JP2005259477A - Electrospray ionization mass spectrometer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an electrospray ionization mass spectrometer in which clogging of the ESI spray nozzle can be prevented with a simple structure and measurement for long time with high reliability is possible. <P>SOLUTION: In an analysis mode, the spray nozzle 7 sprays sample solution and when the analysis mode is completed, it moves to a waiting cleaning mode. In the cleaning mode, cleaning of the nozzle 7 is started and after completion of cleaning, the nozzle 7 is moved to a cleaning position (inside the washing bottle 32) by a multi-dimensional jogging table 31. The tip of nozzle 7 is dipped in a washing liquid in the washing bottle 32. After dipping in the washing liquid and after elapsing a prescribed time, and measurement preparation for next sample is completed, the nozzle 7 is raised from the washing bottle 32 and is returned to an initial position of analysis mode. When the mass spectrometer is stopped operation for a long time, the nozzle 7 is left dipped in the washing liquid in the washing bottle 32, thereby, the nozzle is not dried up and deposit of crystal and adhesion of foreign matters or the like can be prevented. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to an electrospray ionization mass spectrometer for introducing and ionizing a sample solution eluted from a low flow chromatograph into an electrospray ion source, and conducting the mass analysis by introducing it into a mass spectrometer disposed in a high vacuum space.

  Recently, research in the biotechnology field has been remarkable, and its research subjects span multiple limbs. In particular, proteins, peptides, DNA, and the like have a very important role in the living body and have been the subject of research by many researchers.

  In general, these organic compounds derived from living organisms are present in a very small amount in a complex matrix. There has been a rapid increase in demand to extract these extremely small amounts of biologically relevant organic compounds from living organisms and to analyze them with high sensitivity using a liquid chromatograph direct mass spectrometer (LC / MS apparatus).

  The LC / MS apparatus is an apparatus that separates a mixture by LC and performs qualitative quantitative analysis with high sensitivity using a mass spectrometer (MS). A typical ionization means used in this LC / MS is electrospray ionization (ESI). This ESI is ionized by introducing a sample solution eluted from a (very) low flow chromatograph such as micro liquid chromatograph (μ-LC) or capillary electrophoresis (CE) into an electrospray (ESI) ion source. The ions generated at the source are led to a mass spectrometer arranged in a high vacuum space for mass analysis.

  ESI is an ionization technique under atmospheric pressure, and is known as a mild and sensitive ionization technique. Therefore, it has come to be widely used for the analysis of biological materials such as proteins.

  In order to measure a trace amount component stably and highly sensitively using this ESI, it is necessary to optimize some parameters. The flow rate that determines how much solution is supplied to the ESI ion source is one of its parameters.

In order to achieve a sensitive measurement, the flow rate of the solution flowing through the ESI capillary must be within a certain range. In ESI, the range of 10 nl / min (10 ⁻⁸ l / min) to several μl / min (10 ⁻⁶ l / min) is the optimum flow rate.

  That is, if the solution is fed to the ESI capillary at a flow rate higher than this, the ESI ionization becomes unstable, and the expected high sensitivity measurement cannot be achieved.

  Patent Document 1 discloses an improved ESI technology that enables highly sensitive measurement of further trace components. The technique described in Patent Document 1 is called nanospray, and the tip of an ultrafine glass tube having an outer diameter of 0.2 mm and an inner diameter of 0.03 mm is heated and drawn by a burner. This is a technique of performing gold plating or the like on the tip of the nozzle after stretching or sharpening by etching. According to this technique, a nozzle tip having an outer diameter of 5 to 10 μm and an inner diameter of about 5 to 3 μm can be manufactured.

In ESI, a DC voltage of about 1 kV supplied from a high voltage power source is applied to the nozzle tip. The flow rate of the sample solution to the nanospray is about several nl / min (several 10 ⁻⁹ l / min) to 10 nl / min (10 ⁻⁸ l / min), and the sample sucked into the nanospray nozzle only for 1 hour. The above measurement is possible.

