Installing South Korea’s second Stream system at Seoul National University

Installing South Korea’s second Stream system at Seoul National University

DENSsolutions Installing South Korea's second Stream system at Seoul National University

The team at SNU (From left to right) Prof Jungwon Park, Back Kyu Choi, Minyoung Lee and Junyoung Heo.

With the second ever installation of a Stream LPEM Solution in South Korea, we get an insider’s look at the microscopy laboratory at the Seoul National University. We interviewed Prof Jungwon Park from the National Center for Inter-University Research Facilities to find out how our solutions will benefit their research when investigating synthetic mechanisms of inorganic nanocrystals.

Can you tell us a bit about the microscopy facility at Seoul National University SNU?

Seoul National University has a shared research facility called NCIRF (National Center for Inter-University Research Facilities) that has specialities in various fields of analysis, such as organic, inorganic, surface analysis, and x-ray techniques. NCIRF also has a special team in electron microscopy, which provides SEM, TEM, and other pretreatment equipment including FIB and Nanomill.

This shared facility was established around 30 years ago. Recently, two spherical aberration-corrected TEM and STEM, JEM-ARM200F, were installed, providing atomic-resolution electron microscopy images. Also, in our own center, the Institute for Basic Science Center for Nanoparticle Research, we have our own JEOL JEM-2100F TEM in our building which is utilized routinely for a lot of in situ EM studies.

What type of applications are your users interested in with regards to the Stream system installed?

Our users are interested in various nanocrystal dynamics. Regarding the Stream system, we are expecting to investigate the synthetic mechanism of colloidal inorganic nanocrystals by changing the liquid cell temperature and injected precursor solution. Also, we are planning to investigate transformation phenomena of colloidal nanocrystals in various liquid environments. Moreover, we are expecting to observe polymers or proteins in liquid, and their stimuli-responsive reactions using the Stream system.

What particular features of the DENSsolutions Stream solution attracted you to the system?

When it comes to liquid cell TEM experiments, it is crucial to ensure that a controlled amount of liquid is injected to the desired position, while minimizing the decrease in spatial resolution of TEM stemming from the window bulging effect. In this sense, the Stream system by DENSsolutions was quite attractive to us.
With ensured liquid flow from Nano-cell design, controlled injection of liquid, as well as mitigated window- bulging originating from the pressure-based liquid pump, and also along with the liquid heating control system, the Stream solution seemed to help us to design various in situ liquid cell systems which were unachievable with other in situ holders.

What particular features of Stream attracted you to the system?

For our experiments, it was essential to find a way to control the flux of the liquid within the liquid cell in order to look at reactions or processes occurring on the location of the electron beam. This is something we were unable to do with previous generations of holders and chips. The DENSsolutions Stream system is the only system that allows you to completely control the liquid flux. This unique capability is what intrigued us most about the system.
Moreover, as a result of the Nano-cell’s special inlet-outlet design, we are also able to fully control the pressure and liquid thickness. Other features that we found very attractive include the control systems like the heating control unit and the pressure-based pump, which are considerably more elaborate compared to what we had in the past.

In your experience so far, how have you found the Stream system?

At first, the Stream system was quite complicated to us since a lot of elaborate systems were installed. But soon we realized that it was much simpler than it seemed. The method to assemble the Stream holder was easy compared to other liquid cell TEM holders, and the way to control the injection solution was straightforward. And since a lot of O rings are used to encapsulate the Nano-cell, the holder seems to be very stable without leakage problems while operating the TEM. Also, the heating control software was upgraded from the Wildfire version, making it much easier to use the program.

DENSsolutions Prof. Jungwon Park

Jungwon Park, Ph.D
Associate Professor | Seoul National University

Jungwon Park received his B.S. degree from the Department of Chemistry, POSTECH, South Korea, in 2003, and his Ph.D. degree from the Department of Chemistry, University of California, Berkeley, in 2012. After a post-doc with the School of Engineering and Applied Sciences, Harvard University, he started a faculty position with the School of Chemical and Biological Engineering, Seoul National University, in 2016, and he currently serves as an associate professor jointly affiliated with the Center for Nanoparticle Research, Institute for Basic Science (IBS). His research areas include the in-situ study of nanomaterials, liquid-phase TEM, phase transitions, interface chemistry, and low-dimensional materials.

