Miniature Mass Spectrometry Instruments for Biomedical Applications

Introduction:

A multitude of disciplines within the biomedical, chemical, and pharmaceutical fields often rely on mass spectrometry (MS) as a means for identifying compound structure, quantifying metabolites, and measuring molecules in mixtures of varying complexities. This highly sensitive approach for the study of biological systems is also used in drug discovery and is crucial in the development of potentially life-saving therapeutics. Large system size is perhaps the most common limiting factor that may be preventing widespread application of MS in the clinical environment. Additionally, complicated analytical methods can make the system impractical for some healthcare practitioners and nonmedical professionals.

Miniature MS has recently been introduced to help overcome size and weight limitations inherent in conventional MS tools. Benchtop MS instruments have become condensed and modified for portability and accessibility, and some miniature MS systems have been adapted for handheld use. Miniature MS technology has significant utility for chemical process control and environmental monitoring, among other applications. Being able to use miniature MS for in situ analysis, for example, has been one significant reason for developing miniature systems. Also, having a MS system that is approachable and easy-to-use by nonmedical professionals, like firefighters and inspectors of food safety, is also a driving force behind the expansion of miniature MS.

This technology will be highlighted in numerous talks at Pittcon in Chicago, IL, March 5-9, 2017. Sessions will be led by leading researchers in the field of MS and miniature MS, including R. Graham Cooks of Purdue University and Daniel Austin of Brigham Young University. Talks will be given on the subjects of ion traps and the miniaturization of MS, and numerous companies will be in attendance to demonstrate their mass spectrometer products and how they can be used in a variety of scientific applications.

A miniature MS is revolutionary in that it provides quick, easy clinical diagnostics and can sit in a physician’s office without sacrificing space. Mini 12, a miniature MS with an ambient ionization source and developed by Purdue University researchers, is an example of a successful miniature MS system. This miniature MS instrument has been designed for physicians or nurses who require a simple MS analysis in the clinical setting. A finger prick blood sample can be loaded into a cartridge and into the Mini 12 MS, automatically producing analysis of data. The cartridge contains a barcode that is read by a camera in the system, initiating the required analysis. Following a solvent spray onto the cartridge and a number of other processes, the MS scans are performed. This occurs without any operator intervention.

Minimizing MS size, while beneficial in some aspects, also has its own set of limitations. Size reduction of MS can lead to compromised performance of a MS; however, miniature MS has been specifically constructed to maintain a high level of accuracy and sufficient resolutions while offering automatic operation. All mass specs work in a vacuum to avoid intermolecular collision events and remove background signal. Since vacuum systems feature a considerable amount of weight and are fairly large in size, the vacuum represents one of the biggest challenges for shrinking a mass spectrometer.

An exciting application of miniature MS in surgery has been in the field of oncology, specifically brain cancer. A study from Purdue University and Brigham and Women’s Hospital and led by Robert Graham Cooks found that a tool that relied on desorption electrospray ionization, an ambient mass spectrometry analysis technique, was able to test brain tissue to identify cancer grade and type as well as tumor margins in brain surgery patients. Potentially, a miniature MS system that is being developed by this research team may be used for the same study of cancerous tissue, particularly in regard to their molecular structure.

Robert Graham Cooks, one of the authors of the paper, will be providing two talks at Pittcon 2017 in Chicago, Illinois, introducing a session about miniature mass spectrometers while also presenting his study, Searching for Biomarkers Using Ambient Ionization Mass Spectrometry. Pittcon 2017 will also present new, innovative studies in the field of miniature MS, including specific ion traps and novel ionization procedures. Bruker, Photonis, Waters, Hamamatsu, and Thermo Fisher Scientific are just a few of the key exhibitors this year, each providing information and demonstrations of their MS systems and new measurement technologies.

References


Chapter 1 – Miniaturizing Mass Spectrometry

The use of miniaturized mass spectrometers is quickly becoming mainstream, particularly by physicians at the bed side. Their small size allows portability and helps provide answers to real-world scientific- and medical-related questions in a simple and efficient manner. Miniaturized, portable mass spectrometry has also become widely utilized in forensics and security to gather and identify substances and chemical threats quickly. Instruments such as these provide a reliable and relatively quick way to obtain answers without compromising the quality of results.

