Our guest blogger today is Dr. Ozzy Mermut. Ozzy is the Program Manager of Biophotonics at the Institut National d’Optique (INO) in Quebec City and Associate Professor at Laval University. A Ph.D from McGill University, and post doctorate at the University of California Berkeley and the Lawrence Berkeley National Laboratory, Ozzy’s research interests have focused on novel methods and tools for bimolecular spectroscopy and imaging, with the underlying theme of providing technology impact in medicine and life science . At INO, she leads research and development activities to translate biophotonics science from the lab into viable health and life sciences technology platforms for industry.
I met Ozzy in 2011 when I was asked to review the operational concept and procedures for an INO payload called Microflow, an innovative and portable flow cytometer. Development of this device was funded by the Canadian Space Agency (CSA) and flew aboard the International Space Station in 2013 with Chris Hadfield as a technology demonstration.
Microflow operated perfectly. The mission demonstrated that a microflow cytometer could become an essential tool for a range of bioanalysis and clinical applications in space. I asked Ozzy to write a guest blog entry describing the development of Microflow for spaceflight and its potential use in remote health care settings in Canada. Here is her story.
“How can a tiny glass fiber the size of a hair do that!?”
This was a common question that I received in the early days of the Microflow project. Observing the National Optics Institute’s (INO) unique, optical fiber contraption, many people wondered how such a miniature technology could transform into a vital medical platform for lab analysis in near-real time.
Today, biomedical testing of blood and urine for early diagnostic signatures of potential illness requires you to go to a hospital or laboratory. You may then need to wait several days for the test results. But what if you live 250 miles away from the nearest hospital or lab, and from the medical experts who perform bioanalysis? What if you live in space? This was the question I was asked in 2011 and answered in 2013 with a successful demonstration of the Microflow cytometer. But let’s back up and start at the beginning.
As manager of Biophotonics R&D at INO, I have witnessed time and again that there is indeed a lot of power in light. Perhaps when the Book of Genesis said “Fiat Lux” (Let there be light), the incredible impact that electromagnetic radiation would someday have on health research – from cancer screening to therapeutic treatments – was not foreseen. And at the center of all this is the world of biophotonics technologies – technologies that exploit the interaction of light with biological materials to answer life sciences questions and address clinical problems.
The heart of Microflow is an all-fiber optical flow cell innovation that enables real-time cellular analysis (one-at-a-time) and phenotyping within a ~200um core-fiber optic minilab.
You see, light has some exceptional properties that allow us to target, tune, and turn on desired effects, while simultaneously eliminating undesirable ones. Take for example, light used for dental therapeutics. The days of drilling away cavities will soon be gone; the latest treatment is now laser-based, minimally invasive and targeted. No anesthesia is required! By picking the colour and suitable energy profile (eg. in time, space and intensity), a dentist can selectively remove one type of biomaterial while leaving healthy tissues undisturbed. And in the world of ophthalmology, many people have already entrusted their precious vision to light corrective surgery.
By controlling the various features of light, we may also use it to probe specific biological materials and events without inducing an effect upon them, and without impacting living organisms, their tissues, and cells.
Microscopes and flow cytometers are great examples of this. These devices are sophisticated tools that expose biological samples such as blood, urine, saliva and tissue smears to focused lasing light in order to interrogate cells and biomarkers within. Microscopes analyze cells in a stationary state on a surface through magnified visualization, while cytometers analyze cells flowing single file in a stream of fluid to enable individual characterization and classification. Given this much capability, it is a pity that we don’t all own our very own personalized bio-labs! From a spaceflight perspective, such portable and potentially diagnostic tools can be quite handy and vital as astronauts explore space at ever increasing distances from Earth.
Utilizing light technologies for bioanalysis in the ultimate remote setting, space, has its own set of challenges and drawbacks. First, such laboratory technologies are not readily deployable or portable. If you’ve been to a molecular biology lab, you can appreciate that microscopes and cytometers are rather large, heavy and sophisticated systems comprised of interconnected lasers, detectors, lenses and filters. These complex instruments don’t travel well. A classic flow cytometer can weigh 100kg. That’s one inconvenient spaceflight carry-on!
INO and CSA colleagues celebrate at Cape Canaveral following the successful launch of the SpaceX CRS-2 rocket carrying Microflow to the ISS (along with food for the astronauts!). (Ozzy Mermut is third from the left.)