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The first direct observation of pharmaceutical non-classical crystallization

The first direct observation of pharmaceutical non-classical crystallization

Using the Ocean system, scientists achieve supersaturation in LPEM experiments, revolutionizing pharmaceutical crystallization

 

Original article by Jennifer Cookman, Victoria Hamilton, Simon Hall and Ursel Bangert

LPEM video showing the pre-crystallization process of flufenamic acid

Whereas classical crystallization deals with layer-by-layer growth of crystals, non-classical crystallization (NCC) involves multiple different crystallization pathways towards the formation of final stable crystals. Although NCC has been widely documented in research, there is still much to be explored regarding the intermediate stages of crystallization and their direct observation. This is especially true for small organic molecules like flufenamic acid (FFA), an anti-inflammatory drug used for the treatment of rheumatic disorders.

Using the DENSsolutions Ocean LPEM system, Dr. Jennifer Cookman from the Bernal Institute in the University of Limerick and her colleagues were able to capture the intermediate pre-crystalline stages of this small organic molecule. This research marks the first ever direct observation of a pharmaceutical material undergoing NCC, highlighting the rising value and importance of in-situ TEM techniques in the pharmaceutical industry. 

The observed processes of NCC

Crystallization is a fundamental process that occurs in nature to produce some of the most common materials in daily life, such as the popular active pharmaceutical ingredient (API) ibuprofen or FFA. Properties such as solubility and bioavailability are linked to the crystal structure of the active compound. Considering APIs are commonly polymorphic, it is important to understand the intermediate stages of their crystallization. Specifically, if we can identify polymorphs with more desirable properties in the intermediate stages of crystallization, then this opens the door to harnessing and potentially directing their formation.

In this study, Dr. Cookman and her colleagues observed in situ the processes involved in the nanoscale crystallization of FFA. As illustrated in the figure below, this process involves four stages: aggregation, coalescence into a metastable entity, nucleus formation, and finally, crystallization.

A summary of the observed processes involved in the nanoscale crystallization of FFA

The researchers observed that FFA begins as a collection of small independent pre-nucleation clusters (PNCs). These PNCs are essentially stable particle clusters that form prior to the nucleation of a solid phase. They were able to follow three notable aggregates of PNCs that each followed the same transformational events. Particularly, after aggregation, these PNCs each independently coalesced, or merged, and formed a metastable phase. After this, the densification and development of a nucleus occurs, leading to the formation of FFA crystals. The processes of coalescence and densification will be further discussed and depicted below.

Coalescence

The aggregation of the PNCs were shown to have occurred prior to the researchers’ initial observations. Therefore the primary transformation observed for the three aggregates was actually that of coalescence. In the image below, you can see clearly that for each of the three selected aggregates, the individual clusters merge to form one cohesive entity after approximately 3 minutes.

A time-lapse of each of the three aggregates of PNCs undergoing coalescence

Densification towards crystallization

Following coalescence is the densification and development of a nucleus. This nucleus is formed by the successive sacrifice of surrounding material, leading to the formation of a new crystalline-like object, significantly more electron dense than before. Whereas coalescence took around 3 minutes, this densification occurred rapidly in under 10 seconds. The image and three videos below depict this rapid pre-crystallization process of FFA. 

A frame-by-frame summary of the three aggregates illustrating the pre-crystallization process of FFA

Aggregate 1

Aggregate 2

Aggregate 3

Novelty in findings

This research contributes academically in that the direct observations reported for the crystallization of FFA reveal insightful new information about the potential pathways towards crystallization. Moreover, it highlights the need to further investigate the nucleation and resulting crystallization of other small organic molecules via in situ techniques such as LPEM. LPEM presents itself as a required and complementary tool to not only comprehend but also probe chemistry at the nanoscale. This is true especially in regards to the crystallization of pharmaceutical ingredients, in which the development of the end product highly depends on controlling at the molecular building block level. 

The novelty of this research also lies in that it sheds light on the crystallization and nucleation of pharmaceutical products, providing the necessary information to further refine industrial-scale processes. If we can observe and understand the crystallization pathways that small organic molecular crystals like FFA take, we can better streamline production activities and develop effective manufacturing processes for generic drugs. It is precisely our goal at DENSsolutions to enable researchers like Dr. Jennifer Cookman to continue to bridge gaps in research using our solutions and uncover results that can impact this world, in the pharmaceutical industry and beyond.  

DENSsolutions Jennifer Cookman

“The DENSsolutions Ocean holder is a simple solution to native environment metrology that has the potential to revolutionize how we view pharmaceutical crystallization.”

 

“The DENSsolutions Ocean holder is a simple solution to native environment metrology that has the potential to revolutionize how we view pharmaceutical crystallization.”

