The diagnostic industry has come a long way from specialised testing that is limited to hospitals and pathology labs, to the ambitious “at-home” diagnosis , thus paving the way for easier diagnosis of many chronic diseases.
Apurva Bhasin, our next pathbreaker, Lead Scientist at PhageTech Inc (California), develops biosensors for label-free detection of bladder cancer biomarkers.
Apurva talks to Shyam Krishnamurthy from The Interview Portal about doing her PhD in electro-chemical biosensors, driven by her personal experiences and the urge to contribute to healthcare through rapid, cost-effective and straightforward “point-of-care” technologies.
For students, a career is a part of life; your life itself is much more than this. Its good to be ambitious, but even better to apply your skills to contribute to a better living, a better society !
Apurva, what were your initial years like??
Hailing from a middle-class family, I grew up experiencing various flavours of our country. My father is an engineer. Thanks to his job, we moved around four cities, Delhi, Mumbai, Pune, and Ahmedabad, before settling for an extended period in Bhopal. Each city had its warmth. Ahmedabad, in particular, is close to my heart. I made friends and am still friends with them even today! I remember my school, Sri Ram Vidyalaya. I was the teacher’s pet and would mostly be found in the loving arms of our principal then, Shashi Bhatt.
My love for dance as a child has been gratifying. As a 3-year-old in the inner circle of a big Garba group in Mumbai, I was awarded a pencil box by Raveena Tandon. While my parents just watched from a distance, I never failed to be a part of and lead dance performances throughout my school life. Honestly, my grades weren’t bad, my father looked forward to seeing my name in the top three, and I looked forward to the extracurriculars throughout the year. When I reflect, I feel that having something to look forward to sailed me through some of the difficult times.
We moved to Bhopal when I was in sixth grade. An unusual challenge welcomed me into the school. Having studied Marathi, and Gujarati, apart from the usual subjects, I barely passed my Hindi exam for most of my schooling. Interestingly, I was the top scorer in my class in the Hindi 10th board exam.
Apart from dancing, I actively participated in sports, skits, elocution, and debates. I realized I loved strategizing, assigning tasks, and leading a team. I never failed to go along with the fun and laugh away with the class, and those are the only moments I clearly remember more than studying. Being in an environment of ambitious and chilled-out students made it easier to sail through the most challenging decisions: 11th and 12th! I was inclined to creative writing and always thought English literature was the way to go. However, my father urged me to pick science in 11th, given my history of scoring well in science and crying through mathematics. I was very uncomfortable with the much higher standard of understanding required in 11th and 12th. I barely cleared my physics paper in 11th. Again, I don’t remember being overly touched by this. I looked at the other subjects where I was doing well in and moved on. One of my friends pushed me to join coaching classes for physics and chemistry; the environment was fun, and I successfully got through my 12th. At this stage, I was still wondering if I really wanted to do MBBS and clear PMT. My father had filled out so many PMT forms on my behalf and I went through all of those cluelessly, and failed each one of them. Naive to apply independently, I browsed through English literature courses offered at universities. Little did I know I was supposed to apply within deadlines (yes, real-life hardcore training was missing!).
What did you do for graduation/post-graduation?
I did my bachelors, masters and PhD in Chemistry.
My father had already filled in an application on my behalf for BSc Honours (Chemistry) at Institute for Excellence in Higher Education (IEHE, Bhopal). When I had wasted enough time fooling around, my father offered me the option to join this college if I didn’t want to waste a full academic year. Disappointed with the situation, I joined IEHE almost three weeks late. I landed on a day when I scored zero on a unit test (of course, that was my day one). I spent a week on the corner bench alone. Eventually, I was absorbed by a bunch of weird academic friends. We had a fantastic time in the laboratory. I gradually developed an interest in chemistry and enjoyed the practicals. The course was intense, but the teachers were dedicated and set goals for us to push ourselves and prepare for exams and life. Here, I learned to manage my time in the laboratory, clean up after finishing experiments, organize data, and write laboratory notebooks. My teachers were very critical of lab practices and notebooks which eventually helped a lot. I opted for biotechnology as my subsidiary subject. I graduated top of my class with a gold medal.
