University of California, Irvine (UCI)
BioMiNT Lab (Biomolecular Microsystems and Nanotransducers)
Microfluidics & BioMEMS
Dr. Abraham "Abe" Lee is Chancellor's Professor of Biomedical Engineering and Mechanical & Aerospace Engineering at UC Irvine. Director of the BioMiNT Lab and the NSF-supported CADMIM center, Dr. Lee pioneered microfluidic platforms during his time as a DARPA program manager. His lab focuses on single-cell manipulation, acoustic/electric shear poration, and microfluidic technologies to advance precision diagnostics and cell therapy.
Painting with Cells
A single drop of blood carries an enormous amount of information — the identity of every cell suspended in it, the molecular signatures of disease, the fingerprints of a fight the immune system may be winning or losing. Most of that information goes unread. University of California, Irvine bioengineer Dr. Abraham "Abe" Lee has spent more than two decades building the tools to read it, and, increasingly, to rewrite it.
By BioBuilt Editors
Modern medicine has become remarkably good at looking closely at the human body. Blood panels, biopsies, and imaging scans all offer windows into health and disease. But for Dr. Abraham Lee, Chancellor's Professor of Biomedical Engineering and Mechanical & Aerospace Engineering at UC Irvine, those windows are still far too small, and too static. A blood panel can count how many white blood cells a patient has. It cannot easily tell a clinician what shape those cells are in, how they are interacting with one another, or how a course of treatment is changing them in real time. For Dr. Lee, understanding a person's health means finding a way to see, and eventually shape, that much larger and more dynamic picture.
Dr. Lee directs the BioMiNT Lab (Biomolecular Microsystems and Nanotransducers) and the NSF-supported Center for Advanced Design and Manufacturing of Integrated Microfluidics (CADMIM) at UC Irvine, where his team builds microfluidic devices, networks of fluid channels and chambers no wider than a human hair, that interact directly with individual cells. It is a field he helped invent. Before joining UCI in 2002, he served as a program manager at DARPA's Microsystems Technology Office, where he launched a $59 million initiative exploring the intersection of biology, information science, and microscale engineering, and helped found a companion program probing that same boundary between biological, informational, and microscale systems. Those two DARPA programs are now widely credited with helping establish microfluidics and BioMEMS as serious engineering disciplines in the United States, rather than a scientific curiosity. It is worth pausing on that origin story, because it explains something about how Dr. Lee approaches problems: he was present at the moment his own field was being defined, and much of his research since has been an attempt to answer the question that founding moment posed: what happens once engineers can actually reach into a living system at the scale where biology happens?
A Paintbrush for the Life Sciences
Dr. Lee often returns to an analogy borrowed from art. He describes microfluidics as a paintbrush for the life sciences, a comparison that traces back to an unlikely source of inspiration: Impressionist painting.
"Think about the famous impressionist paintings by Monet or Van Gogh," he said. "Their paintings started with simply dots of different colors. The paintbrushes, the colors, and how the paintbrushes were pushed or swiped against the canvas resulted in individual 'pixels' that collectively reveal an artist's vision of the painting."
Biology, in his view, works the same way. Cells are the pixels; molecules are the colors; tissues and organs are the sections of canvas built from thousands of individual strokes. Modern medicine, he argues, is like standing in front of a masterpiece but only being able to inspect it one square inch at a time.
"On one hand, microfluidics can break down the 'pixel' of life (e.g. cells) and understand the color (molecules), and shapes (e.g. structure, morphology)," he explained. "Microfluidics can also start to 'repaint' the picture of life, by reconstructing the life ingredients to understand sections of the painting (e.g tissue, organs, physiology)."
It is a tidy metaphor, but it is worth taking seriously as more than a rhetorical flourish, because it maps onto a real methodological divide in modern bioengineering. One entire branch of the field, flow cytometry, next-generation sequencing, mass spectrometry, has been devoted almost entirely to the "reading" half of Dr. Lee's analogy: characterizing cells and molecules in ever greater detail, but almost always by destroying or discarding them in the process, and almost always by averaging across thousands or millions of cells at once. The other branch, tissue engineering, organoid culture, regenerative medicine, has been devoted to the "repainting" half: building living structures back up, often with only a coarse understanding of the individual cellular pixels going into them. Dr. Lee's career is unusual in that it has tried to occupy both halves of that divide simultaneously, using the same underlying toolkit of fluid channels, droplets, and acoustic fields to move fluidly between them.
From Pixels to Pictures: Engineering Across Scales
Over more than two decades, Dr. Lee's lab has developed a series of foundational microfluidic technologies: an early magnetohydrodynamic micropump, dielectrophoresis-based methods for sorting neural stem cells without chemical labels, pioneering work in droplet microfluidics, and acoustic microstreaming devices capable of trapping and manipulating individual cells using nothing but sound.
