Prof. Mehmet Toner

Life on the Path of Rare Cells

In every scientific laboratory, there comes a point where the human eye alone is not enough, and one must look with greater precision and depth to uncover hidden secrets. At this very point, there are researchers who can see what remains invisible to others with curiosity and meticulousness. One such researcher is Mehmet Toner, and what follows is the story of his life—a journey that began with early curiosity in Istanbul and led him to MIT and Massachusetts General Hospital. His passion for science took shape during his studies in mechanical engineering, when questions far beyond the world of tools and gears captivated his mind. Later, encounters with professors who brought fresh perspectives to inquiry and problem-solving became a turning point in his life, paving the way for his research in microscopy and biomedical engineering.
The Seed of Curiosity
Mehmet Toner was born in 1958 in a small neighborhood in Istanbul. His early years were not particularly tied to a love for academics. He was more drawn to the soccer field and tennis court, seizing every opportunity to ski—a sport he had little access to. Although his inclination toward sports often overshadowed books and studies, the seed of scientific inquiry was planted at home. As he recalls, his family was always eager to learn, and his parents played a significant role in fostering his interest in education and knowledge. In those days, private universities did not exist in Turkey, and higher education was free—a privilege that allowed Toner to receive high-quality, cost-free education in Istanbul. These familial and societal foundations became the bedrock for a transformation that would later draw Toner from the world of sports to the realm of science.
Searching for a Path to Medicine
Although Mehmet Toner dreamed of becoming a surgeon or doctor, his entrance exam score in Turkey’s national university fell short, leading him to study mechanical engineering at Istanbul Technical University. It was there that his encounters with Professors Ester and Ramen Klich deepened his perspective on science. They introduced him to the joy of discovery and taught him that science means venturing into uncharted territories. Up until university, Toner’s main obstacle in the realm of science was his reluctance to study. However, during these years, he truly fell in love with learning. He transformed from an average student into one of the best at his university, and this newfound passion paved the way for his migration to the United States. He applied to several universities and ultimately found himself at MIT, where the emerging field of biomedical engineering was just taking shape. For Toner, this field was the perfect opportunity, as it allowed him to merge engineering with healthcare, bringing him closer to his original dream of contributing to medicine.
When Mehmet Toner arrived at MIT, he was still a mechanical engineer. In his early days there, he engaged in conversations with numerous professors to shape his future. At the time, biomedical engineering was not a Seriously considered field. Despite the skepticism and discouragement that this created, Toner made his choice. He wanted to pursue work that was both innovative and had a direct impact on medicine. He spoke with various professors, learned more, and ultimately decided to pursue biomedical engineering. His passion for healthcare kept him steadfast against all doubts and solidified his decision.
Guiding Hands
Toner pursued his doctorate under the mentorship of Professor Ernest Kravaho, a pioneering scientist in cryobiology at MIT. His doctoral research focused on the theory of intracellular ice formation, a study that first brought his name to prominence in the scientific community and later formed the foundation for his work in bio preserve. His five-year collaboration with Kravaho not only provided him with a strong scientific foundation but also led to a deep friendship that lasted until the death of his professor. This research ties his perspective to the applications of engineering in medicine, particularly in thermodynamics. Following his undergraduate mentors, Kravaho was the third person to profoundly shape his path.
Soon after, collaborations with Professors Martin Yarmush and Ronald Tompkins brought Toner to Massachusetts General Hospital and Harvard Medical School. From the early 2000s, his focus shifted to microfluidics, a technology that simulates the flow of particles in microscopic channels. This technology was applied to the study of rare cells, including stem cells, embryonic cells, and, circulating tumor cells in the bloodstream. Toner recognized that this field holds transformative potential, as isolating rare cells could enable early monitoring and diagnosis of diseases like cancer, as well as the selection of appropriate treatments for patients.
Ideas Do Not Survive on Their Own
The journey from an idea to a product is complex. It all begins with an idea, which must then be scrutinized from various angles to reach the innovation stage, where its societal impact becomes clear and its potential to become a product is evaluated. From there, the real challenge begins: transitioning from invention to mass production. The product must consistently perform with high quality, pass clinical trials and regulatory requirements, withstand competition, and be produced on a global scale. Moreover, this process is costly and often takes more than a decade. Mehmet Toner paid little attention to patenting early in his research career, but a warning from his professor, Rafael Lee, made him realize that without legal protection, no idea could become a tangible product. Today, over a hundred patents are registered under Toner’s name, with a significant portion related to microfluidics. Some of these patents focus on developing microfluidic chips for detecting and analyzing rare cells, which are now applied in diverse fields such as brain health, tissue regeneration, and neurovascular applications.
