Translating research into applications at IDMxS: An interview with Prof Lim Chwee Teck
11 September 2024
Biography: Professor Lim Chwee Teck is a Principal Investigator in the Translation Cluster at IDMxS. He is the inaugural NUSS chair Professor at the NUS Department of Biomedical Engineering. He is also the Director of the Institute for Health Innovation and Technology (iHealthtech) and the Founding Director of the Singapore Health Technologies Consortium.
Prof Lim’s interdisciplinary research interests include human disease mechanobiology and microfluidic and wearable sensing technologies for healthcare applications.
Prof Lim completed his PhD at Cambridge University after graduating with a BEng in Mechanical Engineering from the National University of Singapore. Among his many prestigious accolades, he was recently elected as a Fellow of the Royal Society.
What initially sparked your interest in biomedical applications and molecular analytics?
Prof Lim: I am a mechanical engineer by training and completed my PhD in mechanics at Cambridge, and not in molecular analytics. However, upon returning to Singapore right after my PhD, I was appointed as an Assistant Dean at the National University of Singapore (NUS). One of my initial tasks was to assist in establishing the NUS Bioengineering Programme.
This role really threw me into the deep end of biology and medicine—areas I had limited knowledge in at the time. But it turned out to be a fascinating experience. I became genuinely intrigued by the idea of applying my mechanical engineering skills to these new fields. It was exciting to think about how my expertise could help address some of the challenges in medicine.
While I knew that biomechanics was an existing field, I wanted to take a fresh approach, using mechanics to uncover the underlying causes of certain diseases such as malaria and cancer. So, I started leveraging my engineering background not only in studying diseases, but also leverage on new knowledge gained to develop novel devices for better disease diagnosis and therapy. It’s been a rewarding journey so far to see how my skills can make a difference in these critical areas. Recently, I have moved into exploring the use of aptamers as a form of molecular analytics in disease detection and diagnosis.
What areas of research are you exploring at IDMxS?
Prof Lim: At IDMxS, we’re exploring how electrochemical methods can be used to diagnose diseases. We’re specifically focusing on developing sensors that combine aptamers with electrodes. Aptamers are single-stranded RNA or DNA sequences designed to bind to specific targets. When an aptamer binds to its target, it undergoes a conformational change that alters the current, potential, or impedance of the sensor, allowing us to detect the presence of the target.
Right now, we’re applying this technique to monitor wounds. Our sensors can be placed on a patient’s wound to quickly and remotely assess whether it’s healing properly or if there’s an infection. We’re excited to be moving towards commercializing this technology through a startup collaboration between IDMxS and NUS, with plans to launch within the following year.
What motivated you to join IDMxS?
Prof Lim: When I joined IDMxS as a collaborating PI from NUS, I was excited to dive into the Institute’s diverse range of expertise. My goal has been to enhance the precision of aptamer sensing technology here, aiming to detect even single molecules. The fantastic collaborators at IDMxS, along with the top-notch facilities and support, have been instrumental in advancing my research. I’m particularly enthusiastic about exploring our electrochemical approach to tackle other diseases, like flu viruses and even cancer.
What advice do you have for translating research into real-world solutions?
Prof Lim: We always start by talking directly to the end users—in our case, the clinicians. Our approach is to deeply understand their needs and challenges so that we can tailor our solutions to be more user-friendly in a clinical setting. When we develop solutions that meet their needs, clinicians are more likely to advocate for and use them.
This user-centric approach helps address one of the major challenges of translating technology from the lab to real-world applications. Another key challenge is ensuring that the technology is intuitive and easy for both clinicians and patients to use, so we make usability a priority from the start. Additionally, we consider scalability early in the design process to ensure that the technology can be produced more cost-effectively in the future.
What do you think is unique about IDMxS?
Prof Lim: IDMxS is uniquely equipped to tackle some of today’s most pressing challenges. These problems we’re addressing, such as those in healthcare, are incredibly complex, requiring expertise from multiple fields. That’s why the diverse expertise and collaborative spirit at IDMxS are so crucial—they enable us to navigate these challenges effectively and innovatively.
What are the next steps for your research?
Prof Lim: At IDMxS, our electrochemical sensor represents a versatile platform technology with the potential to detect a range of diseases, including cell-free circulating tumour DNA. These biomarkers, found in blood, are released from lysed cancer cells. We’re working on adapting our technology to identify these circulating tumour DNA markers, focusing initially on lung cancer and specific drug-resistant mutations.
By detecting these mutations quickly—within just 15 minutes—our technology offers a more efficient and cost-effective alternative to traditional sequencing tests. This allows for rapid adjustments in medication to target these mutations more precisely, a process we refer to as precision therapy.
Do you have any advice for young researchers entering this field?