Although effective, the actual construction of miniaturized mass spectrometers can be a challenge to designers of these instruments. Often, the vacuum in these devices is poor due to the instrument’s size and power constraints. Large sample sizes, which are typical of larger instruments, produce more certain results, compared to smaller sample sizes that are often analyzed by miniaturized machines. Fortunately, developers and companies have become more adept at developing technology to circumvent these possible caveats.

Miniaturized mass spectrometry will be frequently discussed at Pittcon 2017 and will include some of the following sessions:

  • Novel Scan Methods Using Miniature Ion Trap Mass Spectrometers
  • Integrated Miniature Mass Spectrometry Systems
  • Cartridge-Based Sampling Ionization Methods for Miniature POC Mass Spectrometry Analysis Systems
  • Embedded Analytics and Automation Challenges and Opportunities with Miniature Field Analyzers

University researchers are also on the forefront of mass spectrometry miniaturization, using these efficient and effective tools for research across all science specialties. Since the construction of the first miniature ion trap in 1991, researchers at Purdue University have developed two basic, effective approaches for miniaturizing mass spectrometry. These two methods include the “bottom-up approach” and the “top-down approach.”

Bottom-Up Approach

In the bottom-up approach, researchers shrink the micro-scale mass analyzer first before constructing the actual instrument. The instrument is essentially built around the miniaturized micro-scale mass analyzer.

Due to the relatively small trap size, developers of the spectrometer must arrange the traps in a parallel to each other in an effort to trap and increase the number of stored ions.

Top-Down Approach

Contrary to the bottom-up approach, the top-down approach starts with an existing lab-scale instrument, and developers work on first miniaturizing the instrument followed by shrinking the individual components of that instrument. This approach, utilizing the advancements in current technology, can reduce instrumentation and doesn’t sacrifice performance in the process. At Purdue University, the top-down approach helped to develop the mini10 and mini11 miniature spectrometers, with no hindrance in overall performance when compared to standard mass spectrometers.

R. Graham Cooks, a speaker at Pittcon 2017, and Raymond E. Kaiser, Jr., have previously reported on their success with building the first miniature ion trap at the University of Purdue. Their paper, published in a 1991 edition of the International Journal of Mass Spectrometry and Ion Processes, discusses methods for overcoming the inherent constraint limitations associated with the quadrupole ion trap mass spectrometer. The authors demonstrate that extending the charge and mass range of the quadrupole ion trap include:

  • Using smaller electrodes
  • Operating the device at lower radio frequencies
  • Resonance ion ejection with the use of a selected voltage at an appropriate frequency

In conclusion, the authors believe frequency reduction with axial modulation and a modest size of the device yields a more effective high-mass biological mass spectrometer.

Photonis, a significantly large supplier of the world’s ion electron detectors and amplifiers used in mass spectrometers and an exhibitor at Pittcon 2017, works to miniaturize mass spectrometers successfully, with the ability to:

  • Reduce machine size overall
  • Provide reliable results in poor elevated pressure and vacuum environments

The detectors offered by Photonis are aimed to support many different types of mass spectrometry, including quadrupole, Time of Flight, and ion trap. Photonis’ Spiraltron™ technology is comprised of compact detectors that achieve high gain without the excessive noise. Additionally, Photonis’ MegaSpiraltron™ technology, another compact detector, have been designed for poor vacuum environments for portable mass spectrometers. Both Spiraltron™ and MegaSpiraltron™ allow detectors to feature up to 6 input channels that are contained within one detector, substantially increasing the sample size. This is essential for high-quality experiments seeking reliable results, as a larger sample size tends to produce results that are more accurate when compared with sample sizes on a smaller scale. The “spiraling” of various channels together in the technology significantly reduces the chance of ion loss or feedback.

Mini-spectrometers offered by Hamamatsu, another company who will be exhibiting at Pittcon 2017, feature condensed optical systems, circuits, and image sensors that are fitted into a small case. The company also provides ultra-compact spectrometer types that can be connected to mobile devices, offering a greater ease-of-use benefit for physicians and other scientific professionals who wish to analyze data remotely. More than 20 types of mini-spectrometers are offered by Hamamatsu. The company’s technology, micro-opto-electro-mechanical-systems (MOEMS), combines both circuits and software with optical technology to provide in-depth analysis and quick measurement without having to bring in large samples or equipment.

