It takes the better part of a year to fly to Mars. And even then, the timing has to be just right for great flying weather.
In 2018, there will be one such window. That May, the European Space Agency (ESA) and Russia’s Federal Space Agency, Roscosmos, will launch the latest automated exploration vehicle bound for Mars, the ExoMars Rover. Aboard the rover will be a contribution from NASA called the Mars Organic Molecule Analyzer, or MOMA.
“I will be on that mission in spirit,” said Bier, a research professor at Carnegie Mellon University, an institution known for its interdisciplinary spirit and its dual focus on the arts and sciences.
On average, 140 million miles of empty space stretch between us and the Red Planet — “average” because the distance between the planets constantly changes as they orbit around the sun. Approximately every two Earth years, we swing closer than usual to our Martian neighbor, and 2018 presents the opportunity to answer a question that many scientists and science-fiction fans have been asking for decades: Is there — or was there ever — life on Mars?
Scientists like Bier and sci-fi fans might have very different interpretations of this question. If there is life on other planets, it’s much more likely to resemble the contents of a petri dish than a reflection in a mirror. That’s why the rover will be searching with a chemical microscope and not a video camera.
The mass spectrometer on the Mars rover will test gas, soil and rock samples from the surface of the planet in search of organic molecules — markers of life. If found, these markers could provide clues to the origin and evolution of life on the Red Planet.
Conceptually, it’s not difficult to understand the idea of “testing a sample” for a substance being sought — people come in contact with the idea constantly, whether testing the blood for indicators of disease, testing food and water for contaminants, or testing the air for pollution. But what are the mechanics? How are tests like these actually done?
The Answer Is Mass Spectrometry
Bier, who has taught and researched in CMU’s Mellon College of Science for two decades, has been an innovator in the field of mass spectrometry, “mass spec” for short. In 1994, he conceived the linear ion trap mass spectrometer and the toroidal ion trap incorporating radial ion ejection while working at what’s now ThermoFisher Scientific, a biotechnology development company. The linear ion trap is now one of the most common types of mass spectrometers in the world, which Bier said is very gratifying. He recalled the moment of its inception vividly, saying the idea came to him fully formed while he wasn’t even working on developing a new device.
“I describe it like a lightning bolt,” he said. “It was like: This is going to work, and it’s going to be much better than what we’re doing right now. It was an ‘a-ha’ moment for sure.”
Different types of spectrometers serve different applications in industries like healthcare, geology, environmental science, space exploration (such as the one on the Mars Rover) and biology — which have many, many uses — but they all more or less follow the same basic operating process: ionization, mass analysis and ion detection.
Particles in a vaporized sample are ionized, meaning that on a molecular level, for example, electrons are lopped off or a proton is hopping on to make the overall charge on the particles positive.
The trajectories of these now-positive ions are changed or modulated in such a way the ions mass-to-charge ratio (m/z) can be determined. The simplest mass analyzer is a time-of-flight analyzer where the ions race to a detector. Measurement of the travel time is then converted to an m/z. In a magnetic sector instrument an electromagnet pushes on the streams of ions, which bend away from the magnet on different trajectories, depending on their m/z. To visualize this, imagine holding a window fan, and someone throws a baseball past it; the air current from the fan isn’t going to deflect the baseball much from its path. Now imagine that someone throws a ping-pong ball past it; the fan will blow the much-lighter ball off-course.
For some magnet based systems, ions on a certain trajectory will make it through the device to the detector — the other streams of ions will be bent off their paths too much or not enough and collide with the walls of the device, becoming neutralized. The detector translates the ion current into a graph that maps the mass-to-charge ratio of the ions against their relative abundance, allowing scientists to understand the constituent parts.
“You basically generate a fingerprint,” Bier explained. “And from those fingerprints, you can generate libraries of fingerprints.”
Using libraries, a graph of an unknown substance can be compared to the graphs of known substances. When a match is found — bingo! Mass spectrometers are like chemical detectives, working on a miniscule scale to determine the weight, structure and composition of molecules. Indeed, these detectives sometimes do criminal investigative work; typically, a mass spectrometer is the means by which blood and urine samples are tested for illegal drugs and steroids.
With a grant from CMU’s Wilton E. Scott Institute for Energy Innovation, Bier and colleague Jeanne VanBriesen will soon be modifying another type of spectrometer, one with a special membrane interface and ionizer for liquid samples. Their intention is to test water samples in the field for potential contamination from hydraulic fracturing, or fracking, the process by which natural gas is extracted from shale rock, when water, sand and chemicals are injected at high pressure into a well site.
Proteomics and metabolomics — the study of proteins and metabolites, respectively — are fields heavily dependent on mass spec, as Josh Lichtman will tell you. Lichtman is a scientist at NGM Biopharmaceuticals, a privately held, clinical-stage biopharmaceutical company with a drug-discovery platform designed to generate a pipeline of first-in-class biologic drug candidates. He uses mass spec as a discovery tool for new drug targets, meaning specific proteins or pathways that seem to be related to a disease.
“Prior to mass spec, people were only able to look at five to10 proteins at a time,” he explained. “Mass spec has now given us the ability to look at hundreds, thousands of proteins simultaneously in very complex samples.”
He said that as inventors, like Bier, create increasingly more sensitive mass spectrometers that can “see” bigger molecules, and at smaller amounts, it will lead to a better understanding of the human microbiome, which is a reference to a mini-ecosystem of micro-organisms, particularly in a specific part of the body. There are trillions of micro-organisms in the human body. In fact, their cells outnumber a human’s 10 to one, and every person’s micro-ecosystem is unique. Research has only begun uncovering the impact that these ecosystems have on health.
Lichtman believes that mass spec “will help reveal interactions between host and microbes that result in disease [a focus of Bier’s research]. Discovering these interactions can allow scientists to tailor treatments, thereby improving health outcomes.” In other words, spotlighting virus vulnerabilities is like knowing where the chink in the armor is so scientists can tailor drugs to attack the virus, thereby improving health outcomes.
Bier envisions a day when a patient’s visit to a doctor’s office for even a simple cold might mean an efficient, definitive diagnosis using a mass spectrometer and customized treatment. Instead of just assuming it’s a rhinovirus — which causes colds — and not, say, allergies, a swab sample could potentially be tested for virus particles at low levels. A positive identification might even tell which particular strain or mutation of the virus a person has contracted, and the doctor might recommend a specific medicine or suggest that the patient steam his sinuses because the particular strain is susceptible to heat.
Scientists, researchers and lab technicians across many fields use mass spectrometers, though Bier said, they’re mostly “black boxes” to their users.
In other words, researchers may know what to put in the devices and how to read and interpret the output, but as far as what goes on inside all the tubes and chambers, they don’t actually need to know in order to do their work effectively.
But it doesn’t take more than a few minutes of talking to Bier to realize that he’s more of an “under the hood” kind of guy and how excited he is about the future possibilities of mass spec.
“The technology, even today, hasn’t come close to reaching its plateau,” he predicted.
The upcoming trip to Mars, he added, serves as a fitting analogy for the field’s boundaries.
(Lead image) A linear quadrupole ion trap with radial ion ejection held in the palm of Bier’s hand. Because of its unique advantages, a linear ion trap with radial ejection is expected to rocket to Mars for the 2018 rover MOMA mission to look for life-related molecules.