Computers, Cleanrooms, and Castles

Over the last few weeks, I have started working with more complex computational techniques including finite element analysis. To conduct finite element analysis, I am using COMSOL Multiphysics software and high-tech computer clusters. After I design an acoustic system, the procedure for finite element analysis involves creating a two-dimensional or three-dimensional representation of the system including geometry, physics, and boundary conditions. Finite element analysis works by approximating the solutions of the resulting differential equations numerically across a user-defined mesh. The final results involve detailed information about the system like pressure and physical stress for each element of the mesh.

Currently, my group is working on creating basic prototypes of the acoustic systems that I designed using additive manufacturing (aka 3D printing) and lab equipment. We are going to be testing these prototypes in a small lab at IMEC.

IMEC Academy also offered tours of the cleanroom and support area at IMEC 1. Fellow JHU intern Chris Argento and I decided to register for the only tour offered in English this summer. For the tour, we dressed up in white cleanroom suits and walked through a class 1000 cleanroom. While there, we learned about types of experiments they conduct such as lithography, nanofabrication, and etching. The cleanroom itself was huge and contained extremely complex equipment and sections designated as class 1. The support area tour gave an introduction to the equipment required to maintain the air quality and humidity of the room, the chemical processes used to neutralize the waste, and the safety procedures in place in a dangerous event like a fire or gas leak.

On the weekends, I have been taking both group and solo trips around Belgium to Antwerp, Brussels, and Ghent. Each city is different with its own distinct attractions and styles. Antwerp had several tourist neighborhoods lined with American brands like Subway, H&M, and McDonalds along with many residential areas. For Brussels, I have so far only visited Central Brussels where Manneken Pis, the Grand Place, and museums are the main attractions. Hopefully, I will have time to visit Brussels again on the evenings since all my weekends are booked! The highlights of Ghent were the architecture, Gravensteen Castle, St. Bavo’s Cathedral, and the Bourgoyen-Ossemeersen Nature Reserve. The city had many scenic walkways along the canals, and the view from the top of the Gravensteen Castle was an awesome sight.

The professional experience working at IMEC has introduced me to new engineering techniques, and the traveling and cleanroom tours have taken me to places that, prior to the program, I could only dream of visiting.

Michael Signorelli is a second-year Biomedical Engineering undergraduate at Johns Hopkins University

IMEC 1

Brussels Grand Place

View of Ghent from the top of the Gravensteen Castle

Belgium brews and summer views

Hallo from Belgium! We arrived in Leuven about a week and a half ago, and things have been going well so far. Our first few days were spent running around Leuven doing some administrative things and settling into our studios at Wisteria, a KU Leuven dorm building near imec. Each of us has our own bathrooms and kitchens, which I’m grateful for, and the rooms came furnished and stocked with some basic cookware and utensils. Michael, Chris, Lakyn, and I all live next to each other on the ground floor, and Lydia is living the penthouse life on the first floor.

We stayed in Leuven for our first weekend since we wanted to get a better feel of the city. A member of Lydia’s lab, Eric, was nice enough to give us a bike tour of Leuven and we got to see Stadhuis (Town Hall), Groot Begijnhof (a monastery built in the 1200s), Botanical Garden Kruidtuin, and Oude Markt (Old Market, also known as the longest bar in the world!). I loved seeing all the old Gothic architecture and seeing how easy-going Belgians are. There are always people sitting outside cafes, sipping on cold beers and talking with friends.

By Monday, we had fallen into our summer work routine. At 8:30 am, we bike from Wisteria to imec and work for a few hours until lunch at 11:30 am with some of our other lab mates. Occasionally, we join a few of them for coffee at Java – the Brody Café of imec – and return to our desks a little before 1 pm. Our workdays usually comes to an end at 4 or 4:30 pm. However, I suspect our afternoons at imec will become longer as our projects progress and more experiments need to be performed.