References

Pittcon Tracks

Bioanalytical & Life Science
Biological molecules and xenobiotics (drugs, toxins) and their metabolites; study of biological systems; biosensors; forensic science and toxicology
Cannabis & Psychedelic
Identification, quantitative measurement, extraction, and quality assurance of cannabis-based and psychedelic products
Environment & Energy
Environmental detection and monitoring; energy production and storage; sustainability, climate, and green chemistry; food science/safety and agriculture
Instrumentation & Nanoscience
Instrumentation, detection, and sensors; laboratory information systems, data analysis, and artificial intelligence; characterization and processing of nanomaterials; art and archeology
Pharmaceutical & Biologic
Evaluating chemical composition and properties/activities of medicinal drugs and biologics; high-throughput screening and process control; drug discovery and design; personal care and consumer products
Professional Development
Leadership and power/soft skills; career navigation, DEI (diversity, equity and inclusion), communication, and entrepreneurship; education and teaching and more

Chapter 2 – Biomedical Applications of Miniature Mass Spectrometry

Desorption electrospray ionization (DESI) is a method commonly used for MS and works by creating molecular maps to tissue sections, allowing researchers to identify the state of disease within a selected tissue without requiring a long sample preparation or labelling time. Typically, DESI is used to determine disease state of tissue, which can be helpful in the surgical room. As a technique that can be performed directly on biological tissue, DESI helps to provide imaging of fatty acids, hormones, lipids, and various other compounds. Promising for detecting and identifying certain types of cancer in situ, DESI can also be used for mass spectrometry when using a miniaturized mass spectrometer.

Paper spray (PS) ionization, however, is a different ionization method that uses electrospray to produce ions to a paper substrate. This technique’s speed and simplicity makes it attractive for small samples in mass spectrometry and offers a quick, effective method for drug monitoring in biofluids (among other applications). Thermo Fisher Scientific, an American biotechnology company and an exhibitor at Pittcon 2017, has developed a PS ionization system called the Prosolia Velox 360™ PaperSpray™ System. This technology is highly sensitive and uses a triple stage quadrupole mass spectrometer for targeted quantitation. High-Resolution Accurate-Mass (HRAM™) Q Exactive™ and PaperSpray is combined together in this system for screening and identification of compounds. This technology can also be used to identify drug abuse by analyzing urine and blood samples. One study was able to identify up to 6 drugs by testing dried blood sports with the PaperSpray system.

Bruker Scientific, one of the leading MS companies presenting at Pittcon 2017, also uses DESI ionization. Handheld, portable mass spectrometers from Bruker, useful for metal and gas detection, may have the potential for DESI application. These products can analyze samples in a nondestructive manner and with sample preparation in the laboratory.

J. Michael Ramsey of the University of North Carolina (UNC) at Chapel Hill will be discussing miniaturized handheld analyzers at his talk at Pittcon 2017. His session titled “High Pressure Mass Spectrometry: A Path to Handheld Analyzers with Specificity and Sensitivity” will explore the emergence of portable MS tools for the identification of low-concentrated compounds in a variety of conditions, including conditions of low pressures. The work presented will also focus on the miniaturization of Paul trap mass analyzers, the use of small ion traps to perform MS at unknown pressures, and the most recent advancements in ion source options as it relates to miniature MS.

R. Graham Cooks, a featured speaker at Pittcon 2017, and Zheng Ouyang describe in their paper “Miniature Mass Spectrometers” the mass analyzer as well as the total analytical system and its many applications. In general, the authors describe how ion traps have been the primary focus when it comes to mass analyzer miniaturization. The vacuum system and the radio frequency electronics are greatly reduced when decreasing the size of the mass analyzer, and this can greatly diminish performance. Introducing optimization systems can be helpful for improving performance following miniaturization. Cooks and Ouyang write that the judgement of a miniature mass spectrometer for optimal performance include these key criteria: a) adequate operation in detection limits, specificity, and resolution; b) reliability; c) ruggedness; d) autonomous performance.

