Abstract:
A method for controlling an electrostatically induced liquid spray includes the steps of: (1) generating a liquid spray from a liquid sample with an electrostatic spray nozzle device using an applied electric field, wherein at least a nozzle portion of the spray device is formed of an insulating material; (2) sensing a current of the liquid spray with a spray current sensing means placed in relation to the spray device; (3) comparing the sensed current of the liquid spray with a pre-selected current value, with a difference between the two representing a control signal; and (4) varying the applied electric field using a computer-controlled positioning mechanism that moves the spray device relative to an inlet of the object that receives the liquid spray and acts as a counter-electrode.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     The present application is a continuation in part to U.S. patent application Ser. No. 11/329,508, filed Jan. 10, 2006, which claims the benefit of U.S. patent application Ser. No. 60/645,165, filed Jan. 18, 2005, which are hereby incorporated by reference in their entireties. 
    
    
     TECHNICAL FIELD 
     The present application relates to an apparatus and methods that improve the performance of spraying a liquid through a nozzle opening solely by means of an electric field. 
     BACKGROUND 
     One type of liquid spraying is known as nano-electrospray or nanospray when used as a sample introduction method in mass spectrometry. The sources of generating such a spray may be quartz or glass capillaries tapered to a tip having a predetermined diameter, or they can be microfabricated nozzles made of silicon or other semiconductor or glass, etc. A liquid spraying apparatus can include the spray nozzle and a mechanism for pumping liquid through the nozzle, as well as a high voltage power supply for supplying the electric field for generating the spray. 
     SUMMARY 
     The sources of generating a liquid spray may be a quartz or glass capillaries tapered to a tip of a few microns to 10&#39;s of microns in diameter, microfabricated nozzles made of silicon or other semiconductor or glass, or injection-molded nozzles with a nozzle opening of ˜20 microns. The apparatus consists of a spray nozzle and the mechanism for pumping liquid through the nozzle, a high voltage power supply for supplying the electric field for spraying, an electric current sensing means in the vicinity of the nozzle, and a negative feedback loop mechanism provided by an electronic circuit or a software program that inputs the current generated by the spray and outputs a signal to either the pumping mechanism or the voltage power supply to regulate the flow rate of the liquid sample or the electric field for spraying, respectively, according to a set level of current. With this apparatus, flow rate of the liquid sample from the nozzle opening can be accurately controlled. 
     Problems such as sample overshoot at the beginning of a spray, flow interruption due to extraneous factors such as air bubbles in the liquid sample, or surface tension changes due to changes in the chemical composition of the sample can be effectively eliminated. If an array of spraying nozzle is used, each spraying nozzle may be assigned a different set current according to the need of the experiment. Another important application of the invention is that the pumping speed of the sample liquid through the nozzle can be varied in a controlled fashion so that the pump speed can be substantially faster at the beginning when the sample liquid is going through the “dead volume” in the channel leading to the nozzle opening, thereby shortening the wait time between samples. This has particular utilization when the nozzles are in an array format and many samples are sprayed from individual nozzles sequentially. 
     The present invention relates to an apparatus and methods that improve the performance of spraying a liquid through a nozzle opening solely be means of an electrical field. Specifically, such a form of liquid spraying, is referred in the industry as nano-electrospray or nanospray when used as a sample introduction method in mass spectrometry. The sources of generating such a spray can be a quartz or glass capillaries tapered to a tip of a few microns to 10&#39;s of microns in diameter or the source can be microfabricated nozzles made of silicon or other semiconductor or glass, or the source can be in the form of injection-molded nozzles with a nozzle opening of about 20 microns. Injection-molded nozzles of this type are described in detail in U.S. Pat. Nos. 6,800,840 and 6,969,850, both of which are hereby incorporated by reference in their entirety. 
     The apparatus, according to one exemplary embodiment, corrects the intermittent spray deficiencies associated with prior art devices and ensures a continuous spray and therefore, continuous acquisition of data by varying the electric field felt by the liquid at the tip of the spray source. 
     The apparatus includes a spray nozzle and the mechanism for pumping liquid through the nozzle, a high voltage power supply for supplying the electric field for spraying, an electric current sensing means in the vicinity of the nozzle, and a computer controlled positioning mechanism to move the spray tip of the spray device toward or away from a mass spectrometer inlet. The apparatus also includes a negative feedback loop mechanism provided by an electronic circuit or a software program that inputs the current generated by the spray and outputs a signal to either the pumping mechanism or the electric field for spraying, respectively, according to a set level of current. 
