Abstract:
A method and system for desorbing and ionizing molecules from a sample for mass spectrometry using a microplasma device is disclosed. The system and method relies upon a microplasma device, or array of such devices, to partially ionize a gas to form a microplasma. The ionized gas can be a mixture of a noble gas, such as neon or argon, and hydrogen (H 2 ). The ionized gas can form a effluent stream directed onto the surface of a sample to desorb molecules from the remainder of the sample. The desorbed molecules can be ionized by the effluent stream as they leave the surface of the sample. The ionization process can include: photoionization, penning ionization, chemical ionization (proton transfer), and electron impact ionization. The ionized particles from the sample can be directed to a mass spectrometer for analysis. This can produce spatially-resolved mass spectral data, and can be conducted concurrently with another imaging system, such as a microscope.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application Ser. No. 60/987,162, filed 12 Nov. 2007, and 61/107,886, filed 23 Oct. 2008, both of which applications are hereby incorporated by reference. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    1. Field of the Invention 
         [0003]    The present invention relates generally to microplasma-assisted desorption and ionization. In particular, the invention relates to a microplasma device serving as an ion source for a mass spectrometer. 
         [0004]    2. Description of Related Art 
         [0005]    Mass spectrometry is an analytical technique that identifies the chemical composition of a compound or sample based on the mass-to-charge ratio of charged particles. The technique requires a portion of the sample to be chemically fragmented and the fragmented segments to be ionized into charged particles. These particles are then passed into any type of mass spectrometer, which will determine their mass-to-charge ratio. 
         [0006]    Three of the most common categories of mass spectrometers are known as time-of-flight mass analyzers, quadrupole mass analyzers, and ion trap mass analyzers. In each case, ions produced from the sample by the ion source are introduced using a variety of ion optics to guide the charged particles into the analyzer. 
         [0007]    In a time-of-flight analyzer, the collection of ions are first accelerated through a region of known electric potential change. This gives each particle with the same charge the same amount of kinetic energy. The collection of accelerated ions are then allowed to travel through a region of zero electric field, and the time of their arrival at a detector at the end of this region is recorded. Particles with the same kinetic energy but different masses will travel through the “drift” region at different speeds, and thus reach the detector at different times. By this method the mass-to-charge ratio can be determined for each particle sensed by the detector. 
         [0008]    A quadrupole mass analyzer operates by accepting the collection of ions into a region of oscillating electric field. By varying the parameters of this electric field the region can be made stable for a range of different mass-to-charge ratios. The quadrupole mass analyzer determines the mass-to-charge ratios for a variety of charged particles by quickly scanning through these stability parameters, keeping track of how many particles for each mass-to-charge ratio scanned through are detected. 
         [0009]    An ion trap mass analyzer operates in a similar manner, but is capable of producing a field that is capable of trapping a number of particles with a range of mass-to-charge particles. The trap can modify the range of mass-to-charge ratios which are trapped, and thus by narrowing the stability region of operation certain mass-to-charge ratio particles can be released from the trap one by one and allowed to reach a detector outside, and the mass-to-charge ratio information recorded by the system. Other types of ion traps are capable of detecting the mass-to-charge ratio of charged particles in the trap without releasing them. This is accomplished by measuring the oscillation frequency of such particles in the trap by detecting the electromagnetic fields they produce, and analyzing the resulting data. 
         [0010]    The use of electron, ion, and laser beams as an ion source for mass spectrometry-based imaging of surface and tissues is well known. Two popular approaches currently used are matrix assisted laser desportion ionization (MALDI) and secondary ion mass spectrometry (SIMS). These techniques are limited to monitoring the desorbed ion yields under high vacuum conditions and have been used to image semiconductor surfaces, insulators, polymers, tissues, and histological samples. Most MALDI and laser desorption/ionization based mass spectrometry approaches, however, are not effective under ambient temperature and pressure conditions. Some approaches such as desorption electrospary ionization (DESI), direct analysis in real time (DART), and radiofrequency plasma assisted desorption ionization (PADI) have been successfully used under ambient conditions. The spatial resolution of these approaches, however, is limited to the mm scale due to limitations inherent in the technology, and their reliance upon detecting ion signals produced as a result of surface or above surface interactions. 
         [0011]    Therefore, there remains a need for an ion source capable of operating under ambient conditions which can be used to analyze condensed-phase targets such as liquids and surfaces with improved spatial resolution. The embodiments of the invention described below meet this need. 
       BRIEF SUMMARY OF THE INVENTION 
       [0012]    Embodiments of the present invention are directed to a method and system for desorption and ionization of a sample for analysis via mass spectrometry using a microplasma device. Embodiments of the present invention rely upon a microplasma device, or an array of such devices, to partially ionize a gas to form a plasma. The ionized gas can be any pure gas or mixture of gasses, including air, argon, helium, neon. The addition of hydrogen (H 2 ) to the rare gas plasma can produce high energy vacuum ultraviolet photons, which can aid in the desorption/ionization process. The gas effluent stream from the plasma, containing electrons, photons, ions, and metastable particles can be directed onto the surface of a sample to desorb and remove molecules from the sample. These desorbed molecules can be ionized by the plasma effluent as they leave the surface of the sample in the path of the effluent stream. The ionization process can include: electron impact ionization, photo-ionization, penning ionization, and chemical ionization (proton transfer). The ionized particles from the sample can be directed to a mass spectrometer for analysis. 