Surgery Applications

Miniature MS can also be a useful tool in the decision-making process during surgery. Cooks et al describe the often-common issue clinicians are faced with when deciding to remove tissue from a patient, particularly if the observable health of the tissue is ambiguous. Tissue characterization in a fast, comprehensive manner relies on MS, particular MS methods such as DESI.

In a study by Cooks et al, 12 samples resected from a patient in surgery were evaluated and diagnosed as a tumor or necrotic tissue via histopathology. MS were correlated to histopathology. Using DESI, researchers were able to classify tumor types and aid in the diagnostics of tissue state. A similar study using DESI was also able to differentiate between normal and tumor breast tissue. These findings indicate that miniature MS can be used safely in the surgical environment to identify cancerous cells quickly and effectively.

Lixian Li will be giving a talk at Pittcon 2017 on the identification of serum biomarkers in triple negative breast cancer, providing insight on how physicians can use quadrupole time-of-flight mass spectrometry for the detection of these biomarkers.

While magnetic resonance imaging (MRI) can be helpful for identifying and diagnosing brain tumors, miniature MS may provide faster diagnostics, especially during surgery. A study from Purdue University and Brigham and Women’s Hospital study and led by Cooks successfully utilized DESI to identify cancer grade and type in 5 brain surgery patients. DESI helped to identify the distribution and quantity of lipids within brain tissue, and software was employed to examine the results in an effort to identify brain tumors. Lipid patterns were also detected and analyzed to determine tumor grade. While the researchers analyzed specimens removed from the brain, there’s hope that miniature MS will evolve to a point where it can evaluate specimens in-tact during surgery.

Pancreatic cancer, which often relies on surgical resection as a potential cure for some patients, can also obtain help from miniaturized MS. DESI as used in miniature MS can be helpful for real-time diagnosis of pancreatic cancer, according to one study. Researchers combined DESI with absolute shrinkage and selection operator (Lasso) statistical method for the diagnosis of pancreatic tissue. They then examined margins of surgical resections from pancreatic surgery. The findings of this study provided some evidence that both DESI and Lasso techniques applied to pancreatic tissue samples may transform the examination and diagnosis surgical specimens. Essentially, these techniques may be used in the surgery room to assess surgical margins of pancreatic cancer.

Protein Analysis

The study of proteins in biological systems, often termed “proteomics,” can be assisted by miniature MS. Many proteins undergo some type of post-translational modification, which can increase the complexity of the proteins. Miniature MS has revolutionized the way researchers see biological systems, particularly since techniques for miniature MS have been developed to identify and study proteins. Using high-throughput, quantitative MS proteomics workflows, researchers have virtually broadened the knowledge base on protein structure and function.

The Environment

Miniature MS can also be used to evaluate the microbes underwater, as a Harvard University study previously reported. This study used a miniature mass spectrometer to examine the effect of microbes on hydrogen and methane content of the ocean. Stanford Research Systems worked with the researchers to develop a commercial quadrupole mass analyzer and custom gas extractor to complete the mission.

References


Chapter 3 – Ionization Methods for Miniature Mass Spectrometry

Adjustments to the way MS is performed by miniaturized mass spectrometers has naturally followed suit after conformation to a portable size. Improvements in simplicity of design and size reductions of these spectrometers have allowed for improvements in medical diagnoses, contraband discovery, and high-consequence fieldable applications, just to name a few examples of miniaturized mass spectrometer applicability.

An advancement in reconceptualizing mass spectrometers include microfabricated arrays of mass analyzers on a chip, enabling higher sensitivity and inherit selectivity of mass spectrometry for data analysis. According to Blain MG et al, the miniaturization of the mass analyzer itself, including its design, characterization, and fabrication, is the first step towards building a complete and efficient micro-MS system. The authors’ paper briefly describes considerations in design of miniaturized mass spectrometers and include results from ion trapping simulations for a small-scale cylindrical ion trap mass analyzer. Their results have been incorporated into the overall miniaturization of small-scale mass spectrometers.

