Patent Publication Number: US-6989532-B2

Title: Mass spectrometer

Description:
The present invention relates to a mass spectrometer including an ion source for spraying a liquid sample into droplets in a predetermined direction in a stable manner, and for atomizing and ionizing the sprayed sample. 
   BACKGROUND OF THE INVENTION 
   In a mass spectrometry, liquid samples are often used as the object to be analyzed. An example is an analysis with a liquid chromatograph mass spectrometer (LCMS), in which a sample dissolved in a solution is separated into components by the liquid chromatography. Then, the components are sequentially sent to the mass spectrometer, which carries out the mass analysis of each component. 
   For the mass analysis of a liquid sample, a liquid sample ionizer using an assist gas (or nebulizing gas) is employed as an ion source for generating ions to be analyzed. In this ionizer, a liquid sample ejected from a liquid supply pipe is nebulized (i.e. broken into droplets) by a strong stream of gas, called an assist gas or nebulizing gas, flowing along the outer surface of the liquid supply pipe. The gas also functions as a carrier and drier of the droplets, and often as an electrifier of the droplets. 
   In general, liquid sample ionizers carry out the ionization with the assist gas at roughly atmospheric pressure. The ions generated thereby are introduced into the mass spectrometer unit, the inner space of which is maintained in a high vacuum state. 
     FIG. 6  schematically shows the construction of a mass spectrometer  10  using an assist gas for ionization. The mass spectrometer  10  includes an ion source  41  for generating ions at roughly atmospheric pressure and a mass spectrometer unit  13  enclosed in a vacuum chamber  12 . 
   The ion source  41  is mainly composed of a gas transport pipe  14  and a liquid supply pipe  15 . The gas transport pipe  14  is cylindrical at its center and tapered at its front end. Located at the center of the tapered end of the ion source  41  is a gas supply passage  17  with an ejection port  16  for ejecting the assist gas. The gas transport pipe  14  has, on its side, a gas inlet  18  and a gas supply conduit  19  for introducing the assist gas into the gas supply passage  17 . The gas supply conduit  19  is connected to the gas supply passage  17  within the gas transport pipe  14 . 
   The liquid supply pipe  15  is inserted into the gas supply passage  17  of the gas transport pipe  14  to form a duplex pipe structure. The liquid supply pipe  15  extends through the hole  20  formed at the rear end of the gas transport pipe  14  and leads to an external source of the liquid sample, e.g. the liquid chromatograph in the case of an LCMS. The front end of the liquid supply pipe  15  is located close to and slightly sticking out from the ejection port  16 . 
   The liquid sample flowing through the liquid supply passage  21  of the liquid supply pipe  15  is sent to the ejection port  16  of the gas supply passage  17 . At the ejection port  16 , the assist gas coming from the gas supply passage  17  blows away the liquid sample located at the front end of the liquid supply passage  21 , nebulizing and drying the liquid sample. The nebulized liquid sample forms a spray, which is directed toward the pore  22  formed in a wall of the vacuum chamber  13 . Thus, the ejection port  16  functions as a spray nozzle for spraying the sample. The sprayed droplets of the liquid sample are dried and atomized before they enter the pore  22 . 
   After passing the pore  22 , the sample is detected by the mass spectrometer unit  13 , which generates signals used for mass analysis. The mass spectrometer unit  13  may be a quadrupole, an ion trap, or any other type selected in accordance with the purpose of the analysis. 
   There are several types of ion sources that use the assist gas.  FIGS. 7A–7D  show examples of conventional ion sources using the assist gas. 
     FIG. 7A  shows an ion source using the electrospray ionization. In this ion source, a high voltage source  25  is connected to the liquid supply pipe  15  to electrify the liquid sample located at the front end of the liquid supply pipe  15  by applying a high voltage to the liquid supply pipe  15 . The electrified liquid sample is drawn in a predetermined direction by a potential gradient to form a spray directed frontward from the ejection port  16 . Each droplet in the sprayed sample becomes smaller in size as a result of the drying process and/or the electrostatic repulsions due to its own charge, and finally turns into ions. In principle, the electrospray ionization does not necessarily require an assist gas. Under practical conditions, however, it is necessary to efficiently perform the spraying and drying processes when a considerable amount of liquid sample is used. Therefore, even in the case of the electrospray ionization, it is common to insert the liquid supply pipe  15  into the gas supply passage  17  and simultaneously supply the assist gas and the liquid sample from the gas supply passage  17  and the liquid supply pipe  15 , respectively. 