Reflection of the Efforts
Mehmet Toner has received numerous scientific awards and recognition after years of dedication and research. Among his extensive accolades is the 2010 AACR Team Science Award. The Thoracic Oncology Research Group at the Dana-Farber Cancer Center received this award for demonstrating the connection between EGFR mutations and therapeutic responses to the drugs gefitinib and erlotinib and for identifying two new mechanisms of drug resistance. Additionally, in earlier years, Popular Mechanics named Toner among the recipients of its Breakthrough Award. In recent years, this researcher was also recognized in the 2025 Mustafa Prize for developing nano/microfluidic devices with clinical applications for isolating rare cells. With these achievements, Toner has created a pivotal intersection between engineering and medicine, opening new pathways for the disease diagnosis and treatment.
Over the years, Mehmet Toner has continued to pursue the path of research, where each small discovery can spark even bigger questions. His more than four decades of scientific work and university teaching have shifted his focus toward mentoring young researchers, securing patents, fostering environments for commercializing ideas, and addressing the ethical implications of emerging technologies. His everyday interests—from sports and visual arts to studying climate change—remain intertwined with his research, forming part of his journey into the uncharted frontiers of biomedical science. Toner believes that setbacks and challenges are inevitable, but the ability to analyze the situation, devise a strategy, and focus on the future rather than dwelling on the past is what matters. As he puts it, curiosity must be nurtured, and excessive structure should be minimized to empower young researchers, enabling progress to happen much faster than before.
 

Miniature Channels, Great Achievements  

The Hidden Journey on the Highway of Life
The body is a fabric woven from billions of cells—cells that, like orderly beads, are meticulously strung together one by one. Everything proceeds flawlessly until a single bead is missed, and if that one is not noticed in time, it can unravel the entire weave. Our story begins with one such cell, the missed bead. A tiny cell that breaks free from the order and, in silence, defies the body’s rules. At first, it might be just an imperceptible speck in a corner, but if this rebellious cell is not identified on time, its uncontrolled and chaotic proliferation can lay the foundation for what we call cancer. This cell is opportunistic, refusing to stay confined to its designated place. Over time, some of its kind hitch a ride on the bloodstream, embarking on a journey to expand their territory—a phenomenon known as metastasis. 
Blood is a highway teeming with millions of travelers: white and red blood cells, platelets, and more, all components of this crimson fluid, tirelessly serving the cause of life. Amid this bustling crowd, those few cancerous cells are unwelcome passengers, carrying sinister plans and evading detection by the immune system. Identifying these cells in such a dense throng is no simple task—and this is where science steps in.
Reporters of the Future in the Heart of Blood  
The significance of detecting Circulating Tumor Cells (CTCs) found in the blood extends beyond early diagnosis. These wandering cells speak of the future, revealing the aggressiveness of the disease, the likelihood of its recurrence, and the body’s response to treatment. This makes them a valuable tool for guiding therapeutic decisions. For instance, in patients with advanced prostate cancer, genetic analysis of these cells can predict which treatments are likely to be most effective. One key gene for such analysis is the AR gene. In its normal state, the AR gene produces mRNA that leads to the creation of the androgen receptor protein in prostate cells. This receptor, an intracellular/nuclear protein, becomes active upon binding to hormones like testosterone, signaling the cell to proliferate. However, in cancerous conditions, the situation changes. In some CTCs, the mRNA from the AR gene is abnormally spliced, producing a variant called AR-V7. This variant creates a receptor that remains active even without testosterone, continuously signaling cell proliferation. If AR-V7 is detected in a cancer cell isolated from a patient, it may indicate that the patient will not respond to certain therapies. Such insights allow doctors to tailor treatments more precisely to the genetic profile of each patient, saving time and resources.  
Diagnosis at the Cost of Consequences  
In critical situations, physicians must assess a patient’s health as quickly and accurately as possible. Meanwhile, researchers aim to identify and study these cancer cells before they spread further, but conventional tools have not always been effective. One of the most common traditional methods relies on antibodies—molecules that bind to specific receptors on the surface of cancer cells, effectively labeling them. Systems like CellSearch, long considered the gold standard, were designed based on this principle. In this method, specific antibodies are attached to tiny magnetic particles. If cancer cells are present in a blood sample, these antibodies bind to specific receptors on the cells, marking them. This binding imparts magnetic properties to the targeted cells. The sample is then introduced into a device with a controlled magnetic field in its walls, which acts like a targeted magnet, attracting the marked cells. Other blood cells are washed away and removed from the sample. However, this process faces significant challenges, including the variability of receptors on cancer cells. Some CTCs undergo changes as they enter the bloodstream, leading to the reduction or loss of the targeted receptors. Since these systems rely entirely on the presence of these receptors, altered cells can evade detection. Other methods, such as mechanical filters, have attempted to exploit differences in cell size and rigidity. However, these approaches often encounter issues like filter clogging or physical damage to the cells. The common weakness of these methods is their over-reliance on biological markers or the separation achieved at the cost of damaging cellular integrity. These inefficiencies have paved the way for the emergence of a new generation of tools.
