Ion spectrometry device program

The SLIM technology is designed to be very flexible and low cost to produce. Recent advances even resolve the problem of manipulating ions of the same or opposite polarities using adjacent radiofrequency electrodes that are out of phase by approximately degrees. This alternating arrangement inhibits the ions from approaching the electrodes.

The confinement can be provided over a range of pressures, from less than 0. SLIM allows the separated ions to be further reacted and their products to be separated again, providing an even greater ability to distinguish different compounds, even isotopic and isomeric differences. This development makes it practical for SLIM to be used as a standalone device, without the need for an MS, if the compounds it is analyzing are known in advance, such as a doctor searching for a particular molecule in a blood sample as a biomarker of a particular disease.

The combination of increased throughput, sensitivity, and resolution makes SLIM a disruptive technology that could completely change how samples are analyzed in any field that requires molecule separation and identification in a rapid, efficient, and precise manner.

Applications include chemical process, quality assessment and assurance, and environmental monitoring, among others. Skip to main content. Technology Overview Advances in medicine, clean energy, and environmental management are held back by the ability to quickly distinguish the presence, structure, and abundance of different molecules in a sample. Advantages Provides high-resolution, lossless ion mobility separation Allows for flexible, low-cost manufacturing Enables new applications utilizing ion mobility and trapping that are not possible with current technology.

The control unit 50 includes a device control unit 51 , an analysis unit 52 , and a display control unit The analysis unit 52 includes an intensity calculation unit and an image creation unit The measurement unit performs measurement of a sample S by mass spectrometry imaging.

The sample chamber 9 is a chamber in which substantially atmospheric pressure is maintained. In the sample chamber 9 , a sample stage 24 and a sample stage drive unit 25 provided with a motor, a speed reduction mechanism, and the like are disposed.

The sample stage 24 is driven by the sample stage drive unit 25 so that the sample stage 24 can move between an image-capturing position Pa at which the image-capturing unit 11 can capture an image of the sample S, and an ionization position Pb at which the laser irradiation unit 21 can irradiate the sample S with a laser beam L.

The sample chamber 9 is provided with the observation window 12 and the irradiation window A surface of the sample stage 24 on which the sample S is to be placed is arranged in the xy plane, and an optical axis Ax of the sample image capturing unit 10 is defined along the z-axis see a coordinate axes 8. The y-axis is parallel to an ion optical axis A 2 described later of the mass spectrometry unit 30 , and the x-axis is perpendicular to the y-axis and the z-axis.

The sample image capturing unit 10 captures an image of the sample S hereinafter, referred to as a sample image. The sample image capturing unit 10 outputs a signal obtained through photoelectric conversion of light from the sample S, to the control unit 50 an arrow A 1. The sample image is not particularly limited as long as it is an image showing a plurality of positions in a portion to be analyzed in the sample S and the corresponding intensity or wavelength of light from the positions.

For example, the sample image is an image of light transmitted through the sample S irradiated with light from a transmission illumination unit not shown , captured by the image-capturing unit In capturing a sample image, a specific structure or molecule of the sample S may be stained with a staining reagent or labeled with a fluorescent substance introduced by antibody reaction or genetic recombination, for example.

The image-capturing unit 11 can then output a signal obtained by photoelectric conversion of light from the stained portion or from the fluorescent substance or the like, to the control unit Light from the sample S placed on the sample stage 24 arranged at the observation position Pa transmits through the observation window 12 and is incident on the image-capturing unit The image-capturing unit 11 photoelectrically converts the light from the sample S with a photoelectric conversion element for each pixel of the image sensor.

The image-capturing unit 11 then outputs the sample image data to the control unit The position in the sample S irradiated with the laser beam L for ionization is referred to as an irradiation position.

The ionization unit 20 sequentially irradiates each irradiation position with the laser beam L to sequentially ionize sample components in an irradiation range corresponding to each irradiation position.

The laser irradiation unit 21 includes a laser light source. The type of the laser light source is not particularly limited as long as each irradiation position in the sample S can be irradiated with the laser beam L to cause ionization of sample components. For example, the laser light source may be a device that emits, through oscillation, the laser beam L having a wavelength corresponding to the ultraviolet to infrared region.

The condensing optical system 22 includes a lens and the like to adjust an irradiation range of the laser beam L on the sample S. The laser beam L having passed through the condensing optical system 22 transmits through the irradiation window 23 and is incident on the sample S.

When the laser beam L is irradiated onto an irradiation position in the sample S, sample components in an irradiation range are desorbed and ionized to generate sample-derived ions Si. In the following, the sample-derived ions Si refer to not only ionized samples S, but also ions generated by dissociation or decomposition of the ionized samples S, ions obtained by attachment of atoms or atomic groups to the ionized samples S, and the like.