     FIG. 7B  shows an ion source using the sonic spray ionization. In this ion source, the high voltage is not applied to the liquid supply pipe  15 . Instead, the liquid sample  21  is electrified into ions by the friction between the droplets (i.e. liquid sample) ejected from the liquid supply pipe  15  and the assist gas ejected from the gas supply passage  17 . 
     FIG. 7C  shows an ion source using the atmospheric chemical ionization. This ion source includes a heater  26  for producing a gas sample by heating the liquid sample flowing through the liquid supply passage  21 . The heater  26  also heats the assist gas flowing through the gas supply passage  17 . The heated assist gas and the heated gas sample are simultaneously ejected to dry the gas sample. The dried gas sample is then ionized by an electric discharge from the needle-shaped high voltage electrode  27  to which a high voltage is applied with the high voltage source  25 . 
     FIG. 7D  shows an ion source using the atmospheric photo-ionization. This ion source includes an excitation light source  28  in place of the high voltage electrode  27  in  FIG. 7C  and ionizes the gas sample by irradiating the excitation light  29 . 
   As shown in  FIG. 8 , in the ion source  41  with the liquid supply pipe  15  inserted into the gas supply passage  17 , the liquid supply pipe  15  is supported only by a cantilever structure at the hole  20  formed at the rear end of the gas transport pipe  15 . This structure, however, does not assure that the liquid supply pipe  15  is always coaxial with the gas supply passage  17  of the gas transport pipe  14 ; it may allow the displacement of the central axis of the liquid supply pipe  15  from the central axis of the gas supply passage  17 . For example, the displacement may be caused by the self-weight of the liquid supply pipe  15 , the use of a liquid supply pipe  15  having an originally poor linearity, or a varying flow of the assist gas. 
   If the displacement occurs, the traveling direction of the ions contained in the gas sample sprayed from the ejection port  16  is also displaced from the center of the pore  22 . This leads to a biased distribution of the ion density, which in turn causes a decrease in the amount of the ions passing through the pore  22 . As a result, the intensity of the detection signal of the mass spectrometer unit  13  decreases, which deteriorates the sensitivity of the mass analysis. 
   One of the simplest methods of solving the above-described problem is to manually adjust the position of the ejection port  16  with respect to the pore  22  and find the best position at which the detection sensitivity is maximized. 
   Another method of maintaining the coaxiality of the liquid supply pipe  15  and the gas supply passage  17  is to fit a bush into the space between the gas transport pipe  14  and the liquid supply pipe  15 . 
     FIG. 9A  is a longitudinal sectional view of the front part of an ion source  42  having a bush  31  for holding the liquid supply pipe  15  within the gas supply passage  17 , and  FIG. 9B  is the cross-sectional view at line A–A′ in  FIG. 9A . 
   The bush  31  is fitted into the gas supply passage  17  of the gas transport pipe  14  with a slight gap (e.g. about 5 μm) between the outer circumference of the bush  31  and the inner surface of the gas supply passage  17 . The bush  31  has a hole  32  formed at its center, and the liquid supply pipe  15  is fitted into the hole  32  with a slight gap (e.g. about 5 μm) between the inner surface of the hole  32  and the outer surface of the liquid supply pipe  15 . Leaving such gaps is necessary to allow the liquid supply pipe  15  and the bush  31  to be removable for cleaning and other maintenance work. 
   From the working point of view, the existence of the gaps means that the above-described fitting is a “loose fit”, not a “close fit”, as specified in the Japanese Industrial Standards as JISB0401. 
   In addition to the hole  32 , the bush  31  has four slits  30  for allowing the assist gas to pass through. The slits  30  may be replaced by holes or other types of openings. 