  For this reason, this nanospray is used in combination with ultra-low flow chromatography such as CE (capillary electrophoresis) and μ-LC, and is also used as a technique for measuring an isolated component with extremely high sensitivity. It became so. Moreover, ESI measurement in a flow rate region of 10 nl / min or less became possible by nanospray.

  In the μ-LC field, since the flow rate is extremely small, such as several μl / min or less, the dead volume (dead volume) of the LC component itself and the pipe connecting the components becomes a big problem. When the dead volume between the microcolumn and the detector is larger than the flow rate, the components separated by the microcolumn are diffusely mixed with the dead volume, and the separation and sensitivity are greatly impaired.

  In addition, the dead volume between the pump and the microcolumn causes a problem of gradient delay. In order to improve the gradient delay, it is important to reduce the dead volume of the mixer, piping, and ESI spray nozzle (Nanospray, etc.). Therefore, the dead volume can be reduced by reducing the diameter of the pipe and further shortening the length of the pipe.

  However, reducing the diameter of the pipe and the diameter of the ESI spray nozzle causes a new problem that the pipe and the ESI spray nozzle are easily clogged. In particular, in the case of analysis of biological samples, biopolymers such as sugars and proteins, salts such as NaCl, and the like present in the sample cause clogging of the piping.

  Moreover, in order to separate proteins and the like, in many cases, it is necessary to add a high concentration salt of 100 mM or more to the LC mobile phase. This high-concentration salt is deposited in the dead volume in the pipe or in the ESI spray nozzle, and finally the pipe or nozzle is packed.

  The clogging of the flow path not only makes it impossible to continue the measurement, but also necessitates replacement of expensive parts (such as a Nanospray nozzle). Also, a lot of time is wasted in parts replacement, system cleaning, resetting, and readjustment.

  For this reason, many techniques have been disclosed in order to solve the problems caused by the clogging of LC sampling channels and MS ion sampling pores.

Patent Document 2 discloses a technique for preventing destruction of a UV cell due to a pressure increase due to clogging of an LC channel and a technique for facilitating replacement of a UV cell.
Non-volatile salts eluted from LC clog MS ion sampling pores, making it impossible to continue measurement, and a method of removing this clog by washing with a jet of water is disclosed in Patent Document 3 and Patent Document 4. However, the technique described in Patent Document 3 is not an ESI spray nozzle but a nozzle for sucking a sample.

  Patent Document 5 discloses a technique for predicting the degree of clogging of a flow path and the time until clogging by monitoring changes in the amount of ions in LC / MS.

  Further, in LC / MS, Patent Documents 6 and 7 disclose a technique in which nonvolatile salts are excluded from the system before being introduced into the MS so as not to clog the ion sampling pores.

In addition, Patent Document 8 discloses a technique for flowing a cleaning solvent through the sample introduction system in order to reduce the memory effect of the sample introduction system.
Patent Document 9 discloses a combined technique of extremely low flow rate ESI and CE (capillary electrophoresis). When the sample solution is injected into the CE capillary, the injection amount fluctuates due to a slight flow caused by the evaporation of the solvent from the tip of the ESI probe. In order to reduce this fluctuation, it is necessary to suppress the evaporation of the solvent at the ESI probe tip. Therefore, solvent droplets are sprayed on the tip of the ESI probe during sample injection.

US Pat. No. 5,504,329 Japanese Patent Laid-Open No. 10-10109 JP-A-10-125276 JP-A-61-95244 PCT WO03 / 0665406A1 JP 2000-123781 A JP 05-325882 A JP-A-08-55601 US Pat. No. 5,788,166

  However, in the LC / MS measurement of micro flow area such as μ-LC, CE, and nanoflow LC, clogging of ESI spray nozzle that cannot be overcome by the above-mentioned conventional technology occurs frequently, and the measurement efficiency is remarkably lowered for the recovery. Is a big problem.