A shipping box labeled “fragile” obviously won’t cut it when your main source of transportation to space is a rocket. Equipment shipped by a SpaceX rocket, for example, experiences high frequency forces not encountered by cargo that is shipped by truck or plane. In some instances, these launch vibrations can amplify into resonant frequencies which could spell doom for fragile items. And then there is the static launch acceleration component – up to 7G (seven times the force of Earth gravity).
Once the equipment arrives in space (hopefully intact), it needs connection to onboard power. This can be a problem if your destination is the International Space Station (ISS). Did you remember to bring your universal adaptor and power supply? What happens if the instrument breaks in space? Launching equipment to the Space Station is only the first step. Sophisticated equipment requires its own set of specialized maintenance procedures and tools. I hope you remembered the 200-page users’ manual!
The INO Microflow space lab is the result of a collision of a team of physical scientists who love to play with light, and biomedical optics researchers who tackle challenging problems in medicine. A key photonics technology that enabled the design of Microflow is the fiber optic. Many people are aware of fiber optics technology for its conventional role in telecommunications. Fiber optic communication is a very simple and highly compact means of transmitting packets of dense light-encoded data from point A to point B – often over thousands of miles of distance. We rely on this miniature (the size of a sewing thread) technology every day to deliver hundreds of TV channels and high speed internet. My fascination with the might of fiber optics began at university while researching its potential as tiny, remotely deployable optical sensors. My appreciation grew as I later worked to route light data at petabit rates (that’s 1000 trillion bits per sec!).
In a world of high-speed, high-bandwidth, real-time acquisition and transmission of information, our challenge at INO was clear: harness this powerful technology to probe biomarkers and enable medical diagnosis in the ultimate frontier, space. Our dream spelled a space lab-in-fiber-optic.
A fiber optic works by constraining and guiding light along its core. It is in essence a “light pipe” transmitting information at light speed. But this is no ordinary pipe. Microns in size, it can encode many ‘colours’ of information simultaneously transmitted over many ‘channels’. Did you know that a single optical fiber can provide voice communications for the entire population of Canada with the USA? Yet this very same technology can be collapsed into a miniature portable laboratory capable of analyzing health biomarkers in the most remote locations.
Microflow’s debut aboard the ISS! Chris Hadfield opens his tech gift and gives it a spin! After successful operation and demonstration of Microflow’s capabilities for blood biomarkers analysis, Chris transmitted the unit’s heartbeat data back to Earth. (Credit: Chris Hadfield, CSA, NASA)
Our INO biophotonics research materialized our space dream into reality, the secret lying literally in a fiber optic core. By creating a hole in the center of an optical fiber (the medium which traps and propagates the light) we realized we could access light while rapidly interrogating biological material. With the fiber, we can ‘bend the light’ from a laser to illuminate and excite a bioanalyte, and then ‘bend the light’ again to transmit the received cell character information back to a detector. By flooding the core of this tiny light pipe with biological fluids, we can optically characterize each particle (cell or biomolecules) as it passes rapidly in front of a light beam (1000s of analytes per sec).
Take blood, for example. It is rich in particles which provide information about the status of health. In a microliter, blood contains 5 million red blood cells, 7000 white blood cells and 200,000 platelets. With colour-specific tags, one can analyze and phenotype entire populations of blood cells and other biomarkers in less than two minutes using Microflow. A very fast and powerful fiber optic space lab that fits in the palm of your hand!
This concept of optically analyzing biological particles individually in flow is nothing new. Flow cytometry has been around since the 1950’s. But cells cannot ‘self-focus’ one at time for interrogation in front of a light beam; they need to be guided. Conventional flow cytometers necessitate large volumes of diluted sample to get the particles placed perfectly in front of the light zone for accurate detection. This generates much waste liquid.
Microflow’s unique fiber optic technology, on the other hand, requires only tens of mL of sample (about the volume of a blood prick). This not only makes the fluid system simpler, but generates significantly less waste fluid. It simplifies cytometry function. In the ISS environment where real estate is a premium and fluids management is a pain, the Microflow is inherently space-friendly.
The potential of this technology as a portable space biolab is endless. In 2011, the task assigned to me and my INO colleagues was to prove this. Well, nothing is more convincing than a demonstration of the technology in the demanding operational environment of the ISS. After 18 near-sleepless months of preparations, Microflow’s launch to the ISS (March 1, 2013) and demonstration tests (March 6 and 11, 2013) were flawless, both carefully and perfectly orchestrated by my INO colleagues and CSA partners. And the icing on the cake? Our very own Chris Hadfield was at the helm of testing Microflow.
Houston, I am happy to report: Microflow is a success!