Mass analyzing method using an ion trap type mass spectrometer

Details Mass analyzing method using an ion trap type mass spectrometer Mass analyzing method using an ion trap type mass spectrometer

2002-09-26

2004-09-07

Lee, John R. (Department: 2881)

Radiant energy

Ionic separation or analysis

Cyclically varying ion selecting field means

C250S281000, C250S282000, C250S291000

Reexamination Certificate

active

06787767

ABSTRACT:

FIELD OF THE INVENTION
The invention relates to an ion trap type mass spectrometer and a mass analyzing method thereof.
BACKGROUND OF THE INVENTION
A mass spectrometer is a highly sensitive and highly precise instrument that can directly mass-analyze a sample and has been widely used in various fields from astrophysics field to bio-technology field.
There are various kinds of mass spectrometers based on different principles of measurement. Among such mass spectrometers, ion trap type mass spectrometers have rapidly become popular because of their compactness and a variety of functions. The original ion trap type mass spectrometer was invented by Dr. Paul in the 1950s. It is disclosed in U.S. Pat. No. 2,939,952. After that, a lot of researchers have improved devices and techniques. For example, a fundamental technique of obtaining mass spectra by an ion trap type mass spectrometer is disclosed in U.S. Pat. No. 4,540,884. Further, U.S. Pat. No. 4,736,101 discloses a mass spectrometry method of applying a supplementary AC voltage and ejecting and detecting ions in resonance. Furthermore, U.S. Pat. No. 5,466,931 discloses a mass spectrometry method of freely ejecting and dissociating ions in an ion trap using that a supplementary AC voltage comprises a plurality of frequency components (noise having a broad frequency spectrum) instead of a single frequency component. This technology uses a resonance of ion secular frequencies and supplementary AC voltages and can eject a lot of ions in resonance at a time. As the purpose of the wide-band noise signal of the invention is to eject ions of a wide range simultaneously, the noises are at an identical voltage. However, the frequency component corresponding to the frequency of an ion to be stored in the ion trap is notched. The ions corresponding to the notch frequency are steadily stored in the ion trap without causing resonance.
In recent years, various ionization methods for chemical analysis such as matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) have been developed. This has also enabled mass analysis of biomolecules such as proteins and DNAs. Particularly, the electrospray ionization (ESI) method can directly extract stable gaseous ions from a solution of biomolecules which are apt to be decomposed by heat.
In ESI, biomolecules such as proteins, peptides which are digestive decomposition of protein, and DNAs produces multiply-charged ions. A multiply-charged ion has two or more charges (n) per molecule (m). As the mass spectrometer (MS) mass-analyzes ions by the mass-to-charge (m/z) ratio, the MS handles an ion of molecular weight m having n charges as an ion of a mass-to-charge value m
. For example, the mass-to-charge (m/z) ratio of protein of molecular weight 30,000 having 30 charges is 1,000 (=30,000/30) and the protein can be mass-analyzed as a singly-charged ion of molecular weight 1,000. Therefore this technology has enabled even a small mass spectrometer such as a quadrupole mass spectrometer (QMS) and an ion trap type mass spectrometer to easily mass-analyze proteins whose molecular weight is over 10,000.
For mass-analysis of a very small amount of components in blood or biological tissue, it is required to remove a lot of interface components (impurities) or to clean up before the mass-analysis.
This clean-up requires lots of time and man-power. However, it is impossible to remove all impurities even by a complicated pre-processing. These impurities disturb the signals of the components of the biological sample. This obstruction is called a chemical noise. To remove or separate such impurities, a liquid chromatography-mass spectrometer (LC/MS) has been developed which comprises a combination of a liquid chromatography (LC) and a mass spectrometer placed before the LC.
FIG. 25
shows the schematic diagram of a conventional LC/MS. The mobile phase
32
(a sample solution) of the LC is pumped into an analysis column
35
through an injection port
34
by a pump
33
. The analysis column
35
separates impurities from the sample solution (biological sample components) and sends the sample solution to the ESI ion source
36
on-line. The sample solution eluted from the LC is introduced into a spray capillary
37
to which a high voltage is applied in the ESI ion source
36
. The sample solution is sprayed from the tip of the capillary
37
into the atmosphere in the ESI ion source
36
to be fine charged droplets (−&mgr;m). The fine charged droplets collide with atmospheric molecules in the ESI ion source
36
and are mechanically pulverized into smaller droplets. This collision and pulverization step is repeated until ions are finally ejected into atmosphere. This is the process of electrospray ionization (ESI). The ions are introduced into a mass spectrometer
40
through an intermediate pressure chamber
38
and a high-vacuum chamber
39
which are vacuumed by vacuum pumps
30
and
31
and mass-analyzed there. The result of analysis is given as a mass spectrum by a data processor
41
.
The high-sensitivity analysis of extremely trace biological components in blood or tissue cannot be attained easily even by means of pre-processing, cleaning up, and a liquid chromatography (LC). This is because the quantity of a sample to be mass-analyzed is extremely small (10
−12
gram or less) and the overwhelming majority of the sample consists of interferences which cannot be fully separated or removed even by preprocessing or the liquid chromatography (LC).
As one of means for solving such problems, U.S. Pat. No. 6,166,378 presents a try to discriminating target components from such interferences components in mass-analysis. Most of interferences in a biological sample are lipids, carbohydrates, and so on whose molecular weight is comparatively low (1,000 or less). These low-molecular-weight components interfere, on the mass spectrum, with bimolecules such as proteins, peptides, and DNAs whose molecular weight is 2,000 or more. This is because the biomolecules give multiply-charged ions and mass peaks appear in a low mass region. In the ESI technology, most of interferences whose molecular weight is comparatively low produce singly-charged ions. Contrarily, most of biomolecules such as proteins and peptides produce multiply-charged ions by the ESI.
Singly-charged ions can be distinguished from multiply-charged ions by accelerating these ions together at a pressure of about 1 torr. By this acceleration, ions repeatedly collide with gas molecules. In this case, if the proton affinity (PA) of the gas molecule is greater than that of the ions, a proton is deprived of the ion and as the result, the ion loses one charge. The multiply-charged ions are apt to cause this ion-molecule reaction and easily transfer protons to neutral molecules such as water. Contrarily, as the ions have fewer charges, this ion-molecule reaction occurs comparatively less. In other words, singly-charged ions are hard to lose charges but multiply-charged ions are apt to lose charges.
U.S. Pat. No. 6,166,378 uses this difference in the ion-molecule reaction and a tandem mass spectrometer which combines three mass spectrometers in tandem to identify mass signals on mass spectrum.
DISCLOSURE OF THE INVENTION
The try to use a tandem mass spectrometer to distinguish singly-charged ions from multiply-charged ions has various problems. One of the problems is that only small part of ions introduced into the tandem mass spectrometer reaches the detector. In other words, the transmission efficiency of ions of the tandem mass spectrometer is very low (−%). Therefore, the measuring sensitivity of tandem mass spectrometer is much lower than the measuring sensitivity that is required by the mass-analysis of biomolecular compounds. Another problem is that the discrimination of singly-charged and multiply-charged ions, that is, the cooperating sweeping of the first and third mass spectrometers (MSs) in tandem can be done only once for one mass spectrum. Therefore, the filtering effect of the signal-to-noise is limite

Affiliated with

Also associated with

Rating

Mass analyzing method using an ion trap type mass spectrometer does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Mass analyzing method using an ion trap type mass spectrometer, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Mass analyzing method using an ion trap type mass spectrometer will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3192826