RONNIE DAS, PHD
CO-INVESTIGATOR & LEAD RESEARCH SCIENTIST / ENGINEER
HUMAN PHOTONICS LABORATORY (HPL)
University of Washington
232 Fluke Hall, 4000 Mason Road
Seattle, WA 98195 USA
(last updated September 2015)
Hello and welcome to my homepage!
I am a lead research scientist/engineer & co-investigator within the Human Photonics Laboratory (HPL) here at the University of Washington in Seattle. HPL is one of two academic laboratories amongst the various spin-off companies located in UW's incubator facility (aka Co-Motion aka Center for Commercialization). We are a highly-interdisciplinary research group and may be broadly classified as an optics laboratory that is focused on cancer detection & diagnosis. Our research covers a large spectrum from simple, benchtop investigations to studies involving clinical applications. As a result, we have long-standing collaborations with the departments of mechanical, electrical & bioengineering, the UW Medical Center and several companies in the Pacific Northwest.
For over a decade, I've worked in R&D and have concentrated my research efforts towards areas encompassing muscle & neurophysiology. That's how it was; that's how I thought it would be for quite some time until several years ago when my research radically shifted (not once, but twice!). The first change involved the controversial subject matter of interfacial water (see "Polarized-oriented multilayer theory" under Gilbert Ling, ref 29) and its role in cell physiology when alongside biological structures, proteins and biomolecules. Then in 2012, a second turn resulted in the transition of my research towards a project (in HPL) that is currently based on pancreatic cancer detection & diagnosis (see CURRENT RESEARCH).
By training I am an engineer, but because of the industry exposure I gained at an early age from companies and the biotech hotbed surrounding UCSD, my thinking and research interests greatly diversified. I was pretty young at that time, so it was an amazing opportunity for me when I was offered a research position in an up-and-coming biotech company that was right in UCSD's historical backyard (i.e., TSRI, the Salk Institute, etc.).
Within a highly-specialized neuroscience division, I was trained as an electrophysiologist by an electrophysiologist in a fashion closely resembling an apprenticeship. The position, related experiences and intricate biophysical techniques completely opened-up my mind to a whole new realm and helped me develop many of my research passions, which also functionalized much of my undergraduate engineering education. The experience (and several others to follow) deeply influenced me as I became (and still am) very passionate about research that is centered on both physiological phenomena and the corresponding development of (novel) bioinstrumentation.
I continued to work for a short time, but I quickly realized that to support my research pathway, I required the proper academic training. To that end, I studied and trained to receive my Bachelor's, Master's and Doctoral degrees in bioengineering from three wonderful programs in three incredible cities. For each program, I specialized in the R&D of instrumentation as it is applied to basic research, physiology and clinical applications. The training and breadth of academic experiences (and mentors) forged a lasting mindset in me and imparted many guiding philosophies which I still follow today.
CURRENT RESEARCH (the cliff's notes version)
Please note that all images and videos on this website have been presented previously at a conference, published in a research journal and/or have been patented, so further descriptions if unclear are available online.
At HPL, I am pursuing research to aid pathologists in the early detection and/or diagnosis of pancreatic cancer by developing a system capable of examining on a microscopic level tissue that is obtained from patients in the clinic (fig 1a-c). On the surface, this project seems like standard pathology except there's one twist — I am using a 3D microscope instead of a standard microscope (fig 2). Consequently, biopsies may be interrogated (and assessed) by the pathologist in 3D (i.e., 3D pathology).
a. Commercially-available clinical coring needle.
b. Coring needle in operation. Procuring a tissue biopsy
from formalin-fixed pancreas tissue (normally, the block
of tissue would be a person).
c. After retracting the coring needle's sheath, the cutting edge
is revealed to have obtained a thin tissue core biopsy.
Figure 1: Clinical coring needle in operation. Needles are typically employed to procure small tissue pieces (biopsies) from patients for disease detection & diagnosis.
Traditionally, patient-procured biopsies undergo numerous procedural steps which are not limited to, but include gross handling, mechanical micromanipulation, chemical washes, bath immersions and fine sectioning. Some of these steps are so standardized that automation is employed by specially designed machines (fig 3a). Other steps however require a singular, organic touch by highly-trained, highly-specialized personnel (fig 3b). Process steps must be run in a distinct sequence and altogether, process, machine and personnel are typically housed within a pathology laboratory. Pathology laboratories not only occupy a significant physical footprint (fig 3c), but on a daily basis require large volumes of expensive wet-bench materials & chemical reagents.
a. Automated tissue processor may perform several important
steps after a biopsy is procured such as chemical-fixation,
alcohol dehydration, wax embedding, etc.
b. Sectioning a block of tissue into very thin slices is nothing
short of an extremely precise, extremely advanced deli slicer
which is operated by highly-trained technicians. If you click
on the image, a link will take you to a video where I
demonstrate rudimentary sectioning of a pancreas tissue
block. In the video, you will also notice that after improper
sectioning, I simply discard the rolled-up tissue slice.
c. A pathology laboratory requires a significant number of resources
(equipment, supplies, chemicals, space, personnel, etc.).
