Patent Application
20100243882
Applicant's teachings relate to apparatuses and methods of cleaning laser optical components, particularly in matrix-assisted laser desorption ionization (MALDI) applications.
Generally, with analytical instruments using laser desorption as the ionization mechanism, such as, for example, in a matrix-assisted-laser-desorption-ionization (MALDI) mass spectrometer, the laser is often located remotely from the sample target. This accommodates the environmental operating conditions of the mass spectrometer, which can include, for example, vacuum conditions.
Various conventional light transmission methods can be used to guide the light from the laser to the sample while maintaining the physical separation between the sample and the laser. Some of these methods can include, for example, but not limited to, positioning optical components, such as mirrors and focus lenses for controlling the beam size between the laser and the sample. The mirrors reflect the laser light to the sample. With known MALDI sources, however, the laser light hits the sample and forms a plume of debris, or vaporized mixture of sample, matrix material and sample ions. The plume expands outwardly from the source and can follow the path taken by the laser. Since some of the optical components, such as, for example, but not limited to, the laser mirror, lie in the path of the expanding plume, the surface of these components can become contaminated. The cleaning of the mirror can be inconvenient and can result in an interruption of workflow. Specifically, mechanical cleaning can involve significant instrument downtime resulting in reduction of sample throughput.
Applicant's teachings relate to apparatuses and methods of cleaning laser optical components, particularly in, for example, but not limited to, matrix-assisted laser desorption ionization (MALDI) applications. In accordance with various embodiments of applicant's teachings, a method for reducing contaminant accumulation on an optical component for use with a laser in laser desorption ionization is disclosed. The method comprises heating the optical component. In accordance with various embodiments of the applicant's teachings, the optical component is heated in high throughput laser desorption applications, for example, but not limited to, high throughput MALDI mass spectrometry. It is generally desirable to increase the rate of analysis (throughput rate) so that more samples can be analyzed in a given time period. For example, one method of performing high throughput MALDI mass spectrometry is to employ a high repetition rate laser where high frequencies of laser pulses generate very intense and stable ion signals that are sufficient for fast sample analysis. Such a high repetition rate laser, however, has the potential of generating greater amounts of vaporized debris in the plume, which increases the contamination of the surface of the optical components generally in the path of the plume. High throughput MALDI mass spectrometry can have lasers running up to 1000 Hz, or higher, for example, but not limited to, in some embodiments of applicant's teachings, as high as 5 kHz. In these applications, the optical components can reveal a contamination spot after running continuously for only one (1) week.
In accordance with some embodiments of applicant's teachings, the optical component is heated by operably coupling a heater to the optical component. The heater can be a resistive heater.
In accordance with various embodiments of applicant's teachings, the optical component is heated while the laser is used in laser desorption ionization, so that the heating of the optical component prevents or minimizes the accumulation of debris on the optical component.
In accordance with some embodiments of applicant's teachings, the optical component is heated to a temperature of about 60-75° C.
In accordance with various embodiments of applicant's teachings, the optical component is heated by increasing the laser power. In accordance with some embodiments of applicant's teachings, the method can comprise after using the laser for laser desorption ionization, increasing the laser power so that the laser cleans the optical component of accumulated debris. The laser power can be increased to about 30-60 μJ. Moreover, the laser power can be increased for a period of time of about 2-60 minutes, as required.
In accordance with various embodiments of applicant's teachings, it can be appreciated that the optical component can be a mirror or a lens that is contaminated by debris from the high throughput application.
Further, in accordance with various embodiments of applicant's teachings an optical component assembly for use with a laser in laser desorption ionization is provided. The assembly includes a support, an optical component coupled to the support, and a heater. The heater can be operatively coupled to the optical component so that the heater heats the optical component to reduce the accumulation of debris on the optical component.
Further, in accordance with some embodiments of applicant's teachings a sensor can be operatively coupled to the optical component, so that the sensor monitors the temperature of the optical component.
Moreover, in accordance with various embodiments of applicant's teachings, three support surfaces are provided on the support to support the optical component. Further, the optical component is coupled to the support by a holder, the holder having a retaining portion thereof spaced from the support surfaces, so that at least part of the optical component is retained between the retaining portion of the holder and the support surfaces. Further the retaining portion of the holder contacts the optical component over at least two opposing edges of the optical component. Moreover, the holder is a plurality of holders with each one having a retaining portion. In accordance with some embodiments of applicant's teachings at least three retaining portions are provided to contact the other face of the optical component, the three retaining portions provided over two opposing edges of the optical component. The holder can be made of a heat resistant material.
