Joshua Smith
1,085,876 views • 12:26

"You have cancer." Sadly, about 40 percent of us will hear those three words within our lifetime, and half will not survive. This means that two out of five of your closest friends and relatives will be diagnosed with some form of cancer, and one will die. Beyond the physical hardships, roughly one-third of cancer survivors here in the US will go into debt from treatment. And they're at least two and a half times more likely to declare bankruptcy than those without cancer. This disease is pervasive. It's emotionally draining and, for many, financially destructive.

But a cancer diagnosis doesn't have to be a death sentence. Finding cancer early, closer its genesis, is one of the critical factors to improving treatment options, reducing its emotional impact and minimizing financial burdens. Most importantly, finding cancer early — which is one of the primary aims of my research — greatly enhances your odds of survival. If we just look at the case of breast cancer for example, we find that those who are diagnosed and treated at stage one have a five-year survival rate of nearly 100 percent — odds that decrease to just 22 percent if treated at stage four. And similar trends are found for colorectal and ovarian cancer.

Now, we're all aware that an early diagnosis that is accurate is critical for survival. The problem is that many cancer diagnostic tools are invasive, costly, often inaccurate and they can take an agonizing amount of time to get the results back. Still worse, when it comes to some forms of cancer, such as ovarian, liver or pancreatic cancer, good screening methods simply don't exist, meaning that often people wait until physical symptoms surface, which are themselves already indicators of late-stage progression. Like a tornado strike in an area without an early warning system, there is no alarm to warn, for the danger is already at your doorstep when your odds of survival are greatly reduced. Having the convenience and accessibility of regular screening options that are affordable, noninvasive and could provide results much sooner, would provide us with a formidable weapon in the fight against cancer.

An early warning would allow us to get out ahead of the disease instead of merely following in its relentless wake. And this is exactly what I've been doing. For the past three years, I've been developing technologies that could ultimately aid clinicians with rapid, early-stage cancer diagnostics. And I've been fueled by a deep scientific curiosity, and a passion to change these statistics.

Last year however, this fight became much more personal when my wife was diagnosed with breast cancer. It was an experience that added a strong and unexpected emotional dimension to these efforts. I know firsthand how life-altering treatment can be, and I'm keenly aware of the emotional havoc that cancer can wreak on a family, which in our case included our two young daughters. Because we found it early during a routine mammogram, we were able to focus primarily on treatment options for the localized tumor, reaffirming to me how important an early diagnosis is. Unlike other forms of cancer, mammograms do offer an early-stage screening option for breast cancer. Still, not everyone has this done, or they may develop breast cancer before the middle age recommendation for having a mammogram. So, there's still a lot of room for improvement, even for cancers that do have screening options, and, of course, considerable benefits for those that don't.

A key challenge then for cancer researchers is to develop methods that make regular screening for many types of cancers much more accessible. Imagine a scenario where during your regular checkup, your doctor can take a simple, noninvasive urine sample, or other liquid biopsy, and present you with the results before you even leave the doctor's office. Such a technology could dramatically reduce the number of people who slip through the net of an early-stage cancer diagnosis.

My research team of engineers and biochemists is working on exactly this challenge. We're working on ways to frequently activate an early-stage cancer alarm by enabling regular screenings that would start when a person is healthy so that action could be taken to stop cancer the moment it emerges, and before it can progress beyond its infancy. The silver bullet in this case are tiny vesicles, little escape pods regularly shed by cells called exosomes. Exosomes are important biomarkers that provide an early-warning system for the development of cancer. And because they're abundantly present in just about every bodily fluid, including blood, urine and saliva, they're extremely attractive for noninvasive liquid biopsies.

There's just one problem. An automated system for rapidly sorting these important biomarkers is not currently available. We've created a technology that we call nano-DLD that is capable of precisely this: automated exosome isolation to aid rapid cancer diagnostics. Exosomes are the newest early-warning weapon, if you will, to emerge on the liquid biopsy front. And they're really, really small. They measure just 30 to 150 nanometers in diameter. This is so tiny that you could fit about a million of them into a single red blood cell. That's roughly the difference between a golf ball and a fine grain piece of sand.