  Even if the ESI spray nozzle is not completely clogged, ESI ionization becomes unstable and high sensitivity measurement becomes impossible. In this case, the measurer stops the apparatus and replaces the ESI spray nozzle with a new one. However, as described above, the nozzle is very thin and difficult to handle, and it takes a long time to replace it. End up. In addition, after replacing the nozzle, the apparatus must be restarted to optimize various parameters, and the measurer spends a lot of time on maintenance, and the measurement efficiency is significantly reduced.

  Although an ESI spray nozzle (such as Nanospray) can be made by itself, it is desirable to purchase and use a quality-controlled commercial product if a highly reproducible measurement is desired.

  In addition, it is considered to be disposable because the replacement work of the nozzle is omitted, but disposing an expensive Nanospray nozzle with a unit price of about several hundred dollars imposes a large financial burden on the measurer, It is not preferable.

  An object of the present invention is to realize an electrospray ionization mass spectrometer that can prevent an ESI spray nozzle from being clogged with a simple configuration and enables highly reliable measurement for a long time.

First, the background to the present invention will be described.
The present inventor encountered and observed many phenomena that the ESI spray nozzle clogged and the ESI ionization suddenly became unstable while repeating the low flow LC / MS measurement.

  Clogging of the ESI spray nozzle and destabilization of ionization frequently occur when there is a gap between measurements, or when the measurement is stopped and started again at night or on holidays.

  That is, clogging is more likely to occur when the measurement is performed intermittently than when the sample is continuously measured.

  The clogging of the ESI spray probe and the destabilization of ionization due to the occurrence of clogging and the microscopic observation of the clogged ESI spray nozzle are caused by the salt deposited on the outer periphery of the nozzle outlet from clogging occurring inside the ESI spray nozzle. It was found that it originates from the dirt at the tip of the ESI spray nozzle due to crystals such as the sample.

  FIG. 5 shows an enlarged view of the tip of the ESI spray nozzle. A state where the ESI spray is normally performed is shown in FIG. As shown in FIG. 5A, during the period in which the charged droplet flow 72 is sprayed from the tip 71 of the ESI spray nozzle 7, both the inside and outside of the tip 71 of the ESI spray nozzle 7 are clean and have dirt and crystals. There is no adhesion. Therefore, a high electric field is stably formed around the ESI spray nozzle 7 by the DC high voltage applied to the ESI spray nozzle tip 71.

  Due to this high electric field, the sample solution introduced into the ESI spray nozzle 7 is stably sprayed into the atmosphere as a charged droplet stream 72. The generated ions are stably taken into a mass spectrometer (MS) and subjected to mass analysis.

  When LC / MS measurement of one sample is completed, the LC mobile phase is changed to water, water / organic solvent, etc., and the LC column, injector, ESI spray nozzle, and the like are washed. The solution at the tip of the ESI spray nozzle 7 slightly overflows around the periphery of the nozzle outlet and wets the tip 71 of the ESI spray nozzle 7. Thereafter, a slight amount of liquid that wets the outer periphery of the nozzle is vaporized.

  As a result, salt, impurities and the like slightly dissolved in the overflowing solution are deposited on the periphery of the nozzle 7. The dirt around the ESI spray nozzle 7 accumulates as the measurement system is repeatedly cleaned and measured.

  As shown in FIG. 5B, when dirt 75 accumulates on the tip end 71 of the nozzle 7 in a biased manner, the dirt 75 becomes an obstacle, and the ESI spray flow 73 becomes in a biased direction. Also, the spray direction and the spray itself become unstable. In this state, the amount of ions taken into the mass spectrometer (MS) becomes extremely small, the fluctuation of the ion amount itself increases, and stable mass spectrometry is no longer possible.

  When the dirt at the ESI spray nozzle tip 71 further grows, as shown in FIG. 5C, the dirt 76 clogs the tip 71 of the ESI spray nozzle 7, and the spray flow 74 becomes a trace amount. The ESI spray is not performed and the measurement is hopeless.