     One exemplary method for varying the electric field according to the present invention is a computer-controlled positioning mechanism to move the spray tip of the spray device toward or away from the mass spectrometer inlet. 
     The electric field needed to generate a spray is typically made up of two components, namely, the electric field due to the applied high voltage V on the small radius R of the small spray tip, i.e., V/R, and the distance D between the spray tip and the counter-electrode, which is the mass spectrometer inlet, i.e., V/D. The detailed forms of these components of the electric field depend on the actual geometric shape and configuration of the spray tip, electrode, etc. Since the radius of the spray tip is typically in the micro-size range, and the distance D is typically on the mm length-scale, changing the distance D to vary the electric field has not been practical. However, with the plastic nozzle where the radius of the nozzle tip does not directly enter into the electric field equation because it is insulating, adjusting D becomes a very effective means for changing the electric field quickly to induce spray. For metallic or silica spray devices, the distance D typically becomes very small (on the order of the size of the radii of the device tips) before the changed electric field will have an effect on the spray performance of the device. Changing the applied high voltage to change the electric field is not practical because the high voltage power supply typically has a large time constant so that the change in voltages is too slow to respond to the change in the spray conditions. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWING FIGURES 
       The present invention will be understood and appreciated more fully from the following detailed description of preferred embodiments of the present invention, taken in conjunction with the following drawings in which: 
         FIG. 1  is a schematic view of an apparatus for spray control according to a first embodiment, with a current sensing element disposed behind but in the vicinity of a spray nozzle device; 
         FIG. 2  is a schematic view of an apparatus for spray control according to a second embodiment, with a current sensing element disposed in front of a spray nozzle device that is placed perpendicular to a mass spectrometer inlet; 
         FIG. 3  is a schematic view of an apparatus for spray control according to a third embodiment, with a current sensing element disposed between a spray nozzle device and a mass spectrometer inlet; 
         FIG. 4  is a schematic view of an apparatus for spray control according to a fourth embodiment, with a current sensing element enclosing a mass spectrometer inlet; 
         FIG. 5  is side schematic view of an apparatus for spray control according to a fifth embodiment, with a current sensing element incorporated into the design of a mass spectrometer inlet; 
         FIG. 6  is a side elevation view of an electrostatic spray system according to a first exemplary embodiment with a spray nozzle thereof being located directly in front of a mass spectrometer inlet; and 
         FIG. 7  is a perspective view of an electrostatic spray system according to a second exemplary embodiment with the spray nozzle thereof being located perpendicular to the mass spectrometer inlet. 
     
    
    
     DESCRIPTION OF PREFERRED EMBODIMENTS 
     Referring to  FIG. 1 , the present invention consists of an electrostatic spray device  10  (e.g., a spray nozzle), a spray current sensing means,  20 , which is placed in the vicinity of the spray device  10  and is connected to a current amplifier  30  and a negative feedback mechanism  40 . The negative feedback mechanism  40  is configured to take the output from the spray current sensing means  20  and compares it to a pre-set reading of the current. The difference of the two is sent as a signal to regulate a pumping mechanism  50  (pump) or a programmable voltage power supply  60 . The so regulated spray is input into the mass spectrometer inlet  70  that is disposed in an axial relationship with respect to the spray device  10  as shown. In other words, the openings of the spray nozzle  10  and the mass spectrometer inlet  70  are axially aligned with respect to one another. 
     In one embodiment, as exemplified in  FIG. 1 , the current sensing means  20  can be an electrode placed close to but behind the opening of the nozzle (spray device  10 ). In another embodiment, the sensing device  20  is an electrical conducting element placed from a millimeter to up to several cm in front of the spray nozzle device  10 . The requirement on the design of the current sensing element  20  is that it does not physically obstruct the spray discharged from device  10  from entering the mass spectrometer inlet  70 . 
     In  FIG. 2 , the spray nozzle  10  is positioned perpendicular to the inlet  70  of the mass spectrometer and the current sensing device  20  is placed directly in front of the nozzle  10  and beyond the mass spectrometer inlet  70  so as not to interfere with the reception of the spray in the inlet  70 . 
     In  FIG. 3 , the current sensing device  20  is placed between the spray nozzle  10  and the mass spectrometer inlet  70 , and the current device  20  has an orifice that allows the spray to enter the mass spectrometer inlet  70  without physical obstruction. 