Once thought to be little bins for unwanted cellular waste, it has been found that cells actually communicate by producing and absorbing these exosomes which contain surface receptors, proteins and other genetic material collected from their cell of origin. When absorbed by a neighboring cell, exosomes release their contents into the receiving cell, and can set in motion fundamental changes in gene expression — some good, and this is where cancer comes in, some bad. Because they are clothed in the material of the mother cell, and contain a sample of its environment, they provide a genetic snapshot of that cell's health and its origin. All of these qualities make exosomes invaluable messengers that potentially allow physicians to eavesdrop on your health at the cellular level.

To catch cancer early, however, you have to frequently intercept these messages to determine when cancer-causing troublemakers within your body decide to start staging a coup, which is why regular screening is so critical and why we're developing technologies to make this possible. While the first exosome-based diagnostics emerged on the market just this year, they are not yet part of mainstream healthcare options. In addition to their recent emergence, another factor that's limiting their widespread adoption is that currently, no automated exosome isolation system exists to make regular screening economically accessible. The current gold standard for exosome isolation includes ultracentrifugation, a process requiring expensive laboratory equipment, a trained lab tech and about 30 hours of time to process a sample. We've come up with a different approach for achieving automated exosome isolation from a sample such as urine. We use a chip-based, continuous flow separation technique called deterministic lateral displacement. And we have done with it what the semiconductor industry has done so successfully for the past 50 years. We shrunk the dimensions of this technology from the micron scale to the true nanoscale.

So how does it work? In a nutshell, a set of tiny pillars separated by nanoscopic gaps are arranged in such a way that the system divides the fluid into streamlines, with the larger cancer-related nanoparticles being separated through a process of redirection from the smaller, healthier ones, which can in contrast move around the pillars in a zigzag-type motion in the direction of fluid flow. The net result is a complete separation of these two particle populations. You can visualize this separation process similar to traffic on a highway that separates into two roads, with one road going into a low-clearance tunnel under a mountain, and the other road going around it. Here, smaller cars can go through the tunnel while larger trucks, carrying potentially hazardous material, are forced to take the detour route. Traffic is effectively separated by size and contents without impeding its flow. And this is exactly how our system works on a much, much smaller scale.

The idea here is that the separation process for screening could be as simple as processing a sample of urine, blood or saliva, which is a near-term possibility within the next few years. Ultimately, it could be used to isolate and detect target exosomes associated with a particular type of cancer, sensing and reporting their presence within minutes. This would make rapid diagnostics virtually painless. Broadly speaking, the ability to separate and enrich biomarkers with nanoscale precision in an automated way, opens the door to better understanding diseases such as cancer, with applications ranging from sample preparation to diagnostics, and from drug resistance monitoring to therapeutics.

Even before my wife's bout with cancer, it was a dream of mine to facilitate the automation of this process — to make regular screening more accessible, similar to the way Henry Ford made the automobile accessible to the general population through development of the assembly line. Automation is the key to accessibility. And in the spirit of the Hoover dream, "a chicken in every pot and a car in every garage," we're developing a technology that could ultimately place an early-warning cancer detection system in every home. This would allow every man, woman and child the opportunity to be regularly tested while they're still healthy, catching cancer when it first emerges.

It is my hope and dream to help people around the world avoid the high costs — physical, financial and emotional — faced by today's cancer patients, hardships that I'm well acquainted with. I'm also happy to report that because we caught my wife's cancer early, her treatment was successful, and she is now, thankfully, cancer-free.


It is an outcome that I would like to see for everyone with a cancer diagnosis. With the work that my team has already done on separation of nanoscale biomarkers for rapid, early-stage cancer diagnostics, I am optimistic that within the next decade, this type of technology will be available, helping protect our friends, our family and future generations. Even if we are so unlucky as to be diagnosed with cancer, that early-stage alarm will provide a strong beacon of hope.

Thank you.