Cancer cells, Biophotonic and Chopsticks

Hello everyone, I hope everyone is doing well on their projects.

Laidlaw internship so far has been a fantastic journey for me. Meeting new friends, exchanging new ideas during CAPOD’s events and most importantly submerging myself into daunting tasks are priceless experience.

As this is the final week of my project I will summarise my process in this blog by starting with some background knowledge.

My project is a part of a bigger project which develops biophotonic tools to study biological processes. The concepts of the project came from many everyday life phenomena. One of them is the Doppler Effect which describes the shift in frequency when there is relative movement between a wave source and a detector. We see this effect regularly whenever an ambulance approaches us, its pitch will rise up and then drop down during its recession.

Simulation of Doppler Effect.
Photo Credit: The Physics Classroom. Access on 4 August 2017.

Within biological cells, there are waves and vibrations which are characterised by stiffness. As we fire a laser beam at the cells, the laser frequency will be shifted with the same concept similar to that of the ambulance. This method is called Brillouin microscopy.

This is how Brillouin microscopy works [1].

Another concept I have learned and used is thin layer interference, where light (consist of many wavelengths) is reflected from a surface and causes wave interference. This interference constructively strengthens the intensity of some wavelengths and destructively suppresses other, which explains why we see rainbow patterns on soap bubbles.

Thin layer interference in soap bubble
Photo credit: zacktionman via / CC BY-NC. Access on 4 August 2017

The cells will be put on a thin layer and as they exert forces, the thickness of layer which is measured by light will change. From the change in thickness, the forces can be calculated. This technique is called Elastic Resonator Interference Stress Microscopy (ERISM).

This is how ERISM works [2]

These two methods will provide us a robust and sensitive mechanical picture of cells. The mechanical properties are very crucial as they can be used to study calcification of heart problem, delivery of drug and especially invasion of cancer cells. The cancer cells have an interesting feature, they have sensors or “feet” that try to probe the weakest points on human membrane to invade. My supervisor’s group has planned to study these processes using the two methods combined, in hopes of understanding and further combating cancer.

Now, let me describe my experience of the past nine weeks using a famous Asian folklore that I learnt when I was eight years old as an analogy. One day, an old man gathered all his sons and daughters and gave them a challenge. The challenge involved breaking a bunch of chopsticks. Even though his children are strong and healthy farmers, none of them can fulfil the challenge due to the toughness of the bundled chopsticks.

An old man setting a challenge with chopsticks for his children
Photo Credit: Access on 4 August 2017

On my first few weeks of my Laidlaw internship, my task was to get the software of Brillouin microscopy working, using the guide lines from previous PhD students and other teams’ software’s notes. Once this part is done, it will be combined with the ERISM software. The software will reduce manual effort significantly and give researchers much more data in a shorter time. The task looked impossible at first glance, I did not even know what most of the elements of the previous software were. With only twelve hours of experience with the programming language, LabVIEW, that was used to program this software from my third-year lab sessions, the whole situation was best described using the pictures below.

This is what I have studied during my lab sessions. Photo Credit: Access on 7 August 2017

This was how the project seemed to look like. Photo Credit: Access on 4 August 2017

After the initial three weeks without producing any codes or ideas, I started looking for help from people around me. All the suggestions converge into one point: breaking up the task into smaller pieces. I tried to look at the bigger picture to understand the concept and find the point where I can start. With that correct methodology, I was able to control the first simple piece of hardware (the stage that moves the sample) in the fourth week. The most important camera was tackled two weeks later and I could finish up our initial plan by the seventh week of my internship. Looking at the process of the first part again, everything seems like an uphill battle for me. Finishing up the first part opened up many routes, acting as a stepping stone for me to delve further in the project. I am now working on combining two software together.

At that point, I suddenly realised the final part of the story from my childhood: After all of the children gave up, the old man showed them how to solve the challenge. The solution is amazingly simple by taking each individual chopstick and break them up one by one. The link between my obstacle and the story struck me strongly. This idea, though very simple, at the right context had further enlightened me. “This is what the cancer cells were trying to do as well” , I thought.

Since then, I can see how beautiful nature is, especially how such a message from a simple folklore is common between different objects. Next time, if anyone challenges me to break a “gigantic bunch of chopsticks”, I would tell them: ”Piece of cake!”.

Bunch of chopsticks
Photo Credit: Access on 4 August 2017

To sum up, I would like to acknowledge all of my supporters:
– To Lord Laidlaw, I am deeply grateful for giving us an opportunity to pursuit our passion and your vision on developing future leaders.
– To my supervisor Professor. Malte Gather, people of Gather Lab and especially Andrew Meek for listening to my problems and answering every single question. I will miss breakfasts and group meetings with lots of cutting-edge Physics on Monday mornings. Sorry to all who had to spend time to share the experimental set-up with me.
– To Cat and Harris, thank you for all of your efforts on creating such good events that inspired me, especially the Networking event and Leadership sessions. I found Action Learning Set (ALS) extremely useful and enjoyable. My ALS group (Billy, Patrick, Erin, Rachel and Veronica) filled me up with joys, discussions and ideas. I would like to thank them as well.
– To all of my friends who have helped me since I started my application and throughout my project: Thanks CD for proofreading my application and encouraging me to express more ideas on it even if it was during our terrific exam revision time; Jason and SinNee for sharing their individual experiences that helped developing my initial idea in a freezing cold evening at Tesco; Ryan Moodie for showing me where to focus and emphasize in my project and Dr. Aly Gilles for immediate support whenever I need help with basic LabVIEW knowledge or bugs.
– To Dr. Chuong Tran for the accommodation and lots of Maths discussions; all of my Vietnamese friends in St. Andrews. The meals we had together helped relieve my stress and strengthen my insight on my project.
– Finally, I deeply appreciate the support provided from my family, friends, Angus, Fiona, Judy and the St Andrews’s Bible study group who are always by my side and shaped who I am today.
[1] Scarcelli, G. & Yun, S.H. Nat. Photonics 2, 39–43 (2008)
[2] Kronenberg, N. M. et al, Nature Cell Biology 19, 864–872 (2017)

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