  According to the experiment observation of the present inventor, the state of the ESI spray nozzle when the ion current value of the mass spectrometer (MS) suddenly decreases and the measurement cannot be continued is as shown in FIG. Most of the states are not shown in FIG. 5B.

  That is, the ESI spray nozzle 7 is not completely clogged, but is in a state where the dirt 75 is attached to the periphery of the ESI spray nozzle tip 71. In that case, although the ESI spraying is performed, the axis of the spray flow 73 is largely deviated from the axis of the ESI spray nozzle 7.

  Therefore, most of the generated ions are sprayed into the atmosphere of the ion source in the mass spectrometer and then discarded to the outside directly through the exhaust port. As a result, very few ions are introduced into the mass spectrometer (MS).

  It is conceivable to remove the dirt 75 from the tip 71 of the nozzle 7 by spraying a liquid from the nozzle 71. However, the inner diameter of the nozzle 71 is extremely small, and a jet flow that can remove the dirt 75 is very small. Have difficulty.

  The present invention has been made from the above observation results, and is a technique for preventing the adhesion of the tip of the spray nozzle from a completely new viewpoint.

  In other words, the present invention has the following simple structure to prevent an ESI spray nozzle from being clogged, and to realize an electrospray ionization mass spectrometer that enables highly reliable measurement over a long period of time. Composed.

  (1) The sample solution 1 is ejected from a fine spray nozzle 7 to have an electrospray ion source 9 that generates ions under atmospheric pressure. The ions generated by the ion source 9 are provided in a vacuum chamber. In an electrospray ionization mass spectrometer that conducts mass spectrometry measurement by leading to the mass spectrometer 20, a cleaning bottle 32 containing a cleaning solvent is disposed in the ion source 9, and during the sample solution ejection period of the spray nozzle 7, There are provided spray nozzle moving means 22, 31, 25 for immersing the tip of the spray nozzle 7 in the cleaning solvent in the cleaning bottle 32.

  (2) Preferably, in the above (1), the spray nozzle moving means has a multi-dimensional fine moving base 31 for moving the spray nozzle 7 in a multi-dimensional direction, and the multi-dimensional fine moving base 31 is driven to perform the spraying. The tip of the nozzle 7 is immersed in a cleaning solvent.

  (3) Preferably, in the above (2), control data processing means 22 for controlling the operation of the mass spectrometer and processing data analyzed by the mass spectrometer 20 is provided. Controls the operation of the multi-dimensional fine movement table 31 to position the spray nozzle 7 before mass spectrometry measurement.

  (4) Preferably, in (1) above, the cleaning solvent is any one of water, an aqueous solution of a volatile acid, an aqueous solution of a volatile base, an aqueous solution of a volatile salt, or an aqueous solution of an organic solvent. Or a mixed solution thereof.

  (5) A mass having an electrospray ion source 9 that ejects a sample solution from a fine spray nozzle 7 and generates ions under atmospheric pressure, and the ions generated in the ion source 9 are provided in a vacuum chamber. An electrospray ionization mass spectrometer that conducts mass spectrometry measurement by introducing it into the analyzer 20 includes cleaning solvent supply means 40, 41, and 42 for supplying a cleaning solvent into the ion source 9, and stopping the spraying of the sample solution from the spray nozzle 7 During the period, the cleaning solvent is supplied from the cleaning solvent supply means to the tip of the spray nozzle 7.

  According to the present invention, it is possible to realize an electrospray ionization mass spectrometer that can prevent clogging of an ESI spray nozzle with a simple configuration and enables highly reliable measurement for a long time.

  Moreover, the time and cost wasted for maintenance can be greatly reduced.

Embodiments of the present invention will be described below with reference to the accompanying drawings.
FIG. 1 is a schematic configuration diagram in an analysis state of an electrospray ionization mass spectrometer which is an embodiment of the present invention. FIG. 2 is a schematic configuration diagram of the ESI spray nozzle according to the present invention during standby and cleaning (sample solution ejection pause period).