At Pittcon 2017, R. Graham Cooks will discuss a number of miniature MS-related topics associated with ionization methods for miniature mass spectrometry. “Novel Scan Methods Using Miniature Ion Trap Mass Spectrometers,” one of his featured sessions, will provide information regarding the newer scan methods for miniature mass spectrometers, methods that emphasize AC over RF scans for MS experiments in a signal ion trap mass analyzer. The session also features discussions about extended mass ranges and linear mass scans, and the illustration of data of biological and forensic applications are also demonstrated. Cooks will also explore paper spray (PS) and desorption electrospray (DESI) ionization methods that are used to assist in diagnosing and monitoring treatments with miniature mass spectrometry. Other topics covered by speakers at Pittcon 2017 include:

  • Integrated Microfabricated Systems for Performing Capillary Electrophoresis – Mass Spectrometry
  • Enabling Large-Scale Discovery, Characterization and Quantitation of Neuropeptides via Multiple Tandem Mass Spectrometry Fragmentation Techniques

Ionization Techniques for MS

Desorption electrospray ionization (DESI), low temperature plasma (LTP), and paper spray (PS) ionization represent three prime examples of the complementary ionization techniques used in miniature MS sampling and data analyzation. DESI is a versatile analytical method for a variety of compounds and helpful for tissue imaging; LTP is important for in-field applications; PS is highly compatible for sample cartridge design and is attractive for quantitative analysis in regulatory and medical situations.

DESI

DESI has been used for direct analysis of explosives, pharmaceutical ingredients, drugs found within body fluids, and agrochemicals. For this ionization method, charge droplets are used for ionizing the analyte molecule in a small sample. To generate a high-velocity-charged droplet that will affect the sample, sheath gas and a high DC voltage electrospray are used. Analytes are then extracted into a liquid, are ionized (usually through proton transfer), and are then moved away from secondary droplets’ surfaces. Analytes’ dry ions form in the air and are moved into a mass spectrometer for analysis.

LTP

Explosives found on surfaces, ingredients in seed and fruit oils, and agrochemical identification are all examples of the applicability of LTP. This ambient ionization method uses active species produced in low-power plasma to both desorb and ionize analytes in samples that are untreated. Low-temperature plasma is produced by dielectric barrier discharge; helium, nitrogen, argon, or air is transferred through an alternating electric field. A device is used to enable extraction of the plasma species out of the discharge region to allow for sampling chemicals on a surface. Low gas flow rate, the ability to use air as discharge gas, ability to sample large areas, and minimal to now sampling angle requirement make LTP an advantageous ionization method.

PS Ionization

For a quick, low-cost ionization and sampling method, PS is often the first choice for quantitative and qualitative MS study of mixtures featuring highly complex structures. This method produces ions from samples directly and is applied on a paper substrate. Paper has been widely accepted as a good material for storage of samples and is often used in methods of chromatographic separation. The application of a spray solvent featuring high voltage and small volume onto a porous substrate generates analyte ions. Then, the sample is either mixed into the spray solution or is preloaded onto the paper. The observation of a spray plume occurs. Signal intensity depends on the geometry of the paper; change the cut angle on the paper tip can affect the efficiency of the ionization.

References


Chapter 4 – New Components for Miniature Mass Spectrometry

Just as miniature mass spectrometers continue to experience greater miniaturization than ever before, the applications for miniature mass spectrometers continues to evolve. Beyond the science of miniature MS, the structures of the spectrometers continue to get smaller and more reliable in terms of analytical results.

Continual improvements in the simplicity of miniaturizing mass spectrometers have been essential for a wide range of fieldable applications. Daniel Austin, researcher at Brigham Young University and speaker at Pittcon 2017 and recipient of the Spectroscopy Society of Pittsburgh (SSP) Starter Grant in 2008, has been one of the leading pioneers in the development of new miniature MS technology. Austin and his research team have developed approaches using lithographically patterned plates as a unique method for producing mass analyzers. Additionally, this approach has been used to shrink linear ion traps, radiofrequency quadrupole, electrostatic ion beam traps, and toroidal. Currently, their team is working on making charge detector arrays using the patterned-plates method, bypassing using machined electrodes as a means for producing cost-efficient products.

Austin’s 2017 Pittcon talk, “Wire Ion Trap,” discusses the miniaturized linear ion trap that utilizes sets of wires between two support plates. His research team will further discuss the production of the wire ion trap, describing how replacing four of the hyperbolic electrodes of the conventional linear ion trap with wires of 80-120 microns in diameter is a step toward trap production. Their development approach of the trap involves using 2-dimensional positioning without interfering with trap accuracy or trapping capacity. Austin will also describe the trap’s immunity to things associated with mechanical misalignment, which is common in miniaturized ion traps.