     In yet another embodiment of the invention, the current sensing device  20  is a part of an enclosure  80  that surrounds the mass spectrometer inlet  70  but is electrically isolated from the mass spectrometer inlet  70 , as schematically depicted in  FIG. 4 . The enclosure  80  acts as an electrical lens that focuses the spray from the nozzle  10  into the mass spectrometer inlet  70 . In still another embodiment, the current sensing device  20  can be a part of the mass spectrometer inlet  70  as shown in  FIG. 5 . 
     To use the apparatus to regulate a spray, a liquid sample typically consists of a volatile organic liquid and water stored in a reservoir which may or may not be attached to the spraying nozzle, is pumped by means of an air or hydraulic pressure through the nozzle opening which is typically from a few microns to over 20 microns in diameter while a high voltage from abut 1 KV to several KV is applied to the nozzle tip or the liquid sample. A conical spray of the liquid sample into a fine mist results beyond the nozzle opening. Such a spray consists of many electrically charged droplets and ions, which when collected by the current sensing element, and input into a current amplifier, forms a measurable current typically from a few nanoamperes to 10&#39;s of microamperes, depending on the concentration of charged particles in the liquid sample, the ionization efficiency of the liquid sample under the electric field at the nozzle, the flow rate of the sample liquid through the nozzle, and the applied high voltage. 
     The dependence of the current over certain ranges of flow rates and applied voltage may be assumed to be more or less linear. Within these ranges where the dependence appears to be linear, the collected current is fairly stable at any fixed flow rate and applied voltage for a given liquid sample and nozzle geometry. When this current is larger in magnitude than that of a set reference current, the difference of the measured current and the set reference current creates a signal to the controller of the pump pumping the sample liquid through the nozzle to slow down or even reverse the pump direction. This change in the pumping action will reduce the flow rate of the liquid sample through the nozzle and thus make the spray current smaller, which when collected by the current sensing element and compared to the set reference current, will send an appropriate signal to control the pump action so that the effect of the regulation over a period of time is a constant spray current. Likewise the control signal may be sent to a programmable power supply that supplies the voltage for generating and maintaining the spray. The details of this close-loop negative feedback control mechanism is well known in the art, and can be implemented with a electronic circuit including a comparator, a signal integrator with a time constant element, or if the time constant is relatively large, directly with a computer with a analog to digital (A/D) input and digital to analog (D/A) output and appropriate software providing the functions of a comparator/integrator circuit. 
     The amplitude of the spray current is dependent on the liquid sample being sprayed. Samples containing a large quantity of ionizable molecules give a much larger spray current at the same pump rate and applied voltage than samples containing very few such molecules, such as the sample buffers. The reference current used to control the spray must be set according to the samples being sprayed. 
     Referring to  FIG. 6 , the present invention according to a first embodiment is in the form of an electrostatic spray assembly that includes an electrostatic spray device  100  (e.g., a spray nozzle), a spray current sensing means,  120 , which is placed in the vicinity of the spray device  100  and is connected to a current amplifier  130  and a negative feedback mechanism  140 . The negative feedback mechanism  140  is configured to take the output from the spray current sensing means  120  and compares it to a pre-set reading of the current. The difference of the two is sent as a signal to regulate a pumping mechanism  150  (pump) or a programmable voltage power supply  160 . 
     The spray device  100  can be any number of different devices as discussed above and in the illustrated embodiment, the device  100  is in the form of a device that has a nozzle  112  that includes a tip that defines a small opening  114  through which the spray is discharged. 
     The system also includes a positioning mechanism  200  that carries the device  100 , the pumping mechanism  150  and the power supply  160 . More specifically, the positioning mechanism  100  is configured so that it can controllably move the device  100 , mechanism  150  and power supply  160  in one or more directions and for a prescribed increment or distance. The positioning mechanism  200  can be any number of different types of programmable mechanical positioning devices that are in communication with an operating system, such as a computer, and are operated, in particular, to move the device  100  relative to another object. The positioning mechanism  200  thus moves the device  100  either closer or further away from another target object as will be described in more detail below. 
     The spray generated by the device  100  that is discharged through the opening  114  is directed toward or injected into some other object which typically is the same object that the positioning device moves the device  100 , and in particular, the nozzle  112  thereof, relative to an object. In one embodiment, the object is a mass spectrometer  170  that has an inlet  172  into which the spray from device  100  is received. 