The sample-derived ions Si released and generated from the sample S pass through the inside of the ion transport tube 26 and are introduced into the vacuum chamber of the mass spectrometry unit The sample stage 24 at the ionization position Pb is configured to be movable in the x direction and the y direction by the sample stage drive unit After an irradiation position in the sample S is irradiated with the laser beam L, the sample stage 24 moves so that the next irradiation position is irradiated with the laser beam L.

In this way, the laser beam L scans over the sample S by relative movement of the sample stage 24 with respect to an optical path of the laser beam L. Note that the irradiation position may be changed by changing the optical path of the laser beam L, instead of moving the sample stage The mass spectrometry unit 30 performs detection through mass separation of the sample-derived ions Si.

Paths of the sample-derived ions Si an ion optical axis A 2 and an ion flight path A 3 in the mass spectrometry unit 30 are schematically indicated by dashed-and-dotted arrows. The sample-derived ions Si introduced into the vacuum chamber enter the ion transport optical system The ion transport optical system 31 includes elements that control movement of ions, such as an electrostatic electromagnetic lens and a high-frequency ion guide, to transport the sample-derived ions Si to the first mass separation unit 32 while converging a trajectory of the sample-derived ions Si.

The vacuum chamber is divided into a plurality of vacuum compartments having different degrees of vacuum. Elements of the ion transport optical system 31 are respectively arranged in a plurality of vacuum compartments. A vacuum compartment located closer to the first mass separation unit 32 has a higher degree of vacuum, with the degree of vacuum increasing stepwise as appropriate. Each vacuum compartment is evacuated by a vacuum pump not shown.

The first mass separation unit 32 includes an ion trap as a mass analyzer, and performs mass separation and dissociation of the sample-derived ions Si. The first mass separation unit 32 and the second mass separation unit 33 described later are evacuated by a vacuum pump, such as a turbo molecular pump, to a degree of vacuum depending on the disposed mass analyzer. The precursor ion derived from the sample S hereinafter simply referred to as a precursor ion is separated by an electromagnetic action based on voltages applied to the endcap electrode and the ring electrode disposed in the ion trap The first mass separation unit 32 dissociates the separated and trapped precursor ion by collision induced dissociation CID to generate fragment ions derived from the sample S hereinafter simply referred to as fragment ions.

The first mass separation unit 32 introduces a CID gas containing an inert gas such as helium from a CID gas inlet not shown and causes the precursor ion and the CID gas to collide with each other with a predetermined collision energy.

The first mass separation unit 32 emits the fragment ions generated by the dissociation toward the second mass separation unit The second mass separation unit 33 includes a time-of-flight mass analyzer. The second mass separation unit 33 performs mass separation of the fragment ions generated by the first mass separation unit 32 , according to a difference in flight time.

The fragment ions accelerated by a pulse voltage applied to the acceleration electrode flies through the inside of the flight tube which defines a flight path of the ion, and changes their travel direction by electromagnetic action based on a voltage applied to the reflectron electrode Thereafter, the fragment ions enter the detection unit The detection unit includes an ion detector such as a microchannel plate to detect the fragment ions having entered thereto.

The detection mode may be either a positive ion mode for detecting positive ions or a negative ion mode for detecting negative ions.

The information processing unit 40 serves as an information processing apparatus that performs processing, such as control of the measurement unit , analysis, and display. Note that the information processing unit 40 may be integrated with the measurement unit into one single device. Further, a part of data used by the imaging mass spectrometry device 1 may be stored in a remote server or the like, and a part of the arithmetic processing to be performed by the imaging mass spectrometry device 1 may be performed by the remote server or the like.

The control of the operation of each component of the measurement unit may be performed by the information processing unit 40 or may be performed by a device constituting each component.

The input unit 41 receives information required for measurement performed by the measurement unit and processing performed by the control unit 50 , for example, from the user. The communication unit 42 of the information processing unit 40 includes a communication device that can communicate via a network such as the Internet with wireless or wired connection.

The communication unit 42 transmits and receives necessary data as appropriate. For example, the communication unit 42 receives data necessary for the measurement of the measurement unit and transmits data processed by the control unit The storage unit 43 of the information processing unit 40 includes a non-volatile storage medium. The storage unit 43 stores fragment ion intensity ratio data described later , measurement data based on a detection signal output from the detection unit hereinafter simply referred to as measurement data , and a program for executing processing by the control unit 50 , and the like.

The display unit 44 of the information processing unit 40 includes a display device such as a liquid crystal monitor. The display unit 44 is controlled by the display control unit 53 to display information on analysis conditions of the measurement by the measurement unit , data obtained by the analysis by the analysis unit 52 , and the like, on the display device.