Figure 3: Traditional pathology with the tools and techniques of the trade.
The eventual output of the pathology workflow (about 1-3 days later) is a series of microscope slides (fig 4). Prepared slides are essentially flat, heavily-processed, stained tissue slices 3-5 microns in thickness. Pathologists directly observe these patient samples (in 2D) using a standard microscope and then ascertain a diagnosis for a patient. Over the twentieth century, this workflow was (and continues to be) perfected, streamlined and optimized to such a degree that any change in the process and/or the pathological sciences requires significant time — remember, there should be no risk to patient diagnoses.
So how does 3D pathology fit into all of this? Well first, let's further explore and/or understand the 3D concept. Whether by television, an IMAX movie theater, an LCD computer screen, or a fancy smart phone, all visual information is still conveyed to us in 2D, even though our natural vision is inherently in three dimensions. For comparison, what do you suppose a 3D television could do for you that a regular television cannot? When I sampled the responses of several non-science individuals, I received many replies that were somewhere along the lines of "it would be in 3D like our vision", or "it'd have depth and be more life-like". Many used wording, phrasing and hand gestures to assert that "3D" would indeed be distinct and more advanced, but most could not exactly describe what they knew on a gut-level, or provide an example that could best convey their natural sense of the idea. In all fairness, it's actually pretty difficult to describe in conversation, so allow me to lend a hand.
The fundamental advantage of 3D imaging is best understood by comparing one frame of a movie on a television screen. Let's say your favorite actor is playing a runner competing against several other teams in a spectacular sports drama. And then, there's that scene: the music crescendos and the shot is squarely focused on the runner's body and his emotional face while he runs towards the camera in slow-mo (fig 5). Freeze that frame in your mind. Because we're looking at a regular television screen, the camera's perspective is fixed. We can never see the back of your hero's jersey. The optical information from that perspective is inherently hidden, or never in view. Now, I know what you're thinking: what if this movie was in "3D", or "in 3D on an IMAX"? The result is still the same. By wearing special 3D glasses, there is a perception of depth as if the runner is running out of the plane of the movie screen. But still, the back of his jersey is hidden from the audience.
Figure 5: Usain Bolt, the fastest person, EVER. How fast? His average ground speed clocks-out around 25 mph!
A true 3D television would project the runner (like a hologram) in a small space of your family room. As a viewer, you would be able to see the runner at any magnification, or perspective of your choosing. For example, while the runner makes his dramatic sprint for the finish line, you could first watch this individual from the side as he passes his competitors one-by-one and wins the race. Then you could rewind the scene and now take the perspective of a losing runner as your hero zips right by you... or may be you want to watch the race from a bird's eye view, or from the perspective of his shoelaces, or (in essence) at any angle not captured by a fixed perspective camera. Do you now see the difference (fig 6)?
a. An actual image of downtown Seattle,
which I took using my digital camera
from the Queen Anne Hill neighborhood.
b. Although at low resolution, this image is produced by images taken
by orbiting satellites from above us. The images are processed in such a way
that we may adopt the same point-of-view within the 3D reconstruction as the
real image I acquired. The three red arrows within my image point to the very
same buildings in the 3D reconstruction. However, while the three buildings
seem like they are very close to the Space Needle, a 3D reconstruction can
reveal simple, but highly informative spatial (optical) information. Click
on the 3D reconstructed image for the animated gif.
Figure 6: From basic imaging to 3D reconstructions.
So there are numerous advantages for a pathologist when a biopsy is being assessed in 3D in order to determine a cancer diagnosis. To be brief, I list the top three:
Best represents what's going on inside you...
Biopsies would remain unsectioned since a standard microscope (which only permits visualization of thin tissue slices) would no longer be necessary. Many processing steps would also be removed from the workflow since these steps are required for the exact purpose of fine sectioning. Subsequently, an intact (unprocessed) sample would best represent the in vivo diseased condition of the patient.
Maximizes the diagnostic potential of the sample (which was so painstakingly taken out of you)...
