Using chemistry in a co-op research job

Co-op is great. As a third year Nanotechnology student who has now completed four of his six 4-month co-op work terms, I am obliged to praise this ever-rewarding system that the University of Waterloo calls “Co-operative Education”. I am not going to delve into details about this because once I start I will likely forget the actual purpose of this article — sharing my internship experiences in Boston, Massachusetts. Finding out about the benefits of co-op education online is certainly not difficult. This is not a shameless advertisement for the University of Waterloo! Other universities also offer co-op for certain programs.

Students wearing t-shirts that read, I love co-op, do you?

I still wouldn’t wear this shirt.

For the curious, I have just finished up an eight month co-op placement at a Nanomedicine research lab (Farokhzad Lab) at Harvard Medical School. It is essentially a cancer research lab where we attempt to efficiently target tumour cells via encapsulating our drug (or similar anti-tumour substance) into targeted nanoparticles. Thankfully, this lab also selected a few other students in my class to work here, and I was not left alone to face a new city.

While most of my work at Brigham and Women’s Hospital —which was my exact work location — is confidential research, I can certainly share some details. Although I am in an engineering program, my favourite courses, by far, are the ones that involve chemistry. This led to most of my co-op placements being in a chemistry environment, and ultimately I was hired by Dr. Xiaoding Xu at Harvard Medical School as an assistant in synthesizing drug-conjugated polymers for targeting tumours. For those interested, I’ll summarize my work over the next few paragraphs.

Over the past few decades, multitudes of new therapeutics have been designed for fighting tumour growth. Most of these new strategies have emerged in the form of new drugs, or new vehicles (therapeutic platforms) to administer those drugs. My work focused on the latter. These therapeutic platforms refer to a wide array of different nanoparticles that can encapsulate a particular drug (or drugs) and deliver it to tumour cells with high specificity. These “nanomedicines” depend on their chemical and physical properties to efficiently guide themselves towards detrimental cells in the body.

Multiple nanomedicines for drug encapsulation and delivery have been synthesized and successfully tested over the past few decades. However, several hindrances still exist. An ideal nanoparticle delivery vehicle needs to incorporate a variety of different functions in its physical, chemical and physiological properties. The nanomedicine needs to deliver the drug to the diseased part of the body without affecting healthy tissue on the way. Once at the tumour site, it needs to deliver its cargo (drug) with sufficient dosage. Moreover, the body should be able to expunge any remaining parts of the nanomedicine in a reasonable amount of time, during which time no toxic side-effects should be inflicted.1 Researchers all around the world have struggled to combine all of these properties into one nanomedicine. For sufficient blood circulation time, the nanoparticles also need to be of a particular size — usually
10-100 nm in diameter. This size enables them to take advantage of the Enhanced Permeation and Retention (EPR) effect. Compared to healthy tissue, the tumour microenvironment contains leakier and more permeable blood vessels with pore sizes ranging from 100 to 780 nm.2

The prevailing nanoparticle types so far have been liposomes, polymer conjugates/micelles, dendrimers, nanoshells and protein based nanoparticles. Among these, polymeric and lipid nanoparticles have proven to be the most promising in clinical trials.3 The following figure displays the relative nanostructure of liposomes and polymeric nanoparticles.

Drawing of liposome molecule in shape of a ball and polymeric nanoparticles in the shape of long strands that form a ball.

Nanostructure of liposomal and polymeric nanoparticles.3

My work focused on the development of polymers that were subsequently tested for making self-assembling nanoparticles. The main properties of the chosen polymer structures revolve around being able to quickly and efficiently degrade when exposed to specific stimuli, thereby releasing the encapsulated drug in the targeted region. I synthesized two main biodegradable polymers — one containing a Reactive Oxygen Species (ROS) responsive functional group and the other containing a UV light responsive functional group. Both these polymers were designed with quick and efficient degradation as priority properties. Condensation Polymerization and Atom Transfer Radical Polymerization (ATRP) were employed.

Although synthesis of just two polymers may not seem like a lot of work, most of the building blocks of these polymers were not commercially available, and I spent the majority of my eight months purifying and characterizing these building blocks.

But hey, I still love chemistry. The feeling induced by proof of pure product by an NMR4 spectrum makes this all worth it. Moreover, even though most things produced in research don’t work in the end, the chemical lessons learned along the way can provide a great stepping stone for other chemists — as well as yourself in future projects.

