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WO2025075952A1 - Appareil et procédé de chauffage contrôlable de particules chargées nébulisées - Google Patents

Appareil et procédé de chauffage contrôlable de particules chargées nébulisées Download PDF

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Publication number
WO2025075952A1
WO2025075952A1 PCT/US2024/049386 US2024049386W WO2025075952A1 WO 2025075952 A1 WO2025075952 A1 WO 2025075952A1 US 2024049386 W US2024049386 W US 2024049386W WO 2025075952 A1 WO2025075952 A1 WO 2025075952A1
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WIPO (PCT)
Prior art keywords
electric field
nebulized
charged particles
time
charged particle
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2024/049386
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English (en)
Inventor
David E. Clemmer
Stephen J. Valentine
Peng Li
Mathew Johnson
Daud SHARIF
Anthony DEBASTIANI
Vikum DEWSURENDRA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
West Virginia University
Indiana University
Indiana University Bloomington
Original Assignee
West Virginia University
Indiana University
Indiana University Bloomington
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Application filed by West Virginia University, Indiana University, Indiana University Bloomington filed Critical West Virginia University
Publication of WO2025075952A1 publication Critical patent/WO2025075952A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/02—Investigating particle size or size distribution
    • G01N15/0266—Investigating particle size or size distribution with electrical classification
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B17/00—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups
    • B05B17/04—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods
    • B05B17/06—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations
    • B05B17/0607—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B5/00—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means
    • B05B5/007—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means the high voltage supplied to an electrostatic spraying apparatus during spraying operation being periodical or in time, e.g. sinusoidal
    • B05B5/008—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means the high voltage supplied to an electrostatic spraying apparatus during spraying operation being periodical or in time, e.g. sinusoidal with periodical change of polarity
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/06—Investigating concentration of particle suspensions
    • G01N15/0656—Investigating concentration of particle suspensions using electric, e.g. electrostatic methods or magnetic methods
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B17/00—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups
    • B05B17/04—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods
    • B05B17/06—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations
    • B05B17/0607—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers
    • B05B17/0653—Details
    • B05B17/0669—Excitation frequencies
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B17/00—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups
    • B05B17/04—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods
    • B05B17/06—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations
    • B05B17/0607—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers
    • B05B17/0653—Details
    • B05B17/0676—Feeding means

Definitions

  • the present disclosure relates generally to processing nebulized charged particles prior to charged particle analysis, and more specifically to processing such nebulized charged particles in a manner which controllably heats the nebulized charged particles prior to, or during, analysis by at least one charged particle analysis instrument.
  • Generation of charged particles from a sample solution is a conventional charged particle generation technique in which the sample solution is nebulized in a manner which produces charged particle droplets.
  • the charged particle droplets typically expelled in the form of a plume, may then be fed into a charged particle analysis instrument or system for analysis by at least one charged particle analysis device or instrument.
  • a method for controllably heating nebulized charged particles may comprise configuring a time-varying electric field to heat the nebulized charged particles passing therethrough with a target degree of heating; and passing the nebulized charged particles through the configured time-varying electric field to heat the nebulized charged particles with the target degree of heating.
  • a second aspect includes the features of the first aspect, and wherein configuring the time-varying electric field may comprise selecting at least one electrical parameter of the time-varying electric field which will achieve the target degree of heating of the nebulized charged particles.
  • a third aspect includes the features of the second aspect, and wherein the at least one electrical parameter of the time-varying electric field may comprise one or any combination of frequency, shape, duty cycle, and peak amplitude of the time-varying electric field.
  • a fourth aspect includes the features of any of the first aspect through the third aspect, and may further comprise establishing the configured time-varying electric field within and along an electric field region.
  • a fifth aspect includes the features of the fourth aspect, and wherein configuring the time-varying electric field may comprise selecting a length of the electric field region which will achieve the target degree of heating of the nebulized charged particles.
  • a sixth aspect includes the features of the fourth aspect, and wherein the nebulized charged particles may have a flow rate with which the nebulized charged particles pass through the configured time-varying electric field, and wherein configuring the time-varying electric field may comprise selecting either or both of the at least one electrical parameter and the length of the electric field region which will achieve the target degree of heating of the nebulized charged particles taking into account the flow rate of the nebulized charged particles through the configured timevarying electric field.
  • An eighth aspect includes the features of any of the first aspect through the seventh aspect, and wherein the target degree of heating may comprise complete evaporation of the nebulized charged particles exiting the configured timevarying electric field.
  • a tenth aspect includes the features of any of the first aspect through the seventh aspect, and wherein the nebulized charged particles may carry at least one protein, and wherein the target degree of heating may comprise at least partial unfolding of the at least one protein.
  • a method of analyzing charged particles may comprise generating nebulized charged particles; passing the generated nebulized charged particles into a pressure-controlled charged particle analysis instrument; within the pressure-controlled charged particle analysis instrument, passing the generated nebulized charged particles through the configured time-varying electric field of any of the first aspect through the tenth aspect to heat the generated nebulized charged particles with the target degree of heating; and within the pressure-controlled charged particle analysis instrument, analyzing at least one molecular characteristic of the generated nebulized charged particles exiting the configured time-varying electric field.