Leuven is a fairly small city – it has the vibes of a nice college town – and the cheapest and most convenient way to get around is by bike. Oude Markt is a great place to hang out and have a cold beer (surprisingly, the legal drinking age is 16 here) with friends after work. In fact, Lakyn’s lab organizes weekly dinners at Oude Markt, which we all joined in on this past Tuesday.

During our second weekend, we took a day trip to Antwerp. Antwerp is an old city with a lot of history, and it was super cool to see the different style of architecture, art, and beer this city had in comparison to Leuven. Unfortunately, some of the museums and churches we wanted to see were closed for that day, so we spent most of our time outside admiring the beautiful building facades. I think our bad luck was made up for by the food: fries and Belgian waffles. So yum! We got back to Wisteria around 8 pm and after walking over 10 miles, we were beat.

Even though it feels like we just got here, the time seems to be flying by fast. Many more weekend trips are to come, and I’m excited to see where our travels take us. Until next time!

Stephanie Cai is a rising junior BME with a focus area in Instrumentation. At Hopkins, she is a member of the Wang lab, a leader for Encore Music Group, and on the board for Society of Women Engineers. 

Weekend Trips to Bruges and Amsterdam

The recent personal highlights of my summer are trips to Bruges and Amsterdam. Two weekends ago, Chris, Lakyn, Stephanie, and I visited Bruges. Chris and I decided to stay overnight in a hostel. Since the weather that weekend was warm and sunny, the train to Bruges was packed with families and school groups heading to the beach city Ostend.

Bruges is the capital of West Flanders and the location where the movie “In Bruges” was filmed. The first and probably the most interesting attraction we visited was the Belfort. We climbed up hundreds of narrow stairs to view different exhibits pertaining to the history and function of the Belfort and culminating with a 360 degree view of the city at the top. While there, we purchased a museum pass that gave us access to several attractions in the city, notably the Groeningmuseum (art) and the Sint-Janshospitaal (a historic hospital that has since been converted into a museum). We also did a canal boat ride, and stayed out until dark to see the canals, the Historic Centre, and the Burg Square lit up at night.

The trip to Amsterdam this past weekend was the most exciting trip yet. I met up with Chris and a BME undergraduate from JHU. We decided to rent bikes, which turned out to be a great idea since there were thousands of bikers and lots to see in the relatively large city. After biking through several famous neighborhoods like The Jordaan, we got free entry to the number one museum in Amsterdam: Rijksmuseum. The Rijksmuseum was huge with artwork ranging from paintings to doll houses to furniture to porcelain. We visited all the exhibits except the “Gallery of Honor” which had about a three-hour wait. We rounded out the day with biking around Vondelpark and taking a canal boat ride. Chris couch-surfed for the night, while I stayed in a hostel.

On the second and final day in Amsterdam, we met up and visited the Anne Frank house (we snatched tickets online a few days before to avoid the long wait). The historical aspects of the place made it an especially intriguing place. We also found cheap student tickets to the Dutch National Opera and visited the Dutch Royal Palace. For dinner, Chris and I tried bitterballen, which are a Dutch snack consisting of a meat paste covered with breadcrumbs that're fried with a side of mustard. That, along with the Dutch version of chicken tikka masala, were interesting meals.

Back at IMEC, we fabricated my prototype using a special type of 3D printer that builds upside down using an ultraviolet laser to cure resin on a plate. It is extremely detailed (albeit expensive) with a precision of 25 microns. I recently received certification to work in the former Clinical Lab at IMEC to conduct the acoustical experiments on my prototype. I will be working with ultrasound transducers, acoustical waveguides, and oscilloscopes.

Michael Signorelli is a second-year Biomedical Engineering undergraduate at Johns Hopkins University

View from the top of the Belfry in Bruges

The Belfry in Bruges at night

Canal in Amsterdam

Figure Captions

· View from the top of the Belfry in Bruges

· Canal in Amsterdam

Groovin’ in Leuven

It’s been a crazy two weeks over here, getting accustomed to living in a new country with a different language, unexplored streets, and countless people to meet. Though it was a little rough at first, I think we’ve finally settled in here in Leuven and we’re starting to fall into a routine.