   The Japanese Patent Publication No. 2003-517576 discloses another method of maintaining the coaxiality of the liquid supply pipe  15  and the gas supply passage  17 . According to this method, the liquid supply pipe  15  is surrounded by plural pieces of gas transport pipes  33  having the same shape and size, through which the assist gas is supplied. 
     FIG. 10A  is a longitudinal sectional view of the front part of the ion source  43  having the liquid supply pipe  15  surrounded by plural pieces of gas transport pipes  33  for supplying the assist gas, and  FIG. 10B  is a cross-sectional view at line B–B′ in  FIG. 10A . 
   The above-described three methods address the problems that the liquid supply pipe  15  is displaced and, accordingly, the gas supply passage  17  and the liquid supply pipe  15  are out of the coaxial position. But they cause some other problems. 
   In the first method, i.e. the manual adjustment of the position of the pore  22  and the ejection port (or nozzle)  16 , the adjustment work is very troublesome. Moreover, if the adjustment is insufficient, it is impossible to obtain an adequately high degree of reproducibility of the mass analysis. 
   In the second method using the bush  31  for holding the liquid supply pipe  15  as shown in  FIGS. 9A and 9B , the position of the bush  31  with respect to the inner surface of the gas supply passage  17  is determined by fitting. Similarly, the position of the liquid supply pipe  17  with respect to the inner surface of the hole  32  of the bush  31  is also determined by fitting. In principle, any fitting structure must have a minimal gap between the two elements concerned. This gap inevitably allows the elements to have a room for displacement, so that their position cannot be completely fixed. 
   This means that the displacement can be as large as the sum of the two gaps, i.e. the first gap between the outer surface of the bush  31  and the inner surface of the gas supply passage  17  and the second gap between the inner surface of the hole  32  of the bush  31  and the outer surface of the liquid supply pipe  15 , and the sum will be at least 5 to 10 μm. This displacement is not negligible with respect to the gap between the gas transport pipe  14  and the liquid supply pipe  15 , i.e. the distance between the inner surface of the gas supply passage  17  and the outer surface of the liquid supply pipe  15 . Such a displacement may cause the detection signal of the mass spectrometer to be weakened or unstable since the ion density varies. 
   According to the third method shown in  FIGS. 10A and 10B , the liquid supply pipe  15  is surrounded by plural pieces of gas transport pipes  33  having the same shape and size, through which the assist gas is supplied. In this structure, the outlets of the gas transport pipes  33  are separated from the outlet of the liquid supply pipe  15  by the thickness of the wall of the gas transport pipe  33 . This separation reduces the amount of the assist gas acting on the liquid sample located at the front end of the liquid supply pipe  15 , so that the liquid-sheering force of the assist gas significantly decreases. As a result, the liquid sample cannot be fully broken into minute droplets, and the atomization, transport and drying of the liquid sample cannot be adequately performed. This causes an inadequate ionization and accordingly weakens the detection signal of the mass spectrometer. To avoid such a problem, it is necessary to compensate for the shortage of ions by increasing the flow rate of the assist gas to compulsorily promote the ionization. 
   In view of the above-described problems, an object of the present invention is to provide a mass spectrometer having an ion source constructed so that the gas supply passage for supplying the assist gas and the liquid supply pipe for supplying a liquid sample are maintained in the coaxial position, and the liquid supply pipe is hardly displaced with respect to the gas supply passage. 
   SUMMARY OF THE INVENTION 
   Thus, the present invention provides a mass spectrometer having an ion source for ionizing a liquid sample, in which
         the ion source includes a gas transport pipe and a liquid supply pipe;   the gas transport pipe has an ejection port at its front end and a gas supply passage for sending an assist gas to the ejection port;   the inner surface of the gas supply passage has a tapered section located in proximity to the ejection port, where the diameter of the tapered section decreases toward the ejection port;   the liquid supply pipe is inserted into the gas supply passage so that the front end of the liquid supply pipe is located in proximity to the ejection port;   three or more spheres having the same size are inserted between the inner surface of the gas supply passage and the outer surface of the liquid supply pipe; and   a pressing mechanism is used to press the spheres onto the tapered section.       

