The section headings used herein are for organizational purposes only and should not to be construed as limiting the subject matter described in the present application in any way.
Many modern mass spectrometers that analyze samples deposited on a solid surface require that the pressure inside the ion source be sufficiently low to ensure that ions produced by the ionization process only rarely collide with present neutral molecules. Such mass spectrometers require a pressure inside the ion source to be less than 10−6 atmospheres (one atmosphere equals 760 Torr), and often even require a pressure inside the ion source to be 10−5 Torr or below. Vacuum pumps used for achieving very low pressure are well known in the art. The time required for achieving a given vacuum level is limited by the various system and vacuum pump parameters, such as the vacuum pumping speed, the volume of the vacuum chamber being evacuated, and contributions from contaminants present on inner walls of the vacuum chamber that may vaporize at rates that are comparable to the speed of the vacuum pump. These parameters limit the ultimate pressure that can be achieved in the ion source and vacuum chamber.
In one prior art mass spectrometer, the ion source chamber is separated from the mass analyzer chamber with a gate valve connecting them. When the gate valve is open, ions and neutral molecules may move freely between the two chambers. When the gate valve is closed, the vacuum levels and pumping speeds of the two chambers are independent, but the system is inoperative because ions are not transmitted. When a mass spectrometry analysis is completed, the gate valve is typically closed and the ion source chamber is typically vented to atmospheric pressure. The plate is ejected and a new plate is then loaded for additional analysis. The ion source chamber is then evacuated to the required vacuum pressure, at which point the gate valve is opened and analysis of the samples on the new plate may begin. During the time required for this vent/evacuate cycle, the mass spectrometer is not operating, and in some cases, the time required for the vent/evacuate cycle may be as long as, or longer than, the time required to analyze the samples, which leads to poor utilization of the instrument.
The present teaching, in accordance with preferred and exemplary embodiments, together with further advantages thereof, is more particularly described in the following detailed description, taken in conjunction with the accompanying drawings. The skilled person in the art will understand that the drawings, described below, are for illustration purposes only. The drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating principles of the teaching. The drawings are not intended to limit the scope of the Applicant's teaching in any way.
Reference in the specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the teaching. The appearances of the phrase “in one embodiment” in various places in the specification are not necessarily all referring to the same embodiment.
It should be understood that the individual steps of the methods of the present teachings may be performed in any order and/or simultaneously as long as the teaching remains operable. Furthermore, it should be understood that the apparatus and methods of the present teachings can include any number or all of the described embodiments as long as the teaching remains operable.
The present teaching will now be described in more detail with reference to exemplary embodiments thereof as shown in the accompanying drawings. While the present teachings are described in conjunction with various embodiments and examples, it is not intended that the present teachings be limited to such embodiments. On the contrary, the present teachings encompass various alternatives, modifications and equivalents, as will be appreciated by those of skill in the art. Those of ordinary skill in the art having access to the teaching herein will recognize additional implementations, modifications, and embodiments, as well as other fields of use, which are within the scope of the present disclosure as described herein.
There is currently a need for methods and apparatus for transferring sample plates between chambers of a mass spectrometer that are faster, simpler, less expensive, and more reliable than the prior art methods and apparatus in order to improve utilization of mass spectrometer instruments. Many analytical applications, such as tissue imaging and biomarker discovery, require measurements on intact proteins over a very broad mass range. For these applications, speed of analysis can be a more important metric than the instrument's resolving power.