The first few days of work at IMEC involved a lot of training, reading, and getting to know the people in my lab group. I didn’t have the greatest background knowledge in my project before I came, but now I’m getting the hang of things and starting experiments next week. Our group is developing heart cell on-a-chip technology for the evaluation of pharmaceuticals in development—with lens-free imaging, contractile measurements with electrode arrays, and calcium imaging, one can analyze a drug’s effect on the typical behaviors of cardiac cells before putting it on the market. I’m excited to start working with electronics, as I’ve learned about them in various classes, but haven’t had a chance to get practical, working knowledge until now.

Besides the 9-5 weekdays at IMEC, we’ve been able to explore some new places. Leuven has fields and rolling countryside in addition to its bustling city center—when we first arrived to our dorm, we saw a couple of goats next door as well as a field of horses down the street. The city has amazing architecture, cobblestone streets, and countless shops and cafes. One of my favorite places that we visited in Leuven was Kruidtuin, Belgium’s oldest botanical garden. It had hundreds of different kinds of flowers, plants, and trees, and the weather was perfect to just walk around and take in the sights. We walked around the Groot Begijnhof, a neighborhood built in the 13th century that once served as a community for pious women and nuns. Within the heart of Leuven is Oude Markt, a street lined with bars, restaurants, and cafes that is always full of people, whether weekday or weekend, night or day.

This past weekend a few of us went on a day trip to Antwerp, a city with more cool architecture and statues. Though some of the museums we wanted to visit were closed, there was plenty of other sites to see, including the train station, which was gigantic and beautiful. We toured a brewery and spent the day walking around sightseeing, which wasn’t complete without a Belgian waffle ;)

Excited to see what else is in store for us here in Leuven! Thanks for reading! 

Lakyn Mayo is a rising junior in Materials Science and Engineering at Johns Hopkins University and an IMEC intern with the Johns Hopkins Institute for NanoBioTechnology International Research Experience for Students program. 

Train station in Antwerp 

Belgian waffle topped with chocolate

Oude Markt

Just a Drop

I have certainly hit the cobblestones running in my first taste of Belgium. Within the course of a week I have moved into my apartment in the converted monastery of Wisteria, biked the storybook streets of Leuven, and sampled one of the local badminton clubs. Badminton is a very popular sport here, which is ideal for an avid player like me. This weekend four of us Johns Hopkins students visited Antwerp, arrived in the world famous rail station and toured the brewery of the local beer, “De Koninck.” We also enjoyed traditional waffles with dark Belgian chocolate drizzled on top, completing the cultural trifecta of beer, waffles, chocolate. Antwerp was a gorgeous, fashionable city, far larger and more tourist-oriented than our new home of Leuven. Already there are machinations for more trips on the days between our diligent weeks of work at IMEC.

In the laboratory at IMEC, I am working on microfluidic droplet technology under Yannick Vervoort, a PhD student who is collaborating through KU Leuven. In this technique, liquid droplets are captured in an emulsion within the micrometer-scale channels of a glass-silicon chip, where they can be manipulated and analyzed in various ways. In one application, numerous different genetically-engineered yeast strains can be grown in separate droplets and evaluated at rapid speeds. The process is orders of magnitude faster than traditional culturing of yeast in flasks. The ultimate goals of this application are characteristically Belgian: to identify superior yeast strains for the production of biofuels, chocolate, and beer.

I have completed most of the procedural and training tasks and have already begun my earliest experiments. My first challenge is to determine a method to extract droplets from the silicon chip, store them in a larger vessel, and then later reintroduce them for examination. This way we can process even more droplets! For now, I’m simply trying to avoid the rain droplets that fall frequently but delicately on the ancient city of Leuven.

Chris Argento graduated from Johns Hopkins with a bachelor’s degree in Chemical and Biomolecular Engineering and has continued on in the same department to pursue a master’s degree in the laboratory of Joelle Frechette.

Leuven badminton club.