   The spheres may be preferably positioned in the gas supply passage so that each sphere is in contact with the neighboring spheres on both sides. 
   The diameter of the spheres may be larger than that of the ejection port. 
   The pressing mechanism may be constructed to press the spheres onto the tapered section via an urging member. 
   The distance between the point at which the sphere is in contact with the liquid supply pipe and the front end of the liquid supply pipe may be thirty times as large as the maximum diameter of the liquid supply pipe, or smaller than that. 
   According to the present invention, the ion source includes: a gas transport pipe having a gas supply passage through which an assist gas flows; and a liquid supply pipe located within the gas supply passage of the gas transport pipe. The gas transport pipe has an ejection port at its front end, and an assist gas is sent through the gas supply passage to the ejection port. In proximity to the ejection port, the inner surface of the gas supply passage has a tapered section, the diameter of which decreases toward the ejection port. 
   There are at least three spheres having the same size between the inner surface of the gas supply passage and the outer surface of the liquid supply pipe. When the pressing mechanism is operated to press the spheres onto the tapered section, the spheres move along the tapered section and come closer to the ejection port. At the same time, the spheres come closer to the liquid supply pipe and push it toward the center of the tapered section, i.e. the central axis of the gas supply passage. 
   Thus, the pressure from the three or more spheres holds the liquid supply pipe at the center of the gas supply passage. The direct contacts of the spheres with the tapered section and the outer surface of the liquid supply pipe eliminate the aforementioned gap observed in the fitting structure. Therefore, it is possible to hold the liquid supply pipe accurately on the central axis of the gas supply. The gas transport pipe and the liquid supply pipe form a duplex pipe structure having a high degree of coaxiality. 
   The spheres may be positioned in the gas supply passage so that each sphere is in contact with the neighboring spheres on both sides. This positioning makes the space between the spheres symmetrical with respect to the central axis, which produces a uniform flow of the assist gas. 
   The diameter of the spheres may be larger than that of the ejection port. This design prevents the spheres from rolling out from the ejection port. Therefore, for example, it never occurs that the sphere accidentally escapes from the ejection port during cleaning or other maintenance work. 
   The pressing mechanism may be constructed to press the spheres onto the tapered section via an urging member. This design allows the user to take out the liquid supply pipe by exerting a force against the urging force of the pressing mechanism, without entirely removing the pressing mechanism. Thus, the user can perform the maintenance work in a relatively simple manner. 
   The distance between the point at which the sphere is in contact with the liquid supply pipe and the front end of the liquid supply pipe may be thirty times as large as the maximum diameter of the liquid supply pipe, or smaller than that. This design ensures the coaxiality of the liquid supply pipe, irrespective of the diameter of the liquid supply pipe. 

   
     BRIEF DESCRIPTION OF THE DRAWINGS 
       FIG. 1  is a longitudinal sectional view of the front part of the ion source used in a mass spectrometer as an embodiment of the present invention. 
       FIG. 2  is a longitudinal sectional view of the front part of the ion source used in a mass spectrometer as another embodiment of the present invention. 
       FIGS. 3A–3C  are sectional views showing the spheres located around the liquid supply pipe. 
       FIGS. 4A–4D  are longitudinal sectional views showing the relation between the size of the spheres in the gas supply passage and the ejection port. 
       FIG. 5  is a longitudinal sectional view showing the distance of the front end of the liquid supply pipe from the spheres in the gas supply passage. 
       FIG. 6  is a longitudinal sectional view of the front part of the ion source used in a conventional mass spectrometer. 
       FIGS. 7A–7D  are longitudinal sectional views showing examples of conventional ion sources. 
       FIG. 8  is a longitudinal sectional view of the front part of an ion source, in which the liquid supply pipe is out of the coaxial position. 
       FIGS. 9A and 9B  show the construction of the front part of a conventional ion source, where  FIG. 9A  is a longitudinal sectional view and  FIG. 9B  is the cross-sectional view at line A–A′ in  FIG. 9A . 