The present teaching relates to methods and apparatus for transferring sample plates between chambers of a mass spectrometer. For example, in one specific embodiment of the present teaching, a sample plate handling system according to the present teaching includes a sample plate with samples of interest on one surface of the sample plate. A first sample plate receiver is positioned in a first chamber. A first and second sample plate receiver is positioned in a second chamber. A first gate valve is positioned between the first chamber and the second chamber so that it isolates the first and second chambers when closed and allows transfer of sample plates between the first sample plate receiver in the first chamber and one of the first and second sample plate receivers in the second chamber when the first gate valve is open. A first linear extender pushes a sample plate from the first sample plate receiver in the first chamber to the first sample plate receiver positioned in the second chamber, and then retracts a second sample plate from the second sample plate receiver positioned in the second chamber and transports the second sample plate to the first sample plate receiver in the first chamber. A first sample plate receiver is positioned in a third chamber. A second gate valve is positioned between the third chamber and the second chamber so that it isolates the third chamber from the second chamber when closed and allows transfer of sample plates between the first sample plate receiver in the third chamber and one of the first and second sample plate receivers in the second chamber when the second gate valve is open. A second linear extender pushes a sample plate from the first sample plate receiver in the third chamber to the first sample plate receiver positioned in the second chamber, and then retracts the second sample plate from the second plate receiver positioned in the second chamber and transports it into the third chamber.
Valve 108 is mounted close to the inlet of the mechanical pump 110 so that the major portion of the volume of the pumping line between turbomolecular pump 104 and mechanical vacuum pump 110 is between the valve 108 and the outlet of the turbomolecular pump 104. A first vent valve 120 is attached to the vacuum line connecting foreline valve 108 to turbomolecular pump 104 and can be opened to vent first chamber 102 to atmospheric pressure for cleaning or otherwise servicing components of the system located therein. The mechanical vacuum pump 110 is also coupled to the second chamber 112 through a second solenoid operated valve 122. The second chamber 112 is coupled to a source of clean dry air by a third solenoid vent valve 116. Both solenoid valves 116, 122 can be mounted directly onto the second chamber 112 to minimize the total effective volume of the second chamber 112. A thermocouple (TC) or other gauge 118 that is suitable for measuring pressure from atmosphere down to 0.01 Torr, monitors the vacuum level at the inlet to the mechanical vacuum pump 110.
The third chamber 124 of the embodiment of the sample plate handling system 100 illustrated in
In the sample plate handling system 100, a first linear extender 134 moves sample plates 300, illustrated in
Referring to
Referring to
One feature of the present teaching is that a second sample plate 300′ can be transferred from the third chamber 524 at atmosphere to the load-lock chamber 512, and the load-lock chamber 512 can then be evacuated while analysis of a first sample plate 300 is simultaneously being performed in the ion source chamber 502. After the mass spectrometer has been turned on and the instrument is in the process of analyzing samples on the first sample plate 300, a new “LOAD PLATE” cycle can be automatically initiated by placing a new sample plate 300′ in plate receiver 400D. In response to this command, the foreline valve 508 is closed, the roughing valve 522 is closed, and the vent valve 516 is opened.
When the second chamber 512 reaches atmospheric pressure, sample receiver 400C on the holder 550 is aligned with the second gate valve 528 by the linear extender 560. In this configuration, sample receiver 400C is designated as the “Load” receiver and sample receiver 400B is designated as the “Eject” receiver. Sample receiver 400D is also aligned with second gate valve 528 by the linear extender 536 positioned in the third chamber 524, which is at atmospheric pressure. The second sample plate 300′, which is mounted on sample plate receiver 400D, is transferred by linear extender 532 to sample receiver 400C in the second chamber 512. The second gate valve 528 and vent valve 516 is then closed. The roughing valve 522 is opened. When the vacuum indicated by TC gauge 518 reaches 0.01 Torr, the foreline valve 508 is opened and the system is in the “Ready” state.
When the analysis in progress on the first sample plate 300 is completed, the gate valve 526 is opened and the completed sample plate 300 is transferred to the currently unoccupied sample receiver 400B on sample plate holder 550. Sample receiver 400C that is carrying the second sample plate 300′ is then aligned with first gate valve 526 so that the second sample plate 300′ can be transferred to the first chamber 502 for analysis. The first gate valve 526 is then closed, and when the BA gauge 506 reads pressure less than a predetermined safe operating pressure, which is typically about 10−5 Torr, the system has returned to the “Ready” state. The mass spectrometer is then turned on and the instrument proceeds to analyze the sample on the second sample plate 300′. This allows the dead time between analyses of sequential plates to be insignificant relative to the time required for the analysis, because the time to reduce the pressure in the lock chamber from atmosphere to the operating pressure of 0.01 Torr does not contribute to the total dead time.