Droplets travel through a microfluidic chip

Living in Leuven and Other Alliterative Accidents

Good morning America! Or, in a more accurate summary of my readership, hi Mom! My name is Lydia and I am one of the five Johns Hopkins students interning with the Inter-university MicroElectronics Center (IMEC) this summer through the Institute for NanoBioTechnology (INBT). I just finished my undergraduate degree in biomedical engineering (BME) and will be starting my Master’s in robotics this fall.

As someone who always wanted to study abroad, applying for the INBT internship program with IMEC wasn’t a hard decision. I’ve worked with robotic prosthetic limbs in the past and am hugely fascinated by the idea of interfacing the human nervous system with machines; I probably read a bit too much science fiction as a child. I was therefore thrilled to find out that I would be working with a new electroencephalography (EEG) headset for the summer. EEG is a non-invasive way to record brain signals. While it can be used to record all kinds of signals, I am most interested in how it could be applied to interpret motor intentions (i.e., this change of voltage indicates my desire to wiggle my robot hand). The headset I’m working with for the summer uses only four dry electrodes and can be easily put on and taken off quickly, so it could potentially be used in real-world settings outside the lab.

However, using dry electrodes instead of the more common gel-based ones comes with drawbacks. So far the headset can only distinguish between two motor classes, left and right. My goal for the summer is to introduce at least one more state, no movement, so the headset can also tell when no command is being sent.

I officially started with the rest of the interns on June 2, but in actuality, that first half week was dedicated to finding internet passwords, hunting down grocery stores and passing safety training. This week the work began for real. Reading someone else’s code is always a tricky business, so it wasn’t until this last Thursday that I really started changing things and trying new approaches. I had brief delusions of grandeur on Friday and thought I had solved the whole problem in my first week; not surprisingly, that did not happen. On the bright side, I still have something to work on for the next nine weeks.

Outside of work, Leuven looks so different from any American town I’ve ever seen. From an infrastructure perspective, the streets are narrower and the bike lanes are wider; from a historical perspective, more than half the buildings are older than the country I was born in. Fortunately I’ve met some really great people who have shown me and the other students around on our recently rented bikes. I share an office with Eric, a PhD student from Beijing, who took us on a bike tour of the city last weekend. We also went out to dinner twice this week, first with Lakyn Mayo’s lab (Lakyn being another INBT-IMEC intern), then with some other interns we met. It’s a really beautiful place to work, and I’m looking forward to exploring more.

Lydia Carroll is a 21-year-old biomedical engineer on her first excursion to the European mainland. In her free time she enjoys taking things apart, putting them back together, volunteering with the Maryland SPCA, and reading any paperback novel she can get her hands on. 

Lakyn and me after a night exploring Oude Maarkt.

Eric, our volunteer tour guide, showing us the KU Leuven library.

The convent in the center of Leuven. Built in the 1200s, for centuries it was one of the only places women could come and be educated. It now serves as dorms for one of the many local universities.  

Work hard, play hard

I think it was the wise Wiz Khalifa who said "work hard, play hard," a phrase that comes to mind when I think about my summer in Leuven so far. My weekdays are filled with many hours at imec, constantly going back and forth between my cozy office desk and the convergence lab where I conduct my experiments. On the weekends I find myself traveling all over - from little towns in Belgium to bigger, more touristy cities like Rome (where I went this weekend with Gwen and Victoria). Between these two, I haven't been able to sleep in past 9AM. Yet, I find this summer to be really interesting, rewarding, and fun.

I've been able to finish the first part of my project!! It dealt with optimizing PCR efficiency by testing different hydrophobic coatings and seeing which gave high fidelity while still producing the similar results to what we had originally. So while I'm processing data for that part, I'm starting a new, but similar project: a digital droplet PCR that takes approximately 10 minutes rather than 1 hour.

 Rodrigo said that I'll be using the best coating (chosen by the data I got from the first part of my project) and testing different assay and surfactant combinations to find the best one for this process. While I will still be using the same equipment and devices for running the experiment and analyzing the data, I think this will definitely show me other aspects of on-chip PCR that I didn't have time to look at previously. And honestly, the best part is that it only takes a fraction of the time from the regular ddPCR so I'll be able to do more experiments within a day.