The dielectrophoresis work is a useful case study in why "reading" cells well is harder than it sounds. Conventional cell sorting typically relies on antibody labels that bind to specific surface markers, a reliable approach but one that inevitably alters the very cells being studied, and one that only works if researchers already know which marker to look for. Dr. Lee's lab instead sorted neural stem cells based on the native electrical properties of their membranes, distinguishing cell types by how they respond to an electric field rather than by what has been chemically stuck onto their surface. It is a small technical distinction with a large practical consequence: the cells can be sorted, studied, and in principle transplanted, without ever being labeled at all.
Each of these tools was, in effect, a way of isolating a single "pixel" of biology, a single cell, a single droplet, a single molecule, and studying or manipulating it without disturbing the surrounding picture. But Dr. Lee has always seen that as only half of the job.
"As we advance in the science of understanding cellular functions and how to alter or manipulate them, we get to affect the fundamental unit of life," he said. "This allows us to more accurately piece together the biological picture, starting from cell lifespan and health state, cell-to-cell interaction, and cell transformation, and moving toward spheroids, organoids, and organs-on-chip, eventually to models that recapitulate the physiological state of a person."
That progression is visible in the lab's own research portfolio. Alongside single-cell tools, Dr. Lee's team has helped develop perfused, vascularized organ-on-a-chip systems and micro-tumor models built in collaboration with UCI vascular biologists—miniature, living tissue constructs, complete with functioning capillary networks, that behave in important ways like actual organs. These systems matter for a fairly unglamorous but consequential reason: a large share of drugs that look promising in a petri dish, or even in animal models, fail once they reach human trials, in part because neither system reproduces the specific architecture of human blood vessels feeding human tissue. A vascularized micro-tumor, grown from real human cells and perfused with fluid the way a real tumor is perfused with blood, is an attempt to close that gap before a drug ever reaches a patient. It is the "repainting" half of the analogy made physical: individual biological elements reassembled into something that begins to resemble the whole canvas, and that can be screened against therapies far more cheaply and quickly than an animal study or clinical trial ever could.
Living at the Interface
Building tools that move this fluidly between engineering and biology requires a particular kind of researcher, one comfortable being, in Dr. Lee's own words, a little bit of an outsider everywhere.
"I was trained as a 'microscope' engineer, so my starting point is usually the mechanistic aspects of the tools, the microfluidic devices and systems, and now extended to the biology," he said. "The challenge is that I am unable to go in depth in any given subject that you mention, but I am driven by curiosity and by seeing the 'gaps' and filling the 'gaps.'"
That approach has defined his career as much as any single invention. His path to UCI wound through Lawrence Livermore National Laboratory, DARPA, and the National Cancer Institute, where he worked to promote the maturation of new biomedical technologies before returning to academia. At each stop, his contribution was rarely to become the deepest expert in one discipline, but to connect disciplines that otherwise rarely spoke to each other, like engineering, biology, medicine, and, increasingly, industry. It is a career shape that is unusual in academic science, where incentives generally reward narrow, deep specialization, and it may explain why so much of his work sits at unglamorous but load-bearing junctions: the interface between a mechanical engineer's toolkit and a cell biologist's questions, or between an academic invention and a manufacturable product.
"The lesson learned is to continue to expand my piece of the puzzle, but also know my limitations and continue to learn from others, collaborate with others, and find the next piece of the puzzle to solve," he said.
That collaborative instinct has extended well beyond the university, and it is worth noting how rare it is for an academic lab's output to reliably reach the commercial world. Technologies developed in Dr. Lee's lab have contributed to the founding of several companies, including Micrus Endovascular Corporation, a maker of devices for treating brain aneurysms that was later acquired by Johnson & Johnson, along with more recent ventures translating his lab's newest platforms toward clinical use. That track record suggests something about his particular version of interdisciplinary work: it is not simply broad for its own sake, but oriented, from the beginning, toward problems specific enough that a technology built to solve them can eventually leave the lab.
Engineering the Tools: Reading and Rewriting Cells
Much of the lab's current work is organized around a handful of platforms that embody both halves of the painting metaphor, reading biology in finer detail than ever before, and rewriting it with new precision.
One platform, known as ADOPT (Arrayed-Droplet Optical Projection Tomography), traps individual suspended cells inside droplets and uses gentle fluid vortices to rotate them in place, capturing a full three-dimensional image of a cell's membrane and internal structures in about five seconds. That may not sound like a dramatic advance, but it addresses a real limitation in how cells are currently studied at scale. Flow cytometry, the standard tool for characterizing large populations of cells, is extraordinarily fast and can measure many markers at once, but it typically reduces each cell to a handful of numbers and cannot capture three-dimensional shape at all. Confocal microscopy can capture that shape in exquisite detail, but far too slowly to look at more than a few cells. ADOPT is an attempt to sit in the gap between those two extremes, fast enough to profile hundreds of cells, but rich enough to capture their actual geometry.
In a 2024 study published in the Proceedings of the National Academy of Sciences, Dr. Lee's team used the technology to image hundreds of individual T cells, showing that the shape of a cell's nucleus and membrane could serve as a kind of signature for the health of the immune system as a whole, effectively, a "selfie" of the body's immune status, built not from one cell but from the statistical shape of many. The underlying premise is that a population of immune cells in a healthy, resting state and a population fighting a losing battle against cancer are not just present in different numbers, but are physically shaped differently, and that this shape has simply been invisible to standard diagnostics. The work recently earned a five-year, $2.2 million grant from the National Institutes of Health to push the technology toward high-throughput, clinical-grade single-cell profiling, a signal that the concept has moved from a proof-of-principle finding toward something intended for real diagnostic use.
