The Golden Ratio of Wires to Cells - Kirby Leo

Navigating the dark Zonneberg caves

Working with the heart-on-a-chip project has been an incredibly engaging experience. The project aims to develop a chip technology for in vitro cardiotoxicity assays. I’ve been testing electrical stimulations on cardiac cells and evaluating the effect of the cells on our microelectrodes. It’s been a lot of fun developing my computational skills (which were quite rusty coming in), and I’ve made it my personal goal to automate my data processing as much as possible. While I get to learn new software, like Origin (which I’ve found to have similarities to GraphPad Prism), I also get to apply some of my experience with image analysis to extract as much data as possible from my experiments. It’s also a pleasant break to only need to pipette around one or two days a week – some of my experiments involve wires more than cells and liquids. There is a lot of debugging that needs to be done with our setup, and I’m looking towards making the jump from MATLAB to Python in my work, but I’ve been getting a lot of helpful support from my supervisor.

With my team’s after-work dinners at Oude Markt, I have been able to share some of my American life while receiving cultural insight from my coworkers. Attending a European-style thesis defense (which, unlike the American public defenses I had been to in the past, was quite stressful with a jury full of questions) and having a blast at imec festival are just some of the highlights. I’ve even been able to connect with someone on my team who was a post-doc at Hopkins in the lab of my advisor! These have been opportunities for me to discuss and juxtapose the American research atmosphere with the one here.

Per suggestion of my team to use Flixbus, I took a weekend trip to Amsterdam with Christina and Sharada. There, we visited the Van Gogh museum, explored the city streets, and had a taste of the Holland gastronomy. Likewise, I took the Belgian rail with Elmer to visit the underground Zonneberg Caves and ENCI quarry in Maastricht. However, I’ve found that there are a lot of places to explore in Leuven itself, and I’ve also been taking time to explore locally with my bike. Starting with the bustling city center and serene libraries, I’ve been gradually immersing myself in Leuven life.

Some of the Zonneberg manmade cave entrances

                                             

The Science and the Medieval - Elmer Zapata-Mercado

Hallo vrienden! (Hello Friends!)

The mill behind me is still used
 by a local bakery in Maastricht.

Welcome back, reader! For the past two weeks I have been fully immersed in the research. As a refresher, my team here at imec is trying to develop a lens-less fluorescence microscope. The project is called Integrated High-Resolution On-Chip Structured Illumination Microscopy (IROCSIM) and is funded by the European Research Council (ERC), whom funds the best research in Europe. Anyhow, lenses are a fundamental part of the light-path and resolution of a microscope, removing these components will mean that loss of resolution will occur. The team has been working on a solution to this by applying a lot of physics, way before I got here, but I will spare you that part. Now the team wants to implement their system into biological samples, and that’s where I come in. I have been able to apply the knowledge I have acquired at JHU for the past four years, into this project. Like everything in science, nothing works perfectly. Cells sometimes “wake up” angry and they don’t want to cooperate with science. So, I have been troubleshooting the system in hopes of good results. Due to confidentiality agreements, I cannot say much about the specifics, but believe me when I say that things are going somewhat well.

Now, not everything has been work and science, since here in Belgium people strongly believe that the weekends are for friends and family. This is one of the most interesting things about Belgium, and Europe in general. Maybe we could learn something from our neighbors across the pond. Another thing I think we should do better in the US is bread! I haven’t had bad bread in four weeks, come on America, we can do better!  

Anyhow, the past two weekends I traveled to two magnificent cities, Brugge (Bruges in English, Brujas en español) in West Belgium, and Maastricht in the Netherlands. Brugge dates to the Bronze Age, those early settlements have nothing to do with the current medieval city that you can see today. The first fortifications were built by Julius Ceasar, and during its golden age the city was fundamental for trade in the area. After surviving both World Wars, nowadays the city is an UNESCO world heritage site for its Medieval architecture. To read more about Brugge here. Another city you can find East of Leuven, is the Southern Dutch city of Maastricht (pronounced ‘Mas-trixt’). Maastricht’s first settlements are believed to be from 50 B.C. but was officially formed in 1204. One of Maastricht’s best attractions are the underground (manmade) caves, Grotten Zonneberg. Spanning for thousands of miles, the caves served as limestone mines, WWII refuge, and path to freedom from the Netherlands to Switzerland. You can read more about it here.

 Tot de volgende keer! (Until next time!)

Me looking at one of the mural inside the caves. There’s an elephant (look above my head towards the center of the picture) when clearly they didn't exist back then. You can also see a skinny Loch-Ness monster looking creature in the direction of my finger.

Cross-Continental Cross-Linking- Hannah Christina Aspinwell

My polymer samples curing under ultraviolet light. 

Aren’t they pretty!