Prof Lim: For young researchers, embrace curiosity, persistence, and a willingness to learn. Collaborate, seek mentorship, and stay updated on advancements in your field. Ask important scientific questions and work on something that not only motivates you, but which will also benefit the society. Treat setbacks as learning opportunities, explore interdisciplinary approaches, and stay passionate.
Click here to learn more about our research and how we are unlocking the power of every molecule in the digital age.
Seminar – Asst Prof Claudio Bussi
Dear All
We would like to invite you to our upcoming seminar on Sep 20, Friday.
We are pleased to have Asst. Prof. Claudio Bussi, from the School of Biological Sciences, NTU, to present his talk on
Navigating Endomembrane Damage: Insights into Lysosomal Function, Stress Granules, and Host Defense
Please register your intent to attend at https://forms.office.com/r/phxrL1LhVN, before 18 Sep, Thur, 12 noon.
Registration will commence at 2:45pm on the day of the seminar event and all attendees are to be seated by 2:55pm. Light refreshments will be provided for registered attendees.
We look forward to your attendance and support for our seminar event.
Thank you.
Early-career Researcher Seminar (IDMxS-ERS)
We would like to invite you to our next Early-career Researcher Seminar (IDMxS-ERS), along with a special guest seminar on 27 Aug 2024, Tue, 10am – 12.15pm in the IDMxS foyer (NTU, EMB Lvl 7). There will be a short intermission between 11am to 11.15am before Talk #3 begins. Refreshments (coffee, tea, and various snacks) will be provided for all registered attendees (beginning 9.30 am, arrive by 9.50 to enjoy).
Register your intent to attend at https://forms.office.com/r/zvemPKjScy.
Our talks for this event will be:
Talk #1: “Science Communication in the Age of ChatGPT”
Presented by: Andrew BREESON, PhD
Project Manager & Communications, NTU – IDMxS
Talk #2: “From Noisy Images to Knowledge – an Introduction to Imaging FCS”
Presented by: Radek MACHAN, PhD
Senior Research Fellow, NTU – NOBIC
Talk #3: “Real-Time Biosensor Technology” (read more here)
Presented by: Prof Tom SOH, PhD
Professor of Radiology (Early Detection), of Electrical Engineering, of Bioengineering, and of Chemical Engineering, Stanford University
This is a continuation of our 2023 IDMxS Postdoc Seminar series, now rebranded to IDMxS-ERS to be more inclusive of other research positions. Our focus remains on giving research communication opportunities to researchers at or near the level of a post-doctoral research fellow. We are very actively looking for speakers in 2024, and anyone interested (postdocs or senior students) can use the registration form or email us at idmxs-events@ntu.edu.sg for more info. Nomination of speakers from peers or advisors is also encouraged.
Thoughts on our seminar format? Let us know what we can do better for future sessions through this feedback form.
We look forward to your attendance and support for our seminar event!
Seminar – Prof Tom Soh
Dear All
We would like to invite you to our upcoming seminar on 27 August, Tuesday.
We are pleased to have Prof. Tom Soh, Professor of Radiology (Early Detection), of Electrical Engineering, of Bioengineering, and of Chemical Engineering at Stanford University, to present his talk on
Real-Time Biosensor Technology
Please register your intent to attend at https://forms.office.com/r/zvemPKjScy, before 26 August, Monday.
Registration will commence at 11:00am on the day of the seminar event and all attendees are to be seated by 11:10am.
We look forward to your attendance and support for the seminar event.
Thank you.
Seminar – Prof Jwa-Min Nam
Dear All
We would like to invite you to our upcoming seminar on 21 August, Wednesday.
We are pleased to have Prof. Jwa-Min Nam, Department of Chemistry, Seoul National University, to present his talk on
Chemical Plasmonics with Nanoparticles for Biomedical Applications
Please register your intent to attend at https://forms.office.com/r/Dq0mzhsJ4u, before 20 August Friday.
Registration will commence at 10:45am on the day of the seminar event and all attendees are to be seated by 10:55am. Lunch will be provided after the talk (for registered attendees only).
We look forward to your attendance and support for the seminar event.
Thank you.
Professor Atul Parikh Explains the “Tango Between Oily Droplets and Liposomes” for Nature Chemical Engineering
Prof Atul Parikh, Lead for the IDMxS Detection Cluster, published a News & Views article in Nature Chemical Engineering on 25 July. Prof Parikh’s piece, titled “Controlling transport across artificial cell membranes,” delves into groundbreaking research on the dynamic interactions between oil droplets and liposomal membranes, exploring new mechanisms for molecular transport in synthetic cells.