  • a method of analyzing charged particles may comprise generating nebulized charged particles; passing the generated nebulized charged particles into a pressure-controlled charged particle analysis instrument; within the pressure-controlled charged particle analysis instrument, analyzing or processing the generated nebulized charged particles according to a first molecular characteristic; within the pressure-controlled charged particle analysis instrument, passing the nebulized charged particles, analyzed or processed according to the first molecular characteristic, through the configured time-varying electric field of any of the first aspect through the tenth aspect to heat the generated nebulized charged particles with the target degree of heating; and within the pressure-controlled charged particle analysis instrument, analyzing the generated nebulized charged particles exiting the configured time-varying electric field according to the first or a second molecular characteristic.
  • an apparatus for controllably heating nebulized charged particles may comprise an electric field region configured to receive the nebulized charged particles therethrough; and means for establishing a time-varying electric field within the electric field region such that the nebulized charged particles pass through the time-varying electric field, the time-varying electric field configured to heat the nebulized charged particles passing therethrough with a target degree of heating.
  • a fifteenth aspect includes the features of the fourteenth aspect, and wherein the time-varying electric field may be configured to heat the nebulized charged particles passing therethrough with the target degree of heating by configuring at least one electrical parameter of the time-varying electric field in a manner which will achieve the target degree of heating of the nebulized charged particles, and wherein the at least one electrical parameter may comprise one or any combination of frequency, shape, duty cycle, and peak amplitude of the time-varying electric field.
  • a seventeenth aspect includes the features of any of the fourteenth aspect through the sixteenth aspect, and wherein the nebulized charged particles may have a flow rate with which the nebulized charged particles pass through the electric field region, and wherein the time-varying electric field may be configured to heat the nebulized charged particles passing therethrough with the target degree of heating by configuring either or both of the at least one electrical parameter and the length of the electric field region which will achieve the target degree of heating of the nebulized charged particles taking into account the flow rate of the nebulized charged particles through the electric field region.
  • An eighteenth aspect includes the features of any of the fourteenth aspect through the seventeenth aspect, and wherein the time-varying electric field may be configured to heat the nebulized charged particles passing therethrough with the target degree of heating by configuring the time-varying electric field in a manner which controls at least one of peak heating temperature, heating rate, and total heating time of the nebulized charged particles passing through the electric field region.
  • a nineteenth aspect includes the features of any of the fourteenth aspect through the eighteenth aspect, and wherein the time-varying electric field may be configured to heat the nebulized charged particles passing therethrough with the target degree of heating by heating the nebulized charged particles to complete evaporation.
  • a twenty-first aspect includes the features of any of the fourteenth aspect through the eighteenth aspect, and wherein the nebulized charged particles may carry at least one protein, and wherein the time-varying electric field may be configured to heat the nebulized charged particles passing therethrough with the target degree of heating by heating the nebulized charged particles in a manner which results in at least partial unfolding of the at least one protein.
  • a twenty-second aspect includes the features of any of the fourteenth aspect through the twenty-first aspect, and wherein the means for establishing the time-varying electric field within the electric field region may further comprise means for generating the nebulized charged particles.
  • a twenty-third aspect includes the features of the twenty-second aspect, and wherein the means for establishing the time-varying electric field within the electric field region may comprise: a rigid substrate; a capillary having one end fluidly coupled to a sample solution and an opposite end forming an emitter with an emitter tip defining an orifice therein, a portion of the emitter being affixed to the rigid substrate; a transducer coupled to the rigid substrate; a waveform generator electrically coupled to the transducer and configured to produce time-varying waveforms, the transducer responsive to the time-varying waveforms to vibrate the rigid substrate to cause the emitter tip to oscillate; a pump configured to pump the sample solution through the capillary so as to exit the orifice of the oscillating emit
  • a twenty-fourth aspect includes the features of any of the fourteenth aspect through the twenty-first aspect, and wherein the means for establishing the time-varying electric field within the electric field region may comprise: first and second conductive sheets or plates spaced apart from one another to define the electric field region therebetween; and at least one voltage source configured to apply a time-varying voltage to and between the first and second sheets or plates to establish the time-varying electric field between the first and second sheets or plates.