The control unit 50 of the information processing unit 40 includes a processor such as a CPU. The control unit 50 performs various types of processing by executing programs stored in the storage unit 43 or the like, such as control of the measurement unit , analysis of measurement data, and display of data obtained by the analysis.

The device control unit 51 controls the operation of each component of the measurement unit The device control unit 51 controls irradiation of the sample S with the laser beam L and controls mass separation, dissociation, detection, and the like, based on analysis conditions set by the input from the input unit 41 and the like. The analysis unit 52 performs analysis of measurement data, including creation of an intensity image described later. After performing processing for reducing noise such as background removal, the intensity calculation unit calculates a peak intensity or a peak area of a peak in a mass spectrum as a value indicating the intensity of the fragment ion corresponding to the peak.

Furthermore, the intensity calculation unit identifies peaks of the mass spectrum corresponding to the same fragment ion at respective irradiation positions, based on the mass separation accuracy of the mass spectrometry unit The intensity calculation unit causes the storage unit 43 to store intensity data in which an irradiation position and the intensity of a fragment ion obtained by irradiating the irradiation position with the laser beam L are correlated with each other, for each fragment ion.

Note that the way of expression of the intensity data is not particularly limited as long as the analysis unit 52 can analyze the intensity data. The image creation unit of the analysis unit 52 creates data corresponding to the intensity image hereinafter referred to as intensity image data based on the intensity data. The image creation unit assigns each irradiation position to one pixel and converts the intensity of the fragment ion corresponding to each irradiation position into a pixel value to create intensity image data, and then stores the data in the storage unit The image creation unit creates data hereinafter referred to as individual intensity image data corresponding to intensity image hereinafter referred to as individual intensity image showing the intensity of each fragment ion dissociated from the precursor ion, and also creates data hereinafter referred to as integrated intensity image data corresponding to intensity image hereinafter referred to as an integrated intensity image showing the intensities corresponding to the plurality of fragment ions dissociated from the precursor ion without distinction between different fragment ions.

The image creation unit acquires intensity data on each fragment ion stored in the storage unit 43 and converts the intensity of the fragment ion at each irradiation position in the intensity data into a pixel value to create individual intensity image data.

The image creation unit creates individual intensity image data so that the intensities of the fragment ion are displayed in a distinguished manner in the individual intensity image. The image creation unit preferably allows the intensities to be displayed in a distinguished manner in the individual intensity image, by changing any one of hue, saturation, and brightness in accordance with the intensity of the fragment ion.

The way of calculation of a pixel value of the individual intensity image from the intensity by the image creation unit is not particularly limited; however, the image creation unit can perform the calculation as follows, for example.

The image creation unit can compare intensities at all irradiation positions for each fragment ion to acquire the maximum intensity and the minimum intensity, and then convert the intensity at each irradiation position into a pixel value based on at least one of the maximum intensity and the minimum intensity. As a more specific example, assuming that the maximum intensity is A.

An intensity value between the maximum intensity value and the minimum intensity value can be converted so that a change in intensity value and a change in pixel value have a predetermined relationship such as first order. Here, the sample S is assumed to be a tissue section or the like taken from an organism; however, the type of the sample S is not particularly limited thereto. In FIG.

A pixel that is not hatched among the pixels Px indicates that the detected intensity of the fragment ion A or B is less than a detection threshold based on the measurement accuracy and the like, when an irradiation position C corresponding to the pixel Px is irradiated with the laser beam L for mass spectrometry the same applies the following intensity image.

Although the examples of FIG. For example, in the mass spectrometry at the irradiation position corresponding to a first pixel P 1 , the fragment ion A is detected while the fragment ion B is not detected. In the mass spectrometry at the irradiation positions corresponding to a second pixel P 2 and a fourth pixel P 4 , the fragment ion B is detected while the fragment ion A is not detected.

In the mass spectrometry at an irradiation position corresponding to a third pixel P 3 , the fragment ions A and B are both detected, but the intensities are different. In tandem mass spectrometry, such a mismatch in the distribution of fragment ions is therefore likely to occur because the detected intensity is lower than that in a case where dissociation is not performed.

Thus, even when the user or the like views these individual intensity images Mk, it is difficult for the user to recognize the tendency of the distribution of the molecule corresponding to the precursor ion, which would be a problem. The image creation unit creates integrated intensity image data corresponding to an integrated intensity image showing the intensities corresponding to the plurality of fragment ions generated from the same precursor ion without distinction between different fragment ions.

The image creation unit calculates a pixel value corresponding to each irradiation position C in the integrated intensity image data, based on intensities of a plurality of fragment ions generated from the same precursor ion and based on a correction parameter. If you are staying in a motel, be careful of where you put your clothing - keep it packed or hang the clothing up, so as not to pick up any substance particles.

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