         [0013]    The ionization attained by embodiments of the present invention can occur under ambient temperature and pressure conditions. The ionization achieved by the embodiments of the present invention is preferably primarily a non-thermal process, therefore, thermal fragmentation and damage to the sample is minimized or eliminated. The addition of hydrogen into the gas mixture increases the proton transfer probability and also produces Lyman-α photons. These photons can lead to further desorption and photo-ionization. 
         [0014]    Embodiments of the present invention can be employed to ionize a wide variety of solid surfaces, including skin or cell cultures, or liquid samples. Embodiments of the present invention can be applied to mass spectrometry for surface analysis, proteomics, metabolomics, glycomics, cancer research, and studies of drug discovery and immune response. 
         [0015]    Embodiments of the present invention can pair microscopy with mass spectrometry. A microplasma device can be disposed inline with a microscope. The microscope and sample can translate relative the microplasma device to position a desired area of the sample in the path of the effluent plume. In this manner, a specific area of a sample can be selected for analysis by mass spectrometry. 
         [0016]    In an exemplary embodiment of the invention, a method for analyzing a sample using a microplasma device and a mass spectrometer comprises generating a field by exciting a first electrode and a second electrode separated by a dielectric element and injecting a gas through a first aperture to form a plasma, the first aperture traversing the first electrode, the second electrode, and the dielectric. The method further comprises directing an effluent stream from the first aperture onto a target surface of the sample and desorbing and ionizing molecules from the target surface using the effluent stream. The method additionally comprises deflecting the paths of the ionized molecules to a mass analyzer and determining the composition of the molecules 
         [0017]    In an exemplary embodiment of the invention, the method for comprise an imaging mass spectrometry system comprises an ion source comprising a first electrode, a second electrode, a dielectric element disposed between the first and second electrodes, and a first aperture traversing the first electrode, second electrode, and dielectric element. The system further comprises a mass analyzer and a device for detecting charged particles. 
         [0018]    In an exemplary embodiment of the invention, an ion source for an imaging mass spectrometry system, the ion source comprises a first electrode, a second electrode, and a dielectric element disposed between the electrodes. The ion source further comprises a first aperture traversing the first electrode, second electrode, and dielectric element, wherein a excitation of the first and second electrode transforms a gas flowing through the first aperture into a plasma, the first aperture adapted to direct a effluent stream of the plasma onto the surface of a sample to desorb molecules from the surface. 
         [0019]    The Detailed Description and accompanying Drawings further describe these and other exemplary embodiments of a system and method for spatially-resolved chemical analysis using microplasma desorption and ionization of a sample. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0020]      FIG. 1A  illustrates an exemplary embodiment of a microplasma device. 
           [0021]      FIG. 1B  illustrates a cross sectional view of an exemplary embodiment of microplasma device. 
           [0022]      FIG. 1C  illustrates a cross sectional view of an exemplary embodiment of the composition of a microplasma device. 
           [0023]      FIG. 2  illustrates an exemplary embodiment of a microplasma device array. 
           [0024]      FIG. 3  illustrates an exemplary embodiment of the array having separately addressable electrodes. 
           [0025]      FIG. 4  illustrates a cross sectional view of an exemplary embodiment of a microplasma device in relation to a sample surface. 
           [0026]      FIG. 5A  illustrates a cross sectional view of an exemplary embodiment of a microplasma device with a guide electrode. 
           [0027]      FIG. 5B  illustrates a cross sectional view of an exemplary embodiment of a microplasma device with a solenoid. 
           [0028]      FIG. 6A  illustrates a cross sectional view of an exemplary embodiment of a sealed microplasma device. 
           [0029]      FIG. 6B  illustrates an exploded perspective view of an exemplary embodiment of a sealed microplasma device with a gas transport channel. 
           [0030]      FIG. 7  illustrates a cross sectional view of an exemplary embodiment of a microplasma device for use with a microfluidic sample. 
           [0031]      FIG. 8A  illustrates a cross sectional view of an exemplary embodiment of a mass spectrometry analysis system. 
           [0032]      FIG. 8B  illustrates a cross sectional view of alternative orientation of an exemplary embodiment of a mass spectrometry analysis system. 
           [0033]      FIG. 9A  illustrates a cross sectional view of an exemplary embodiment of a mass spectrometer comprising a microplasma ion source. 
           [0034]      FIG. 9B  illustrates an exemplary embodiment of an orthogonal orientation of an imaging mass spectrometry system comprising a microplasma ion source. 
       
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
       [0035]    Referring now in detail to the drawing figures, wherein like reference numerals represent like parts throughout the several views,  FIG. 1A  illustrates a frontal perspective view of an exemplary embodiment of a microplasma device. In all of the Figures, the microplasma device(s) and features thereof are not illustrated to scale. The Figures are intended to clearly illustrate all of the elements and their functional relationships, rather than actual relative proportions. The microplasma device  100  can comprise a first electrode  110  and a second electrode  120 . The first and second electrodes,  110  and  120  can be separated by a dielectric  130 . The microplasma device  100  can comprises a first side  101  and a second side  102 . 