  In FIG. 1 and FIG. 2, the mobile phase solvent 1 is sent out by an LC pump 2 and sent to an analysis column 4 through an autosampler (injector) 3. The sample solution is injected from the autosampler 3, introduced into the analysis column 4, and separated for each component. The sample components that have passed through the analysis column 4 are sent to the ESI spray nozzle 7 via the pipe 5.

  The ESI spray nozzle 7 is fixed to a multi-dimensional fine movement base 31 disposed on the upper part of the ESI ion source container 9 via an insulator. The multi-dimensional fine movement table 31 can be multi-dimensionally positioned by fine movement in the X-axis, Y-axis, Z-axis direction, and rotation direction.

  The control data processing device 22 sends a control signal to the multi-dimensional fine moving table drive power supply 25 via the signal line 23 to control and drive the multi-dimensional fine moving table 31. Thereby, the ESI spray nozzle 7 can be freely positioned in the ion source 9.

  The tip of the ESI spray nozzle 7 is coated with a conductive film, and a DC voltage of about 1 kV is applied from the high voltage power supply 26. The sample solution sent by the LC pump 2 and reaching the tip of the ESI spray nozzle 7 becomes a fine charged droplet and is sprayed on the atmosphere 8 in the ESI ion source 9.

  The charged droplet sprayed from the ESI spray nozzle 7 is further refined in the atmosphere 8 in the ion source 9 to generate ions. The generated ions are taken into the vacuum chamber 13 from the ESI ion source 9 via the ion sampling capillary 11 provided in the vacuum partition 12.

  The mass spectrometer container 27 of the mass spectrometer (MS) includes a plurality of vacuum chambers 13, 16, 19 having different pressures, and each of the vacuum chambers 13, 16, 19 is an independent vacuum pump 28, 29, 30. Is evacuated.

  A skimmer 14 is disposed in the vacuum chamber 13, an ion guide 17 is disposed in the vacuum chamber 16, a high vacuum is maintained in the vacuum chamber 19, and a mass spectrometer 20 and a detector 21 are disposed. The vacuum chambers 13 and 16 are separated by a partition wall 15, and the vacuum chambers 16 and 19 are separated by a partition wall 18.

  Ions generated by the ESI ion source 9 are introduced into the vacuum chamber 16 through the ion sampling capillary 11, the vacuum chamber 13, and the skimmer 14. The ions introduced into the vacuum chamber 16 are introduced into the mass spectrometer 20 of the vacuum chamber 19 through the ion guide 17 and subjected to mass analysis.

The ions are separated for each mass by the mass spectrometer 20 supplied with power from the mass spectrometer power source 24 and detected as an ion current by the detector 21. An ion current signal corresponding to the mass is sent from the detector 21 to the control data processing device 22 and collected as a mass spectrum.
The ion source 9 has an exhaust port 10 formed therein.

  Here, the ion sampling capillary 11 that communicates the ion source 9 and the vacuum chamber 13 is a capillary pipe made of stainless steel or glass, and has an inner diameter of about 0.3 mm and a length of about 10 cm. In addition, the ion sampling capillary 11 is used in which a heater for heating is covered.

  The ion guide 17 is composed of a cylindrical electrode in which four, six, or eight metal columns are arranged at equal intervals on a certain circumference. Every other cylinder is connected and a high frequency voltage is applied between the two sets of electrodes to form a high frequency electric field inside the ion guide 17. When ions are introduced on the central axis of the ion guide 17, the introduced ions vibrate according to a high frequency electric field, collide with gas molecules, and converge on the axis of the ion guide 17.

  In this way, ions can be transferred from the low vacuum portion to the high vacuum portion without loss by the ion guide 17.