In accordance with various embodiments of applicant's teachings the holder includes a clamp to secure the holder to the support. The clamp can be made of a heat resistant material, such as, for example, but not limited to, a fluoropolymer or a poly(tetrafluoroethylene) or poly(tetrafluoroethene).
In accordance with various embodiments of applicant's teachings, the optical component can be retained so that one face of the optical component contacts the support surfaces, and at least a portion of the other face of the optical component is contacted by the retaining portion of the holder. Moreover, the support can have a recessed portion adapted to receive the optical component.
Further, in accordance with various embodiments of applicant's teachings, the heater is positioned between one surface of the optical component and the support.
In accordance with some embodiments of applicant's teachings, the heater can be a resistive heater.
Further, in accordance with some embodiments of applicant's teachings the sensor can be positioned between the one surface of the optical component and the support, the sensor spaced from the heater.
The skilled person in the art will understand that the drawings, described below, are for illustration purposes only. The drawings are not intended to limit the scope of the applicant's teachings in any way.
After beam 12′ enters chamber 23 through view port 21, it is deflected by a mirror 24 to form beam 12″. Beam 12″ is thereby directed to the sample plate 26. When the laser beam 12″ hits the sample on the sample plate 26, a plume 28 of debris, or vaporized material, can be generated. For example, with MALDI sources, the plume 28 that defines the debris can be a mixture of sample, matrix material and sample ions, but also can comprise, for example, but not limited to, salts and tissue membranes. The plume 28 expands outwardly and can follow back along the path that the laser light had taken, i.e., beam 12″. Since some of the optical components, such as, for example, but not limited to, the mirror 24, lie in the path of the expanding plume, the surface of these components can become contaminated with debris from the plume.
The plume 28 of vaporized material tends to dissipate or lose momentum as a function of distance. Accordingly, an optical component, such as, for example, but not limited to, a mirror 24 mounted sufficiently far from the sample plate 26 will generally be less contaminated than a mirror positioned closer to the sample plate. However, the mirrors set distance is generally determined by instrument design and physical constraints. The mirror 24 can be, for example, but not limited to, 194 mm away from the sample plate 26.
Further, it is generally desirable to increase the rate of analysis (throughput rate) so that more samples can be analyzed in a given time period. For example, one method of performing high throughput MALDI mass spectrometry is to employ a high repetition rate laser where high frequencies of laser pulses generate very intense and stable ion signals that are sufficient for fast sample analysis. Such a high repetition rate laser, however, has the potential of generating greater amounts of vaporized debris in the plume 28, which increases the contamination to the surface of the optical components, for example, the surface of mirror 24. For example, typical use running the laser at 200 Hz. can result in contamination of the mirror about every 12-18 months of heavy use. But high throughput MALDI mass spectrometry having lasers running up to 1000 Hz. can reveal a contamination spot on the laser mirror after running continuously for only one (1) week.
Accordingly, with high throughput analysis operations, the optical components would require periodic cleaning to maintain performance. Cleaning of mirror 24, for example, involves shutting down the instrument and wiping the surface. For example, the mirror 24 can be wiped with methanol or any organic solvent soluble to the matrix. To fully clean the mirror without damaging the surface, it is found that using an acetone and a KimWipe™ can be effective.
In accordance with various embodiments of Applicant's teaching heating the mirror can reduce contaminant accumulation on mirror 24. In accordance with some embodiments of applicant's teachings, the mirror 24 is heated by increasing the power of the laser 10. For example, the laser 10 is used in a laser desorption ionization application, such as, for example, (MALDI). After a period of use, the laser power is increased so that the laser 10 heats and thereby cleans the mirror 24 of the accumulated debris. For example, but not limited to, in some embodiments of applicant's teachings, the period of use can be determined by the loss of sensitivity of the ion source in general, i.e., the full laser power is no longer being transmitted and deflected by the optics to the sample plate 26. For example, and as discussed in more detail in Applicant's co-pending patent application, Attorney Reference No. 571-1106, the entire contents of which are hereby incorporated by reference, the cleaning of the mirror by increasing the laser power can be timed to coincide with the bake-out process performed on the ion optics of the mass spectrometer. For example, but not limited to, when a performance loss by the instrument is detected beyond a set threshold, or as a scheduled event after a predetermined number of samples have been analyzed. In some embodiments, the period can be substantially equal to a week. In other embodiments, the period can be substantially equal to five (5) days. In some other embodiments, the period is measured in terms of the number of samples processed rather than the time elapsed between the first and last samples. In various embodiments in which the bake-out times of the ion optics are determined by performance loss, the set threshold can be 50% of peak performance. It is understood that in other embodiments the performance threshold can be set to other values other than 50% of peak performance.