The part of the education I appreciate the most is that our exams are detail-oriented and require explanations. I loved to use a board and chalk to memorize concepts. Making notes on every topic prescribed in the syllabus was a great way to be prepared for exams. I relied on making flowcharts, using my funny mnemonics, acronyms, and acrostics. Most ideas were intuitive, and I framed answers based on these techniques. I liked verifying information from three books, at least, in the library. I want to say I liked the library more than I liked to google.
It is essential to mention that it mattered to me that my friends were very grounded in nature and had a tremendous influence on my personality. They were empathetic, helpful, skilled chefs and inspired me to learn beyond science.
What made you choose such an offbeat, unconventional and uncommon career?
Most of my friends had plans to deviate from science, and I was the only one to pursue master’s in chemistry. At this point, I had a goal in mind. I wanted to explore science and pursue a PhD at a foreign university. Even though my college was not one of the known colleges in India, I decided to stick to it for the quality of education and to make the most of it. I completed my master’s in chemistry with an internship in biochemistry from IEHE.
I spent most of my college time around young faculty. They used to share their undergraduate/ graduate or PhD experiences. They inspired me, encouraged me to pursue science, and even pushed me to apply abroad if possible.
How did you plan the steps to get into the career you wanted? Tell us about your career path
Research is very different from other fields. It can be utterly unpredictable in terms of how you end up in your desired career. It is a path that develops and even changes its course every 2-3 years. My first encounter with research was when I actively browsed through options to work for my master’s thesis project.
One must start looking for opportunities six months before the deadline. You would want to know the kind of research conducted in the prospective lab, associated publications, and whether those align with your research interests. I was not stuck on any one idea of research. My goal was to start at someplace in research. I chose Nirma University Ahmedabad, and the director of the Institute of science agreed to make an exception and accept me into the dissertation program.
My Research experience at Nirma University: Master’s thesis project
I worked with Dr. Mili Das, a protein biochemist. I worked on a project – Isolation, Purification, and Characterization of the enzyme from extremophiles.
The motivation of the research was to identify and understand the molecular basis of thermostable enzymes present in extremophilic bacteria. These enzymes find applications in industries as catalysts for reactions with non-natural substrates and under non-physiological conditions.
I successfully isolated the enzyme and identified it; however, I could never get to the molecular sequencing and understanding of the critical aspects for their stability in extreme environments.
Well, that is how science works. Remember that you can contribute to ongoing research or start something new, and someone else will continue it. Never live with the burden of finishing a theory.
Thesis writing is a crucial step in defending the research and the presentation. I had no experience in writing such scientific documents. But I indeed had the experience of making notes. For every section in the thesis, I asked myself what questions might crop up on the technique or the result. I summarized all my methods and added genuinely written procedures and observations. Uploading real setup pictures was an added plus. It shows you worked, and it becomes very relatable to read when the images are not just downloaded from websites. There is a lot of written content on everything available online. Just make sure you open four-five sites before choosing a pick to guide you through a question.
Research associate at Amity university:
Sometimes situations do not go in a pre-planned manner. I experienced a setback in my journey when I couldn’t apply for PhD at foreign universities after my master’s due to personal reasons. I had to steer my career path to an unexpected stop at Amity university. My mentor introduced me to polymeric hydrogels at this point. I had the basic skills necessary for synthesis, and now I learned how to read literature, prepare protocols, record observations, and optimise a procedure.
Thermosensitive hydrogels are an essential class of biomaterials primarily used as drug delivery systems. They are relatively inexpensive and well suited to deliver drugs in a minimally invasive manner. Many synthetic and naturally derived materials have been reported to form hydrogels. I worked on a thermosensitive hydrogel, a hybrid of natural and chemical composition.