       FIGS. 10A and 10B  show the construction of the front part of another conventional ion source, where  FIG. 10A  is a longitudinal sectional view and  FIG. 10B  is the cross-sectional view at line B–B′ in  FIG. 10A . 
   

   DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT 
   An embodiment of the present invention is described with reference to the attached drawings.  FIG. 1  is a longitudinal sectional view of the front part of the ion source used in a mass spectrometer as an embodiment of the present invention. In  FIG. 1 , those elements which have already been shown in  FIG. 6  are denoted by the same numerals, the explanations for these elements are partially omitted. The front part of the ion source in this embodiment is attachable to and detachable from the rear part of the ion source, which is not shown in  FIG. 1 . As described later, when the front part is detached, the user can adjust the pressing member located within the ion source. The front and rear parts of the ion source are connected, for example, by a flange mechanism having a seal for closing the space between the connection faces of the two parts when they are combined. Other features of the construction of the rear part of the present embodiment are basically the same as shown in  FIG. 6 . 
   The mass spectrometer  10  includes an ion source  11  exposed to approximate atmospheric pressure and a mass spectrometer unit  13  enclosed in the vacuum chamber  12 . 
   The ion source  11  includes a gas transport pipe  14  having a gas supply passage  17  and a liquid supply pipe  15  inserted into the gas supply passage  17 . 
   The inner surface of the gas supply passage  17  has a tapered section  5  in proximity to the ejection port  16 , where the diameter of the tapered section  5  decreases toward the ejection port  16 . The tapered section  5  is worked with a lathe, and its central axis coincides with that of the gas supply passage  17 . The inner surface of the gas supply passage  17  also has a thread groove  6  worked with a lathe, and a tightening ring  4  having a thread on its outer circumference is screwed into the thread groove  6 . 
   In the gas supplying passage  17 , six spheres  2  of the same size are inserted between the outer surface of the liquid supply pipe  15  and the inner surface of the gas supply passage  17 , though  FIG. 1  shows only two of the six spheres  2 . It should be noted that the number and size of the spheres  2  could be varied, as described later. The spheres  2  are pressed onto the tapered section  5  by a pressing cylinder  3 , which is fixed by the tightening ring  4  screwed into the thread groove  6 . 
   The liquid supply pipe  15  is set in the ion source  11  as follows. 
   First, with the spheres  2  and the pressing cylinder  3  set in the gas supply passage  17 , the liquid supply pipe  15  is inserted into the gas supply passage  17  so that the front end of the liquid supply pipe  15  is located at the ejection port  16 . It is preferable to adjust the liquid supply pipe  15  so that its front end slightly sticks out from the ejection port  16 . Particularly, as in the case of the electrospray ionization ( FIG. 7A ), if a voltage is applied to the liquid supply pipe  15 , it is recommended to make the front end stick out so that the electric field can concentrate on it. 
   Next, the tightening ring  4  is screwed into the thread groove  6  to press the spheres  2  onto the tapered section  5  via the pressing cylinder  3 . Then, being pushed by the pressing cylinder  3 , the spheres  2  come closer to not only the ejection port  16  but also the central axis of the tapered section  5 , while pushing the liquid supply pipe  15  toward the center of the tapered section  5 , i.e. the central axis of the gas supply passage  17 . Since the six spheres  2  have the same size and the tapered section  5  is symmetrical with respect to its central axis, the six spheres  2  uniformly move toward the center of the tapered section  5  and finally hold the liquid supply pipe  15  exactly on the central axis of the gas supply passage  17 . Thus, the gas supply passage  17  and the liquid supply passage  15  are maintained in the coaxial position. 
     FIG. 2  shows a modification of the above-described embodiment. The ion source shown in  FIG. 2  includes a spring  7  inserted between the pressing cylinder  3  and the tightening ring  4 . 