In accordance with some embodiments of Applicant's teaching, the laser power is increased to, for example, but not limited to, about 60 μJ to heat and clean the optical components, such as, for example, but not limited to, mirror 24. The laser power can be increased to this level for a period of about 10 minutes. It can be appreciated, however, that the invention is not limited to only about 60 μJ and only about 10 minutes. For example, but not limited to, about 30 μJ could be used to heat and clean the mirror for longer running periods. Further, shorter running periods of a few minutes might be possible with increased laser power.
In accordance with various embodiments of Applicant's teachings, the optical components, such as, for example, but not limited to, a mirror 24, can be heated to reduce contaminant accumulation by operably coupling a heater to the optical component. In these embodiments, the optical component can be heated while the laser is used in laser desorption ionization, so that the heating of the optical component prevents or minimizes the accumulation of debris on the component during use. In accordance with some embodiments of Applicant's teachings the optical component can be heated to a temperature of about 60-75° C., during operation of the instrument.
Referring to
In accordance with some embodiments of applicant's teachings, assembly 34 also includes a sensor 40. The sensor 40 can be spaced from the heater 38. The sensor 40 is operatively coupled to the mirror 24, so that the sensor 40 can monitor the temperature of the mirror 24. The sensor 40 is connected to a control unit (not shown) that adjusts the temperature of the heater 38 and thereby the mirror 24 in response to the temperature sensed.
In accordance with some embodiments of applicant's teachings, the support 36 has a recessed portion 42. Recess 42 is adapted, that is of a shape and configuration, to receive at least a portion of the mirror 24. In particular, the mirror 24 is retained so that one face 44 of the mirror 24 contacts or rests on support surfaces 45, 47 and 49 in recessed portion 42. A pocket 43 is machined into the recessed portion 42 of support 36. Pocket 43 is adapted to receive the heater 36 and sensor 40, and the associated wires so that these components are within the recessed portion and do not form part of support for the mirror 24.
In accordance with various embodiments of applicant's teachings slightly the raised surfaces 45, 47 and 49 (see
According to various embodiments of applicant's teachings, a holder couples the optical component to the surfaces 45, 47 and 49 of the recessed portion 42. In some embodiments of applicant's teachings, for example, but not limited to, as illustrated in
In accordance with various embodiments of applicant's teachings, the retaining portion 52, 52′ and 52″ of the holder 50, 50′ and 50″ contacts the face 46 of the optical component over at least two opposing edges, 54 and 56, respectively. In various embodiments of applicant's teachings, and as illustrated in
Moreover, the retaining portion, such as retaining portions 52, 52′ and 52″ should be so shaped and flexible to substantially prevent the optical component from bending when the optical component is subject to heat (i.e., thermal expansion), and to the clamping force required to secure the optical component in place.
In accordance with some embodiments of applicant's teachings the holders 50, 50′ and 50″ can be made of a heat resistant material, for example, but not limited to, thermally non-conductive materials, such as polymer-type materials like Peek™ or Techtron™. Such materials allow the use of a relatively small heater. Less heat resistant materials, such as, for example, metal or ceramic based materials would conduct the heat from the optical component requiring a larger heater.
In accordance with various embodiments of applicant's teachings the holder can also include a clamp, such as clamps 58, 58′ and 58″, as illustrated in
In accordance with various embodiments of applicant's teachings the support 36 is provided with an opening 60 (see
It can also be appreciated that applicant's teachings can be applied to other optical components in the system, particularly in optical components in chamber 23. For example, lens in view port 21, although not generally directly in the line-of-sight of the plume 28, can also become contaminated over many samplings. For example, in some embodiments of applicant's teachings, for example, as shown in
While the applicants' teachings are described in conjunction with various embodiments, it is not intended that the applicants' teachings be limited to such embodiments. On the contrary, the applicants' teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art.
This patent application claims priority to U.S. Provisional Patent Application Ser. No. 61/164,137, filed on Mar. 27, 2009, the entire disclosure of these patent applications are incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 61164137 | Mar 2009 | US |