In the article, Prof Parikh reviews the recent paper, “Interfacial energy-mediated bulk transport across artificial cell membranes,” by Assoc Prof Nan-Nan Deng et al., which explains how energy-dissipating oil droplets can form reconfigurable passageways that can shuttle biomolecules across liposomal boundaries.
Prof Deng’s work presents a novel approach for achieving transmembrane transport without the need for sophisticated protein machinery. Their approach also circumvents the conventional endocytic routes in living cells, which induce large-scale membrane disruptions. By leveraging the wetting-dewetting transitions of oil droplets within liposomes, researchers have achieved a programmable movement of the droplets and, thus, the molecular cargoes such as enzymes, ions, and DNA oligomers contained within them.
Prof Parikh’s commentary emphasises the potential of these findings to inspire new strategies in reconstituting cell-like behaviours in synthetic compartments and capsules. It highlights how these oily condensates can provide a generic and less energy-intensive alternative to traditional protein-mediated transport mechanisms. This work not only enhances our understanding of cellular transport but also opens up new avenues for facilitating discrete, quantised, and digital molecular communication and material exchange between single synthetic cells and their surroundings.
For a more detailed exploration of this innovative research, read Prof Parikh’s full News & Views article on the Nature Chemical Engineering website.
Seminar – Extended Live-cell Imaging at Nanoscale Resolution
Dear IDMxS PIs, research staff and students,
We are pleased to have the speaker, Dr Adam Cliffe, from Leica Microsystems to present a STED talk on Extended Live-cell Imaging at Nanoscale Resolution.
Please register your intent to attend at https://forms.office.com/r/VTPvMffsJT or scan the QR code below.
Details
Date: 2 Aug 2024, Friday
Time: 3pm to 4pm
Venue: EMB, IDMxS Level 7 Foyer
Attendees to be seated by 2:55pm
Refreshments will be provided.
We look forward to your attendance and support for the event.
Thank you.
Early-career Researcher Seminar (IDMxS-ERS)
We would like to invite you to our next Early-career Researcher Seminar (IDMxS-ERS) on 30 Jul 2024, Tue, 10 – 11 am in the IDMxS foyer (NTU, EMB Lvl 7). Refreshments (coffee, tea, and various snacks) will be provided for all registered attendees (beginning 9.30 am, arrive by 9.50 to enjoy). Please share this announcement widely! Register your intent to attend at https://forms.office.com/r/zanDqu0mxn.
Our talks for this event will be:
Talk #1: “Discriminating Single-Molecule Binding Events from Diffraction-Limited Fluorescence)”
Presented by: YIN Yueming, PhD
Research Fellow NTU – IDMxS
Talk #2: “Revolutionizing Tear Film Assay, Advancing Vision Health”
Presented by: YEO Yee Phan, PhD
Research Fellow NTU – IDMxS
This is a continuation of our 2023 IDMxS Postdoc Seminar series, now rebranded to IDMxS-ERS to be more inclusive of other research positions. Our focus remains on giving research communication opportunities to researchers at or near the level of a post-doctoral research fellow. We are very actively looking for speakers in 2024, and anyone interested (postdocs or senior students) can use the registration form or email us at idmxs-events@ntu.edu.sg for more info. Nomination of speakers from peers or advisors is also encouraged.
Thoughts on our seminar format? Let us know what we can do better for future sessions through this feedback form.
We look forward to your attendance and support for our seminar event!
Seminar – Asst Prof Dong Xueming
Dear IDMxS Community
On behalf of the IDMxS Seminar Committee, we would like to invite you to our Seminar on Aug 7, Wednesday, followed by lunch.
Our speaker is Asst Prof Dong Xueming, from the NTU School of Biological Sciences, and he will be presenting his talk on
Targeted Proteomics and Their Applications in Clinical Proteomics
Please register your intent to attend at https://forms.office.com/r/c52CsN6ErE, before 1 Aug Thursday, 12 noon.
Registration will commence at 10:45am on the day of the seminar event and all attendees are to be seated by 10:55am.
We look forward to your attendance and support for our seminar event.
Thank you.
5 Advantages of Digital Assays That Will Dramatically Accelerate Analytics and Diagnostics
28 June 2024
Authors: Dr Andrew Breeson and Prof Atul N. Parikh
Traditional (analogue) assays have been crucial in advancing scientific understanding and clinical diagnostics, but they come with limitations that can affect the accuracy, efficiency, and scalability of biological testing. Today, digital assays are transforming our approach to diagnosing diseases and reshaping healthcare by allowing researchers to detect and analyse single molecules in messy, crowded, and heterogeneous biological environments. This blog discusses some of the main drawbacks of traditional biological assays and gives real-world examples of how digital assays can overcome them.
