Episode 9: Biotechnology and DNA Microarrays with Associate Professor Meng Lu

In this episode, our guests are Associate Professor Meng Lu and his graduate student, Shirin Parvin, from the Department of Electrical and Computer Engineering (ECpE) at Iowa State University (ISU). Here, we talk about his research on sensors, microelectronics, optics and photonics, and the resources available for students to get involved in this area. This episode was conceptualized, recorded, edited, and produced by Santosh Pandey from the ECpE Department of Iowa State University. The initial sound editing was done by Ankita, while the transcript was prepared by Yunsoo Park and Richa Pathak from the ISU ECpE Department. The communications and digital hosting was handled by Kristin Clague from the ISU ECpE Department. The music was provided by ZakharValaha from Pixabay (Track Title: Melody of Nature (Main)).

Transcript

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Welcome to our ECpE podcast series, where we talk about exciting activities within our department. I'm your host, Santosh Pandey. Our guest today are Professor Meng Lu and Shirin Parvin, his Ph.D. graduate student, from Electrical and Computer Engineering at Iowa State University. Meng and Shirin, thank you so much for coming today. We want to talk about your research at Iowa State on Sensors, Microelectronics, Optics, and Photonics, and more importantly on how our students can get involved in your research efforts. To start with, Meng, could you introduce your field of research and why is it so important and relevant in this era of COVID-19 pandemic? Thank you, Santosh. It's very exciting opportunity to talk about our research here. We have two parts of the project. One part is the sensor. We make biosensors for sensing biomarkers, including proteins and DNA. We do have one work on COVID-19 detection to detect amino acids, in particular the RNA sequences to identify COVID-19 virus. And not only COVID-19, we are also working with a Professor in Veterinary Medicine, Professor Qijing Zhang. So, we are looking at PRRS and influenza virus for other types of infections. The virus concentration could be low and there are lots of interfering molecules. So , we use like centrifuge, we use on-chip technologies like magnetic beads to purify the viruses, and then do the downstream analysis. That's part of the bio-related project we are working on. So, on the other half, we are working on biomanufacturing. In particular, we try to synthesize genome, starting from short oligo that you can order from vendors like IDT (Integrated DNA Technology), but that's short sequence. So if you know, DNA consists of like four different type of nucleotides. So, we can order up to 100 nucleotide sequence. And then we got to connect them together. In the lab, we look at different ways. So, how to connect DNA molecules together to form a genome. And this type of work can also be related with COVID-19 right? For example, for the mRNA vaccine, it starts from a DNA template and amplified that and then do the translation to go from a DNA sequence to RNA, and then grab the RNA with lipid. And that became the mRNA vaccine. That is all fascinating research. Is that all of it done within electrical engineering department or some of it is done in the veterinary medicine school? Yeah, we do have collaboration, but most of the work, we do it here. We know how to do fabrication. We make portable devices to solve those problems. Great. So Shirin, I can ask you a related question. Could you talk about your particular research project and what does it involve? Yes, surely, the project that I'm working right now. Is a CRISPR based biosensor. For my project, I'm trying to detect nucleic acids for antimicrobial resistance. Dr. Lu, could you describe some of the facilities and equipment that are available in y our lab and Iowa state in general, for students interested in your group or in bioengineering, in general? When we build a lab, we looked at photonic type of sensor. We have a lot of spectroscopy instruments, like for example, spectrometer that can go from UV wavelengths all the way to infrared. From 200 - 300 nanometer to two micron to three micron wavelength range. Also we have Fourier Transform Infrared Spectrometer. And in addition to spectrometer, we do have different types of light source like lasers, LEDs, and pulse laser system. And we also have a couple of microscopes. In particular, we are using hyperspectral microscope. The hyperspectral microscope allows us to look at sample response for individual wavelengths. So you pick one wavelength and at that wavelength, we either measure transmission or measure reflection. And those systems are built for our sensors. When we have a sensor such as the microarray that Shirin is working on, we can measure hundreds of samples together. Our sensor for each spot is only around 100 micron size. So on a sensor size of like 10 by 10 millimeter, there will be hundred by hundred spots that can run 10,000 experiments simultaneously. And, for biological experiment, that's pretty well established - like bio safety cabinet, centrifuge, PCR, and gel electrophoresis. And if we need some expensive equipment or equipment needs maintenance, we just go to shared facility, for example, like flow cytometer or confocal microscope or SEM, there are shared facilities on Iowa State campus that we can use. Shirin, what are some of the tools and facilities that you fancy in your research? So obviously here, I would like to thank the ISU DNA Facility because, over there, we can do qPCR, try to manufacture oligos and such stuffs. It is directly not under the domain of EE but due to the shared facilities that really enables us to go for our research without any hindrances. Are there resources available within Iowa State that helps you train or do you work with the technician that is working with the instruments and get trained? For the instruments that we have in our lab, we generally get trained by Dr. Lu or any other senior students who have already used those equipment. And for the shared facilities, mostly we work with the technician, although