         [0036]    The microplasma device  100  can further include an aperture  140 . The aperture  140  can traverse the width of the microplasma device  100 , forming a cylindrical channel through the first electrode  110 , dielectric  130 , and second electrode  120 . The cross-section of aperture  140  is preferably circular. 
         [0037]    The microplasma device  100  can have a thickness of 10-1000 μm. The electrodes  110  and  120  can each have a thickness of 100 nm-1000 μm. The diameter of the cross-section of the aperture  140  can be 10-1000 μm. In a preferred embodiment, the thickness of the microplasma device  100  can be 10-2000 μm, the thickness of the electrodes  110  and  120  can be 200 nm-1000 μm, and the diameter of the aperture  140  can be 10 μm-300 μm. The first electrode  101  can have a length and width less than that of the dielectric  130 . This can reduce arcing between the electrodes  110  and  120  along the edges of the device  100  and formation of plasma at the edges as well. In other contemplated embodiments, the first electrode  110  can have the same length and width as the dielectric  130  and the second electrode  120  can have a smaller length and width than the dielectric  130 . In further contemplated embodiments, insulation can be applied to the edges of electrode  110  and  120 , enabling both electrodes  110  and  120  to have a width and length substantially equal to the dielectric  130 . Additionally, it is contemplated that the first electrode  110  and the second electrode  120  can have a smaller length and width then the dielectric  130 . 
         [0038]    The electrodes  110  and  120  can be composed of a metal such as molybdenum or nickel. The dielectric can be composed of any suitable insulating material, such as silicon dioxide or polyamide. 
         [0039]    The microplasma device  100  can generate a plasma by passing a gas through the aperture  140  while the electrodes  110  and  120  are excited by, for example applied AC or DC voltage, in either continuous or pulsed mode. In an exemplary embodiment, a gas can be injected through the aperture  140  from the first side  110  to the second side  120 . The electrodes  110  and  120  can be excited by DC, radio-frequency, AC or a pulsed voltage. If the field strength within the aperture  140  exceeds a threshold value, the gas passing though the aperture  140  can become partially ionized and form a low temperature plasma. 
         [0040]      FIG. 1B  illustrates a cross sectional view of an exemplary embodiment of a microplasma device  100 . The dielectric  130  can be disposed between electrodes  110  and  120 . The aperture  140  can traverse the entire thickness of the microplasma device  100 . The first side  101  as illustrated is disposed at the top of the microplasma device  100  and the second side  102  is disposed at the bottom. 
         [0041]      FIG. 1C  illustrates a cross sectional view of an exemplary embodiment of the composition of a microplasma device  100 . The dielectric  130  can be disposed between electrodes  110  and  120 . The aperture  140  can traverse the entire thickness of the microplasma device  100 . The first side  101  as illustrated is disposed at the top of the microplasma device  100  and the second side  102  is disposed at the bottom. 
         [0042]    The second electrode  120  can be a composed of a semiconductor or a conductor. For example, but not limitation, the second electrode can be composed of silicon (Si), nickel (Ni), or molybdenum (Mo). The dielectric  130  can be grown or deposited on the surface of the second electrode  120 . For example, but not limitation, the dielectric  130  can be composed of silicon dioxide, mica, or polyamide. The first electrode  110  can be deposited on the surface of the dielectric  130 . For example, but not limitation, the dielectric  130  can be composed of molybdenum (Mo). In other contemplated embodiments, the first electrode  110  can be composed of a semiconductor and the second electrode can be composed of a metal. In further contemplated embodiments, the electrodes  110  and  120  can both be composed of a metal or a semiconductor. 
         [0043]      FIG. 2  illustrates an exemplary embodiment of a microplasma device array  200 . The array  200  can be composed of a plurality of microplasma devices  100  as described above. The microplasma devices  100  can be integrally formed or coupled together to form the array  200 . 
         [0044]      FIG. 2  illustrates an embodiment wherein the array  200  can comprise 25 integrally formed microplasma devices  100 . In other contemplated embodiments, the array  200  can comprise a different number of microplasma devices  100 . 
         [0045]    The array  200  can comprise a first electrode  210  and a second electrode  220 . A dielectric  230  can be disposed between the electrodes  210  and  220 . The array  200  can further comprise a plurality of apertures  240 . In the illustrated embodiment, the array  200  comprises 25 apertures  240 . The electrodes  210  and  220 , the dielectric  230 , and the apertures  240  can be substantially similar to the corresponding elements described above with regard to  FIGS. 1A and 1B . 
         [0046]      FIG. 3  illustrates an exemplary embodiment of the array having separately addressable electrodes, which produce separately addressable plasmas. The array  300  can comprise a first front electrode  311 , a second front electrode  312 , and a third front electrode  313  disposed in parallel on the first side  301  of the array  300 . The electrodes  311 ,  312 , and  313  can traverse the width of a dielectric element  330 . The array  300  can further comprise a first back electrode  321 , a second back electrode  322 , and a third back electrode  323  disposed in parallel on the second side  302  of the array. The electrodes  321 ,  322 , and  323  can traverse the width of the dielectric element  330 . The electrodes  311 ,  312 , and  313  can be oriented parallel or orthogonal to electrodes  321 ,  322 , and  323 . In the illustrated example, the relative orientation is orthogonal. 