  • FIG. 1 is a simplified diagram of an embodiment of a system for analyzing nebulized charged particles including an apparatus for controllably heating the nebulized charged particles prior to charged particle analysis;
  • Fig. 4 is a plot of electric field vs. time illustrating an example timevarying electric field generated in a region of the nebulized charged particles by the vibrating capillary emitter of the apparatus of Fig. 2;
  • Fig. 5 is a plot of charge state vs. applied DC voltage for an example solution sample containing Ubiquitin using the system of Fig. 2;
  • Fig. 7 is a plot of relative abundance vs. mass-to-charge ratio of Ubiquitin using the system of Fig. 2 and operated with an applied DC voltage of 350 volts which corresponds to VDC2 in the plot of Fig. 5;
  • Fig. 8 is a plot of relative abundance vs. mass-to-charge ratio of Ubiquitin using the system of Fig. 2 and operated with an applied DC voltage of 600 volts which corresponds to VDCS in the plot of Fig. 5;
  • Fig. 9 is a plot of relative abundance vs. mass-to-charge ratio of Ubiquitin using the system of Fig. 2 and operated with an applied DC voltage of 1000 volts which corresponds to VDC4 in the plot of Fig. 5;
  • Fig. 10 is a simplified diagram of another embodiment of the system of Fig. 1 including another embodiment of an apparatus for controllably heating the nebulized charged particles prior to charged particle analysis;
  • capillary vibrating sharp-edge spray ionization or “CVSSI” means and refers to a conventional field-free (i.e., voltage- free) ionization technique which generates a droplet stream from a liquid sample supplied to a capillary coupled to the sharp edge of a surface that is mechanically vibrated. This technique provides for nebulization of the liquid sample infused directly through the capillary without the use of a nebulization gas or application of an electric field.
  • FE-CVSSI field-enabled capillary vibrating sharp-edge spray ionization
  • FE-CVSSI field-enabled capillary vibrating sharp-edge spray ionization
  • Conventional FE-CVSSI is generally understood to be comparable to conventional electrospray ionization (ESI) in terms of makeup and charge state distributions of the generated analyte ions.
  • ESI electrospray ionization
  • the charged particle source 12 may illustratively be conventional, examples of which may include, but are not limited to, one or any combination of an electrospray ionization (ESI) source, a surface acoustic wave nebulization source, a mechanospray ionization source, a CVSSI source, an FE-CVSSI source, and any conventional ultrasonic nebulization source.
  • ESI electrospray ionization
  • CVSSI source chemical spray ionization
  • FE-CVSSI source any conventional ultrasonic nebulization source.
  • operation of the charged particle source 12 is controlled by a voltage source 16 configured to produce one or more time-varying, i.e., AC, output voltage(s) and, in some embodiments, one or more constant, i.e., DC, output voltage(s).
  • the voltage source 16 is electrically coupled to the charged particle source 12 via a number, J, of signal paths, where J may be any positive integer.
  • the voltage source 16 is illustratively operable to control operation of the charged particle source 12 by producing one or more DC and/or one or more AC voltages on one or more of the J signal paths.
  • the voltage source 16 may, in some embodiments, be a single voltage source, although in alternate embodiments the voltage source 16 may be provided in the form of multiple voltage sources each configured to produce one or more AC voltages and, in some embodiments, one or more DC voltages.
  • the charged particle analysis instrument or system 20, in embodiments which include it, may be or include one or a combination of any conventional charge particle analysis instrument(s), examples of which may include, but are not limited to, one or any combination of conventional instruments for separating charged particles as a function of one or more molecular characteristic such as, but not limited to, mass-to-charge ratio, e.g., one or more conventional mass spectrometers, mass-to-charge ratio and charge, e.g., one or more conventional charge detection mass spectrometers, mobility, e.g., one or more conventional ion mobility spectrometers, retention time, or the like.
  • mass-to-charge ratio e.g., one or more conventional mass spectrometers, mass-to-charge ratio and charge
  • mobility e.g., one or more conventional ion mobility spectrometers, retention time, or the like.
  • any such charged particle analysis instrument(s), if included, may illustratively include one or more conventional instruments for processing charged particles, examples of which may include, but are not limited to, one or any combination of at least one instrument for collecting or storing charged particles, e.g., one or more conventional ion traps, at least one instrument for guiding or transporting charged particles, e.g., one or more conventional, RF-only multi-pole instruments, at least one instrument for filtering charged particles according to a molecular characteristic, e.g., one or more conventional multi-pole instruments configured to filter charged particles according to a specified range of mass-to- charge ratio, at least one instrument for dissociating ions, e.g., one or more conventional charged particle fragmentation instruments or devices, and at least one instrument for normalizing or shifting ion charge states.
  • at least one instrument for collecting or storing charged particles e.g., one or more conventional ion traps
  • at least one instrument for guiding or transporting charged particles e.g., one or
  • the voltage source 16 may be configured to produce one or more AC voltages and, in some embodiments, one or more DC voltages, for controlling operation of the charged particle analysis instrument or system 20, although in alternate embodiments at least one operating feature of the charged particle analysis instrument or system 20 may be controlled by a separate voltage source configured to produce one or more AC voltages and, in some embodiments, one or more DC voltages (e.g., in the form of a single voltage source configured to produce the voltage(s), or in the form of multiple voltage sources each configured to produce the voltage(s)).
  • a separate voltage source configured to produce one or more AC voltages and, in some embodiments, one or more DC voltages (e.g., in the form of a single voltage source configured to produce the voltage(s), or in the form of multiple voltage sources each configured to produce the voltage(s)).
  • FIG. 10 A non-limiting example of the electric field generation device 28 is depicted in Fig. 10, and will be described in detail below.
  • Operation of the charged particle source 12 and/or operation of the voltage source 16 may illustratively be controlled by at least one conventional processor 30.
  • one or more memory devices 32 illustratively has/have stored therein instructions which are executable by the processor(s) 30 to cause the processor(s) 30 to control operation of the charged particle source 12 and/or operation of the voltage source 16.