A second platform, AESOP (Acoustic-Electric Shear Orbiting Poration), addresses the opposite challenge: not reading cells, but engineering them. To understand why AESOP matters, it helps to understand the problem it is trying to solve. CAR T-cell therapies, which re-engineer a patient's own immune cells to attack cancer, have produced some of the most dramatic results in modern oncology, but they carry a serious risk of cytokine release syndrome, a sometimes life-threatening overreaction of the immune system. Research has increasingly tied that risk to how much of the engineered receptor ends up on each cell's surface: too much, and the immune response can spiral out of control; too little, and the therapy may not work at all. The two dominant manufacturing methods, viral vectors and bulk electroporation, are both fairly blunt instruments; viral vectors carry their own safety concerns around uncontrolled gene insertion, while electroporation uses a jolt of voltage that damages a meaningful fraction of cells and delivers genetic material unevenly across the population. AESOP combines gentle acoustic shear with a low-intensity electric field to open temporary pores in a cell's membrane, allowing genetic material to be delivered with a precision and uniformity that neither older method can match. In direct comparisons, the platform has shown roughly 76 percent delivery efficiency with about 80 percent cell viability, compared with under 50 percent on both counts for bulk electroporation, and, more importantly, a far tighter, more controllable dose per cell, the difference between manufacturing a therapy with a firehose and manufacturing it with a titration.
A third project, focused on artificial antigen-presenting cells, aims to build synthetic particles capable of directly activating T cells by mimicking the molecular handshake that naturally occurs between an immune cell and the antigen it is meant to recognize. It is a more speculative line of work than AESOP or ADOPT, but its logic runs in the same direction: rather than extracting and reprogramming a patient's own cells, it asks whether an engineered stand-in could do part of that job instead, with potential applications reaching beyond cancer into autoimmune disease and even neurodegenerative conditions such as Alzheimer's.
Together, these tools represent the two directions Dr. Lee has spent his career moving in simultaneously: deeper resolution into the pixel, and a steadier, more controllable hand repainting the picture. What is notable, looking at the three side by side, is that they are not separate side projects but complementary pieces of a single pipeline. ADOPT reads out the state of a cell population, AESOP and the artificial antigen-presenting cell platform act on that population, and in principle the two halves could eventually close a loop, with morphological readouts guiding how a therapy is engineered for a given patient.
From Repair to Restoration
Looking ahead, Dr. Lee believes the most meaningful shift in medicine over the next decade will not be a single new device or drug, but a change in the underlying goal of treatment itself.
"I hope we will transform from focusing on treating sick people to keeping people healthy and vibrant," he said. "It is like the sports analogy, the best defense is a preemptive offense. If we develop more biological understanding of the painting, we can treat life with biological solutions, such as cell therapy, instead of chemical drugs, and restore health instead of repair health."
The distinction he draws between repair and restoration is not merely semantic, and it echoes a broader argument taking shape across regenerative medicine more generally: that many conventional drugs manage symptoms by force, chemically overriding a malfunctioning system, whereas cell and gene therapies attempt to hand a damaged system the actual biological components it is missing and let it recover on its own terms. Repair, in his framing, often comes with scars and side effects, the biological equivalent of a hasty patch job. Restoration, rebuilding biological systems using the body's own cellular machinery, offers something closer to rejuvenation. It is a vision that treats the "holy grail" of his field not as a single breakthrough, but as a full diagnostic-and-therapeutic loop: sampling a patient's blood, reading its cellular picture in real time using tools like ADOPT, and feeding that information directly back into a therapy engineered with tools like AESOP, tailored to that individual.
Advice for the Next Generation
For students hoping to work at the boundary of engineering, biology, and medicine, Dr. Lee's advice begins with self-knowledge rather than a specific skill set.
"I would first find out what drives you and what makes you click," he said. "Each person is different and contributes to the field best with their unique skillset and mindset."
He is candid that his own path, driven by curiosity, comfortable with not knowing everything, always chasing the next gap to fill, is not the only way to make an impact, and is in some ways a difficult one, prone to being mistaken for a lack of expertise rather than a different kind of it. Some researchers, he notes, are better suited to going deep in a single discipline, becoming true experts in a particular cell type, molecule, or fabrication technique. Both paths, he argues, are equally capable of producing meaningful innovation, and a field like microfluidic precision medicine, which sits at the crossing point of half a dozen disciplines, arguably needs both kinds of researchers in roughly equal measure to function at all.
"No matter what," he said, "my advice is to always be learning, always seek advice and collaboration, and learn how to work on teams."
It is fitting advice from a researcher who has spent his career treating the boundaries between fields not as walls, but as the places where the most interesting brushstrokes get made, and whose own body of work suggests that the most useful pictures of human health may only emerge once enough of those boundary-crossing brushstrokes have been laid down side by side.