  A cleaning bottle 32 containing a cleaning liquid (cleaning solvent) is disposed in the ion source 9, and as shown in FIG. 2, the tip of the nozzle 7 is in the cleaning bottle 32 during standby and cleaning of the nozzle 7. Soaked in a cleaning solution. Then, as shown in FIG. 1, in the analysis state, the nozzle 7 moves out of the cleaning bottle 32 and sprays the sample.

  Next, the operation in one embodiment of the present invention will be described based on the operation flowchart of FIG.

  (1) Positioning of ESI Spray Nozzle 7 in Analysis Mode (During Measurement) (Step S1) The position of ESI nozzle 7 is stored in control data processing device 22, and the control data processing device is used during standby, cleaning and measurement. 22 can quickly drive the multi-dimensional fine adjustment table 31 to position the ESI spray nozzle 7. Prior to the measurement, the control data station apparatus 22 sends a control signal via the signal line 23 to the multi-dimensional fine moving table drive power supply 25 to control and drive the multi-dimensional fine moving table 31. Then, the ESI spray nozzle 7 is moved to a position where the ESI spray nozzle 7 is directed from the cleaning bottle 32 toward the ion sampling capillary 11 by the multi-dimensional fine moving base 31.

(2) ESI-HV ON (Step S2)
The control data processing device 22 sends an ESI high voltage application signal to the high voltage power supply 26 and applies a DC high voltage to the ESI nozzle 7 from the high voltage power supply 26.

(3) LC ON initialization (step S3)
After confirming that the ESI spray nozzle 7 is disposed at the initial position (Pa0) in the analysis mode, the control data processing device 22 sends an operation start signal to the liquid chromatograph (LC) to initialize the LC separation conditions. (Initialization) is performed. Thereafter, the pump 2 starts feeding the mobile phase solvent 1.

(4) Optimization of the position of the ESI spray nozzle (step S4)
In step S <b> 1, the position of the ESI spray nozzle 7 is set to the position (Pa0) stored in the memory of the control data processing device 22. However, it is not certain whether the position (Pa0) is the optimum position. This is because the movement history of the tip of the ESI spray nozzle 7 is different for each measurement. Therefore, the position of the ESI spray nozzle 7 is slightly moved to search for a new point (Pa1) where the maximum sensitivity can be obtained. The control data processing device 22 stores the obtained position information as new position information (Pa1 → Pa0).

(5) Sample introduction (step S5)
The control data processor 22 waits for the LC to be initialized, instructs the autosampler 3 to introduce the sample, and introduces the sample.

(6) Mass spectrum collection (step S6)
A sample solution is introduced and separated for each component in the analysis column 4. The separated components are sent to the ESI spray nozzle 7 to be ionized and taken into a mass spectrometer (MS). The mass spectrometer 20 repeats mass sweep and collects mass spectra one after another. Then, a data file is formed in the control data processing device 22. The control data processor 22 determines whether or not one sample has been completed, and collects mass spectra until one sample is completed.

(7) End of analysis (step S7)
All sample components are eluted from the analytical column 4 and one measurement is completed. Then, the control data processing device 22 completes the data file.

  In steps S1 to S7, the analysis (measurement) mode ends, and the process proceeds to a standby cleaning mode between sample measurements.

(8) Cleaning of LC and ESI spray nozzles (Step S8)
The control data processing device 22 sends an initialization signal to the LC, changes the mobile phase, and starts cleaning the LC and ESI spray nozzles 7.

(9) ESI-HV OFF (Step S9)
After the LC cleaning is completed and the liquid feeding by the pump 2 is stopped, the control data processing device 22 sends a DC voltage OFF signal to the high voltage power supply 26. That is, the ESI spray is turned off by setting the applied voltage of the ESI spray nozzle 7 to the ground potential.

(10) Movement of the ESI spray nozzle 7 to the cleaning position (step S10)
The control data processing device 22 drives the multi-dimensional fine moving base 31 to move the ESI spray nozzle 7 to the cleaning position (in the cleaning bottle 32).