Miniature MS tools can also be applied in electrophoresis applications. Ramsey of UNC at Chapel Hill will also lead a talk at Pittcon 2017 that will provide an overview of miniature MS analyzers for the performance of capillary electrophoresis. His talk will discuss his group’s recent developments in miniaturizing ion trap MS systems that include microfabricated sections. The analysis of blood for glycated hemoglobin and the examination of bioreactor broth for the detection and identification of amino acids are two such examples of applications that will be explored.

One of the most popular mass analyzer choices for producing miniature MS systems are quadrupole mass analyzers. Toroidal ion traps can help reduce the size of mass analyzers, yet they can’t be described by mathematical equations of the quadrupole device. Stephen Lammert of PerkinElmer also brings to light recent research in trapping fields and miniature mass spectrometers in his Pittcon 2017 talk, “Describing and Optimizing Toroidal Trapping Fields for the Development of Miniature Mass Spectrometers.” In his talk, he describes a recent effort in developing analytical tools necessary for studying and optimizing trapping fields in a toroidal coordinate system.

Research and product development teams at PerkinElmer, in turn, have produced a portable device containing a mass analyzing trapping field. The Torion® T-9 GC/MS is a small, portable MS, offering quick and accurate information. The product features a low thermal mass capillary gas chromatograph and high-speed temperature programming. Additionally, The Torion® T-9 GC/MS features a miniaturized toroidal ion trap mass spectrometer, as described by Lammert in his upcoming talk.

Customized miniature mass spectrometers are also being offered by some companies, including Hamamatsu, a manufacturer of products used in spectroscopy. Hamamatsu’s micro-spectrometers have been produced using MEMS technology and have been miniaturized to the size of a fingertip. The head of these fingertip-sized spectrometers support a long wavelength region (850 nm) and are highly sensitive. This unique and minute size has allowed easy incorporation into a variety of instruments in the medical and scientific fields. Hamamatsu’s ultra-compact spectrometer heads have adopted a newly developed optical system, which is innovative for the market.

The miniature spectrometers from Hamamatsu are also compatible with portable mobile devices. Also, Hamamatsu offers a series of spectrometer heads that can be integrated into equipment, providing a reflective grating and CMOS image sensor that is designed for use in visible measurements. Miniature spectrometers with light guidance into optical fibers allow for measurement of the light spectrum by a detector, with output from the spectrometer’s USB port transferred to a computer for data collection and evaluation. The size of these mini spectrometers, like the ones by Hamamatsu, measure 20.1 x 12.5 x 10.1 mm and weigh up to 5 grams. The spectral response range is between 340 and 850 nm (340 to 780 nm for the C12666MA) and are trigger-compatible.

References


Chapter 5 – Future of Miniature Mass Spectrometry

Mass spectrometry’s future is unknown; however, its rate of utilization growth has shown that its evolution and advancement is certain. In chemical analysis, pharmaceutical applications, and forensics, MS serves a powerful study tool that will certainly continue toward improving research on all fronts. Miniature mass spectrometers are quickly emerging as a powerful adjunct in research and are easy to use and highly sensitive. Their ability to be used outside of the laboratory by untrained professionals across many different subsets of science broadens its use. In addition, the development and swift adoption of Purdue University’s Mini 10, Mini 11, and Mini 12 systems may be a useful tool in biomedicine, pharmaceutical, and agrochemical industries, both now and in the future. The development and implantation of these systems will help these industries’ nurses, biologists, and doctors access information rapidly without needing to send samples to a laboratory.

Smaller systems than those that are currently available must be made to perform more complex, intricate procedures. For example, identification of a smoker using blood tests, while feasible with a miniature mass spectrometer, can’t always be performed easily with the current technology available. With smaller devices, physicians may also be able to monitor therapeutic drug administration during surgery in at-risk patients.

Similar to what Purdue’s Mini 12 miniature mass spectrometer has demonstrated, future direction for miniature MS systems include the inclusion of ambient ionization methods with the devices. In something like the Mini 12, a miniature ion trap mass spectrometer is combined with paper spray ionization. Inside a sample cartridge, a blood sample is placed on the paper substrate. Researchers can push this sample into the system, which then adds an organic solvent to the cartridge. Then, a 4 kV voltage is applied. The elution of organic compounds and spray ionization then occurs on the paper substrate at its tip. Exactly two MS-MS scans are performed on the analyte and internal standard.

Future miniature analytical systems may also be used more frequently by non-professionals, or non-instrumentalists. Analytical chemists can apply their knowledge regarding chromatography to these systems in time, enabling for further development of miniature mass spectrometers. Helping these chemists move beyond liquid chromatography columns to sample cartridges that can provide real-time extraction and ionization may also be important in the next few years.

While the future of miniature MS systems appears promising, selling these products on a large scale may be challenging. Many instrument companies have difficulty transitioning into the production of small systems. Also, data regarding these systems aren’t impressive or “groundbreaking,” which can reduce the likelihood of these companies moving into production.

The integration of ambient ionization into miniature mass spectrometers has advanced in the past few years and continues to be used to develop systems that can be operated by non-experts. One study previously described how combining DESI with a miniature mass spectrometer could potentially develop a brand new instrument in the near future. This instrument may enable direct evaluation of samples of practically any type in an ambient environment. Applications, according to authors of the paper, may be diverse. For example, such a device could be used to indicate disease type, detect the content and toxicity of dangerous compounds on surfaces and in water, and examine tissues for tumor margins via lipid distribution examination in tissue sections. The device could also analyze skin lesions and needle biopsies right in the physician’s office.

Miniature MS in Space

There are some initiatives in place for using miniature mass spectrometers to advance the United States space program. Studying planetary atmospheres and their composition as well as monitoring the quality of air on space missions are two primary application fields for miniature MS. Since systems used in the space program need to be portable, lightweight, and have a high level of sensitivity, miniature mass spectrometers make for the perfect analytical systems to be used in future space study programs. Previous studies have demonstrated successful deployment of MS instruments on the Mars Viking Lander and Pioneer Venus missions. Future opportunities for MS instruments in space include studying human breath to examine microgravity’s effects on respiratory function in humans. MS instruments for space applications include time-of-flight, sector instruments, quadrupole ion traps, quadrupole arrays, and cylindrical ion trap mass spectrometers.

References


Conclusion

The drive for developing miniaturized forms of mass spectrometers is multifactorial. Portability and ease-of-use are perhaps two of the most common reasons physicians wish to use miniature MS instead of the larger MS instruments. The ability to use an instrument onsite or at the bedside are also important for retrieving data quickly. Also, the ability to use these MS products without having to learn a complicated analytical method makes miniature MS an attractive option for the clinical environment. Rapid data retrieval and analysis, two key benefits of many miniature MS methods, also play a role in facilitating the development of this technology.

To overcome the size and weight limitations in conventional MS tools, miniaturized versions continue to be developed. These tools can sit in a physician’s office, and some have been developed to connect with mobile devices for quick retrieval and analysis of information. Many miniaturized instruments can provide in-depth analysis of metabolites or disease state efficiently and reliably, and the market for these products has grown exponentially in the past few decades.

Companies such as Bruker, Photonis, Waters, Hamamatsu, and Thermo Fisher Scientific, all of whom produce instruments used in mass MS and miniature MS, will be important exhibitors at Pittcon 2017. Each company will not only provide visual and hands-on product demonstrations, but also give new insights into current applications in science, forensics, agriculture, and pharmaceutical industries. Also featured at Pittcon 2017 are leading researchers in the field of MS and spectrometer miniaturization, including R. Graham Cooks, Daniel Austin, Christopher Brown, and Jingren Deng, among others.

Speakers’ presentations will cover topics such as scan methods with miniature ion trap mass spectrometers, miniaturized wire ion traps, miniature field analyzers, and miniaturized electrochemistry in medicine. More than 150 sessions are devoted specifically to mass spectrometry and cover a broad range of industries and fields, including medicine and surgery, forensics, and chemical safety. Scientists involved in every industry and environment and who are interested in learning more about new MS technology for compound identification and analysis are encouraged to attend this informative annual event.