Method and system of atmospheric pressure megavolt electrostatic field ionization desorption (APME-FID)

Abstract

On field ionization under ambient conditions is described and applied on both ionization and desorption of various chemicals and biochemical present on the surface of materials in solid, liquid or gas states. The Atmospheric Pressure Megavolt Electrostatic Field Ionization Desorption (APME-FID) method generates ions directly from the surface of samples connected to a high electrical voltage at megavolt conditions. Megavolt electrostatic potential is generated and gradually accumulated directly on the sample surface by a Van de Graaff generator without causing damage to the sample. Therefore, when coupled with mass spectrometric system, the APME-FID-MS method enables direct detection of analytes on the surface of samples in different sizes and diverse types.

Claims

1. A method of employing electrostatic potential, comprising: injecting a sample into a first end of a sample transfer tubing, the sample being a liquid or a gas; applying a megavolt electrostatic potential to a second end of the sample transfer tubing via an electrical conducting material; ionizing, by the megavolt electrostatic potential, analyte molecules of the sample within the sample transfer tubing, wherein ions of the analyte molecules are electrically repelled from the sample transfer tubing at the second end of the sample transfer tubing; transferring the ions to an inlet of a mass spectrometer; and detecting the ions by the mass spectrometer.

2. The method of claim 1, wherein the megavolt electrostatic potential gradually accumulates on the sample.

3. The method of claim 1, further comprising preventing the sample from being electrically grounded.

4. The method of claim 1, a magnitude of the megavolt electrostatic potential being applied to the sample is tuneable.

5. The method of claim 1, wherein the sample is of biological origin.

6. The method of claim 1, wherein the sample is of non-living objects comprising different physical states, including gas and liquid.

7. The method of claim 1, wherein the method is compatible with the sample in variable size.

8. The method of claim 1, wherein the detecting the ions by the mass spectrometer is performed without the use of an assisting reagent, a laser desorption technique, or a combination thereof.

Description

BRIEF SUMMARY OF THE DRAWINGS

(1) The drawings illustrate the features and other objects of the current invention, namely Atmospheric Pressure Megavolt Electrostatic Field Ionization Desorption (APME-FID) technique. Components of the drawings are not necessarily to scale, certain dimensions may be exaggerated in particular for clear description.

(2) FIG. 1 is a schematic diagram of megavolt electrostatic charging of samples for ionization and desorption, and then detected by a mass spectrometer. The samples can include but not limited to human body, intact food or herbal samples, or pharmaceutical tablet.

(3) FIG. 2 is a schematic drawing depicting a configuration of the APME-FID interfacing device for the detection of liquid and gas samples. The liquid/gas samples can include but not limited to flammable solvents/human breath gas, respectively.

DETAILED DESCRIPTION

(4) The APME-FID technique employs a megavolt electrostatic potential to ionize analytes on samples. Sample is electrostatically-charged to a megavolt electrostatic potential. This technique enables the generation of ions directly from samples connected to a high electrostatic potential in the range from 10,000 V to megavolt conditions (greater than or equal to 100,000 V). The ions (e.g. molecular ions and/or fragment ions) generated by field ionization (or other mechanisms) on the sample surface are desorbed (e.g. by electrical repulsion) from the sample surface which possesses a high density of electrostatic charges, and then are directed to the inlet of a mass spectrometer for the detection, identification and quantitation.

(5) This technique allows the direct analysis of samples of all sizes (e.g., ranged from an adult human to drug powder) and types (e.g. solid, liquid and gas) by using a mass spectrometer. The technique enables a diversified range of mass spectrometry applications such as real-time chemical/biochemical analysis of volatile substances exhaled from large living organisms, quality monitoring of herbal plant samples, and forensic/security checking of illicit drugs and explosives on human skin, without extensive sample preparation procedures. This invention breaks the current restriction and limitation of mass spectrometric analysis, and will open a new path to widen the application areas of MS technology to different aspects of field testing, including but not limited to security checking, forensic analysis, metabolic profiling, and other daily life sample analysis.

(6) An aspect of the present invention employs a high electrostatic potential generated by a Van de Graaff generator or other similar electrostatic-charge generating devices, which enable gradual accumulation of high electrostatic potential on samples. The Van de Graaff electrostatic generator could generate either positive or negative charges at megavolt potential, for the field ionization of either or both positive and negative ions from the sample. In certain embodiments, the magnitude and polarity of the megavolt electrostatic potential can be varied before or during ionization. In certain embodiments, more than one megavolt electrostatic generator can be connected to the sample for ionization and desorption. In certain embodiments, the magnitude and polarity of the megavolt electrostatic potential can be controlled electronically.