(11) Infiltration of the ESI spray nozzle 7 tip into the cleaning liquid (step S11)
The ESI spray nozzle 7 is lowered into the cleaning bottle 32 filled with the cleaning liquid, and the tip of the ESI spray nozzle 7 is immersed in the cleaning liquid.
After immersing the tip of the spray nozzle 7 in the cleaning liquid, it is determined whether a predetermined cleaning time has elapsed. When the predetermined time has elapsed and the preparation for measurement of the next sample is completed, the ESI probe 7 is cleaned. The ESI probe 7 is returned to the initial position (Pa0) in the analysis (measurement) mode. Then, it is determined whether or not the measurement of a series of samples is completed. If not completed, the process returns to step S1 and proceeds to the analysis of the next sample.

(12) A series of measurements is completed (step S12)
When the measurement of a series of samples is completed, the control data processing device 22 creates a data file and completes it. When a series of sample measurements are completed and the mass spectrometer is stopped for a long time, the ESI spray nozzle 7 is kept in a standby mode, that is, immersed in the cleaning liquid in the cleaning bottle 32.

  Thereby, the tip portion of the ESI spray nozzle 7 is not dried, and precipitation of crystals and adhesion of foreign matters can be prevented. Further, since the LC, analysis column, piping, and ESI spray nozzle 7 are cleaned by the liquid feeding operation in steps S8 to S10, there is no possibility of clogging in the system. In addition, since the cleaning liquid penetrates not only outside the tip of the nozzle 7 but also inside the nozzle 7, it is possible to prevent crystal precipitation inside the nozzle 7.

  Note that the ESI spray nozzle 7 is kept immersed in the cleaning liquid when measurement is not performed at night or on holidays.

  Further, the immersion of the nozzle 7 in the cleaning liquid is sufficient if it is about 5 mm to 7 mm from the tip.

  Further, the start of the cleaning operation of the nozzle 7 may be automatically executed when it is determined that the analysis of the sample is completed, or may be manually instructed by the operator.

  In the above-described embodiment of the present invention, the cleaning liquid has been described as being stored in one cleaning bottle 32.

  In order to enhance the cleaning effect, the cleaning bottle can be made into two large and small bottles, which can be cleaned with a new cleaning liquid. That is, as shown in FIG. 4, the small bottle 44 is put in the large bottle 43, and the small bottle 44 is filled with the cleaning liquid. A drain 45 is provided under the large bottle 43 so that the cleaning liquid overflowing from the large bottle 43 can be discarded from the drain 45 to the outside.

  Further, the cleaning liquid is sucked by the pump 41 from the bottle 40 filled with the cleaning liquid, and is supplied into the small bottle 44 through the faucet 42. From the faucet 42, the cleaning liquid is fed into the bottle 44 at a flow rate of about 0.1 ml / min.

  The cleaning solution overflowed from the small bottle 44 overflows into the large bottle 43 and is discarded to the outside through the drain 45. As a result, the cleaning solution in the small bottle 44 is constantly updated, and the memory effect of the previous sample does not remain.

  In addition, in order to improve the cleaning efficiency of the ESI nozzle 7, it is also possible to move the ESI nozzle 7 up, down, left and right while being immersed in the cleaning liquid.

  It is also possible to improve the cleaning efficiency by placing an ultrasonic transducer 46 under the cleaning bottle 43 and causing the ESI nozzle 7 to vibrate minutely by the ultrasonic waves from the ultrasonic transducer 46.

  The faucet 42, the bottles 43 and 44, the ultrasonic transducer 46, and the drain 45 may be arranged in the ion source 9, and the pump 41 and the cleaning liquid bottle 40 may be arranged outside the ion source 9, as shown in FIG. All the members can also be arranged in the ion source 9.

  As another embodiment of the present invention, the cleaning liquid discharged from the cleaning liquid supply port such as the faucet 42 shown in FIG. The form which supplies to the front-end | tip part of 7 can be considered. In the case of this other embodiment, the cleaning liquid may be supplied to the nozzle tip portion at a constant period while waiting for the analysis operation, or the supply of a trace amount of the cleaning liquid may be continued.