Let's talk about my travels: I went to Rome this weekend! I've never been to Italy before and let me just say, every part of it was amazing. The food, the sights, the people - all perfect. I think the weather was a little too hot for me (I got my first sunburn ever) but I just ignored that and cooled down by eating a lot of gelato.

What I liked most about Rome was all the fountains spread across the town. This seems like such an insignificant thing when you compare it to Palatine Hill or the Coliseum. But after spending hours in 34C degree heat, these little spouts seemed like gold to me. I'm being dramatic, yet I do think having these potable drinking fountains were nice especially since it let me avoid spending mucho dinero on the water bottles from tourist traps.

Overall, the past weeks have been wonderful, both work and play wise. I'll definitely keep updating as my new project goes along and as I continue my adventures to Germany this weekend.

---Rachel Bang

PCR, programming and Dublin

Since my last blog post, my research project has moved from doing some preliminary testing using a commercially available PCR cycler to a droplet-in-oil PCR setup. The setup is challenging because it involves lots of tiny microfluidic elements, but the process has started to become easier as I gain experience with it.

St Michan's Church

We are using ImageJ and Matlab to analyze our data, so I’ve had to familiarize myself with ImageJ and refresh my memory slightly on Matlab programming. As a computer science minor, I have been enjoying putting some of those skills to practical use! At Imec I think we have settled into our work and have a better understanding of what to expect.

This past weekend, I returned to the English-speaking world by making a trip to Dublin, Ireland. It was my first time traveling alone, but it went smoothly and I’m glad I made the trip! My favorite part of the trip was visiting Bray, a seaside town not far from Dublin. There I was able to hike up a large hill called Bray’s Head to some incredible views of the surrounding sea, town, and mountains. 

Another highlight was a tour of the crypts at St. Michan’s church. There, the constant temperature, the release of methane gas from the ground, and moisture absorbing limestone walls caused the bodies in the crypts to become mummified. The tour was extremely interesting and engaging in large part because the excellent tour guide. Overall I found Dublin to be friendly and enjoyable!

---Gwen Hoffmann

After climbing Bray's Head

The Comfort Zone

While planning this blog, I had a really great idea to do a “Top Five Things I Learned From Leuven” post, with cute little anecdotes illustrating how I’ve changed and what challenges I’ve faced working in this environment. But as I started brainstorming ideas, I realised that everything I was thinking of all fell under the same umbrella, and could be summed up nicely in one sentence:

It’s okay to feel like you have no idea what you’re doing.
From the moment I stepped off the plane and had to search for my luggage, find which train headed to Leuven from signs in a new language, and make my way to our dorm, I was bewildered, confused, and unsure every step of the way - all before even getting to work! Perhaps where I felt it most poignantly was in my second week of work, when I analysed waveguides on my own for the first time. Though I’d used the system several times before, I was still second-guessing myself the entire time getting the laser aligned and the microscope ready. The whole time I wondered to myself, why are they letting me be in charge of this (very expensive) equipment all by myself, when I haven’t even been working for a full week?

Moments like this were a common occurrence: finding the right train to get to Brussels, buying food without understanding what was in it, trying to navigate a completely new city, working on projects at IMEC that were completely new from what I’ve done at Hopkins. I was completely, totally out of my comfort zone.

But from this, I learned. I learned that you have to trust yourself, and trust the skills you didn’t know you had. Though I had never worked with waveguides or optical fibres, within a couple weeks I could analyse entire sets in an hour or two, more efficiently than anyone expected. Though I’d never worked with cardiac cells or micropatterned chips, I worked entirely independently for two weeks while my supervisor was at a conference in the States, and was able to get a lot of good data and refine our protocol along the way. In high school and at Hopkins I’d learned the basics - how to use a microscope, how to culture cells, how the cells actually work, how to analyse and present data. And for the first time, it was up to me to use these skills without anyone looking over my shoulder, and make something meaningful using them. “What am I doing?” turned into “Yeah, I got this,” and I’ve come out of it much more confident in my skills, both in what I’ve been used to doing, and my ability to adapt to new situations and use what I know to solve the problems I’m given.

