Amogh Desai

Nanopore Technology in Acute Heart Failure Management

During my academic journey, I was involved in various research projects encompassing mathematical modelling, molecular simulations, and protein biochemistry. My interdisciplinary skillset has nurtured my enthusiasm for scientific innovation. In my HTRIC PhD project, my focus is on developing nanopore sensors for detecting sodium levels in heart failure patients. By merging my interdisciplinary background with cutting-edge technology, I aim to create a meaningful impact in healthcare and biotechnology.

This project is applied for by Prof. Dr. Giovanni Maglia (FSE) and Dr. Kevin Damman (UMCG).

Project start: September 2023

Protein nanopores to measure urinary sodium for personalized diuretic therapy

20/09/2024

Heart failure is a condition that affects millions worldwide, and it boils down to this: the heart can’t pump blood as efficiently as it should. This struggle to keep up with the body’s demands leads to fluid buildup, causing symptoms like swelling (edema) and shortness of breath. As the heart weakens, it can no longer maintain a balance of fluids, and patients often end up feeling weighed down by their own bodies. To combat this, doctors commonly perform diuretic therapy which involve medications designed to help the body get rid of excess fluid by promoting urine production.

The standard goal of heart failure treatment is to bring the body’s fluid levels back to normal. However, monitoring whether a patient is losing enough fluid isn’t always straightforward. Doctors often rely on indirect signs like weight loss, but these can be slow and unreliable. Some patients show little response to the treatment early on, which can lead to further complications.

This is where natriuresis, or sodium loss in the urine, comes into play. Since diuretics work by helping the body excrete sodium (which pulls water along with it), monitoring sodium levels in urine could provide a clearer picture of how well the therapy is working. Studies have shown that patients who don’t excrete enough sodium have poorer outcomes, including higher chances of death or being readmitted to the hospital. On the flip side, those who lose more sodium tend to fare better, even if their overall fluid loss isn’t as dramatic.

By using molecular biology and advanced electrophysiological techniques, our goal is to develop a , protein-based biosensor that can accurately measure sodium levels in urine. This biosensor would be able to give real-time feedback on how much sodium a patient is excreting, offering a more precise way to tailor diuretic therapy. Current methods of sodium measurement involve collecting urine samples over a 24 hour time frame. For nurses, this process can be labor-intensive. Collecting spot urine samples requires careful timing, coordination with the patient, and proper labeling to ensure accuracy. In busy hospital environments, managing multiple patients means balancing these tasks with other essential duties, such as monitoring vitals, administering medications, and attending to patient needs. Therefore, our goal is to develop a proof of concept for automated sodium measurement in urine, enabling personalized treatment for heart failure.

Working as a PhD student in the lab has been both challenging and rewarding. One of the highlights of my experience has been developing my project from the ground up. I’ve enjoyed the freedom to design experiments and brainstorm creative solutions to address the key issues in my research. I’m also fortunate to be part of a supportive lab team, always ready to offer advice, troubleshoot problems, and teach me new techniques. This sense of camaraderie makes even the toughest moments easier to navigate. Outside of lab work, we often bond through activities like international potlucks, racquet sports, and even go-karting! Overall, my time in the lab has been incredibly fulfilling, and I’m excited to continue learning and growing as I progress through my project.

Ion channels and academic funnels: reflections on year one of my PhD

25/04/2025

It’s official — I’ve crossed the one-year mark of my PhD, and that means I can no longer get away with calling myself a “first year.” A lot has changed since I packed my bags, left home, and moved to a new country and city to begin this journey. Groningen, with its cosy streets and easy pace, quickly became a comfort blanket amid the chaos of starting a PhD.

In just twelve months, I’ve adapted to things I never thought would become second nature — like cycling everywhere (yes, even in sideways rain), or religiously checking weather apps before stepping outside. I also survived my first European winter, and let me tell you — the sun has never felt more sacred.

But enough about my personal life — let’s talk science.

The core of my project is to develop nanopore-based sensors for detecting sodium in urine, a promising tool for the personalised treatment of heart failure. Sodium levels in urine can help clinicians fine-tune diuretic therapy for patients in the ICU with acute heart failure, potentially leading to better outcomes.

My initial idea was to use bacterial sodium channels as detectors. In theory, this was a great approach — but theory doesn’t always survive the lab. The sodium channels I purified struggled to function reliably in our electrophysiology setup, giving inconsistent results that made analysis difficult.

Digging deeper into the literature, I discovered another complication: potassium interference. It turns out that for every five sodium ions detected, the channel lets in one potassium ion — a significant source of error for precision measurements.

So now, we’re flipping the script.

Instead of fighting the potassium, we’re embracing it by looking into potassium channels as highly selective potassium sensors. These channels are famously picky (they really love potassium and not much else), which opens up an exciting possibility: if we can accurately measure urinary potassium, we could estimate how much potassium is sneaking through the sodium channels, improving the precision of our sodium readings.

Better yet, this approach may allow us to develop dual sensors for both sodium and potassium, providing a more complete picture for patient monitoring.

As I wrap up my first year, I find myself at a turning point. We’ve faced challenges, changed directions, and stumbled on new ideas — and I’m incredibly excited about what’s next. There are many experiments on the horizon, and a lot of unknowns to navigate, but that’s the fun of it.

 

If this past year has taught me anything, it’s that science, much like life in a new city, requires a mix of curiosity, patience, and the occasional detour. Here’s to the next chapter — may it be as chaotic, enlightening, and rewarding as the first.