  • the charged particle source 12 may include a pump operable to draw the sample solution from a container, and in such embodiments the memory device(s) 32 may include instructions executable by the processor(s) 30 to control such a pump, and/or other device associated with the operation of the charged particle source 12, in a conventional manner.
  • any such pump and/or other device may be manually controllable or may be configured to be manually programmed for operation.
  • the memory device(s) 32 may include instructions executable by the processor(s) 30 to control operation of the voltage source 16 to control the frequency, shape, duty cycle, and/or amplitude of one or more AC voltage signals produced thereby and, in some embodiments, to control the amplitude and/or polarity of one or more DC voltage signals produced thereby, and in such embodiments control outputs of the processor(s) 32 is/are electrically connected to one or more control inputs of the voltage source 16 via any number, L, of signal paths, where L may be any positive integer.
  • the voltage source 16 may be manually controllable or programmable to produce one or more AC voltages with selected frequency, shape, duty cycle, and/or amplitude and, in some embodiments, to produce one or more DC voltages with selected amplitude and/or polarity.
  • the at least one processor 30 may be any conventional circuit or circuits configured to execute instructions stored in the memory device(s) 32, examples of which may include, but are not limited to, one or more conventional microprocessors, one or more microcontrollers, or the like.
  • the at least one memory device 32 may likewise be any conventional memory circuit or circuits configured to store instructions therein for execution by the processor(s) 30.
  • the processor(s) 30 and/or the memory device(s) 32 may take the form of analog circuitry designed to carry out the tasks described herein.
  • the time-varying electric field 26 established in the electric field region 25, between the charged particle outlet 14 of the charged particle source 12 and the charged particle inlet 18 of the charged particle analysis instrument or system 20, is configured in a manner which controllably heats the charged particle droplets generated by the charged particle source 12 prior to entrance into the charged particle analysis instrument or system 20 via the charged particle inlet 18.
  • the time-varying electric field may be established within the charged particle analysis instrument or system 20, and in such embodiments will operate to controllably heat charged particle droplets within the charged particle analysis instrument or system 20.
  • controllably heat means to control a degree, i.e., amount, level, or extent, of heating of nebulized charged particles, i.e., charged particle droplets, in terms of one or more heating parameters including, for example, but not limited to, one or any combination of peak heating temperature, heating rate, and total heating time, so as to achieve a target degree of heating of the nebulized charged particle droplets.
  • Such one or more charged particle droplet heating parameters will generally be dependent upon a number of different selectable parameters of the system 10 including, for example, but not limited to, one or more electrical parameters of the time-varying electric field 26 such as the frequency, shape, duty cycle, and peak amplitude of the time-varying electric field 26, one or more physical parameters of the system 10, such as the length of the electric field region 25 in which the charged particle droplets are exposed to the time-varying electric field 26, e.g., the distance D1 , and one or more temporal parameters of the system 10, such as the time spent by the charged particle droplets moving through the electric field region 25, i.e.
  • one or more electrical parameters of the time-varying electric field 26 such as the frequency, shape, duty cycle, and peak amplitude of the time-varying electric field 26
  • one or more physical parameters of the system 10 such as the length of the electric field region 25 in which the charged particle droplets are exposed to the time-varying electric field 26, e.g., the distance D1
  • temporal parameters of the system 10 such as the time
  • nebulized charged particles i.e., charged particle droplets
  • the time-varying electric field 26 is selected one or more of the electrical parameters of the time-varying electric field 26, one or more of the physical parameters of the system 10, and/or one or more of the temporal parameters of the system 10 so as to achieve a target degree of heating of the nebulized charged particles.
  • one or more of the electrical, physical, and/or temporal parameters will be selected so as to cause nebulized charged particles passing through the resulting electric field region 25 with the resulting time-varying electric field 26 established therein to be heated but not completely evaporated.
  • the charged particle source 12 includes a container 40 containing the sample solution 42 therein.
  • the container 40 may be any type of container configured to carry the sample solution 42.
  • a pump 45 is included to pump the sample solution 42 out of the container 40.
  • the container 40 is depicted in the form of a syringe.
  • the syringe 40 may include a pump, and in other embodiments the system 10’ includes the pump 45 separate from the syringe 40 to pump the sample solution 42 from the syringe 40.
  • the pump 45 (or syringe pump) may illustratively be programmable or controllable by the processor 30 to pump out the sample solution 42 at a selected flow rate.
  • One example flow rate which should not be considered limiting in any way, is 1-2 micro-liters per minute (pL/min).
  • the container 40 illustratively includes an outlet fluidly coupled to one end 46A of a capillary 44, as shown in Fig. 2.
  • a portion of the capillary 44 adjacent to an opposite end 46B of the capillary 44 than the end 46A defines an emitter 46 having an emitter tip with an orifice at the end 46B that defines a charged particle outlet orifice 14 of the charged particle source 12.
  • the capillary 44 has an outer diameter of 360 micro-meters (pm), and an inner diameter of 100 pm, and the emitter 46 is illustratively pulled using a conventional P20000 micropipette puller to obtain an emitter tip 46B with a charged particle outlet orifice 14 of approximately I Q- 20 pm.