         [0047]    The array  300  can comprise a plurality of apertures  340 . The apertures traverse the thickness of the electrodes  311 - 313  and  321 - 323  and the dielectric  330 . The apertures  340  can be substantially similar to the aperture  140  and  240  discussed above.  FIG. 3  illustrates nine apertures  340 . In other contemplated embodiments, other desired numbers of apertures can be employed. 
         [0048]    The front electrodes  311 ,  312 ,  313  are preferably electrically isolated from each other. Similarly, the back electrodes  321 ,  322 , and  323  are preferably electrically isolated from each other. Each of the electrodes  311 - 313  and  321 - 323  can be independently excited. For example, electrodes  312  and  322  can be excited while electrodes  311 ,  313 ,  321 , and  323  are not excited. By selectively exciting certain electrodes, a magnetic and electric field can be generated in a desired aperture. For example, if electrode  313  and electrode  323  are excited, a field can be generated in the aperture in the upper right corner of the array  300 . 
         [0049]    By selectively generating a field in the apertures  340  in the array  300 , desired portions of a sample surface can be ionized. Placing the array  300  above a sample surface, the area of the surface ionized by an effluent plume can be selected by exciting particular electrodes. This provides spatial mapping of the surface area of the sample. In this manner, portions of the sample can be analyzed by mass spectrometry separately without moving the sample or the array  300 . 
         [0050]      FIG. 4  illustrates a cross sectional view of an exemplary embodiment of a microplasma device  400  in relation to a sample  470  surface. The microplasma device  400  illustrated in  FIG. 4  can be a stand alone device or represent a single device within an array as described above in  FIGS. 2 and 3 . The microplasma device  400  can comprise a first electrode  410  and a second electrode  420  separated by a dielectric  430 . A first aperture  440  can traverse the thickness of the electrodes  410  and  420  and the dielectric  430 . The aperture  440 , electrodes  410  and  420  and dielectric  430  can be substantially similar to the corresponding elements described above with regard to  FIGS. 1A and 1B . 
         [0051]    The microplasma device  400  can further comprise a third electrode  450 . The third electrode  450  can be substantially similar in dimension and composition to the second electrode  420 . The third electrode  450  can be disposed substantially parallel to the second electrode  420 . The third electrode  450  can be spaced apart from the electrode, preferably no further than 1 mm. The distance between the third electrode  450  and second electrode  420  can vary between embodiments and applications of the microplasma device  400 . The third electrode  450  can be unexcited and maintained at a ground potential, or excited with a varying or constant potential. 
         [0052]    The third electrode  450  can comprise a second aperture  451 . The second aperture  451  can traverse the thickness of the third electrode. The second aperture  451  can be concentrically aligned with the first aperture  440  and similar or smaller in diameter to the first aperture  440 . 
         [0053]    The microplasma device  400  can be positioned over the surface of a sample  470 . The sample  470  and/or microplasma device  400  can be positioned such that the second aperture  450  is directly above a target site  471  that is to be analyzed. 
         [0054]    A gas mixture  480  can be injected through the first aperture  440 . The gas mixture  480  is preferably composed of molecules that may be readily ionized to form a plasma. The mixture  480  can comprise different types of molecules or a single type of molecule or atom. In an exemplary embodiment, the mixture comprises neon and hydrogen. In other embodiments, the gas  480  may comprise neon or another noble gas alone, or a mixture such as air. 
         [0055]    The field generated by the excitation of electrodes  410  and  420  can partially ionize the gas mixture  480 . In an exemplary embodiment, the first electrode  410  can be an anode and the second electrode  420  can be a cathode. In other contemplated embodiments, the first electrode  410  can be a cathode and the second electrode  420  can be an anode, in this configuration the field generated within the aperture  440  can minimize the number of ionized particles passing through the aperture  440 , allowing primarily VUV photons to pass therethrough. As described above, in each of the exemplary embodiments, the excitation source can be a pulsed voltage. A pulsed voltage can result in an increase in the concentration of metastables and VUV photons produced, as well as reducing the increase in temperature of the plasma  481 . The gas mixture  480  forms a plasma  481  as it passes through the aperture  440 . The plasma  481  can comprise metastable particles, highly excited hydrogen atoms and molecules, high energy electrons, high energy photons, and other ions. A plasma effluent stream  482  can be ejected from the aperture  440  and continue to diffuse across the gap between the second electrode  420  and the third electrode  450 . The effluent stream  482  can comprise energetic electrons, VUV photons, metastable particles, ions, and neutral gas. Upon reaching the third electrode  450  and passing through the second aperture  451 , the effluent stream  482  can interact with the target site  471 . The interaction of the effluent stream  482  with the surface of sample  470  can be delimited by the diameter of the aperture  451 . The diameter of aperture  451  can be selected to correspond to the area of the surface of sample  470  that is desired to be analyzed. Accordingly, the diameter of aperture  451  can be different from the diameter of aperture  440 . 