I’m fully in research mode now and it’s going well. To recap: my research project focuses on developing a polymer composition for 3D printing microfluidics by UV-lights. Advancements in digital light processing and two photon polymerization are making it easier to make many, high resolution, devices quickly. If we want these devices to function as microfluidic ones then we need to strike the correct balance in polymer-resin composition to ensure they have suitable properties. Among other things, we want the product to be hydrophilic enough for passive flow, strong enough to not break, and transparent so we can see what’s going on in there!

To achieve this, I am varying the concentration of photoinitiator and several polymers as well as the curing time. When exposed to UV-light, the photoinitiator begins a radial reaction that links the polymers together forming a new substance that needs to be characterized. It’s a lot like baking and, if I’m honest, the UV-curing station looks a lot like an oven.

Me preparing to contact angle measurements.

My day typically consists of planning, data analysis, and meetings in the morning and then experiments in the afternoon. So far fabrication issues have made contact angle measurements difficult but the Raman spectra revealing extend of curing looks promising! Hopefully, next week I will move to testing mechanical properties and incorporating a second polymer for crosslinking.

Working king at imec continues to be rewarding. The 

people are pleasant and there’s been no shortage of opportunities to socialize with them. The fluidics team held a BBQ where Tom and I got to swap homemade dishes with our coworkers. Also, a sweet American couple invited all the IRES interns to their home. We all appreciated their tips on living in Belgium and delicious caprese salad. Imec held a summer festival for the company with plenty of free food and people dancing in lab-safe shoes.

Outside of work, I’ve been traveling! Sharada and I went to Amsterdam with Kirby and we ran into Tom at the Paris catacombs. It’s fascinating to see how different the culture and language changes over the short distance between the two cities. Amsterdam was energetic and charming. I highly recommend the Van Gogh Museum. In Paris we saw Musee d'Orsay’s fantastic impressionist art and Sainte-Chapelle, which is breathtakingly beautiful, in addition to the catacombs and elegant city.

Kirby, Sharada, and I stranded at a rest stop when our bus to Amsterdam had to stop for 45 minutes after a traffic delay. 

It’s still difficult to parse how much of each experience here is European culture, imec’s culture, or engineering culture in industry. From what I can tell: unrefrigerated milk and eggs are European, having fries in the “health” section is an imec thing, and nobody knowing where the good lab tweezers are? Well that’s just science in general. Nice to know somethings never change.

Growing Responsibility-Thomas DiSorbo

Beautiful sky on the path
from imec to my residence

With a few weeks under my belt, my work at imec has gradually risen in complexity to the point where I feel fully immersed in the details and necessities of my project. I consider all my time under the tutelage of my supervisor Chengxun Liu to be learning experience and I feel that I have reached a milestone, one where I have the necessary training to offer real, independent contributions to our work.

With much of the infrastructure already in place (we are hoping to capture and lyse the cell using pre-existing electrode designs), one of my key tasks has been to design the nature of the electrical pulse. This is in part an optimization problem, as I have been using the mathematical models of our cells and electrodes to determine the boundaries in which our pulse must exist if we want lysis to be possible. Too high or too low a frequency can repel the cell instead of attract it, and too strong a voltage can damage the electrodes delivering the charge. 

Beyond working on modeling, my responsibility on the project has grown rapidly. That being said, I have yet to feel overwhelmed, as there exists a healthy amount of supervision at imec, where I am never sent to perform a difficult task I have not been walked through previously. My mentor and those who work around me take the time to explain to me any processes I am unfamiliar with, and all have the patience to discuss the theory behind everything we do. Once I have indicated I understand a process however, I am left to perform it alone. In this way, I can operate in an environment tailored to augment my professional confidence. While my work in the United States was organized with a similar trend of growing responsibility, I have noticed that my mentorship was less team oriented. Instead of receiving help from multiple sources within a department, my time at Hopkins has been spent under the tutelage of a single supervisor. While there are advantages and disadvantages to both systems, it has been a pleasure to embrace the more community-oriented feel at imec.

In my spare time on the weekends, I take advantage of my proximity to a number of fantastic cultural destinations. This past weekend I visited Paris in an incredibly memorable trip that I was lucky enough to be able to schedule without interrupting my workflow. 

Paris from the arc de Triomphe.

One month in!-Sharada Narayanan

The chip I am using to 
run my DNA extractions.

Not to sound cliché, but its so hard to believe that I’ve already been here for almost a month. I feel like a newbie, just got here, still trying to figure out imec’s convoluted floor plan, but when I step back and think about my time here, I’ve really experienced so much.

I’ve now begun to properly dive into my project here at imec.I’m working on optimizing DNA extraction on microchips to develop a simple and efficient process for PCR-on-a-chip: a huge step in the realization of point-of-care medicine. One of the best parts of working on my first truly engineering project is that the work has a clear purpose. The goal of my project is to go beyond the on-chip extraction of DNA in blood and viruses and begin developing a protocol for extracting DNA from bacteria, something that hasn’t been done before at imec. After running some preliminary experiments using blood, I’ve recently started running the DNA extraction using bacteria. Things have gone wrong and there aren’t a lot of people who can tell me how to solve my problems, but it’s exciting to be able to spend every day solving mysteries using both science and (organized) guesswork, knowing that my work is really going somewhere.