     The so regulated spray is input into the mass spectrometer inlet  172  that is disposed, in this embodiment, in an axial relationship with respect to the spray device  100  as shown in  FIG. 6 . In other words, the nozzle opening  14  of the spray nozzle device  100  and the mass spectrometer inlet  172  are axially aligned with respect to one another. 
     In one embodiment as exemplified in  FIG. 6 , when the current sensing means  120  detects a current smaller than the set current, the negative feedback mechanism  140  sends a signal through the computer to the positioning mechanism  100  to move the nozzle  112  of the spray device  100  toward the mass spectrometer inlet  172 , thereby making the electric field felt by the liquid at the tip  114  of the spray device  100  become stronger. 
     Once the spray discharged from the device  100  generates a current larger than the set current as measured by the current sensing means  120 , the feedback mechanism  140  sends a signal via the computer to increase the distance between the spray device  100  and the mass spectrometer inlet  172 , thereby reducing the electric field felt by the liquid sample at the tip of the spray device  100 , which in turn reduces the spray current. 
     Now turning to  FIG. 7  in which another embodiment of the present invention is shown. In this embodiment, the spray nozzle device  100  is positioned perpendicular to the inlet  172  of the mass spectrometer  170 . In addition, the positioning mechanism  200  can be configured to move the device  100  in at least two directions and in particular, the positioning mechanism  200  can move the device  100  in two directions that are perpendicular to one another. In  FIG. 7 , the positioning mechanism  200  moves in a first direction “a” and in a second direction “b” that is perpendicular to the “a” direction. 
     By allowing the positioning mechanism  200  to move in two directions, the nozzle  112  of the spray device  100  can be placed at an optimal position to attain the best electric field for spraying. 
     It will also be appreciated that the positioning mechanism  200  can be configured to move in three directions (three axes of motion, such as x, y, and z directions). This permits even greater control over the position of the device  100  relative to the target object, in this case the inlet  172 . However, in general, no more than two axes of motion are needed. The positioning mechanism  200  can consist of motorized linear motion stages or rotary motion stages. 
     To use the apparatus of the present invention to regulate a spray, a liquid sample typically consists of a mixture of volatile organic liquid and water is connected to the spray nozzle  112  of the device  100  and is then pumped by means of air pressure or hydraulic pressure through the nozzle opening  114  which is typically from a few microns to over 20 microns in diameter, while a high voltage from about 1 KV to several KV is applied to the nozzle tip  114  or the liquid sample. A conical spray of the liquid sample results in a fine mist being formed beyond the nozzle opening  114 . This spray consists of many electrically charged droplets and ions, which when collected by the current sensing element  120  and input into the current amplifier  130 , forms a measurable current typically from a few nanoamperes to 10&#39;s of microamperes, depending on a number of parameters, including but not limited to, the concentration of the charged particles in the liquid sample, the ionization efficiency of the liquid sample under the electric field at the nozzle  112 , the flow rate of the sample liquid through the nozzle  112 , and the applied high voltage. 
     When this measurable current is greater in magnitude than that of a set reference current (threshold value), the difference of the measured current and the set reference current is creates a signal to the controller of the positioning mechanism  200  to move the nozzle  112  away from the mass spectrometer inlet  172 . This change in the nozzle position will reduce the electric field for the spray and thus, make the spray current smaller. When the current sensing element  120  collects the smaller spray current and compares it to the set reference current, the element  120  sends an appropriate signal to control the positioning mechanism  200  so that the effect of the regulation over a period of time is a constant spray current. 
     The amplitude of the spray current is dependent on the liquid sample being sprayed. Samples containing a larger quantity of ionizable molecules give a much larger spray current at the same pump rate and applied electric field compared to samples containing very few such molecules, such as the sample buffers. Samples containing a varying composition of mixtures as is commonly the case in reverse phase liquid chromatography will also generate currents of different magnitudes for a given pump rate and applied electric field. The reference current used to control the spray must be set according to the sample being sprayed. 
     It will also be appreciated that the components or arrangements of the devices set forth in the embodiments of  FIGS. 1-5  can be combined and employed in the arrangements shown in  FIGS. 6-7 . For example, two or more embodiments can be combined into a single embodiment (e.g., the spray device and electronic components and mass spectrometer arrangement of  FIG. 3 ,  4  or  5  with the positioning mechanism  200  shown in  FIG. 6  or  7 ). 
     While the invention has been particularly shown and described shown and described with reference to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention.