Miniature Time-of-Flight Mass Spectrometer
Richard S. Potember, Ph.D.
Johns Hopkins University Applied Physics Laboratory
- To design, develop and test a fast, portable, gas-chromatograph time-of-flight mass spectrometry (GC-MS) system for future human space flight applications. It will provide complementary information to the MALDI method.
- To demonstrate that the miniature TOF system is capable of detecting and quantifying different biomarkers that appear in serum or urine during space flight. Detection and quantification of critical biomarkers using the miniature TOF technology will allow real-time monitoring of damage on-orbit, and the mass spectrometer can also be used to study the effectiveness of countermeasures in space flight. The results of this effort should be comparable to measurements made in a clinical laboratory facility using established assays.
- To validate that the miniature time-of-flight mass spectrometer is an important diagnostic tool that can be applied to measure important bone biomarkers and the effectiveness of applied countermeasures in human urine and serum samples.
- To compare standard methods of hormone analyses for melatonin and cortisol to that of the Miniature Mass Spectrometer. The development of online methods for monitoring and assessing the status of circadian organization is listed as one of the five primary themes for the Human Performance Factors, Sleep and Chronobiology Team.
- To develop sampling and sample preparation techniques that enable the MALDI TOF mass spectrometer system to reliably detect, identify and quantify extremely low levels of chemical and biological substances in complex body fluids with very low error rates.
We have designed and built a new miniature, mass-spectrometry (GC-MS) system with a three-inch analyzer for human space flight applications. This miniature instrument will provide new capabilities in the area of sampling, sample preparation, rapid quantification of biomarkers and it will allow us to apply our technology to other space-based problems such as monitoring the spacecraft environment for chemical and biological contaminants.
We have also completed our initial studies on melatonin. In year 3 we will test melatonin in urine samples at this concentration level.
One of the specific aims of this project is to develop sampling and sample-preparation techniques that enable the MALDI TOF mass spectrometer system to reliably detect, identify and quantify extremely low levels of chemical and biological substances in complex body fluids (urine, blood, breath) with very low error rates. In year 2, we reviewed several protocols for urine sampling and we have chosen a procedure to conduct measurements for year 3.
Impact of Findings
We are developing and testing a small, efficient, time-of-flight mass spectrometer coupled to a miniature gas chromatograph to rapidly identify important biomarkers and countermeasures for human space exploration. We are using the time-of-flight mass spectrometer to evaluate critical biomarkers and countermeasures that are indicators of bone loss, oxidative stress and the human sleep cycle associated for extended space travel.
Mass spectrometry is a technique for determining the masses of molecules and specific fragmentation products formed during vaporization and ionization. From detailed analysis of the mass distribution of the molecule and its fragments, molecular identification is accomplished. These molecular measurements can be carried out at the attomole (10-18 mole) level of material using specialized laboratory-based instruments. The combination of specific molecular identification and extreme sensitivity makes mass spectrometry one of the most powerful analytical laboratory tools yet developed for detection and identification of chemical and biological substances.
Proposed Research for the Coming Year
- Miniature Mass Spectrometry System: In year 3, we will complete testing and evaluation of the new instrument system. We will use the results of this aspect of the project to make a recommendation as to the specific type of instrument that should be built in a follow-on program.
- Measurement of Oxidative Stress using TOF Mass Spectrometry: In year 3, we will complete the study of oxidative stress biomarkers in urine samples.
- Zoledronate: a Countermeasure to Bone Loss in SCI Patients: In year 3, we will analyze urine samples for zoledronate and related by-products.
- Assessment of Circadian Status Using the Miniature Mass Spectrometer: In year 3, we will analyze the urine samples from Dr. Kenneth P. Wright Jr. for the excretion of the melatonin metabolite, 6-sulphatoxymelatonin.