Dr. Jennifer Cookman
Post Doctoral Researcher | University of Limerick

Original article:

 

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Meet our new Regional Sales Manager, Dr. Eva Bladt

Meet our new Regional Sales Manager, Dr. Eva Bladt

DENSsolutions Eva Bladt
DENSsolutions Eva Bladt

Building strong and long-standing customer relationships has always been a paramount objective at DENSsolutions. In efforts to increase our impact in the Nordics, Benelux, the U.K. and Ireland, we needed somebody who could further strengthen our ties with customers and expand our user base in these regions.

We have found just the right person to carry out these responsibilities, Dr. Eva Bladt, our new Regional Sales Manager. Eva has a comprehensive understanding of materials science and electron microscopy, as well as a strong interpersonal skillset that allows her to communicate her extensive knowledge with ease. Her role at DENSsolutions is focused on further establishing relationships with our customers in the Nordics, Benelux, the U.K. and Ireland, enabling scientists to tackle their complex research questions using our innovative in-situ solutions.

We asked Eva to introduce herself so you can learn more about her education, background and role at DENSsolutions.

Eva’s academic journey

“My name is Eva Bladt and I am 30 years old. I was born and raised in Antwerp, Belgium and have lived there my whole life except for last year when I moved to Melbourne, Australia for 6 months. When deciding what I wanted to study after high school, I actually had three options, all of which were exceptionally different from one another: a Bachelor’s in Dance, a Bachelor’s in Medicine and a Bachelor’s in Physics. After months of deliberation, I decided to pursue a Bachelor’s in Biomedical Sciences. Six weeks later, I realized I had made the wrong choice. I discovered that medicine didn’t excite me the way physics did, so I changed my studies and pursued a Bachelor’s in Physics instead. I immediately felt that this degree was a better fit for me.

I graduated with a MSc in Physics in 2013 from the University of Antwerp. During my Physics education, I developed a passion for materials science and electron microscopy. This translated into a Bachelor and Master thesis under the supervision of Prof. Dr. Sara Bals, a true expert in the field of electron tomography. After graduating, I started as a PhD in Sara’s group at EMAT (Electron Microscopy for Materials Science), one of the leading electron microscopy centers in the world. I focused on the 3D structural characterization of functional nanoparticles, particularly metallic and semiconductor nanoparticles. To pursue this PhD fellowship, I received a personal FWO (Research Foundation – Flanders) grant.

After receiving my PhD degree in 2017, I continued as a post-doctoral researcher at EMAT, which was also funded by a personal FWO grant. I mainly carried out atomic structure characterization studies of perovskite nanostructures and 3D thermal stability investigations of metallic nanoparticles. During my post-doc research, I was very fortunate to have had the opportunity to perform a research stay at the Monash Centre for Electron Microscopy in Melbourne, Australia, under the supervision of Prof. Dr. Joanne Etheridge. During this research period, I focused on the 2D and 3D characterization of twinned metallic nanoparticles. This was a truly unique experience both on an academic and personal level.”

A new career path

“Although I’ve been a part of the academic world for quite some time now, I decided it was time for me to embark on a new career path. Moving away from academia was definitely not an easy decision, as nanoscience is undoubtedly where my passion lies. However, I couldn’t deny that I was longing for some change in my life. I wasn’t quite sure exactly what role I was searching for, but I knew it had to allow me to stay close to the field.

“I knew right away that this position was meant for me, not only because it allows me to stay close to the field of nanoscience, but also to exercise my passion for communication.” – Dr. Eva Bladt

When searching for positions a couple months ago, I came across an opening for Regional Sales Manager at DENSsolutions, a company whose solutions I was highly familiar with already. During my thermal stability studies, I worked extensively with the DENSsolutions Wildfire solution, an in-situ TEM heating system that has always impressed me, particularly for its extreme stability even at high temperatures. I knew right away that this position was meant for me, not only because it allows me to stay close to the field of nanoscience, but also to exercise my passion for communication. Aside from conducting research, I have always enjoyed communicating and presenting my results and have done so at various international conferences.

I think that my background in materials science and electron microscopy is of high value to this role particularly because I am able to understand customers’ specific research needs. This will allow me to step into the mind of the customer and better address their needs, ultimately enabling them to perform more meaningful research studies. I am really excited to be getting in touch with scientists in different fields and hope to expand DENSsolutions’s customers base with satisfied customers who will achieve ground-breaking insights using our solutions.”

Thank you for reading this article. If you would like to know more about Eva, don’t hesitate to contact her via email or LinkedIn.

Discover Eva Bladt’s Wildfire publications

3D characterization of heat-induced morphological changes of Au nanostars by fast in situ electron tomography 

 

Thermal stability of gold/palladium octopods studied in situ in 3D

 

Quantitative 3D characterization of elemental diffusion dynamics in individual Ag-Au nanoparticles with different shapes 

 

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