1. High Sensitivity and Low Detection Limits
Most traditional assays are not sensitive enough to detect very low concentrations of biomolecules. This limitation can be critical when diagnosing clinical conditions or diseases early on using blood-based biomarkers or detecting low-abundance environmental toxins. In both cases, target molecules can be present in samples at vanishingly low (femto-, atto-, or zeptomolar concentrations) corresponding to as few as 1-100 copies per microlitre of the sample.
Digital bioassays break this barrier by pushing the limit of detection to single-molecule levels to offer significantly higher sensitivity. These assays achieve this remarkable feat simply by (1) dividing the sample into fractions, isolating individual molecules or particles in microwells or droplets, and (2) digitally amplifying otherwise weak signals corresponding to single molecules.
Consider, for example, the case of early diagnosis of a disease or a clinical condition such as cancer by “liquid biopsy.” Some of the earliest biomarkers are circulating tumour DNA fragments and circulating microRNA, present in various biofluids (blood, urine, cerebrospinal fluid, and pleural fluid) at sub-attomolar concentrations. Digital bioassays can isolate and detect these trace concentrations of tumour DNA in a patient’s blood (or other) sample. This heightened sensitivity allows for cancer detection at a much earlier stage when treatment options are more effective, and the chances of a favourable prognosis are significantly higher.
2. Quantitative Precision
Analogue assays often suffer from variability in measurement and limited quantitative precision. Factors such as operator technique, environmental conditions, and the quality of reagents can influence the results, leading to less reproducible results.
Digital assays use advanced imaging and computing technologies to count every single discrete event (like individual molecule interactions). Because these assays count each event, they need (in principle) no calibration or benchmarking and can serve as absolute assays. Therefore, they produce highly precise and reproducible quantitative data (however, there are practical limitations when the assay fails to count all of the targets in the sample volume).
This quantitative precision can be crucial. For instance, during a viral outbreak, public health officials rely on precise diagnostic data to track the spread of the virus and implement control measures. Variability in analogue assay results can lead to incorrect estimates of infection rates, hampering efforts to contain the outbreak. Digital assays, with their high precision and reproducibility, provide reliable data that public health officials can trust. The precise quantification offered by digital assays allowed for early detection of infection surges, enabling timely public health responses and interventions.
3. Smaller Sample Volumes
Traditional assays typically need relatively large sample volumes, which can be a drawback in situations where only small amounts of biological material are available.
By leveraging micro- or nano-scale technologies, digital bioassays require much smaller sample volumes. This conserves precious or rare samples and reduces reagent costs.
For example, in paediatric oncology, obtaining large blood samples from young patients can be challenging and distressing. Digital bioassays, which can perform highly sensitive analyses on minute blood volumes, allow for comprehensive diagnostic tests and monitoring with minimal sample collection. This not only eases the burden on young patients but also ensures that critical information about their health is gathered efficiently and accurately. Additionally, in research involving rare or endangered species, where biological samples are limited, digital assays enable scientists to conduct extensive studies and obtain reliable data without depleting the scarce resources available.
4. Automated Processes
Many traditional bioassays are labour-intensive and time-consuming, requiring significant manual labour for setup, monitoring, and analysis. This can lead to delays in obtaining results and increased costs.
Digital bioassays are amenable to automation and integration for sample handling, processing, and analysis. This automation speeds up the assay process, minimises labour-intensive tasks, and eliminates handling errors, together leading to faster turnaround times for critical diagnostics.
During a disease outbreak, rapid and accurate diagnostics are essential for effective response and containment. Automated digital PCR systems can quickly process and analyse large numbers of samples with minimal human intervention, providing timely results that are crucial for identifying and isolating infected individuals. This efficiency not only reduces the workload for laboratory personnel but also ensures that healthcare providers receive critical information faster, improving patient outcomes and public health responses.
5. Easy to Scale Up
Scaling up traditional assays for high-throughput screening can be challenging and costly, as it often requires extensive re-optimisation and can increase the risk of errors.
Digital bioassays are designed to be easily scalable, allowing for the simultaneous processing of thousands to millions of micro-reactions. This scalability is advantageous for high-throughput screening applications in drug development and genetic testing.
In the pharmaceutical industry, drug discovery processes often involve screening vast libraries of compounds to identify potential therapeutic candidates. Traditional assays may struggle to handle the volume efficiently and accurately. Digital bioassays, however, can simultaneously evaluate the effects of millions of compounds on target proteins or cells by partitioning the reactions into microdroplets. This approach not only speeds up the drug discovery process but also increases accuracy and reduces costs, ultimately accelerating the development of new medications.
In conclusion, digital assays represent a significant advancement in the field of molecular diagnostics and analytics. At IDMxS, we are at the forefront of this revolution, harnessing the power of digital molecular analytics to push the boundaries of science and improve global health outcomes. To learn more about our work, click here.