Soy protein (SPI) was deployed as the natural polymeric backbone upon which N-vinyl caprolactam was chemically grafted. Both the integral components work synergistically, giving rise to biocompatible, stimuli-responsive hydrogel, which was further evaluated for application in controlled/targeted drug delivery. A thermosenstive hydrogel is temperature sensitive. The hydrogel was designed to swell and expel entrapped drug molecules at temperatures higher than body temperature. I studied the drug release kinetics for paracetamol. The application intended was to make a capsule that would, in case of fever, release a drug like paracetamol as the body temperature rises.
I had clarity about what I wanted to do after my research experience at Amity university. My fascination to contribute in research labs that can aid existing healthcare, motivated me to pursue work on hydrogels. However, my career had different plans for me.
Subsequently, I secured admission for the PhD program at UC Irvine (University of California, Irvine).
Research at UCI:
I did try hard to continue research on polymeric hydrogels. However, I eventually chose a research group developing biosensors. My interest in contributing to healthcare urged me to explore research in biosensors.
The diagnostic industry has come a long way from specialised testing that is limited to hospitals and pathology labs, to the ambitious “at-home diagnosis” , with an exciting journey ahead to ease the diagnosis of many chronic diseases, including the infamous cancer. It has found motivation in the growing prevalence of chronic diseases, the expense associated with the diagnosis and limiting access to a large population in need.
Undoubtedly, electrochemical biosensors have been amongst trending research over the past few years. The idea of marrying point of care systems with electrochemical transducers has demonstrated an excellent potential for rapid, cost-effective and straightforward on-site healthcare. The first-ever glucose sensor is the most successful example in this field. Electrochemical sensors can be based on transduction principles of amperometry, potentiometry, conductometry, chronoamperometry, electrochemical impedance spectroscopy (EIS), field effect transistors (FET).
This opportunity to develop an electrochemical biosensor as a point of care tool for the detection of cancer inspired me to join the project.
I developed and optimized an electrochemical biosensor, “The Virus-Bioresistor,” at UCI, under the supervision of Prof. Reginald Penner. I had theoretical knowledge but no hands-on experience in electrochemistry. The coursework at UCI, especially electrochemistry with a practical lab component, helped me understand the basics of the subject in a practical sense. I started with a new sensor construct, making gold trenches to house bacteriophage particles. My project was changed to making polymer-based biosensors. The sensor was in its initial stage of development, and a coworker had procured initial data. I did not hesitate to take up the new project. I failed to produce results for four months straight. A bit of literature reading helped me surf through the problems in sensor fabrication. I had 500 sensors worth of data with 40 % sensors that worked. A trip to the library and skimming through data helped me screen parameters that yielded working sensors. Thus, after constructing this prototype, I focused my PhD on characterising the sensor and learning how to tweak it. I did not deviate from the project hoping the sensor could be realised into something meaningful. VBR is a bacteriophage based detection platform, the bioengineered phage (a group of viruses that infect bacteria) detects the protein of interest. This research was possible in collaboration with a phage display laboratory. The sensor successfully detected molecules like human serum albumin, a kidney dysfunction indicator, DJ1 a potential bladder cancer biomarker, and IgG antibodies. It was licensed by PhageTech Inc to develop it further as a point of care diagnostic tool for detecting bladder cancer. Urine samples are the easiest to collect, and there is a deficit of non-invasive means of cancer detection. This sensor was developed to address the detection of cancer via biomarkers present in urine.
At the end of my PhD journey, I received the Graduate student award 2020 from the American Chemical Society. It was awarded in a virtual ceremony, thanks to the pandemic, while I was cooking rajma.
How did you get your first break?
The key to cracking the GRE was perseverance. Applying and getting admitted to UC Irvine was a path-breaking event. I had very little help. I had to rely on people already studying there, wait for answers, google a lot, and the rest of it was hard work. I had limited financial resources; I couldn’t join any coaching institutes. I relied on real experiences and aspirations while writing the “statement of purpose” document and carving my resume. I strongly encourage students to work on their resumes seriously and take professional help. While choosing universities, I felt it is best to search for reliable websites that rank universities for the specific program. Once you pin down the website, choose a mix of top, middle and lower-ranked universities.
