Christopher C. Mulligan (right) is a professor of analytical chemistry at Illinois State University. He has more than 15 years of experience in developing miniaturized analytical devices, with specific expertise in portable and miniaturized mass spectrometric instrumentation development, novel ionization methods, and application development. Through his research, Mulligan seeks to demonstrate the impact and practicality of portable MS systems for use in crime scene investigation, law enforcement, security applications, and environmental science.
Daniel E. Austin (left) is a professor of chemistry at Brigham Young University (Provo, UT). He received his PhD at the California Institute of Technology and subsequently worked as a senior member of the technical staff at Sandia National Laboratories in Albuquerque, NM. His research interests include developing miniaturized ion trap mass analyzers, experiments in surface induced dissociation of fast neutrals, and charge detection mass spectrometry. He received the 2018 Curt Brunnée Award from the International Mass Spectrometry Foundation, and has received several other awards.
Q: Please explain your experience with developing portable mass spectrometers.
Christopher Mulligan: My group combines fieldable mass spectrometry (MS) technologies with so-called “ambient” ionization methods, where samples of interest are analyzed with little to no preparation. In this way, we hope to provide the first response, forensic science, and environmental monitoring communities with near-real time chemical information, but in a platform that is easy to use, reliable, and, for samples of legal concern, court-admissible. Our efforts are split between instrumentation development, investigating novel ionization sources, and applications for disciplines that would benefit from such an analysis strategy.
Daniel Austin: For several years, we have focused on using microfabrication and novel electrode geometry to make smaller ion trap mass analyzers that retain as much performance as possible and can be used in portable systems. Much of our work uses ion traps made using lithographically patterned substrates. We have also done work on toroidal ion traps, which have a larger trapping capacity. As ion traps become smaller, it is important to maintain analyte sensitivity by keeping the ion trapping capacity as large as possible.
Q: Why is there a need to bring mass spectrometers out of the lab and into the field for analysis?
Christopher Mulligan: For field-borne samples, the main determiner of overall analytical throughput is not how fast you can analyze the sample, but how quickly you can transport it to the traditional off-site laboratory. The old axiom of “time equals money” applies, but for time sensitive situations like chemical spills, criminal investigations, and homeland security events, this downtime between sample collection and processing can determine how effective response efforts are.
Daniel Austin: For many applications, it is possible to collect samples and send them off to a mass spectrometry facility for analysis, although it can take time to get the results. However, on-site and rapid analysis allows quick decisions to be made, which would be particularly helpful in emergency response, national security, forensics, etc. In addition, many samples are too complex spatially, or vary in time, and multiple samples are needed. For some types of analysis, the sample could change during storage and transport—problems avoided with on-site analysis.
Q: What challenges can you run into when trying to develop and build a smaller, portable spectrometer? How can these challenges be overcome?
Christopher Mulligan: As a general trend, smaller would be better with portable MS systems—the pinnacle achievement would be a device akin to the Tricorder from Star Trek, handheld and diverse in the data it can yield. However, reducing the size of the MS typically reduces the analytical performance, as well. Historically, the size of the MS device was dictated by the vacuum system it employs and the necessary RF/DC electronics for operation. Advances in vacuum technology and electronics have allowed even lab-scale MS systems to undergo a massive size reduction. Further miniaturization has a cost, though. Less vacuum leads to fewer ions being sampled and lower sensitivity (for atmospheric pressure and ambient ionization sources). Smaller, lower performance electronics lead to lower resolution spectra and/or a reduced mass range. In this way, there is a natural divide in fieldable MS development, that being miniature/handheld devices that may have reduced performance and portable devices that maintain some performance attributes of lab-scale systems.
Daniel Austin: There are many challenges, and some that we didn’t anticipate when we started working in this area. Interestingly, most groups in recent years have moved away from trying to make the mass analyzers smaller and are focusing on making everything else smaller. We have continued to try to make the mass analyzers smaller, as have a small handful of other groups. A lot of the competition is now from companies. One of the challenges is that there are so many sub-systems to a mass spectrometer that it is out of reach for academic groups to actually produce an instrument. There is a lot of engineering, electronics, computer interfacing, etc. that is necessary to generating a mass spectrum, but it is not what we can expect from graduate students in a single discipline such as chemistry. That is one reason my group has focused on the analyzer itself.
We have had challenges related to engineering small devices—what materials work or don’t work, how to make small but reliable electrical connections, what to do when we don’t see signal, contamination issues, burned out components, etc. Everything scales differently at smaller scale, so we sometimes don’t correctly anticipate heat build-up or cooling, misalignments and their effects, etc.
Q: What limitations are associated with current portable spectrometer technology on the market compared to regular-sized instruments in the lab?
Daniel Austin: There are several portable mass spectrometers on the market, typically in the range of 15-20 kg. This is still a sizeable instrument. I’ve also seen larger instruments, or in some cases full-sized lab-scale instruments, made portable for specific applications by putting the instrument in a vehicle. There are still challenges even with that. These types of applications underscore the potential for truly portable instruments to come.
Q: Can you put into perspective the difference in size and weight of a portable mass spectrometer compared to a bulkier one in the lab?
Christopher Mulligan: Lab-scale mass spectrometers are deceiving, as the instrument itself is big, but there are also roughing pumps, gas tanks, etc. that are required for operation. For portable mass spectrometers, the goal is that all of the required consumables (such as compressed gases, delivered solvents, etc.) and any needed voltage sources for sample ionization are included in a form factor that is person-portable. What you see is what you get.
Daniel Austin: Benchtop instruments are often two to three times the size and weight. So you can see that there has been some miniaturization, but not yet as dramatic a difference as we really need to take mass spectrometers into the field as easily as we take a cell phone.
Q: Aside from spectrometers, what other instruments are being developed to be portable?
Christopher Mulligan: There are quite a few commercially-available, portable technologies for chemical analysis now. Portable GC-MS systems have been around for almost 20 years, and companies such as Advion now offer “compact” LC-MS systems for varying applications like reaction monitoring. Several types of spectroscopy (e.g. XRF, NIR, Raman, FTIR) have portable versions that offer point and shoot chemical screening. And there are even benchtop scale NMRs now.
Q: How do you see mass spectrometers evolving in the future (over the next 5-10 years)?
Christopher Mulligan: Five to 10 years may be ambitious, but I think advances in miniaturization will eventually yield the handheld “personal” mass spectrometer. Combining such a technology with the Internet of Things could revolutionize fields like medicine, public safety, etc.
Daniel Austin: Several new companies have emerged in recent years with the intention of developing portable mass spectrometers. A lot of progress is being made, and I think this will continue. At the same time, many applications are being reported that make use of the existing portable instruments.