Infusing lysed blood into my chip.

Something else I have really appreciated about my internship at imec is the complete freedom I have during the weekends (and generally after about 5 PM every day) to go anywhere I want. Last weekend, I went to Paris. From the moment I arrived, I was overcome by the staggering old-world opulence of the city; it was truly unlike any other European city I’d visited. Not only was it beautiful, it was also enormous. Compared to Amsterdam and the small Belgian cities I’d visited, Paris went on forever: a behemoth of European culture and architecture. Though I have enjoyed travelling (and will be returning to Paris at least twice more this summer), I am looking forward to a few upcoming weekends of relaxation at home, exploring the beautiful city of Leuven, and finally cleaning my room.

Admiring the sweeping view of Paris 

from the Sacre Coeur.

Settling In - Sharada Narayanan

Me in Bruges

I’ve been living in Leuven for a week now and I have been quite busy with administrative chores ranging from registering as a visitor at city hall, setting up Wi-Fi in my dorm, and completing a myriad of trainings to begin work in the lab. Additionally, I’ve been spending a lot of time reading papers on my research project.

Buzzwords like “personalized medicine” and “point-of-need” medical care boil down to the need for fast, efficient, and cost-effective ways to identify genes in a patient’s DNA. Polymerase chain reaction (PCR) is a method that amplifies DNA for gene identification. However, PCR methods require sophisticated lab equipment, expensive reagents, and have long wait times.

Many advancements have been made in lab-on-a-chip technology, that is, using microchips with microfluidic reactors to perform PCR using the tiniest pin-prick of blood or cells. But the initial purification of DNA remains challenging to perform on a microchip without using a large, complex set-up. Alongside my mentor Rodrigo, we are refining the use of silicon micropillars for on-chip sample preparation of bacteria, and testing its efficacy using DNA concentration quantification methods and on-chip PCR assays.

Beyond work, I have been acclimating to Belgium life and exploring the surrounding area. There are bikes everywhere, no water fountains, friendly and laid-back people, and good bread. Everyone speaks English, but a lot of signs, menus, etc. are in Flemish, a particular challenge for me, a vegetarian, but I’ve been able to avoid catastrophe thus far.

Leuven is beautiful. Nestled between farmland, the residential area I live and work is lush and green with wood pigeons cooing in the trees. The city center is a quintessential European town complete with cobblestone streets bursting with shops and restaurants. This weekend Christina and I visited Bruges, Antwerp, and Brussels. Interwoven with canals, soaked with sunshine, and a waffle shop every 50 ft, Bruges felt like the perfect place to retire after a long and interesting life. Antwerp, cloudy and gritty, was the city to sit at a cafe in a black turtleneck and smoke. Brussels was historic and bustling and felt like the first truly big city I’d see in Belgium, fitting its moniker as “the capital city of Europe”.

The view from my dorm room in Wisteria

Digging Up Leads to an Exciting Adventure - Thomas DiSorbo

My first 10 days in Belgium were characterized by a positive uncertainty. Soon after arriving, a pervasive sense of anticipation followed me as I was introduced to my new environment, the small details of my work and lodgings, and of the city of Leuven itself coming together to paint a picture of this summer’s staggering potential. Even in the earliest days, this was apparent, that at no point during my stay will I ever feel like my routine has become predictable or sedentary, that I will have to be always on my toes, ready for the next exciting opportunity, fully aware it could be waiting just around the corner.

 A Liège Waffle

My work at imec this summer revolves around electrical partial cell lysis, and, like many challenges in microfluidics, it is in some elements an optimization problem. The project’s overarching project has two parts: develop a reliable process for electrically disassembling the membrane of an isolated single cell, and capture the intact, free floating nucleus once the cell membrane is ruptured. While I am in the early preparation stages of my experiment, the work I have completed in literature review and mathematical modelling has me flush with that positive uncertainty. There is so much room for growth and adaptation in the project that I am expecting very few days to look exactly the same.

Settling into Leuven was surprisingly easy, something I would attribute in part to the warm reception and introduction we received from members of the imec staff such as Laurien Mols and Carl Van Den Bulcke, who helped us settle into our lodgings and acclimate to our surroundings. The city itself maintains a surprising level of familiarity for its large population of over 100,000, and in the first week I found myself wandering its beautifully antiquated streets with no objectives beyond simple observation.

Me on the Brugge Canal

In the face of a more than adequately historical and interesting city, it is amazing to think how close I am to a number of other fantastic travel destinations. Belgium’s proximity to much of Western and Central Europe again fills me with that positive uncertainty. On any given weekend I could be in Paris, or London, or close to home in Brussels, exploring cultures I am extraordinarily fortunate to be so close to. 

There is little to be decisively said about my trip so far into Belgium. One of the only things I can say with certainty is that no day will come without the promise of adventure and achievement.