  • a substantially rigid glass slide or glass side coverslip 48 is provided, and the emitter 46 of the capillary 44 is affixed to a top surface 48A of the glass slide 48 adjacent to one edge 48B of the glass slide 48, although in alternate embodiments the emitter 46 may be affixed to the bottom surface of the glass slide 48 opposite the top surface 48A.
  • the emitter 46 is affixed to the glass slide 48 using a conventional adhesive 50 and/or other conventional bonding medium or material.
  • a conventional piezoelectric transducer 52 is also affixed via an adhesive or other bonding medium or material 54 to the top surface 48A of the glass slide 48 adjacent to an opposite edge 48C of the glass slide 48, although in alternate embodiments the transducer 52 may be affixed to the glass slide 48 anywhere along the top surface 48A or the bottom surface of the glass slide 48.
  • a single piezoelectric transducer 52 is affixed to the glass slide 48, although in alternate embodiments two or more piezoelectric transducers may be affixed to the glass slide 48.
  • the voltage source 16 is illustratively provided in the form of a conventional amplifier 56, a conventional waveform generator 60, and a conventional DC power supply 64.
  • a signal output of the amplifier 56 is electrically connected, via wires 58, to a signal input of the transducer 52, and a signal input of the amplifier 56 is electrically connected to a signal output of the waveform generator 60 via wires 62.
  • the waveform generator 60 is illustratively operable to produce waveforms in the radio frequency (RF) range, although the waveform generator 60 may in alternate embodiments be configured to produce waveforms outside of the RF range.
  • RF radio frequency
  • the mechanical vibrations of the emitter 46 nebulize the sample solution 42 near the emitter tip 46B (e.g., provided thereto via operation of the pump 45 or other pump carried by the container 40) to produce a spray or plume 70 of analyte ions via the charged particle outlet orifice 14 of the emitter 46.
  • the waveform generator 60 and amplifier 56 may be configured such that the emitter 46 of the capillary 44 produces plumes 70 of charged particle droplets from the sample solution 42 in a frequency range outside of 90-100 kHz and/or with waveform amplitudes outside of the 5-12 Vp-p range.
  • the FE-CVSSI system 10’ further includes the DC power supply 64 configured to produce a DC output voltage VDC.
  • the DC voltage output of the power supply 64 is electrically connected to a wire 66, e.g. a platinum wire, which is affixed to the outer surface of the capillary 44 or to the outer surface of the emitter 46, e.g., via a conventional adhesive or other bonding medium or material.
  • the DC power supply 64 is turned off so that no DC electric field is applied to the sample solution 42 moving through the capillary 44 and the emitter 46.
  • the DC power supply 64 is set or controlled to produce a DC voltage, VDC, to induce a corresponding electric field in the capillary 44 and/or the emitter 46.
  • VDC DC voltage
  • the magnitude of VDC will be a positive value so as to orient the electric field to direct positively charged ions out of the charged particle outlet orifice 14 of the emitter 46
  • the magnitude of VDC will be negative so as to orient the electric field to direct negatively charged ions out of the charged particle outlet orifice 14 of the emitter 46.
  • the position “C” of the emitter tip 46B similarly represents the position of the emitter tip 46B to which the emitter tip 46B, and thus the charged particle outlet orifice 14 of the emitter 46, are moved by the vibrations induced in the glass slide 48 at the negative peak of the AC (e.g., RF) waveform generated by the waveform generator 60.
  • the emitter tip 46B, and thus the charged particle outlet orifice 14 of the emitter 46 oscillate between the two positions “B” and “C.”
  • an example AC (e.g., RF) electric field 26’ induced in the electric field region 25 of Fig. 3 between the charged particle outlet orifice 14 of the emitter 46 and the charged particle inlet 18 of the charged particle analysis instrument or system 20 is shown.
  • the time-varying electric field 26’ illustratively results from the combination of the oscillating movement of the emitter tip 46B, and thus of the charged particle outlet 14 of the emitter 46, illustrated in Fig. 3 and just described, and the DC voltage, VDC, produced by the DC power supply 64 of Fig. 2.
  • a peak positive electric field of approximately 700 V/cm occurs at the position “B” of the emitter tip 46B depicted in Fig. 3
  • a peak negative electric field of approximately -1300 V/cm occurs at the position “C” of the emitter tip 46B depicted in Fig. 3.
  • the processor 30 may control operation of one or more of the amplifier 56, the waveform generator 60, the pump 45 (or pump carried by the container 40), and the DC power supply 64.
  • control outputs of the processor(s) 30 is/are electrically connected to one or more control inputs of the amplifier 56 via any number, M, of signal paths, where M may be any positive integer.
  • control outputs of the processor(s) 30 is/are electrically connected to one or more control inputs of the waveform generator 60 via any number, N, of signal paths, where N may be any positive integer.
  • one or more of the amplifier 56, the waveform generator 60, the pump 45, and the DC power supply 64 may be manually controllable or programmable, and in such embodiments, the role of the processor(s) 30 and memory device(s) 32 may be correspondingly reduced or omitted altogether.