         [0056]    The interaction between the effluent stream  482  and the target site  471  can desorb and remove molecules from the sample  470 . The metastable molecules in the effluent stream  482  can transfer energy in collisions with the sample, breaking apart bonds between molecules of the sample, and between atoms and molecules on the sample. Further, the excited hydrogen molecules emit photons in the VUV wavelength also breaking apart bonds. The primary VUV photons assist in removing atoms and molecules from the surface. This process of desorption and removal from the surface of the target site  471  with the effluent stream  482  can be primarily nonthermal. In other embodiments, thermal desorption may be occurring in conjunction with nonthermal desportion. The combination of metastables, excited hydrogen molecules, electrons, photons, and ions in the effluent stream  482  can efficiently desorb molecules from the surface of the target site without thermal damage occurring to the remainder of the sample  470 . 
         [0057]    The desorbed molecules from the target site  471  are ejected from the surface of the sample  470  and can form a plume  483  located directly above the target site  471 . As the desorbed sample molecules are ejected forming plume  483 , the molecules in the plume  483  can be ionized by the effluent stream  482 , which passes through the plume  483 . The effluent stream  482  can ionize the sample molecules in the plume  483  through one or more possible ionization channels. The metastable molecules in the effluent stream  482  can ionize the sample molecules in the plume  483  through penning ionization. Further, the excited hydrogen molecules can emit VUV photons, which photoionize the molecules. Additionally, proton transfer ionization can occur given the presence of water. 
         [0058]      FIG. 5A  illustrates a cross sectional view of an exemplary embodiment of a microplasma device  500  with a guide electrode. The microplasma device  500  illustrated in  FIG. 5  can be a stand alone device or represent a single device within an array as described above in  FIGS. 2 and 3 . The microplasma device  500  can comprise a first electrode  510  and a second electrode  520  separated by a dielectric  530 . A first aperture  540  can traverse the thickness of the electrodes  510  and  520  and the dielectric  530 . The device  500  can further comprise a third electrode  550  having a second aperture  551 . The apertures  540  and  551 , electrodes  510 ,  520 , and  550 , and dielectric  530  can be substantially similar to the corresponding elements described above with regard to  FIG. 4 . 
         [0059]    The microplasma device  500  can further comprise a fourth electrode  560 . The fourth electrode  560  can be disposed between the second electrode  520  and the third electrode  550 . The fourth electrode  560  is preferably substantially parallel to the second electrode  520  and third electrode  550  and spaced apart approximately 1 mm between the second  520  and third  550  electrodes. 
         [0060]    The fourth electrode  560  can comprise a cylindrical wall  561  orthogonal to the surface of the fourth electrode  560 . The wall  561  can define a cylindrical conduit  562 . The conduit  562  can be substantially similar in diameter to the first aperture  540 . The conduit  562  can be concentrically aligned with the first aperture  540 . 
         [0061]    A gas  580  can be injected through first aperture  540  to form a plasma  581 . This process is substantially similar to the plasma formation process described above. The effluent stream  582  can continue through the conduit  562  upon exiting the first aperture  540 . The fourth electrode  560  can be excited to generate an electric and magnetic field within the conduit  562 . The field within the conduit  562  can serve multiple functions. First, the field can block the passage of ions within the effluent plume  582 . Second, the field can focus the effluent stream  582  and minimize the spreading of charged particles exiting the first aperture  540 . This can concentrate the stream  582  and increase the portion of the effluent stream  582  that passes through the second aperture  552  and interacts with the target site  571  of the surface of the sample  570 . This can also be used to remove cations and focus a beam of electrons and negative ions from the effluent stream  582 . This would allow mass spectrometry of negative ions from the sample. Absent the fourth electrode  560 , the effluent stream  582  may spread to a diameter greater than the diameter of the second aperture  551 , consequently not all the charged particles in the plume  581  may reach the target site  571 . The effluent steam  582  can interact with the target site  571  to form a plume  583  in substantially the same manner as described above. 
         [0062]      FIG. 5B  illustrates a cross sectional view of an exemplary embodiment of a microplasma device  500  with a solenoid  565 . In other contemplated embodiments, the solenoid can encompass the microplasma device  550  and the sample  570 . The microplasma device  500  can be substantially similar to the device illustrated in  FIG. 5A . In the embodiment illustrated in  FIG. 5B , however, the fourth electrode  560  can be replaced with a solenoid  565 . The solenoid  565  can be disposed proximate the second electrode  520 . The solenoid  565  can define a solenoid aperture  566 . The solenoid aperture  566  can be substantially equal in diameter to and concentrically aligned with the first aperture  540 . 
         [0063]    The solenoid  565  can comprise helically stacked conductor coils, coplanar spiraling coils, or a combination of both. A DC voltage can be applied to the solenoid  565  to generate a magnetic field passing through the aperture  566 . The magnetic field can serve to focus the effluent stream  582  or to prevent charged particles from passing through the aperture  566 . In this manner, the solenoid  565  can serve as either a focusing lens or a filter. In other contemplated embodiments, the solenoid  565  can serve as both a lens and a filter. 
         [0064]    The embodiments of the microplasma device  400  and  500  can be employed as an ion source for a mass spectrometer. The embodiments of the microplasma device  400  and  500  desorb molecules from a sample surface and ionize the molecules in the resulting plume. In these embodiments, the devices  400  and  500  are not sealed off from ambient air. These embodiments rely upon extraction and transport of the ionized sample molecules from the surface of a target site to a mass analyzer of a mass spectrometer. The following exemplary embodiment discloses a microplasma device that is sealed off from ambient air and comprises channels for directing flow of gasses. 
