# US 10,319,576 B2 · Laser ablation cell

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- Number: US 10,319,576 B2
- Document ID: US10319576B2
- Status: Granted
- Kind: B2
- Application number: 15/336,361
- Filed: 2016-10-27
- Published: 2017-05-25
- Granted: 2019-06-11
- Earliest claimed: 2013-03-22
- Assignees: ETH Zurich; Paul Scherrer Institut
- Applicants: Eth ZüRich; Paul Scherrer Institut
- Inventors: Detlef Günther; Daniel Grolimund; Hao Wang
- Web page: https://patentgrep.com/patent/US10319576B2

## CPC

- H01J 49/105: {using high-frequency excitation, e.g. microwave excitation, Inductively Coupled Plasma [ICP]}
- G01N 33/57515: of the breast
- G01N 33/60: involving radioactive labelled substances
- G01N 33/6848: {Methods of protein analysis involving mass spectrometry}
- H01J 49/0004: {Imaging particle spectrometry}
- H01J 49/0031: {Step by step routines describing the use of the apparatus (H01J49/0081 takes precedence)}
- H01J 49/04: Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
- H01J 49/0409: {Sample holders or containers (containers for retaining a material to be analyzed, B01L3/50, for DNA, C12Q1/6834, for biological materials, G01N33/543)}
- H01J 49/0459: {for solid samples}
- H01J 49/0463: {Desorption by laser or particle beam, followed by ionisation as a separate step (sample holder per se H01J49/0418)}
- H01J 49/40: Time-of-flight spectrometers (H01J49/36 takes precedence)
- 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)

## Abstract

A laser ablation cell (1) comprises a flow channel (11) having an essentially constant cross-sectional area so as to ensure a strictly laminar flow in the flow channel. A sample chamber (21) is provided adjacent to a lateral opening (14) of the flow channel. A laser beam (41) enters the sample chamber (21) through a lateral window (16) and impinges on a surface (24) of a sample (23) to ablate material from the sample. The sample may be positioned in such a distance from the flow channel that the laser-generated aerosol mass distribution has its center within the flow channel. This leads to short aerosol washout times. The laser ablation cell is particularly well suited for aerosol generation in inductively coupled plasma mass spectrometry (ICPMS), including imaging applications.

## Claims

### Claim 1

A laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) system for imaging of biological samples, comprising:
a laser ablation cell comprising a flow channel and a sample chamber;
wherein the flow channel extends from a carrier gas inlet to a mixed gas outlet;
wherein the flow channel comprises a lateral opening and a lateral window;
wherein the sample chamber comprises a sheath gas inlet;
a laser adapted to shoot a laser beam through both the lateral window and the lateral opening of the ablation cell and impinge on the surface of a sample received by the sample chamber to generate a plume from the sample;
an inductively coupled plasma (ICP) torch coupled to an outlet of the ablation cell for receiving and ionizing the plume; and
a mass analyzer coupled to the ICP torch.

### Claim 2 (depends on 1)

The system of claim 1, wherein the carrier gas inlet is outside the sample chamber.

### Claim 3 (depends on 1)

The system of claim 1, wherein carrier gas flowing through the carrier gas inlet does not pass through the sample chamber.

### Claim 4 (depends on 1)

The system of claim 1, wherein the system is arranged to deliver Argon into the carrier gas inlet and Helium into the sheath gas inlet.

### Claim 5 (depends on 3)

The system of claim 3, wherein the system is arranged to deliver Argon into the carrier gas inlet and Helium into the sheath gas inlet.

### Claim 6 (depends on 1)

The system of claim 1, wherein the lateral opening but not the lateral window is adjacent to the sample chamber.

### Claim 7 (depends on 1)

The system of claim 1, wherein the laser ablation cell is adapted to have a washout time of 100 ms or less.

### Claim 8 (depends on 1)

The system of claim 1, wherein the flow channel is in a cell top of the laser ablation cell.

### Claim 9 (depends on 8)

The system of claim 8, wherein the cell top is detachable from the sample chamber.

### Claim 10 (depends on 1)

The system of claim 1, wherein the system further comprises a positioning device operable to change the relative position between a sample received by the sample chamber and the laser beam.

### Claim 11 (depends on 10)

The system of claim 10, wherein the positioning device is operable to scan the laser beam over the sample surface.

### Claim 12 (depends on 1)

The system of claim 1, wherein the lateral opening has a cross sectional area that is not more than 20 mm2.

### Claim 13 (depends on 1)

The system of claim 1, wherein the laser is a UV laser.

### Claim 14 (depends on 1)

The system of claim 1, wherein the laser is operable to shoot a pulsed laser beam, and wherein each laser pulse will generate the plume from the sample in the sample chamber.

### Claim 15 (depends on 1)

The system of claim 1, wherein the laser has a laser spot size of 4 μm or less.

### Claim 16 (depends on 1)

The system of claim 1, wherein the mass analyzer is a time-of-flight mass analyzer.

### Claim 17 (depends on 1)

The system of claim 1, wherein the sample chamber comprises a biological sample comprising a plurality of different target molecules each labeled with an antibody attached to a lanthanide labeling atom.

### Claim 18 (depends on 17)

The system of claim 17, wherein the biological sample comprises at least 10 different labeling atoms.

### Claim 19

A laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) system for imaging of biological samples, comprising:
a laser ablation cell comprising a flow channel and a sample chamber;
wherein the flow channel extends from a carrier gas inlet to a mixed gas outlet;
wherein the carrier gas inlet is outside the sample chamber;
wherein the flow channel comprises a lateral opening and a lateral window;
wherein the sample chamber comprises a sheath gas inlet;
a laser adapted to shoot a laser beam through both the lateral window and the lateral opening of the ablation cell and impinge on the surface of a sample received by the sample chamber to generate a plume from the sample;
an inductively coupled plasma (ICP) torch coupled to an outlet of the ablation cell for receiving and ionizing the plume; and
a mass analyzer coupled to the ICP torch.

### Claim 20

A laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) system for imaging of biological samples, comprising:
a laser ablation cell comprising a flow channel and a sample chamber;
wherein the flow channel extends from a carrier gas inlet to a mixed gas outlet;
wherein the flow channel comprises a lateral opening and a lateral window;
wherein the sample chamber comprises a sheath gas inlet;
wherein carrier gas flowing through the carrier gas inlet does not pass through the sample chamber;
a laser adapted to shoot a laser beam through both the lateral window and the lateral opening of the ablation cell and impinge on the surface of a sample received by the sample chamber to generate a plume from the sample;
an inductively coupled plasma (ICP) torch coupled to an outlet of the ablation cell for receiving and ionizing the sample; and
a mass analyzer coupled to the ICP torch.