(7) In certain embodiments, accumulation of megavolt electrostatic potential on a sample can be accomplished by direct contact of the sample to electrostatic generator (e.g. for analysis of human body/breath). In another embodiments, the sample is indirectly connected to the electrostatic generator via a sample container (e.g. a probe, a tubing, a holder, a plate, etc) made of conductive (or dielectric) materials, for the ionization of any solid, liquid or gas samples. In certain embodiments, the sample is transferred within an insulating sample container (e.g. a probe, a tubing, a holder, a plate, etc), where only a part of the insulating sample container is connected to the electrostatic generator for ionization and desorption of analytes in the sample container. In certain embodiments, a sample container is put in the vicinity of the electrostatic generator without electrical connection. In certain embodiments, an automatic sample transport and changing system can be coupled with the electrostatic generator.

(8) In certain embodiments, the sample is placed at the vicinity of the inlet of a mass spectrometer (or other ion detection/analysis devices) for ion collection. In certain embodiments, a transferring device (e.g. a capillary tube, etc) can be employed to transfer and/or guide ions and neutrals from the sample to the inlet of a mass spectrometer (or other ion detection/analysis devices).

(9) In certain embodiments, the sample is placed in a housing with pressure control. In certain embodiments, the sample is placed in a housing with variable atmosphere composition (e.g. humidity level control, nitrogen level control, oxygen level control etc). In certain embodiments, the sample is placed in a housing, in which reagents can be introduced in gaseous, vapor or liquid form.

(10) In certain embodiments, the sample to be analyzed can be in solid, liquid or gas states (or a mixture of these states). In certain embodiments, the sample could be in any physical shape (e.g. sharp, round, blunt, etc). In certain embodiments, the sample could have different physical sizes (e.g. adult human, luggage, pharmaceuticals, biological cells, etc). In certain embodiments, the sample could be commodities (e.g. crops, meat, vegetables, etc) and industrial products (e.g. pharmaceuticals, clothes, etc). In certain embodiments, the sample could be of biological origin (e.g. food, biological fluid, etc). In certain embodiments, the sample could be living biological samples (e.g. living human, living plants, living biological cells, etc). In certain embodiments, samples (e.g. blood, cytoplasm, fluids, etc) would be drawn from a living biological sample (e.g. living animal, plants, cell, etc) for real time chemical/biochemical monitoring. In certain embodiments, samples can be introduced from an instrument (e.g. a separating instrument).

(11) In certain embodiments, the sample could be analyzed in its original state. In certain embodiments, the sample can be analyzed at ambient temperature, or under temperature control. In certain embodiments, additional reagents (e.g. solvent, inert gas etc) could be used to enhance detection sensitivity (e.g. facilitate ion generation and/or ion collection, etc). In certain embodiments, reference reagents (e.g. gas, liquid, powder, solution, etc) could be analyzed together or sequentially with the sample as an internal standard for analytical performance check and quantitative measurement applications.

(12) In another aspect of the invention, ions desorbed or generated from the sample can be analyzed in multiple levels (e.g. chemically, spatially, etc). For example, ions can be characterized based on their mass, charge, cross-section area, mobility, velocity, momentum, etc), hence ion identity and location of desorption from a sample could be revealed.

(13) In another aspect of the invention, photo energy can be directed or focused onto a selected area of sample to assist the ionization and/or desorption of at least one type of analytes (or ions).

(14) In another aspect of the invention, the electrostatic potential could be applied at multiple stages, to assist or control the analyte being ionized. In certain embodiments, the electrostatic potential applied could assist the extraction of analytes from samples (e.g. disrupting biological membrane potential)

(15) In another aspect of the invention, a replaceable sample probe (e.g. a disposable tip or sorbent, etc) which contains the analytes (e.g. in form of purified analytes, sample extract or raw sample, etc) can be connected to the electrostatic generator (directly or via electrical connection) for ionization of analyte and subsequent ion detection by a mass spectrometer (or other detection devices). The use of replaceable sample probe allows combination of sampling, sample storage and chemical analysis to be performed together without further sample extraction. This would simplify analysis procedure and enhance the efficiency of the analysis workflow. In certain embodiments, materials of the sample probe can be changed (e.g. polyester, polyethylene, cellulose, bonded silica sorbent, etc) for extracting different types of analytes from samples. In certain embodiments, reagents (e.g., solvent, acids, base) are added to enhance the detection of certain analytes or suppress the inference effect of sample matrix. In certain embodiments, the sample probe would be replaced by an automatic device during analysis.

(16) The invention can be a method and system for ionization and desorption of molecules (analyte) at ambient pressure and temperature from a given sample at different physical states (e.g. solid, liquid, gas). The system includes an electrostatic generator 1 for generating and applying a megavolt electrostatic potential on the sample 2. The megavolt electrostatic generator 1 used in the experiments generate a potential in the range from +10,000 V to +1,000,000 V or wider in positive ion mode, and in the range from −10,000 V to −1,000,000 V or wider in negative ion mode. The system also includes electrical connecting device (e.g. sample holder) for directing the megavolt electrostatic potential on the sample 2. The sample 2 is electrostatically charged and analyte on sample 2 is ionized and desorbed by the megavolt electrostatic potential. The desorbed ions 4 are directed to any suitable detector, for example a mass spectrometer 5 for detection, identification and quantitation.