         [0065]      FIG. 6  illustrates a cross sectional view of an exemplary embodiment of a sealed microplasma device  600 . The microplasma device  600  illustrated in  FIG. 6  can be a stand alone device or represent a single device within an array as described above in  FIGS. 2 and 3 . The microplasma device  600  can comprise a first electrode  610  and a second electrode  620  separated by a dielectric  630 . A first aperture  640  can traverse the thickness of the electrodes  610  and  620  and the dielectric  630 . The device  600  can further comprise a third electrode  650  having a second aperture  651 . The apertures  640  and  651 , electrodes  610 ,  620 , and  650 , and dielectric  630  can be substantially similar to the corresponding elements described above with regard to  FIG. 4 . In another contemplated embodiment, the device  600  can comprise a fourth electrode substantially similar to the fourth electrode described above with regard to  FIG. 5 . 
         [0066]    The device  600  can further comprise an enclosure  690  substantially surrounding the outer portion of the first electrode  610 . The enclosure  690  can be dome shaped, square, or another suitable configuration. The enclosure  690  can define a chamber  692 . A gas mixture  680  can be injected through a first port  691  in the enclosure  690  into the chamber  692 . The gas mixture  680  can be substantially similar to the gas mixtures described above. The gas  680  can flow from the chamber  692  through the first aperture  640 . The injection of the gas  680  into the chamber  692  and resulting passage through first aperture  640  can be pulsed. 
         [0067]    As the first and second electrodes  610  and  620  are excited, the gas  680  can form a plasma  681 . The plasma  681  can flow from the first aperture  640  through the second aperture  651  where it can interact with the target site  671  on the surface of sample  670 . The effluent stream  682  can desorb molecules from the surface of sample  670  at the target site  671  and ionize the molecules after they have broken away from the surface. In contemplated embodiments, the effluent stream  682  can ionize molecules from the target site  671  as the molecules are bring desorbed. 
         [0068]    The device  600  can further comprise a tube  693  disposed parallel to and between the second  620  and third  650  electrodes. The tube  693  can traverse the width of the device  600 . The tube  693  can comprise portals  696  aligned with the first aperture  640  and second aperture  651 . The portals  696  can allow the effluent stream  682  to pass through the tube  693  as the effluent stream  682  flows from the first aperture  640  to the second aperture  651 . 
         [0069]    The tube  693  can further comprise an inlet port  694  and an outlet port  695 . A transport gas  682  can be injected through the inlet port  694  and flow into the tube  693 . As the transport gas  682  flows through the tube  693  it can direct the ionized fragments of the sample  670  above the target site  671  toward the outlet port  695 . The sample gas  683  flowing toward the outlet port  695  can be a mixture of the transport gas  682  and ionized sample fragments. The outlet port  695  can lead to the mass analyzer of a mass spectrometer. 
         [0070]    The embodiment described above in relation to  FIG. 6  disclose a device  600  wherein the gas, ionizing plasma effluent stream, and ionized sample molecules are isolated from the ambient atmosphere. This embodiment enables transporting ionized sample fragments to a mass analyzer without contamination from, for example, the ambient air. This improves the accuracy of the sample analysis. 
         [0071]    In embodiments wherein the device  600  comprises an array of microplasma devices, as described in  FIGS. 2 and 3 , the enclosure  690  can surround all of the apertures in the device. In other contemplated embodiments, each aperture can have a separate enclosure such that gas flow through each aperture can be independently regulated. 
         [0072]      FIG. 6B  illustrates an exploded perspective view of an exemplary embodiment of a sealed microplasma device with a gas transport channel. The device  600  is substantially similar to the embodiment illustrated in  FIG. 6A . The enclosure  690  is not pictured to simplify illustration. The present embodiment differs from that of  FIG. 6A  in that the tube  693  is replace with a channel element  660 . 
         [0073]    The channel element  660  can be disposed between the second  620  and third  650  electrodes. The element  660  can abut against both the electrode  620  and  650 . The element  660  can comprise a channel  661  carved or other with formed along the entire width of the element  660 . When the element  660  is proximate the second electrode  620 , the channel  661  can define a conduit for conveying gas. The element  660  can comprise a channel aperture  662 , substantially equal in diameter and concentrically aligned with the first aperture  640 . The effluent stream  682  can pass through the channel aperture  662  and continue to the second aperture  651 , where can interact with the target site  671  of sample  670  as described above. The plume  683  resulting can extend into the channel  661  above the aperture  662 . 
         [0074]    A transport or sweeper gas  684  can be injected into the channel  661  and carry matter from the plume  683  to a mass analyzer. The excitation of the electrode  610  and  620  can be pulsed as described above. Similarly, the injection of gas  684  can be pulsed and synchronized with excitation of the electrodes  610  and  620  to avoid diverting the effluent stream  682  to the mass analyzer, preventing it from reaching the target site  671 . In other contemplated embodiments, the enclosure  690  can be omitted. In additional contemplated embodiments, the enclosure  690  can be incorporated in substantially similar form to all of the embodiments of the microplasma device(s) described herein. 