Professional Cancer Hunters
In the realm of biomedical science, a profound transformation is underway. Once, diagnosing diseases relied on observing clinical symptoms or invasive biopsies. Today, a new horizon called liquid biopsy is emerging—a method that, instead of cutting and extracting, seeks to uncover the body’s hidden secrets with just a sample of blood. This technology hunts for rare cells and molecules that have escaped from tumors, inflamed tissues, or even the immune system into the bloodstream. At the heart of these advancements, microfluidic chips have carved out a unique place. These tiny devices can channel fluids like blood through pathways as narrow as a hair strand, enabling the separation, analysis, and examination of their various components. Practical examples of this technology were pioneered in the early 2000s through the work of Mehmet Toner. His team designed a chip called the CTC-Chip, revolutionizing the detection of stray tumor cells in the blood. The inner surfaces of this chip are coated with specific antibodies. As a blood sample flows gently through, cells bearing receptors for these antibodies—often tumor cells—are captured on the chip, while other blood cells pass through unaffected. Unlike traditional methods, this chip requires no pre-labeling of cells and can identify and trap cancer cells among billions of blood cells with remarkable precision.
To meet the growing need for processing larger blood volumes, Toner’s team developed an advanced version called the CTC-iChip. This chip employs a multi-stage process for cell separation, offering high precision and efficiency. In the first stage, cells are arranged in specific paths using ingeniously designed channels and inertial forces, as if guided by the silent laws of physics. Next, non-target cells, such as white blood cells pre-labeled with magnetic antibodies, are diverted using a magnetic field in a process called magnetophoresis. What remains are cancer cells, collected alive and intact without the need for direct labeling. This clever combination of physical separation and magnetophoresis enables the rapid, precise isolation of cancer cells from large blood samples, eliminating the need for complex and time-consuming methods. This breakthrough has enhanced human diagnostic capabilities, paving the way for more precise and personalized analyses. It marks another step toward a medical future that sees more and treats with greater accuracy.
The latest generations of microfluidic chips go beyond mere separation. They can now create simulated environments mimicking the human body. These chips are miniature laboratories that place cells under a microscope, studying their responses to drugs. No longer are cells merely isolated for observation under a microscope; instead, a dialogue is established with them. Each cell tells a story, and these cutting-edge technologies allow us to read and redirect those stories before they reach a tragic chapter.
Invading Caravans
In the course of his research, Toner discovered that it’s not always about a single rogue cell. Sometimes, cancer cells travel in groups. These floating structures, known as CTC clusters, possess greater invasive power than individual cancer cells. Studies have shown that their collective nature gives them the audacity to infiltrate, evade the immune system, and conquer new territories within the body. In this process, platelets—once recognized solely as immune and blood-clotting cells—play a surprising role by shielding and preserving these CTC clusters, hiding them from the immune system and aiding their escape. It’s clear that metastasis is not a solo act. To hunt these cancer caravans, chips like Cluster-Chip and PANDA have entered the fray—delicate yet intelligent tools that isolate these clusters from blood without the need for chemicals or specific labels, preserving their structure intact. The design of these chips hinges on characteristics such as the clusters’ shape, size, volume, and even their speed of movement in the bloodstream. Creating conditions that allow both single cells and complex cellular structures to be extracted without damage can enable precise molecular analyses, offering insights into how these cells evade the immune system.
Advancing the Medical Frontier
Until recently, microfluidics was seen solely as a hunter of cancer cells. Today, this tiny, intelligent technology has stepped into new arenas. The same chips that once tracked cancer cells can now identify stem cells, minute intercellular particles like extracellular vesicles, and even viruses. This technology is a sharp-eyed observer, fixed on blood and other bodily fluids, capable of detecting the smallest signals. With the help of nanostructures, which possess unique properties due to their minuscule size, the precision and efficiency of these systems have soared. These advancements not only aid in disease treatment but also deepen our understanding of cell-to-cell communication and signaling, potentially identifying warning signs before a disease even shows symptoms. These tools are currently being tested in research to study immune responses or detect certain infectious diseases early. While they have not yet reached widespread clinical use, they hold immense promise. No longer must we wait for severe symptoms or resort to complex, costly methods. These precise, silent chips provide valuable information that can transform the course of treatment from the outset.
Moreover, the success of this technology extends beyond laboratories and hospitals. In recent years, some of the technologies developed by Toner’s team have entered clinical trials and have been adopted as commercial diagnostic tests in clinics. These tools enable doctors to monitor cancer patients under treatment more precisely, quickly assess drug effectiveness, and adjust therapies as needed. Microfluidic advancements, particularly through the efforts of researchers like Toner, have paved the way for personalized medicine—a medical approach where each patient’s biological profile is uniquely analyzed, and treatments are tailored specifically to them.
These cutting-edge technologies have shown how tiny microfluidic tools can profoundly transform human lives on a grand scale. Within droplets of blood, among invisible particles, and at the heart of structures too small to be seen by the naked eye, their impact on human lives is strikingly visible. Researchers have built a bridge between biology and engineering, shaping the future of medicine—a future where every cell has a story to tell. In a world where treatment must be tailored to each individual, the key to this path may lie in reading these hidden cellular stories, which hold the power to alter the course of treatment and save lives.