Once I had offers, I not only chose to look into the research of interest but also the fun around the university. It is essential to accept the personality type you are. It is perfectly okay not to be so ambitious that you overlook what makes you happy. I chose beaches 😊
It was a bit nerve-wracking to start in a new country. However, good friends are the key to adjustment in a foreign land. The pressure to join a research group may tempt you to accept any offer. But if you are a PhD aspirant, I advise you to take your time. I appreciate that the US universities practice a rotation system that allows you to spend a couple of months with every research group. Study the culture apart from the science. Many people start with a passion for pursuing research thinking the environment won’t matter. But trust me, you choose an academic family for the next five years. Going through failures can be depressing, but a pepped-up environment can help you heal quickly.
My professor collaborated with phage display company PhageTech. And, he encouraged me to participate in the company scientific update meetings. My work at UCI was of interest to the company since the sensor was based on utilising the phage display and phage entrapment in sensors to detect biomarkers of diseases. I had proven the sensor’s reproducibility and versatility via my publications. The company was keen on establishing a sensor testing station of their own, and I was offered to set up the sensor lab and undertake clinical studies on the sensor. The company did not sponsor my PhD. My decision to take a bold chance at exploring research that I was unfamiliar with, was a stepping stone to being an essential key to the invention of VBR. And then, who fits the role of VBR research scientist better than the inventor? 😊
What were some of the challenges you faced? How did you address them?
Challenge 1: Adjusting to the quarter system from the semester system and in a new world. The challenge was accompanied by new teaching assistant responsibilities and choosing a research group for the Ph.D. program. Sometimes it is hard to juggle three things; this becomes harder away from the comfort of home and family. Find ways to discuss your problems. Never be ashamed to accept that the situation is complicated. Seek help. I also found solace in cooking. Find something that insinuates a sense of achievement. A minor achievement can give strength and confidence to sort things and move forward.
Challenge 2: My health degraded in the middle of my PhD. I was working on developing a biosensor prototype that would eventually detect bladder cancer. Unfortunately, I was diagnosed with thyroid cancer. However disheartening it was, I am grateful to have had the support of my advisor, lab mates, and other friends. Going through a major operation in a foreign country was a bit terrifying. I had to stop working on my project briefly. I perceived the situation as a way to take a rest and rejuvenate.
Where do you work now? What research problems do you address?
I work as a lead scientist at PhageTech Inc. It is a diagnostic company that has licensed the VBR (Virus BioResistor) technology. Since this is the technology I invented, all the observations recorded during my PhD were a great resource. Other than that, I learned how to align scientific experiments with company goals. A PhD is different from a research job. A problem may present the temptation to try many experiments to explore the cause. It would be best if you learned to choose which one will answer the question, be concise, and do not stretch over months. Unlike a PhD, every problem that is solved has a more significant implication. For example, the sensor at UCI was developed in a very controlled environment. All measurements were mostly recorded in buffers. On the other hand, the sensor had to be re-optimized at the company to keep the yield percentage high.
Troubleshooting is an inseparable part of research. It requires attention to detail and meticulous data recording and statistical analyses. Every day, experiments are planned, and modified as the day progresses.
How does your work benefit society?
At present, I am continuously testing sensors in actual patient urine samples. It is very satisfying to see a sensor developed in PhD produce a reproducible response, and take a baby step towards a point of care.
The hope is that the device can someday become a point of care tool for bladder cancer detection.
Tell us an example of a specific memorable work you did that is very close to you!
The VBR attracted a lot of attention at UCI. I got a chance to participate and lead live VBR demonstrations to potential investors and TAE board members. It was also streamed to celebrate UCI’s physical sciences department. It was the most amazing and successful teamwork put to display.
Your advice to students based on your experience?
We make things a bit difficult by being harsh on ourselves. Being focused is great, but acknowledging and practicing empathy is essential too! Don’t forget to spend time with your parents, chat with your friends, and smile at every opportunity you can. A career is a part of life; your life itself is much more than this.
I would like to continue being associated with science and help build diagnostic tools. However, life has its ways of throwing challenges and presenting opportunities. I am just open to anything that is in the store my way, anywhere I can contribute to a better living, a better society 😊