, and, of course, professional microscopists.

Why do you think collaboration between scientists from different fields is so important?

I think it brings us opportunities now and then. We can’t be experts in all areas. Technology advances so fast. If we work together, then other experts could solve the problem you stumbled upon without striking a blow. Beyond that, you can also see more possibilities through the collaborations. Such collaborative research challenges, helps and inspires me from time to time.

When did you first come into contact with DENSsolutions?

It was during an in-situ workshop in Hamburg in 2014 where I met the VP of Business Development, Dr. Qiang Xu. He introduced me to the Wildfire heating system and DENSsolutions’ visions and ambitions in the in-situ world. I read a lot of literature about in-situ TEM starting from my master time and had done some heating/cooling experiments using the old traditional copper grids before I met Qiang. So, the low drift and precise control of  DENSsolutions’ Wildfire system really blew me away at that time. It was a very impressive and inspiring discussion.

How did you decide to switch from academia to a company and why did you choose DENSsolutions?

I actually wanted to step further into in-situ for some years. This feeling grows as my expertise in quantitative TEM improves. This might sound weird because a lot of people will tell you it is difficult/impossible to be precise/quantitative in in-situ worlds. But I really got depressed when coming to collaborators with quantitative TEM data and being told it was difficult to correlate it with their interests. I know it is not easy for the lab world to replicate the real world, which makes direct correlation between these two worlds less convincing or just impossible.

So I believe any effort in narrowing these two worlds makes sense for lab work to really contribute to real-world science and, eventually, applications. I want to see how these points improve as technology advances. In short, I want to bridge the lab world and real world with the pursuit of accuracy, precision and, ideally, also quantifications to make my devotion to scientific research more meaningful to human society.

For me, the visions and expectations of DENSsolutions’ vacant position in in-situ science attracted me to DENSsolutions, and then the switch from academia to industry happened as it came.  DENSsolutions has impressed me a lot in the past few years. It’s not only because of the overall capability of their products, but more importantly, the detailed features, parameters, and high level of scientific support to customers they keep pursuing. From my talks with people inside and outside the company, I got the idea that DENSsolutions has an excellent grasp of its area. The solutions they provide really touch the key concerns of scientific researchers. In short, the consensus in in-situ science with DENSsolutions and the belief in my own scientific curiosities and pursuits led me to join DENSsolutions.

I believe that by working at DENSsolutions I can benefit in seeing more possibilities of my former expertise and extend my scientific vision and possibilities. I would also be happy to communicate with the wider community to share each other’s knowledge, experiences and expertise.