  The cleaning liquid (cleaning solvent) may be any of water, an aqueous solution of a volatile acid, an aqueous solution of a volatile base, an aqueous solution of a volatile salt, an aqueous solution of an organic solvent, or a mixed solution thereof. .

It is a schematic block diagram in the analysis mode of the electrospray ionization mass spectrometer which is one Embodiment of this invention. It is a schematic block diagram in the standby mode of the electrospray ionization mass spectrometer which is one Embodiment of this invention. It is an operation | movement flowchart in one Embodiment of this invention. It is a figure explaining washing | cleaning of the ESI spray nozzle part in other embodiment of this invention. It is a figure which shows the observation result of the stain | pollution | contamination of an ESI spray nozzle which reached this invention, and charged droplet spraying.

Explanation of symbols

1 Mobile phase solvent 2 LC pump 3 Injector (autosampler)
4 Analysis Column 5 Piping 7 ESI Spray Nozzle 9 ESI Ion Source 10 Exhaust Port 11 Ion Sampling Capillary 12, 15, 18 Vacuum Bulkhead 13, 16, 19 Vacuum Chamber 14 Skimmer 17 Ion Guide 20 Mass Spectrometer 21 Detector 22 Control Data Processing Equipment 23 Signal line 24 Mass spectrometer power supply 25 Multi-dimensional fine moving table drive power supply 26 ESI high pressure power supply 27 Mass spectrometer container 28, 29, 30 Vacuum pump 31 Multi-dimensional fine moving table 32, 40 Washing bottle 41 Pump 42 Faucet 43 Large washing bottle 44 Small washing bottle 45 Drain

Claims (5)

A sample solution is ejected from a fine spray nozzle and has an electrospray ion source that generates ions under atmospheric pressure. The ions generated in this ion source are led to a mass spectrometer installed in a vacuum chamber, and mass analysis is performed. In an electrospray ionization mass spectrometer for measuring,
A spray bottle moving means is provided in which a cleaning bottle containing a cleaning solvent is disposed in the ion source, and the tip of the spray nozzle is immersed in the cleaning solvent in the cleaning bottle during a sample solution ejection period of the spray nozzle. Electrospray ionization mass spectrometer characterized by the above.   2. The electrospray ionization mass spectrometer according to claim 1, wherein the spray nozzle moving means includes a multidimensional fine moving base that moves the spray nozzle in a multidimensional direction, and the multidimensional fine moving base is driven to drive the tip of the spray nozzle. Electrospray ionization mass spectrometer characterized by immersing in a washing solvent.   3. The electrospray ionization mass spectrometer according to claim 2, further comprising control data processing means for controlling the operation of the mass spectrometer and processing data analyzed by the mass spectrometer. An electrospray ionization mass spectrometer characterized by controlling the operation of a multi-dimensional fine movement table and positioning the spray nozzle before mass spectrometry measurement.   2. The electrospray ionization mass spectrometer according to claim 1, wherein the cleaning solvent is water, an aqueous solution of a volatile acid, an aqueous solution of a volatile base, an aqueous solution of a volatile salt, or an aqueous solution of an organic solvent. Alternatively, an electrospray ionization mass spectrometer characterized by being a mixed solution thereof. A sample solution is ejected from a fine spray nozzle and has an electrospray ion source that generates ions under atmospheric pressure. The ions generated in this ion source are led to a mass spectrometer installed in a vacuum chamber, and mass analysis is performed. In an electrospray ionization mass spectrometer for measuring,
An electrospray comprising cleaning solvent supply means for supplying a cleaning solvent into the ion source, and supplying the cleaning solvent from the cleaning solvent supply means to the tip of the spray nozzle during a sample solution ejection period of the spray nozzle. Ionization mass spectrometer.

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