Flight time based mass microscope system for ultra high-speed multi mode mass analysis

Abstract

The present invention aims to provide a time-of-flight based mass microscope system for an ultra-high speed multi-mode mass analysis, for using a laser beam or an ion beam simultaneously to enable both a low molecular weight analysis such as for drugs/metabolome/lipids/peptides and a high molecular weight analysis such as for genes/proteins, without being limited by the molecular weight of the object being analyzed, and for significantly increasing the measuring speed by using a microscope method instead of a microprobe method.

Description

TECHNICAL FIELD[0001]The present invention relates to a time-of-flight (TOF) based mass microscope system for an ultra-high speed multi-mode mass analysis.[0002]Most mass spectrometer [MALDI-TOF and time-of flight secondary ion mass spectroscopy (TOF-SIMS)] using a mass analysis method based on a time-of-flight (TOF) have been currently used in a microprobe mode at the time of analyzing a sample surface. However, as technologies in various fields are rapidly developed, limitation in a subject to be analyzed in the mass spectrometer or limitation in an analysis speed is a setback for a study. That is, a mass spectrometer capable of currently achieving a wide range of analysis from a low molecular weight mass analysis such as a drug to a high molecular weight mass analysis such as proteins and simultaneously and rapidly measuring by 100 times or more as compared to existing mass analysis devices has been demanded.[0003]A detailed description thereof will be provided below. A digitaliz...

AI Technical Summary

Benefits of technology

[0023]With a time-of-flight (TOF) based mass microscope system for an ultra-high speed multi-mode mass analysis according to the present invention, the TOF based microscope mode measurement may be achieved to significantly increase a measuring speed (by 100 times or higher) as compared to the existing microprobe mode mass analysis equipment used in analyzing a sample surface. In addition, the wide range of mass analysis from the low molecular weight analysis such as the drugs / metabolome / lipids to the high molecular weight analysis such as genes / proteins present on the surface may be achieved by changing only the condition of lens in the samples such as biotissues / biochips / microarray.

[0024]Further, the following effects may be expected. Demand for medical diagnostic equipment capable of increasing objective, quantitative and accurate properties of the disease diagnosis through development of the multi-mode integrated diagnostic system per individual kits, kits for kinds of disease, and kits for various kinds of diagnosis will be increased, and in addition, novel measuring technology not enabled before may be developed by convergence and integration of BT-NT-IT technology and the ultra-high speed multi-mode molecular diagnosis may be achieved based on the development. Therefore, change in the research into from structure or shape of the biopsy tissue using fluorescent stain or Bio-SEM / TEM to the integrated mass imaging measurement connected with functions of various atoms and molecules may be achieved to create diagnostic tool capable of simultaneously connecting the structural change and the functional change. In particular, it seems that the gap between technologies from the inside and outside of the country in the mass analyzing equipment related technology is not large.

[0025]Therefore, the time-of-flight based mass microscope system for the ultra-high speed multi-mode mass analysis according to the present invention may be utilized to achieve the early stage diagnosis of diseases, the realization of personalized medicine, and the reduction in the new medicine screening cost, and to significantly increase the possibility of developing the biomarkers such as metabolome, lipids, and proteins, having a close relationship with the disease, thereby achieving a new drug discovery much more smoothly. That is, the time-of-flight based mass microscope system for the ultra-high speed multi-mode mass analysis according to the present invention may have significant effects in various views such as providing new clinical diagnostic environment and information, creating the medical diagnostic industry, and increasing life quality and global competitiveness.

Problems solved by technology

As described above, at the Korea Research Institute of Standards and Science, the microprobe mode MALDI imaging equipment having a micron level of spatial resolution (hereinafter, referred to as Prior Art 1) was manufactured and applied to an mass imaging of various bio samples; however, the equipment has a low-throughput having a limitation in a measuring speed as described in the above description, which may be possibly be utilized at a R&D research facility rather than in a hospital or a health examination center.

However, the above-mentioned technologies still have a low-throughput due to limitation in the measuring speed since an imaging measurement is performed in a microprobe mode).

However, the above-described equipments according to the Prior Arts or the MALDI imaging research currently conducted by world's leading research groups (including US Caprioli, and the like) and national research groups (including Konkuk University) has actual spatial resolution of merely about 30 to 50 μm or does not still overcome the limitation in the measuring speed.

Therefore, since the measuring speed (1 sample / sec for MALDI-TOF, 0.01 sample / sec for TOF-SIMS) is too low to be used in hospital or a medical diagnostic system for health examination, the above-described equipment are merely used in R&D research but the utilization range thereof has a limitation.

In the above-described Prior Art 4, a micro level of spatial resolution imaging technology was secured and various technologies were introduced in order to increase the measuring speed; however, as shown in FIG. 1, since position sensitive detector (x, y) & mass gating (Δt) was used, mass range should be selected, such that a problem that mass analysis of an unknown sample is not capable of being performed still needs to be solved.

In addition, according to the above-described Prior Arts, molecules having a wide range of mass from low molecular weight to high molecular weight are not capable of being measured by one medical diagnostic equipment.

Therefore, measuring equipment needs to be changed depending on molecular weight, which is inconvenient for measuring work, and equipment purchasing cost becomes increased.

Images