(17) FIG. 1 illustrates schematically one embodiment of a system for practicing the invention. In this system, a sample 2 is electrically connected to a megavolt electrostatic generator 1. The sample 2 is under ambient condition. A megavolt electrostatic potential is generated by the megavolt electrostatic generator 1, which can be a Van de Graaff electrostatic generator. The sample 2 is then electrostatically charged. For large-sized samples 2 such as an adult human, an insulating block 3 is used to prevent it from being electrically grounded. The insulation box 3 can be made of insulating materials such as wood or plastic. The accumulation of high electrostatic charge is essential for ionization of analyte on the sample. Alternatively, if small- and medium-sized sample are being analyzed, they are connected to the megavolt electrostatic generator 1 via an electrically conductive sample holder without touching the ground, and hence the insulation block 3 is not required. Although a Van der Graaff electrostatic generator is described here, any device capable of generating a megavolt electrostatic potential may be used for electrostatic charging of the sample.

(18) In positive ion mode, the megavolt electrostatic generator 1 generates a positive megavolt electrostatic potential. Hence a positive electrostatic potential is accumulated on the sample 2. Analytes on the surface of the sample 2 are ionized by electrostatic potential. Cations and radical cations 4 could be formed and desorbed from the sample surface due to electrical repulsion, as the surface of the sample 2 is positively-charged. The desorbed ions 4 could be transferred to the inlet of a mass spectrometer 5 for mass analysis and detection. The desorbed ions 4 are either collected by the inlet of mass spectrometer 5 directly, or transferred to the inlet of the mass spectrometer 5 with the assistance of an ion transferring device. Although the generation and detection of positive ions are described here, the invention can also be operated in negative ion mode for generation and detection of anions and radical anions. Briefly, a negative megavolt electrostatic potential is generated and applied to the sample, and negative ions are generated and detected using a mass spectrometer. The sample 2 can be a living organism at different sizes, for example an adult human, or some biological cells. The sample 2 can also be non-living materials, including but not limited to a slice of herbal plant tissue, fine chemical powders, a pharmaceutical tablet, flammable solvent absorbed in clothes, or explosives placed on the table (such as pharmaceutical tablet in solid phase, flammable solvent in liquid phase, and human breath in gas phase).

(19) FIG. 2 illustrates schematically another embodiment of a system for practicing the current invention. In this system, an insulating sample transfer tubing 6 is connected to the electrostatic generator 1 via electrical conducting materials 8. The choice of electrical conducting materials 8 includes but not limited to metals or electrical conducting plastic. Gas or liquid sample 7 is injected from another end of the tubing 6. A megavolt electrostatic potential is generated by the megavolt electrostatic generator 1, which can be a Van de Graaff electrostatic generator. Analyte molecules in the samples 7 is ionized and desorbed by the megavolt electrostatic potential from the other end of the tubing 6. The tubing 6 is made of insulating material, including but not limited to wood, plastic and glass.

(20) In positive ion mode, the megavolt electrostatic generator 1 generates a positive electrostatic potential which is applied to the sample transfer tubing 6. Cations and radical cations 4 could be formed and desorbed from the sample transfer tubing 6 due to electrical repulsion, as the tubing 6 is positively-charged. The stream of ions 4 is directed to the mass spectrometer 5 for mass analysis and detection, by pointing the exit of tubing 6 towards the inlet of the mass spectrometer 5. Although the generation and detection of positive ions are described here, the invention can also be operated in negative ion mode for the generation and detection of anions and radical anions. The samples 7 can be in either gaseous or liquid states. Gas samples may include but not limited to human breath gas, air pollutant samples, or samples output from gas chromatographic instrument or likewise; while liquid samples may include but not limited to water samples, drink samples, or samples eluted from liquid chromatographic instrument or likewise.

(21) The examples illustrate the subject invention. Unless otherwise indicated in the following examples and elsewhere in the specification and claims, all parts and percentages are by weight, all temperatures are in degrees Centigrade, and pressure is at or near atmospheric pressure.

(22) With respect to any figure or numerical range for a given characteristic, a figure or a parameter from one range may be combined with another figure or a parameter from a different range for the same characteristic to generate a numerical range.

(23) Other than in the operating examples, or where otherwise indicated, all numbers, values and/or expressions referring to quantities of ingredients, reaction conditions, etc., used in the specification and claims are to be understood as modified in all instances by the term “about.”

(24) While the invention has been explained in relation to certain embodiments, it is to be understood that various modifications thereof will become apparent to those skilled in the art upon reading the specification. Therefore, it is to be understood that the invention disclosed herein is intended to cover such modifications as fall within the scope of the appended claims.