         [0075]      FIG. 7  illustrates a cross sectional view of an exemplary embodiment of a microplasma device  700  for use with a microfluidic sample. The microplasma device  700  illustrated in  FIG. 7  can be a stand alone device or represent a single device within an array as described above in  FIGS. 2 and 3 . The microplasma device  700  can comprise a first electrode  710  and a second electrode  720  separated by a dielectric  730 . A first aperture  70  can traverse the thickness of the electrodes  710  and  720  and the dielectric  730 . The device  700  can further comprise a third electrode  750  having a second aperture  751 . The apertures  740  and  751 , electrodes  710 ,  720 , and  750 , and dielectric  730  can be substantially similar to the corresponding elements described above with regard to  FIG. 4 . In another contemplated embodiment, the device  700  can comprise a fourth electrode substantially similar to the fourth electrode described above with regard to  FIG. 5 . 
         [0076]    The device  700  can further comprise a tube  790 . The tube  790  can be a tube defining a conduit  791 . The diameter of the conduit is preferably less than or equal to 1 mm. The channel can further comprise a portal  794  forming an opening between the second aperture  751  and the conduit  791 . The portal  794  can be concentrically aligned with and approximately equal in diameter to the second aperture  751 . 
         [0077]    The tube  790  can further comprise an inlet port  792  and an outlet port  793 . A sample can be injected through the inlet port  792  into the conduit  791 . The sample can be a microfluidic specimen. For example, the sample  770  can be, but is not limited to, a cell, spore, or other biological entity. In other contemplated embodiments, the sample  770  can be a different micro scale specimen. The tube  790  can receive other fluid or fluidized samples as well. The diameter of the channel can be varied depending on the size and parameters of the sample to be analyzed. The sample  770  can flow through the conduit  791  toward the outlet port  793 . As the sample  770  passes underneath the portal  794  it can be exposed to the effluent stream  782 . The effluent stream  782  can fragment and ionize the surface of the sample proximate the portal  794  in substantially the same manner as described above. The ionized fragments of the sample  770  can be directed to a mass analyzer of a mass spectrometer. The sample  770  can continue along the conduit  791  and exit the tube  790  through the outlet port  793 . 
         [0078]    In other contemplated embodiments, a tube or channel element could be disposed between the second  720  and third electrodes  750  as described above with regard to  FIGS. 6A and 6B . Further, tube  790  can be replaced by a channel element substantially similar to channel element  660  to transport a microfluidic sample. 
         [0079]      FIG. 8A  illustrates a cross sectional view of an exemplary embodiment of a mass spectrometry analysis system  800 . The system  800  can comprise a microplasma device  801 . The microplasma device  801  illustrated in  FIG. 8  can be a stand alone device or represent a single device within an array as described above in  FIGS. 2 and 3 . The microplasma device  801  can comprise a first electrode  810  and a second electrode  820  separated by a dielectric  830 . A first aperture  840  can traverse the thickness of the electrodes  810  and  820  and the dielectric  830 . The device  801  can further comprise a third electrode  850  having a second aperture  851 . The apertures  840  and  851 , electrodes  810 ,  820 , and  850 , and dielectric  830  can be substantially similar to the corresponding elements described above with regard to  FIG. 4 . In another contemplated embodiment, the device  801  can comprise a fourth electrode substantially similar to the fourth electrode described above with regard to  FIG. 5 . 
         [0080]    The system  800  can further comprise a microscope  890 . The microscope  890  can be an optical microscope. For example, the microscope  890  can be a Raman microscope, a fluorescence microscope, and both near-field and far-field optical imaging systems. In other contemplated embodiments, the microscope  890  may be a microscope other than an optical microscope. In other contemplated embodiments, the microscope  890  can be replaced with another suitable imaging device. 
         [0081]    The microscope  890  can be disposed inline with the device  801 . In particular, the line of sight of the microscope can be parallel to the propagation axis of the effluent stream  882 . In other contemplated embodiments, the line of sight of the microscope  890  can be offset from the axis of the effluent stream  882 . 
         [0082]    In an exemplary embodiment, the microscope  890  can be positioned to view a sample  870  from underneath. The sample  870  can be a specimen on a slide. In other embodiments, the sample can be any specimen suitable for imaging by a microscope. The device  801  can be positioned above the sample  870  and microscope  890 . The microscope  890  can be used be used to locate the position of a target portion  871  or area within the sample  870 . For example, the microscope  890  can be used to locate a particular cell within the sample  870 . The target portion  871  may be anywhere within the sample  870 . Because the sample  870  can be substantially larger than the aperture  851 , the target portion  871  is not likely to be initially located directly underneath the aperture  851 . Consequently, the target portion  871  might not be immediately ionized by the effluent stream  882 . 
         [0083]    After locating the target portion  871  within the sample  870 , the microscope  890  and/or sample  870  can be repositioned such that the target portion  871  rests directly below the aperture  851 . In this manner, a molecules at a particular target portion  871  can be desorbed and ionized by the effluent stream  882 . The system  800  can further comprise a mass analyzer and detector  895  having an inlet port  896 . The fragmented and ionized molecules from the target portion  871  of the sample  870  can be directed through the inlet port  896  for analysis. The optical analysis can also be performed simultaneously with the mass spectral imaging. 