By now, I have spent over a year working in chemistry research labs. I have learned that although advanced chemistry knowledge is certainly necessary in designing and carrying out reactions to perfection, concepts that surface most frequently in the laboratory are actually ones that are developed in high school. No one at the lab is going to sit down with you and re-teach you basic mole calculations and acid-base equilibria, and you will need such concepts frequently. These aren’t just skills to be discarded in exchange for more advanced chemistry knowledge. The most important of such high school skills is most definitely basic lab safety and protocols. Wearing essential safety equipment, and the correct handling/disposal of chemical waste should be engraved inside students’ minds.

There can be a lot of things to focus on in the lab, and it is easy to make small but dangerous mistakes such as throwing chemical waste down the sink, discarding sharp needles in regular garbage bins, forgetting to put on lab goggles/gloves, or even eating/drinking near chemicals.

I hate to admit it, but two other vital skills that originate right in high school are report writing and lab book entries. I have often been asked by my supervisors to create a summary of my past month’s work or even the entire co-op. Moreover, my engineering program requires that I write detailed — usually over 30 pages including front/back matter — reports on my projects during an internship. With this in mind, keeping detailed and complete lab books is now arguably even more important to me. Honestly, I was one of the students who placed very little value in keeping lab notes during high school. Now, my chemical lab notes always involve a reaction scheme, a reagent table listing the names, molecular weights, moles, equivalents, masses/volumes, and — if needed — densities of the chemicals involved, as well as detailed observations of the reaction — especially regarding unusual or unexpected results. I try to also work out the mechanism of the reaction on rough paper before the actual reaction. This ensures that I fully understand what is going to happen — or is expected at least — once I start placing chemicals in the reaction vessel, which also minimizes potential mistakes and makes me much more comfortable while at the fume hood.

As much as I enjoyed my chemical synthesis, I did find time to do other things during my internship. Boston is a great city to live in. The lively, fast-paced environment is certainly relished by university students such as myself. However, it comes at a cost — literally. The cost of living here is high, and working at a research lab certainly hasn’t helped my cause. I used to complain about paying my $450 rent in Waterloo. The average rent in Boston is over a thousand dollars (US) per month.

Monopoly 1 dollar bill.

Not sure if this is real because I cannot recognize money anymore.

Do I regret accepting my position in Boston? No way. Working here has been one of the best experiences of my life. Of course, paying tuition for the next few school terms will be difficult. Thankfully, there are lots of scholarships, bursaries and student loans available to me, not to mention my next co-op placement.

Another thing worth mentioning — Boston is a cold place! Initially, I was fooled by the thought of moving from ‘Canada’ to ‘USA’. After an embarrassingly large amount of time, I realized

Boston is only 1 degree of latitude below Waterloo, Ontario. I should have expected the temperature to be roughly as cold.

Car buried in snow.

Look carefully to see the car buried under the snow bank — the passenger-side mirror is sticking out.

Moreover, my co-op term overlapped with one of the worst — perhaps best if you love snow and freezing temperatures — winters in the history of Boston. The majority of cars parked on the street had been completely engulfed in snow at least once over the past few months. Normally I would whine and complain endlessly about this weather, but fortunately I managed to acquire some extra cash via snow shoveling.

I have mentioned that I was fortunate enough to arrive along with a few of my colleagues. However, there is no need for any student to worry about travelling alone for co-op. There are always other interns to be found at your destination. Over the course of my internship, tens of other students from around the world have become new members of our lab. It is highly unlikely that you will be the only student hired by your employer.

Dr. Xiaoding Xu and Sushant Basin.

Dr. Xiaoding Xu (left) and I at a work party.

I have no doubt that co-op greatly enhances a student’s experience in many ways. I have relished all of my work terms so far, and they get more delightful each time. International co-op? Even better.

Currently I’m finishing up my third year of Nanotechnology Engineering, and preparing for my upcoming co-op position at Apple. To those who might be interested, I’ll be happy to share my experiences once it is over — although unfortunately this one won’t involve as much chemistry as before.

References and notes

  1. V.K. Khanna, Targeted Delivery of Nanomedicines, ISRN Pharmacology, 571394, 2012.
  2. J. Wang, Z. Lu, Y. Gao, M.G. Wientjes and J.L.-S. Au, Improving delivery and efficacy of nanomedicines in solid tumours: Role of tumour priming, Nanomedicine (London, England), 6.9, 2011: 10.2217/nnm. 11.141.
  3. V. Sanna, N. Pala, and M. Sechi, Targeted therapy using nanotechnology: focus on cancer, International Journal of Nanomedicine, 9, 2014: pages 467-483.
  4. Nuclear magnetic resonance (NMR) spectroscopy.