  • the time-varying electric field 26' established in the electric field region 25 between the charged particle outlet 14 of the emitter tip 46B and the charged particle inlet 18 of the charged particle analysis instrument or system 20 is illustratively established so as to controllably heat the charged particle droplets in the spray or plume 70 of charged particle droplets.
  • the amount or degree of such controlled heating of the charged particle droplets in the plume 70 of charged particle droplets will generally be a function of one or more electrical parameters of the time-varying electric field 26’, one or more physical parameters of the system 10’, and/or one or more temporal parameters of the system 10’.
  • the time-varying electric field 26’ one or more physical parameters of the system 10’
  • the temporal parameters of the system 10’ one or more temporal parameters of the system 10’.
  • the frequency, shape, duty cycle, and peak-to-peak voltage applied to the transducer 52 to induce vibrations in the glass slide 48 are illustratively held constant, e.g., by controlling the waveform generator 60 to produce sinusoidal, 50% duty cycle, approximately 10 volts peak-to-peak RF waveforms of approximately 100 kHz, and the length D1 of the electric field region 25 is approximately 3 millimeters.
  • the flow rate of the charged particle droplets in the plume 70 of charged particle droplets passing through the time-varying electric field 26’ will generally be a function of the flow rate of the plume 70 exiting the charged particle outlet 14 of the emitter tip 46B and the pressure differential between the ambient pressure about the emitter tip 46B, e.g., atmospheric pressure, and the vacuum conditions in the region 22 of the charged particle analysis instrument or system 20 established by the pump 24.
  • FIG. 10 another embodiment is shown of the system 10 of Fig. 1 provided in the form of a system 10” including another embodiment of an electric field generation device 28 for controllably heating the nebulized charged particles prior to charged particle analysis.
  • the system 10 is identical in many respects to the system 10 illustrated in Fig. 1 and described above, and like numbers are therefore used to identify like components.
  • the charged particle source 12, for example, may be or include any of the charged particle sources described above with respect to Figs.
  • the charged particle analysis instrument or system 20 may be or include any one or combination of instruments and/or devices as described above.
  • the time-varying electric field generation device 28 is provided in the form of opposed, electrically conductive sheets or plates 82 and 84 spaced apart from one another to form the electric field region 25 therebetween.
  • the voltage source 16’ is illustratively configured to produce an AC voltage, AC, as described above with respect to Figs. 1 -9, which is applied to and between the plates 82, 84 to establish the time-varying electric field 26 within the electric field region 25 as also described above.
  • the plates 82, 84 are positioned symmetrically about the central axis 18A which bisects the charged particle inlet 18 of the charged particle analysis instrument or system 20, although in alternate embodiments the plates 82, 84 may not be so symmetrically positioned.
  • the distance D1 is depicted consistently with Fig. 1 as the distance between the charged particle outlet 14 of the charged particle source 12 and the charged particle inlet 18 of the charged particle analysis instrument or system 20.
  • the length of the electric field region 25 defined by the plates 82, 84 is defined by the respective lengths D2 of the plates 82, 84.
  • D2 is less than D1 (D2 ⁇ D1), and in such embodiments the difference between D1 and D2 (D1 - D2) or the ratio of D1 to D2 (D1/D2) may be another physical parameter of the system 10” having a bearing on the amount or degree of heating of the charged particle droplets traveling between the charged particle outlet 14 of the charged particle source 12 and the charged particle inlet 18 of the charged particle analysis instrument or system 20.
  • D2 may be equal to D1 as illustrated by example in Fig. 1.
  • the distance D3 between the plates 82, 84 may be yet another physical parameter of the system 10” which may have a bearing on the amount or degree of heating of the charged particle droplets traveling between the charged particle outlet 14 of the charged particle source 12 and the charged particle inlet 18 of the charged particle analysis instrument or system 20.
  • the plates 82, 84 may be planar, e.g., flat, such that the inwardly-facing surfaces of the plates 82, 84 are parallel with one another. In some alternate embodiments, either or both of the plates 82, 84 may be non-planar.
  • an electrically conductive gate or grid 86 may be positioned between the electric field region 25 and the charged particle outlet 14 of the charged particle source 12, e.g., adjacent to and vertically between the respective ends of the plates 82, 84, and a DC voltage outlet DC1 of the voltage source 16’ may be electrically connected to the gate or grid 86 as depicted in dashed-line representation in Fig. 10.
  • the DC voltage DC1 may be controlled to selectively allow charged particle droplets in the plume 80 of charged particle droplets to enter the electric field region 25, and to selectively reject or prevent charged particle droplets in the plume 80 of charged particle droplets from entering the electric field region 25.
  • the DC voltage DC2 may be controlled to selectively allow charged particle droplets moving through the electric field region 25 to exit the electric field region 25 and enter the charged particle inlet 18 of the charged particle analysis instrument or system 20, and to selectively reject or prevent charged particle droplets moving through the electric field region 25 from exiting the electric field region 25 so that such charged particle droplets do not enter the charged particle inlet 18 of the charged particle analysis instrument or system 20.