   The spring  7  presses the spheres  2  onto the tapered section  5  via the pressing cylinder  3 . Similar to the case in  FIG. 1 , the spheres  2 , which are pressed by the pressing cylinder  3 , come closer to not only the ejection port  16  but also to the center of the tapered section  5 , while pushing the liquid supply pipe  15  toward the central axis of the gas supply passage  17 . Since the six spheres  2  have the same size and the tapered section  5  is symmetrical with respect to its central axis, the six spheres  2  uniformly move toward the center of the tapered section  5  and finally hold the liquid supply pipe  15  exactly on the central axis of the gas supply passage  17 . Thus, the gas supply passage  17  and the liquid supply passage  15  are maintained in the coaxial position. 
   When the liquid supply pipe  15  needs to be cleaned or replaced with a new one, the user can easily take it out by exerting a force against the urging force of the spring  7 ; there is no need to loosen the tightening ring  4 . 
   [Number and Size of Spheres] 
   The number and size of the spheres  2  inserted into the gas supply passage  17  are determined on the basis of the following principles. 
   It is preferable to determine the diameter of the liquid supply pipe  15  and that of the spheres  2  so that there is no space, or only the smallest space, left between the neighboring spheres  2 . Uneven spacing of the spheres  2  may lead to a poor symmetry of the flow of the assist gas with respect to the central axis and accordingly deteriorate the form of the spray, even though the assist gas can diffuse and uniform itself to some extent. 
   In principle, use of the three spheres  2  would suffice to coaxially hold the liquid supply pipe  15  with respect to the gas supply passage  17 . However, in order to satisfy the aforementioned requirement that there should be no space left between the neighboring spheres  2 , it is necessary to considerably increase the diameter of the gas supply passage  17  (and accordingly the size of the gas transport pipe  14 ) when there is only a small number of spheres  2  used. For example, in the case of using six spheres  2 , the diameter of the spheres  2  is the same as that of the liquid supply pipe  15 , as shown in  FIG. 3A . If the number of the spheres  2  is decreased to four or three, it is necessary to increase the diameter of the spheres, as shown in  FIGS. 3B and 3C . Therefore, if there is an upper limit for the size of the ion source  11 , it is necessary to use a relatively large number of spheres  2 . In view of the balance with the diameter of the liquid supply pipe  15 , it is normally recommendable to use four to six pieces of the spheres  2 . 
   The user needs to so some maintenance work to the liquid supply pipe  15  when, for example, it is damaged by an electric discharge or it is clogged. In such a case, it is necessary to release the sphere  2  from the pressure caused by the pressing cylinder  3  and pull out the liquid supply pipe  15 . Then, if the diameter of the sphere  2  is smaller than the ejection port  16 , the sphere  2  may escape from the ejection port  16  and get lost during the maintenance work after the liquid supply pipe  15  is pulled out, as shown in  FIGS. 4A and 4B . 
   This problem can be avoided by making the sphere  2  larger than the ejection port  16  so that it cannot escape from the ejection port  16 , as shown in  FIGS. 4C and 4D . 
   [Spatial Relation Between Spheres and Ejection Port] 
   As the point at which the spheres  2  support the liquid supply pipe  15  is more distanced from the front end of the ejection port  16 , the coaxiality of the liquid supply pipe  15  becomes lower due to sagging or other factors. Therefore, the spheres  2  should be positioned close enough to the ejection port  16 . More specifically, with the diameter of the liquid supply pipe  15  denoted by α, the distance from the front end of the liquid supply pipe  15  to the supporting point should be preferably about 30a or smaller, as shown in  FIG. 5 . This condition provides an adequate degree of coaxiality. 
   In the case of using a liquid supply pipe  15  that is tapered toward the front end, the aforementioned diameter can be measured at the position where the liquid supply pipe  15  is supported by the spheres. 
   As the supporting point of the spheres  2  is closer to the ejection port  16 , the coaxiality of the liquid supply pipe  15  becomes higher. Therefore, it is preferable to make the wall of the tapered section  5  thinner so that the spheres  2  are allowed to come closer to the ejection port  16 , provided that the thinning work is technically feasible and the tapered section  5  retains an adequate mechanical strength.