After analysis of second plate 300′ has begun, a new “LOAD PLATE” cycle can be automatically initiated by placing a third sample plate 300″ (
When the analysis in progress on the second sample plate 300′ is completed, a new “LOAD PLATE” cycle can be initiated by removing completed sample plate 300 from sample plate receiver 400D and installing a fourth sample plate 300′″ (
Thus, a feature of the methods and apparatus of the present teaching is that the dead time, which is the time between analyses of sequential plates, can be an insignificant time relative to the time required for the analysis. This results from the fact that the time to reduce the pressure in the lock chamber from atmosphere to the operating pressure of 0.01 Torr does not contribute to the total dead time. A feature of the embodiments of the sample plate handling systems illustrated in
Another feature of the methods and apparatus of present teaching is that it allows great flexibility in the speed and convenience of sample analysis. In applications requiring high throughput, the speed is limited almost entirely by the time required to analyze the samples on the sample plate. In other applications where the throughput is lower, but where it is desirable to obtain results on a sample quickly after the sample is prepared for analysis, the minimal dead time is also important. Often it is desirable to obtain results on a high priority sample as quickly as possible even though the instrument may be engaged in analyzing samples of lower priority. In this case, if a sample plate is labeled “high priority” the analysis in progress can be paused and the high priority sample loaded and analyzed with minimal delay. When a “high priority” sample is loaded into sample plate receiver 400D, acquisition of the sample plate on sample plate receiver 400A is paused and the position of the plate at the time of the pause is recorded by the data system. This plate is immediately ejected to sample plate receiver 400B and the plate in sample plate receiver 400C is transferred to sample plate receiver 400A in chamber 502.
A “LOAD PLATE” cycle is then initiated and the “high priority” sample is transferred to receiver 400C, and the paused plate is transferred from 400B to 400D. The second chamber 512 is then evacuated and the plate in receiver 400A in chamber 502 is transferred to receiver 400B, after which time the “high priority” plate is transferred to chamber 502 and analysis of the “high priority” sample begins. In one embodiment, the total time required for loading the “high priority” sample and beginning the analysis is less than one minute. When the “high priority” sample analysis is completed, the paused sample can be automatically reloaded and the analysis can proceed from the point that it was paused.
The embodiment illustrated in
In some applications of mass spectrometers, the time required to collect and prepare samples and to deposit samples onto the sample plate is long compared to the time required to analyze the samples in the mass spectrometer. The sample plate handling system of the present teaching provides optimum performance for these applications. For these applications, it is important to begin mass spectrometric analysis as quickly as feasible following loading of a sample plate. In systems according to the present teaching, the dead time between presenting a sample to the plate receiver at atmospheric pressure and beginning the mass spectrometric analysis is the time required to evacuate the load lock chamber. This time is determined by the volume of the load lock chamber and the pumping speed of the mechanical vacuum pump as modified by the conductance of the roughing valve and associated pumping line. In one embodiment, the time to reach a desired pressure of 0.01 Torr is less than one minute.
In other applications of mass spectrometers, samples can be prepared and deposited on the sample plate more rapidly than the samples can be analyzed in the mass spectrometer. The sample plate handling system of the present teaching also provides optimum performance for these applications. In applications requiring high throughput, the important dead time between analysis of sequential sample plates is the time required to remove a completed plate from the first chamber and to load the next plate from the load lock. In one embodiment, this time is less than 10 seconds because of the design described herein. The time required to evacuate the load lock from atmospheric pressure to a desired pressure of 0.01 Torr or less is not limiting since this is accomplished while the first plate is simultaneously being analyzed by the mass spectrometer. In most practical applications, the time required to analyze the samples on a plate is substantially greater than one minute. Thus, the time required to evacuate the load lock in the sample plate handling system according to the present teaching does not reduce the throughput.
While the Applicants' teaching is described in conjunction with various embodiments, it is not intended that the Applicants' teaching be limited to such embodiments. On the contrary, the Applicants' teaching encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art, which may be made therein without departing from the spirit and scope of the teaching.
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