  • the DC voltages DC1 and DC2 may be controlled to selectively establish an electric field within the electric field region 25, e.g., in the direction 27 for positively charged particle droplets as illustrated by dashed-line representation in Fig. 10, or in the opposite direction for negatively charged particle droplets.
  • the charged particle source 12 and the time-varying electric field generation device 28 are both subject to the same pressure conditions, e.g., atmospheric pressure in the embodiment illustrated in Fig.
  • one or more of the electrical parameters of the time-varying electric field 26, one or more of the physical parameters of the system 10”, and/or one or more of the temporal parameters of the system 10” may be selected and/or controlled as described above so as to controllably heat the charged particle droplets in the spray or plume 80 of charged particle droplets exiting the charged particle outlet 14 of the charged particle source 12 to a target degree of heating of the nebulized charged particles, as described above.
  • the amount or degree of such controlled heating of the charged particle droplets in the plume 80 of charged particle droplets exiting the charged particle outlet 14 of the charged particle source 12 and entering the charged particle inlet 18 of the charged particle analysis instrument or system 20 will generally be a function of such physical, electrical, and temporal parameters, as also described above.
  • the one or more electrical parameters of the time-varying electric field 26 may be any one of more such parameters described above.
  • the one or more physical parameters of the system 10 may be or include, but are not limited to, any one or more of the distances or lengths D1 , D2, D3, one or more ratios of any combination of D1 , D2, D3, and the positioning of the time-varying electric field generation device 28 within the space D1 (e.g., the length of the gap between the charged particle outlet 14 of the charged particle source 12 and the charged particle inlet of the electric field generation device 28, and the length of the gap between the charged particle outlet of the electric field generation device 28 and the charged particle inlet 18 of the charged particle analysis instrument or system 20).
  • the one or more temporal parameters of the system 10 may illustratively be or include, but are not limited to, the time spent by the charged particle droplets moving through the time-varying electric field 26, the time spent by the charged particle droplets moving through one or more portions of the region of D1 not occupied by the time-varying electric field generation device 28, and/or the time spent by the charged particle droplets moving through the entire region D1 between the charged particle outlet 14 of the charged particle source 12 and the charged particle inlet of the charged particle analysis instrument or system 20.
  • the flow rate of charged particle droplets between the charged particle outlet 14 of the charged particle source 12 and the charged particle inlet 18 of the charged particle analysis instrument or system 20 may depend on a number of different factors relating to the particular configuration of the system 10”.
  • D1 D2
  • the flow rate of charged particle droplets between the charged particle source 12 and the charged particle analysis instrument or system 20 will be defined by the flow rate of charged particle droplets through the electric field region 25 defined by the time-varying electric field generation device 28.
  • the flow rate of charged particle droplets through the electric field region 25 will further depend on the magnitude and direction of the DC electric field 27 established between the gates or grids 86, 88.
  • the flow rate of charged particle droplets between the charged particle source 12 and the charged particle analysis instrument or system 20 will generally be defined by a combination of (i) the flow rate of charged particle droplets through the region of D1 between the charged particle outlet 14 of the charged particle source and the inlet or entrance to the electric field region 25 of the time-varying electric field generation device 28 (FR1), (ii) the flow rate of charged particle droplets through the electric field region 25 (FR2), and (iii) the flow rate of charged particle droplets through the region of D1 between the outlet of the electric field region 25 of the time-varying electric field generation device 28 and the charged particle inlet 18 of the charged particle analysis instrument or system 20 (FR3).
  • the target degree of heating of the charged particle droplets may further take into account potential cooling of the charged particle droplets over the portion of D1 between the outlet of the time-varying electric field generation device 28 and the charged particle inlet 18 of the charged particle analysis instrument or system 20.
  • FR1 will typically depend at least on the flow rate of charged particles exiting the charged particle outlet 14 of the charged particle source 12 and the distance between the charged particle outlet 14 of the charged particle source 12 and the inlet or entrance to the electric field region 25 of the time-varying electric field generation device 28.
  • FR3 will typically depend at least on the flow rate of charged particles exiting the electric field region 25 of the time-varying electric field generation device 28, the distance between the outlet of the time-varying electric field generation device 28 and the charged particle inlet 18 of the charged particle analysis instrument or system 20, and the pressure differential between the pressure of the portion of D1 between the outlet of the time-varying electric field generation device 28 and the charged particle inlet 18 of the charged particle analysis instrument or system 20 and the pressure established in the region 22 of the charged particle analysis instrument or system 20 established by the pump 24.
  • FR2 will depend primarily on the flow rate of charged particles exiting the charged particle outlet 14 of the charged particle source 12, the distance between the charged particle outlet 14 and the entrance to the time-varying electric field generation device 28, the length D2 of the electric field region 25 defined by and within the time-varying electric field generation device 28, and the effect, if any, on the pressure differential between the electric field region 25 and the region 22 of the charged particle analysis instrument or system 20 over the distance between the outlet of the time-varying electric field generation device 28 and the charged particle inlet 18 of the charged particle analysis instrument or system 20.