         [0084]    The embodiment described above of system  800  can incorporate various features of any of the previously described embodiments. For example, the device  801  can be sealed from ambient air, incorporating features of the embodiment illustrated in  FIG. 6 . The device  800  can also incorporate a fourth electrode as illustrated in  FIG. 5 . In other contemplated embodiments, the third electrode can be omitted. In further contemplated embodiments, a channel element substantially similar to element  660  can be disposed between the second  820  and third  850  electrodes to direct matter from the plume  883  to the mass analyzer  895 . Additionally, in contemplated embodiments, the sample  870  can be a microfluidic sample within a tube or channel element substantially similar to those described above. 
         [0085]      FIG. 8B  illustrates a cross sectional view of alternative orientation of an exemplary embodiment of a mass spectrometry analysis system  800 . The system  800  is substantially identical to the system described above in  FIG. 8A . In this embodiment, however, the microscope  890  can be disposed above the device  801 , which can be sandwiched between the microscope  890  and a sample  870 . The line of sight of the microscope  890  can pass directly through the first aperture  840  and second aperture  851 , allowing a user to see the target sight  871  on the sample  871 . If the sample  870  is a cell culture and the target site  871  is a particular cell, this orientation allows a user to see the side of the cell that will be actually analyzed, rather than the bottom of said cell as in the orientation of  FIG. 8A . 
         [0086]    The embodiment variations described above with regard to  FIG. 8A  can also be applied to the embodiment of  FIG. 8B . In particular, it is contemplated that a channel element substantially similar to element  660  can be disposed between the second  820  and third  850  electrodes to direct matter from the plume  883  to the mass analyzer  895 . Additionally, it is contemplated that sample  870  can be a microfluidic sample within a tube or channel element substantially similar to those described above. 
         [0087]      FIG. 9A  illustrates a cross sectional view of an exemplary embodiment of a configuration for an imaging mass spectrometry system  900  comprising a microplasma ion source  901 . The mass spectral imaging system  900  can comprise an ion source  901 , a mass analyzer  990 , and a detector  991 . The ion source  901  can be a microplasma device in accordance with any of the embodiments described above. 
         [0088]    In an exemplary embodiment, the ion source  901  can be a microplasma device comprising a first electrode  910 , a second electrode  920 , and a dielectric  930  disposed between the electrodes  910  and  920 . The ion source  901  can further comprise an aperture  940  traversing the thickness of the electrodes  910  and  920  and the dielectric  930 . The dimensions and function of the electrodes  910  and  920  and the dielectric  930  can be substantially similar to the corresponding elements described in the embodiments above. The ion source  901  can comprise a single microplasma device or an array of such devices as illustrated in  FIGS. 2 and 3 . 
         [0089]    The electrodes  910  and  920  are designed to generate electric and magnetic fields. In particular, the electrodes  910  and  920 , can be excited by DC, radio-frequency, AC or a pulsed voltage to generate an electric and magnetic field within the aperture  940 . A gas  980  can be directed to flow through the aperture  940  to form a plasma  981 . The composition of the gas  980  can be substantially similar to the gas mixtures described in relation to the embodiments disclosed above. 
         [0090]    The effluent stream  982  from the aperture  940  can desorb and ionize molecules at a target portion  971  of the surface of a sample  970  in substantially the same manner as described above. The neutral and ionized molecules in the plume  983  from the target portion  971  of the sample  970  can be directed around the sample  970 , as shown by arrow  984 , first to a mass analyzer  990  and then to a detector  991 . The mass-to-charge ratio of the molecules passing through the mass analyzer  990  can be determined by the detector  991 . This data can be analyzed to calculate the composition of the molecules. 
         [0091]    In the above described embodiment of the mass spectrometry imaging system  900 , the ion source  901  and mass analyzer  990  are arranged substantially inline. In particular, the sample  970  can disposed directly between the ion source  901  and the mass analyzer  990 . Various types of samples, however, may not allow for such an arrangement. In other contemplated embodiments, the ion source  910  and the mass analyzer  990  can be oriented orthogonally.  FIG. 9B  illustrates an exemplary embodiment of an orthogonal orientation of an imaging mass spectrometry system  900  comprising a microplasma ion source  901 . In other contemplated embodiments, the ion source  910  and mass analyzer  990  can also be orientated at other angles depending upon the sample and particular implementation of the mass spectrometer  900 . For example, the ion source  901  and mass analyzer  990  can both be disposed above the surface of the target portion  971  at 45 degree angles relative to the surface. 
         [0092]    The embodiment described above of ion source  901  can incorporate various features of any of previously described embodiments. For example, the ion source  901  can be sealed from the ambient air, incorporating features of the embodiment illustrated in  FIG. 6 . Further, the ion source  901  can also incorporate a fourth electrode as illustrated in  FIG. 5 . Additionally, in other embodiments, the ion source  901  can include a third electrode as illustrated in  FIG. 4 . 
         [0093]    Various exemplary embodiments have been disclosed above. It will be apparent to those skilled in the art that many modifications, additions, and deletions, especially in matters of shape, size, and arrangement of parts, can be made therein without substantially departing from the design function of the embodiments described herein. Therefore, other modifications or embodiments as may be suggested by the teachings herein are particularly reserved as they fall within the breadth and scope of the claims here appended.