# US 9,040,906 B2 · Droplet manipulation using gas-phase standing-wave ultrasound fields in MS sources

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- Number: US 9,040,906 B2
- Document ID: US9040906B2
- Status: Granted
- Kind: B2
- Application number: 14/359,811
- Filed: 2012-11-22
- Published: 2015-01-01
- Granted: 2015-05-26
- Earliest claimed: 2011-11-22
- Assignees: Micromass UK Limited
- Applicants: Micromass UK Limited
- Inventors: Michael Raymond Morris; Steven Derek Pringle; Keith Richardson
- Web page: https://patentgrep.com/patent/US9040906B2

## CPC

- H01J 49/165: {Electrospray ionisation}
- G01N 27/623: combined with mass spectrometry
- G01N 29/22: Details {, e.g. general constructional or apparatus details}
- H01J 49/0031: {Step by step routines describing the use of the apparatus (H01J49/0081 takes precedence)}
- H01J 49/022: {Circuit arrangements, e.g. for generating deviation currents or voltages (regulating electric or magnetic variables in general, e.g. current, magnetic field G05F); Components associated with high voltage supply (high voltage supply per se H02M)}
- H01J 49/0454: {with means for vaporising using mechanical energy, e.g. by ultrasonic vibrations}
- H01J 49/24: Vacuum systems, e.g. maintaining desired pressures
- H01J 49/26: Mass spectrometers or separator tubes
- Y10T 137/0391: Affecting flow by the addition of material or energy
- Y10T 137/206: Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system]
- H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

An ion source for a mass spectrometer is disclosed comprising an ionization device which emits a stream of droplets and one or more ultrasonic transmitters which create one or more acoustic standing waves. The acoustic standing waves may be used to further nebulize the stream of droplets and induce internal mixing of the droplets.

## Claims

### Claim 1

An ion source for a mass spectrometer comprising:
an Atmospheric Pressure Ionisation (“API”) ionisation device comprising an Electrospray ion source, arranged and adapted to emit a stream of charged droplets; and
one or more ultrasonic transmitters or sonotrodes arranged and adapted to create one or more acoustic standing waves downstream of said ionisation device;
wherein said one or more acoustic standing waves are arranged and adapted:
to induce internal mixing of said stream of droplets;
to further nebulise said stream of droplets; and
to result in a reduction of an average size of droplets in said stream of droplets.

### Claim 2 (depends on 1)

An ion source as claimed in claim 1, wherein said ion source comprises an ultrasonic transmitter or sonotrode and a reflector.

### Claim 3 (depends on 1)

An ion source as claimed in claim 1, wherein said ion source comprises two ultrasonic transmitters or sonotrodes.

### Claim 4 (depends on 2)

An ion source as claimed in claim 2, wherein said ultrasonic transducer is arranged and adapted to emit ultrasonic waves having a frequency in the range: (i) 20-30 kHz; (ii) 30-40 kHz; (iii) 40-50 kHz; (iv) 50-60 kHz: (v) 60-70 kHz; (vi) 70-80 kHz; (vii) 80-90 kHz; (viii) 90-100 kHz; and (ix) >100 kHz.

### Claim 5 (depends on 1)

An ion source as claimed in claim 1, wherein said one or more ultrasonic transmitters are positioned so that said one or more acoustic standing waves interact with said stream of droplets.

### Claim 6 (depends on 1)

An ion source as claimed in claim 1, wherein said one or more acoustic standing waves are arranged and adapted to move or translate said stream of droplets.

### Claim 7 (depends on 1)

An ion source as claimed in claim 1, wherein in a mode of operation said one or more acoustic standing waves are arranged so as to trap said droplets for a period of time.

### Claim 8 (depends on 1)

An ion source as claimed in claim 1, further comprising a device arranged and adapted to introduce or mix a reagent or reagent ions with said droplets.

### Claim 9 (depends on 8)

An ion source as claimed in claim 8, wherein said reagent or reagent ions react or interact with said droplets.

### Claim 10 (depends on 9)

An ion source as claimed in claim 9, wherein said reagent or reagent ions react or interact via Electron Transfer Dissociation, Electron Capture Dissociation, ozonolysis, Hydrogen-Deuterium exchange (“HDx”), charge reduction, photo dissociation or thermal dissociation.

### Claim 11 (depends on 1)

An ion source as claimed in claim 1, further comprising a control system arranged and adapted to control a residence time or interaction time between droplets and a reagent or reagent ions.

### Claim 12 (depends on 1)

An ion source as claimed in claim 1, wherein said one or more ultrasonic transmitters are arranged and adapted to create one or more gas phase acoustic standing waves.

### Claim 13 (depends on 1)

An ion source as claimed in claim 1, further comprising one or more grid electrodes for applying an electric field to droplets held in said one or more acoustic standing waves.

### Claim 14 (depends on 13)

An ion source as claimed in claim 13, wherein said one or more grid electrodes are at least partially acoustically transparent at a frequency at which said one or more ultrasonic transmitters emit ultrasonic waves.

### Claim 15

A mass spectrometer comprising an ion source including:
an Atmospheric Pressure Ionisation (“API”) ionisation device comprising an Electrospray ion source, arranged and adapted to emit a stream of charged droplets; and
one or more ultrasonic transmitters or sonotrodes arranged and adapted to create one or more acoustic standing waves downstream of said ionisation device;
wherein said one or more acoustic standing waves are arranged and adapted:
to induce internal mixing of said stream of droplets;
to further nebulise said stream of droplets; and
to result in a reduction of an average size of droplets in said stream of droplets.

### Claim 16 (depends on 15)

A mass spectrometer as claimed in claim 15, wherein said mass spectrometer comprises an ion inlet.

### Claim 17 (depends on 16)

A mass spectrometer as claimed in claim 16, wherein said ion inlet leads from a substantially atmospheric pressure region to a substantially sub-atmospheric pressure region.

### Claim 18 (depends on 16)

A mass spectrometer as claimed in claim 16, wherein analyte molecules or ions are arranged to emerge from said one or more acoustic standing waves adjacent said ion inlet so that said analyte molecules or ions enter said mass spectrometer via said ion inlet.

### Claim 19 (depends on 15)

A mass spectrometer as claimed in claim 15, further comprising a gas phase ion mobility spectrometer or separator, wherein said ion mobility spectrometer or separator is arranged and adapted to separate analyte ions temporally according to their ion mobility.

### Claim 20

A method of ionising a sample comprising:
emitting a stream of charged droplets from an Atmospheric Pressure Ionisation (“API”) device comprising an Electrospray ion source; and
causing said stream of droplets to interact with one or more acoustic standing waves;
whereby said one or more acoustic standing waves are arranged and adapted:
to induce internal mixing of said stream of droplets;
to further nebulise said stream of droplets; and
to result in a reduction of the average size of droplets in said stream of droplets.

### Claim 21 (depends on 20)

A method of mass spectrometry comprising a method of ionising a sample as claimed in claim 20.