  • the flow rate of charged particle droplets through the electric field region 25 will further depend on the magnitude and direction of the DC electric field 27 established between the gates or grids 86, 88.
  • FIG. 11 yet another embodiment is shown of the system 10 of Fig. 1 provided in the form of a system 10”’ including the electric field generation device 28 of Fig. 10 positioned within the front end of the charged particle analysis instrument or system 20.
  • the system 10”' is identical in structure and operation to the system 10” illustrated in Fig. 10 described above, except that the time-varying electric field generation device 28 is disposed within a stage 90 of the charged particle analysis system 20 which represents the charged particle inlet from outside of the charged particle analysis instrument or system 20 and which is fluidly coupled to the charged particle inlet 18 of the charged particle analysis instrument or system 20.
  • the voltage source 16A is configured to produce one or more voltages for controlling the charged particle source 12, in a conventional manner, to produce charged particle droplets in the form of the plume 80 of charged particle droplets.
  • the voltage source 16B is configured to produce at least the AC voltage for establishing the time-varying electric field within the time-varying electric field generation device 28 as described above with respect to Fig. 10 (and in some embodiments, to also produce the DC voltage(s) DC1 , DC2, and/or DC3 as depicted by example in Fig. 10).
  • the stage 90 illustratively has a charged particle inlet 92 via which charged particle droplets in the plume 80 of charged particle droplets, generated by the charged particle source 12, enter the stage 90.
  • the charged particle droplets in the plume 80 of charged particle droplets entering the stage 90 then enter the timevarying electric field generation device 28 (in which the time-varying electric field 26 is generated as described above), and charged particles exiting the electric field generation device 28 enter the charged particle inlet 18 of the charged particle analysis instrument or system 20.
  • the stage 90 is fluidly coupled to a conventional pump 94, and the pump 94 is controlled to a pressure that is less than the pressure in the environment of the charged particle source 12, e.g., atmospheric pressure, and that is greater than the pressure established by the pump 24 in the region 22 of the charged particle analysis instrument or system 20.
  • the pressure differential in the differentially pumped stages 90, 22 of the instrument or system 20 serves to move the charged particles through the stage 90 and into the stage or region 22.
  • the DC voltage output DC3 of the voltage source 16B therefore may not be electrically connected to the electric field generation device 28 as illustrated in Fig.
  • FIG. 12 still a further embodiment is shown of the system 10 of Fig. 1 provided in the form of a system 10 lv including the time-varying electric field generation device 28 of Fig. 10 positioned between charged particle analysis and/or processing stages of the charged particle analysis instrument or system 20.
  • the system 10 lv is illustratively identical in structure and operation to the system 10’” illustrated in Fig. 11 , except that a charged particle analysis and/or processing stage 93 of the charged particle analysis instrument or system 20 is positioned upstream of the stage 90 in which the time-varying electric field generation device 28 is disposed, i.e., such that the stage 90 is positioned between the stage 93 and the stage 22 of the charged particle analysis instrument or system 20.
  • the stage 93 is fluidly coupled to a conventional pump 95, and the pump 95 is controlled to a pressure that is less than the pressure in the environment of the charged particle source 12, e.g., atmospheric pressure, and that is greater than the pressure established by the pump 94 in the stage 90 of the charged particle analysis instrument or system 20.
  • the pressure differential in the differentially pumped stages 93, 90, 22 of the charged particle analysis instrument or system 20 serves to move the charged particles sequentially through the stages 93, 90, and 22.

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Abstract

L'invention concerne un appareil pour chauffer de manière contrôlable des particules chargées nébulisées, qui peut comprendre une région de champ électrique conçue pour recevoir les particules chargées nébulisées à travers celle-ci et des moyens pour établir un champ électrique variant dans le temps à l'intérieur de la région de champ électrique de telle sorte que les particules chargées nébulisées passent à travers le champ électrique variant dans le temps. Le champ électrique variant dans le temps est conçu pour chauffer les particules chargées nébulisées le traversant avec un degré cible de chauffage.
PCT/US2024/049386 2023-10-02 2024-10-01 Appareil et procédé de chauffage contrôlable de particules chargées nébulisées Pending WO2025075952A1 (fr)

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US202363587216P 2023-10-02 2023-10-02
US63/587,216 2023-10-02

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090078800A1 (en) * 2007-09-21 2009-03-26 Matsushita Electric Works, Ltd. Electrostatic atomizer and hot air blower having the same
US20160187297A1 (en) * 2013-08-08 2016-06-30 David Sharp Method and portable ion mobility spectrometer for the detection of an aerosol
US20210315278A1 (en) * 2015-06-29 2021-10-14 Nicoventures Trading Limited Electronic aerosol provision systems

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090078800A1 (en) * 2007-09-21 2009-03-26 Matsushita Electric Works, Ltd. Electrostatic atomizer and hot air blower having the same
US20160187297A1 (en) * 2013-08-08 2016-06-30 David Sharp Method and portable ion mobility spectrometer for the detection of an aerosol
US20210315278A1 (en) * 2015-06-29 2021-10-14 Nicoventures Trading Limited Electronic aerosol provision systems

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