we can get trained to use the SEM or the confocal microscopes by paying some kind of fees. Mostly it is like you talk with the technician, we set up a date and set up an appointment, which works for both of us. And then we take the samples, both together look at it Yeah. It's like project dependent. So if your project needs more fabrication, we are going to go to Microelectronic Research Center. MRC is also a shared facility. The lab hosts many different types of fabrication tools. So anything you can think of, it is possible to make them at MRC. You can do a fabrication, go from nano meter to micron, go from 2D to 3D. We have the capability to make it. We also have the characterization capability in the same lab. You can characterize, you can look at structure made, and you can measure the optical response and electrical properties of the devices at MRC. So for a new student, if they want access to all these fantastic equipment and all, how do they go about? Do they contact you or is there a formal way of getting access to these facilities and equipment? Yeah. So usually, I will just give some instruction to tell the student who to contact. So they're all available on the ISU webpage. Iowa State has a Biotechnology Office. They list all their equipment, send them an email, they will reply, and then you can meet them to discuss the projects with them, schedule time, and then run the experiment. Very simple. What are some of the challenges that you face in your research projects? Is it the difficulty in acquiring these nanoscale samples detecting very low levels of DNA or RNA, understanding the linguistics of biology or the tradeoffs between the cost of consumables versus how long does it take to finish a research project? Yeah, it's a good question. Actually those issues are the problems we are trying to solve. I would see that that's our goal, not really the challenge. And for the challenge, when we work on a project as an electric engineer, trying to solve biology problems, it's like how to interpret the data. And most of the samples we handle - its just like water. You won't be able to see it. So we are trained to measure current, measure voltage, waveforms, right? We know how to analyze the waveforms, but we don't know how to rate the testing result. When we plan our experiment, we need to prepare sufficient reference like negative controls and positive controls. If we are missing one of those control, the results may not be reliable. That's kind of the challenging part. So if we are missing a control sample, we have to repeat our experiment. That consumes more time and effort. I will say when we learn more and more, or we have a biomedical engineering program to train students, in that case, we will not have this problem, right? So when we start to plan the experiment, we need to think carefully. Additionally, I would like to add that acquiring the samples is definitely one of the challenges, because those samples need to come from lab sources, right? So we generally get our samples from either the CBE department or the Veterinary Medicine department. Especially for clinical samples, we are very much dependent upon the veterinary department. But even if we get those samples, then handling them, especially keeping in mind the safety procedures, that's a challenge. And also to add to it, the shelf life of most of these biological samples is very small. When you get the samples, you have to right away run the experiments and you can't wait till the next day, especially in the samples that you were talking about. Moving on Dr. Lu to the next question. How do you recruit new students to your group? What is the application process and are there funding that is provided to new students? Yes, of course. So if you are a student with interest in biomedical engineering or microfabrication, you're welcome to contact me, right? So you can just feel free. Send me an email. I will reply in 24 hours, guaranteed. And for the application process, we just follow the standard process set up by the university. You can contact me first. So if I see your background fit our research needs, so I will encourage you to apply. So most of the time, new students who come especially undergraduate students, they don't have much background in nanotechnology or any of the research that you are talking about. There is a hesitancy or reluctance What is your advice in such cases? I do have several of my graduate student. They got their undergrad degree from Iowa state, from our department. I taught those undergraduate courses, for example, EE 332 for semiconductor physics and material. And 432/532. Those students, they took my class. So we discussed after the class. And then before they make their decision whether they want to go to graduate school or not, we work on the senior design project. If they think graduate studies is what they want to do, they will stay. And also lots of those students get experience from the senior design and then that's helpful for them when they look for industry job. Yeah. So seems like you are a wonderful instructor and you have a good record of retaining students from undergraduate to graduate curriculum? Yeah, we have very good undergrad students here. So I think we, as faculty, train them pretty well. And in particular, they have very strong hands-on skill. Most of the courses, we have a lab component or we have lots of lab courses. So they not only learned knowledge in the classroom, and they can also apply that to steer their own project. Right. That is great. Dr. Lu, you're leading the biomedical engineering program initiative at the college level from our department. Could you tell us more about the biomedical engineering for students to enroll? Yeah, I'm part of that college's effort to organize a new biomedical engineering major. This got faculty input from mechanical engineering, chemical & biological engineering and electrical engineering. Also, we get help from outside of our engineering college, for example, biomedical science department in the Vet Med and also kinesiology. Right now, we are still in the planning phase. There will be three different tracks - biomechanics, biomaterials, and bioinstrumentation. And also we have faculty within bioelectronics and biosensors, yeah, that would contribute to the courses there. Yeah. I was thinking in the future, they are also planning for a new department. So if we can get enough number of enrollment, more and more students, so that will develop from one major in the chemical & biological engineering department, and then grow into a new department. That is a great vision for the future. What are some of the courses you recommend for students to excel in this field of bioengineering and sensor technologies, both within the department and outside the department? Yeah, it depends, right, whether it's an undergrad student or graduate student. They have very different requirement on the curriculum. If you are an undergrad student, there are many courses related with bio instrumentation and bioMEMS. And also some fundamental biology course will be very useful. And for graduate student, we do have graduate student courses. So for bio instrumentation and biosensors, we do have overlap of our research with semiconductor and material. Usually my students should take EE 432/532 for the micro/nanofabrication, EE 535, EE 536 for semiconductor physics and EE 438/538 for optoelectronics. And they build very solid background in electronics or electromagnetics, and then they can apply those knowledge to solve biological issues. Yeah. It seems like we have a wealth of courses, especially at the 500 level for graduate students. Yep. What are the specific courses you teach at Iowa state and what is the importance of taking these courses for students? So I have been teaching EE 432/532 for semiconductor fabrication, since I joined Iowa state at 2013. That is the course that teaches students how to fabricate, right, how to fabricate semiconductor devices like transistors and diodes. And also if you are not in the semiconductor field, you will learn how to do nano/micro fabrication from that course. So those are the processes you will use to make something that is small. And from time to time, I also teach EE 332. That's a fundamental course about semiconductor material. That's a biosensor course. We just introduce different types of sensors to students. Those sensors are from very different backgrounds, for example, we have electrochemical sensor, acoustic sensor, mechanical sensors, and of course, optic sensor, that's what I'm working on. So I'm also teaching for mechanical engineering department, ME 370. The course is called Engineering Measurement. That's about the principle about how to measure things. We just use off the shelf sensors like thermistors or accelerometers. And then we design the experiment to collect data. The course has quite heavy lab component, but students learn a lot from the lab. So Shirin, coming to you, what are your thoughts on the courses that are taught at Iowa state? The courses that you have taken and the value of teaching labs? First of all, I would really like to add that having lab components in the classes that I'm taking, obviously exponentially increases the whole experience of it. So for example, when I had taken EE532, I really learned the different processes of photolithography, oxidation, and all those step-by-step processes. Having the perfect combination of class and the lab makes the whole package deal, I would say. What's the career path that you are aiming for after you graduate from Iowa state? As everybody in our group usually takes those electromagnetics based classes or semiconductor based classes, I have taken all of them. I've taken EE 532, I've taken EE 538, EE 535, EE 536. So those really is preparing me for a career in the semiconductor business, if I choose to do so. At the same time, being able to make those devices and understanding the physics behind it, really is helpful because you are working on some experiments, it is reinforcing your learning. Dr. Lu, the students that have graduated from your group, what kind of companies have they gone after? And could you name some of the companies that have recruited your students in this field? Sure. Our student are trained as electrical engineer. So most of them went to semiconductor companies. For example, Sandisk, Western Digital, Intel or the companies they work for serves the semiconductor industry. Like for example, we had one student graduate last year, he went to Newport. So Newport is a company that makes optical component like lasers, opto-mechanical parts. Actually, his team is supporting ASML - it's the only company making high-end photolithography machine. Just the last question. What advice do you have for students who are hoping to build a career in biomedical engineering? If you are student who are interested in biomedical engineering, I will say follow the new development. So if you look at technology, like DNA sequencing technology or DNA synthesis technology which are pretty popular right now, if you look back like 20 years ago, they didn't even exist. Things change quickly! If you want to work in a field, want to have a career in this field, so you got to follow the new development. Spend some time every day to look at the news - whether some new technology comes out. Follow the Science magazine or Scientific America. They usually have the report, right? Talk with your peers or you can talk with a lab instructor, course instructor, the faculty members in the department. So they could explain that to you. So, Shirin, what is your final word of advice, especially for incoming students or potential students department? The sky is the limit. And obviously like Dr. Lu said, keep updated on the latest happenings around and talk your peers, talk to your mentors, talk to your professors, talk to anybody and everybody, and just try to gather information as much as possible and just approach people. That's. It? Yeah. That's great. So thank you both of you for our discussions today. I hope our listeners and students learned a lot about bioengineering, biosensors and particularly what department has to offer in these topics. Thank you again. All right, sounds great. Thank you. Thank you.