Traditionally, pathologists observe multiple microscope slides and then mentally reconstruct these optical data in their mind to visualize what is occurring physiologically. Naturally, there is a lot of interpretation going on here, which is intrinsically linked to the experience of the pathologist and their specific training. This established process also includes inherent processing error, or the fact that series of microscope slides may not be exactly consecutive — you may have processed and prepared your patient-procured biopsy into 20 microscope slides, but between slides #12 and #13, some of the specimen was discarded since the tissue was improperly sectioned. 3D microscopy would therefore maximize the diagnostic potential of a patient sample and permit visualization of trends extending throughout the entire specimen in three space. This feature would allow the pathologist to better hone-in on a more accurate diagnosis.
Works within the system - "Getting something from nothing..."
Most importantly, 3D imaging represents nondestructive, noninvasive interrogation. This is a major selling point. If a veteran pathologist prefers the more orthodox route, then a patient sample may be removed from the 3D microscope and sent to traditional pathology as if it was just procured from the patient. Our method may integrate seamlessly into the pathology workflow. The pathologist may thus gain further insight about the sample with little loss in time and little to zero cost to the integrity of the biopsy because the specimen would remain intact and preserved.
(click here first, then on
each subsequent image)
At this point, if you're super critical, you might realize that there's one important (and obvious) aspect of 3D pathology that I haven't addressed: processing whole, unsectioned, intact tissue specimens. Remember, for nearly a century, protocols, process steps and procedures have been essentially dialed-in for flat (2D) tissue slices. Thus, how would you perform pathology and the related process steps on tissue biopsies?
Figure 7: Pathology-in-a-tube. A pancreas tissue core biopsy obtained in a fashion similar to figure 1 was
deposited into my simple, microfluidic device. Then the same rudimentary steps performed in pathology
(fixation, staining, washing, etc.) were replicated within a microfluidic channel. The tissue core was
transported using microfluidic flow to the 3D microscope for imaging. This is the first time that basic
pathology has been done within a microfluidic device and the first time ever whole, intact tissue has been
transported using microfluidic technology.
In 2014, my team and I developed for the first time a novel microfluidics platform, which replicates the rudimentary operations of a large-scale pathology laboratory on a credit card-sized device (fig 7). Because this was the first time microfluidics was employed on bulk tissue (i.e., large tissue pieces) and the fact that the device will eventually be combined with our 3D microscope (or any 3D microscope for that matter), the work became an instant hit amongst the academic & professional communities as well as local, domestic and international media. For further information, use the terms "ronnie das, pancreatic cancer" in any search engine. Nevertheless, the most important achievement for our project to date has been the successful securing of an NIH exploratory grant to develop this science & engineering into a system which may aid pathologists and, ultimately, help patients. In this regard, I am grateful and honored to be pursuing this research which is few degrees removed from the clinical realm, but has the potential to make direct medical impact through bridging benchtop research with bedside application.
So why pancreatic cancer? We focus on the detection and diagnosis of pancreatic cancer because of its severity. Any iota of research which contributes to the understanding of this disease is paramount. There are various statistics out there, but generally-speaking, pancreatic cancer patients follow a "95-5-5" trend — 95% of all patients stand a 5% chance of survival 5 years following a diagnosis. The situation is further compounded by the fact that what exactly causes pancreatic cancer, or how it manifests (even by expert accounts) is still relatively unknown despite its long history (i.e., first official case was documented nearly 140 years ago).
I hail from the Bay Area and come from a tight-knit Bengali family. I go out often with friends and am drawn to people who are humorous, like socializing and possess vivid imaginations. I sincerely enjoy learning about others, their cultures and thinking, especially since I often contemplate about identity as 1) a scientist/engineer, 2) a child of immigrants and 3) an individual in today's hyperconnected society.
When I'm not totally engrossed in research, I cycle as much I can and do so around Seattle to take-in the beautiful Northwest atmosphere and the ongoing activity of the city. I've been a cyclist for most of my life and have been riding seriously for nearly 20 years. I never imagined that it would eventually become so engrained in my life as it is a spiritual activity for me as well as a means to staying healthy & happy.
On weekends, I ride much further than the weekdays and average about 4-5 hours for a single day as I try to visit and see all parts of Seattle. Part of one of my
more frequent routes, (left) this is the waterfront of West Seattle, which looks across the Puget Sound. It's a very pretty route. When (right) I come home to the
Bay Area, I am so lucky to ride some of the driest, windiest routes in the back country of San Jose with little to no people for miles in every direction.
I hope that gives you a good unofficial summary — thanks for your patience and thanks for visiting!