I’ve also learned how important a supportive team can be. My first time using the fancy confocal microscope, I wasn’t very confident that I would do it right. But two of my team members were there, who offered to answer every question I had and help if I didn’t know how to use the system or something wasn’t working. My supervisor himself, if we were struggling getting something to work, would suggest that we take a water break and just have a few minutes to chat before returning to our work with clearer heads. Even though they’d only known me for a day or two, my team welcomed me with the proverbial open arms, and I never felt like I wasn’t part of the team for a single second. Something as simple as having lunch together every day made the experience much more meaningful than just getting the work done and collecting data - I made new friendships, heard the suggestions of others, and gained practical knowledge pertaining to both the lab and life in Leuven.

So, I learned it was okay to feel like I didn’t know what I was doing. Because I could trust myself and what I know to solve the problems in front of me. Where I stumbled, I could trust my supervisor and my team to be there to help and guide me, or even just make me laugh in a day full of hour upon hour of imaging cells.

Being out of your comfort zone isn’t a bad thing in the least - it’s when you find out how much you can really do and how much you can really grow. Because of that, I’ve learned to trust my own abilities, and how important having a diverse group of people to work with can be. More than anything I’ve learned about heart cells or lens-free imaging, these are the lessons that will stick with me.

--- Rebecca Black

This is Not a Microscope

This is not a microscope. This is only an image of a microscope, an image of a lens-free microscope to be exact. This is the first you’ve heard of a lens-free microscope? Well, the technology has been around since the 1950s, although they used mercury lamps instead of lasers, which were invented in 1960. It was developed around the same time as electron holography, which is used in transmission electron microscopes, that we are now familiar with and by the same scientist Dennis Gabor.

This microscope utilizes the principle of digital in-line holography. Very simply the main components are a small laser and a complementary metal oxide semiconductor imaging chip that is used as a platform. It uses a laser which when in contact with an object on a platform creates interference waves which are picked up by the chip, converted via several complex algorithms and displayed on a computer.

Figure 1: Schematic of in-line digital holography. The laser (L) illuminates a pinhole (P) which acts a point light source. Spherical waves are produced from the pinhole. First the waves illuminate the object (O) and produce reference waves ( ¾ )and interference waves (−−−) that constitute the hologram at the screen (C). (http://www.pnas.org/content/98/20/11301.full)

What are the advantages to this microscope? It has a larger field of view than traditional microscopes, which means the data it collects is more likely to be statistically significant. It’s also much smaller and portable, and it’s lack of significant hardware makes it easier to conduct experiments, especially when you want to keep your cells alive in an incubated environment.

At imec we’re using the lens-free imaging to track cancer cell migration. On paper it doesn’t sound that exciting, but in practice it means that the possibility of understanding how cancer cells work in 3-D environments within humans. This is exciting for a lot of reasons including the fact that we can change a variety of variables that will impact these cells. For example, we can treat cells with a chemotactic drug, image them and see how that impacts motility with the general hope that it will halt metastatic process. Of course there are lots of steps in between for these conclusions to be upheld, but in the meantime, I get to run experiments on breast and prostate cancer cells using a lens-free microscope.

Figure 2: Lens-free imaging prototype

A side note: the popular phrase “this is not a pipe” or “ceci n’est pas une pipe,” which was adapted for my title, is from René Magritte’s The Treachery of Images. Magritte is a Belgian surrealist artist who is featured in a four-story exhibition in the Royal Museum of Fine Arts in Brussels. The idea is that the pipe is only a representation since you can’t physically hold the pipe or fill it with tobacco. At the Royal Museum you can see an extensive collection of Magritte’s art as well as works from the Renaissance to the Contemporary periods.

Figure 3: “This Continues Not to be a Pipe” (a successor to “This is Not a Pipe”) featured at the Royal Museum of Fine Arts, Brussels. The original Treachery of Images is currently housed in the Los Angeles County Museum of Arts.

---Victoria Laney