Sample probe systems and associated methods

Abstract

In one example, a system includes a sample transfer assembly configured to transfer ablated material from a sample to an analyzer inlet of an ion analyzer. The sample transfer assembly includes a sample transfer conduit and one or more gas inlets, each gas inlet configured to receive a respective flow of gas. A mass flow rate into the analyzer inlet is equal to or greater than a total mass flow rate of the gas stream into the one or more gas inlets. In another example, a method includes entraining an ablated material in a flow of sample material flowing within a sample transfer assembly, ionizing the ablated material, and delivering the ionized sample particles to an analyzer inlet of an ion analyzer. In another example, a computer readable medium includes stored processor executable instructions that, when executed by a processor, cause the processor to adjust a flow rate of a flow of sample material.

Description

Technical Field

[0001] The present disclosure generally relates to sample probe systems and associated methods for ionizing and delivering a sample for analysis by an ion analyzer. Background Art

[0002] In recent years, gas flow assisted ion sources for mass spectrometry have become popular, such as in the form of laser ablation electrospray ionization (e.g., MALDESI), gas flow assisted desorption electrospray ionization (AFA DESI), atmospheric pressure plasma assisted laser desorption and ionization (AP PALDI), atmospheric pressure chemical ionization (APCI), and thermal desorption using APCI. However, due to high ion losses between the sample and the mass spectrometer, the sensitivity of such ion sources remains low. Summary of the invention

[0003] Sample probe systems and associated methods are disclosed herein.

[0004] In a representative example, a system includes a sample transfer assembly configured to receive ablated material discharged from a sample and to deliver the ablated material to an ion analyzer. The sample transfer assembly includes: a sample transfer conduit configured to deliver the ablated material to an analyzer inlet of the ion analyzer; and one or more gas inlets disposed upstream of the analyzer inlet. Each gas inlet is configured to receive a corresponding gas flow that flows toward the analyzer inlet and delivers the ablated material toward the analyzer inlet. The sample transfer assembly is configured so that a mass flow rate entering the analyzer inlet is equal to or greater than a total mass flow rate of the gas flow entering the one or more gas inlets.

[0005] In another representative example, a method includes: ablating a sample to produce ablated material; and entraining the ablated material in a sample material flow, the sample material flow including the ablated material and flowing within a sample transfer assembly. The method additionally includes: ionizing the ablated material to produce ionized sample particles; and transmitting the ionized sample particles to an analyzer inlet of an ion analyzer such that a mass flow rate entering the analyzer inlet is equal to or greater than a mass flow rate of the sample material flow [TP385906CNSEC1]

[0006] The entraining of the ablated material in the sample flow includes flowing a downstream inlet gas flow to the analyzer inlet to at least partially induce the sample material flow. The entraining of the ablated material in the sample material flow is performed such that the sample material flow is laminar within at least a portion of the sample transfer assembly.

[0007] In another representative example, a computer readable medium includes stored processor executable instructions that, when executed by a processor, cause the processor to adjust a flow rate of a sample material flow. The sample material flow is induced to flow within a sample transfer assembly by at least a sampling capillary gas flow and a downstream inlet gas flow, such that the sample material flow is laminar within at least a portion of the sample transfer assembly. The sample material flow includes ablated material that is ablated from a sample and entrained into the sample material flow and directed into an analyzer inlet of an ion analyzer. The adjusting of the flow rate is performed so that a mass flow rate entering the analyzer inlet is equal to or greater than a total mass flow rate of the sampling capillary gas flow and the downstream inlet gas flow.

[0008] The foregoing and other objects, features and advantages of the disclosed technology will become more apparent from the following detailed description made with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1A is a schematic diagram of a sample probe system according to one example.

[0010] Figure 1B yes Figure 1A Illustration of an area of ​​a sample probe system.

[0011] Figure 2 is a schematic diagram of a sample probe system according to another example.

[0012] Figure 3A is an upper left isometric view of a portion of a probe system according to yet another example.

[0013] Figure 3B yes Figure 3A Lower right isometric view of the probe system.

[0014] Figure 3C yes FIG. 3A to FIG. 3B Cross-sectional side elevation view of the probe system.

[0015] Figure 4 is a flow chart depicting a method of ionizing a sample for analysis by an ion analyzer according to one example.

[0016] Figure 5 is a schematic diagram of a computing system that can be used to perform one or more methods of the present disclosure, according to one example. DETAILED DESCRIPTION

[0017] The present disclosure generally relates to systems and methods for ionizing sample material for analysis by an ion analyzer such as a mass spectrometer (MS). Such systems and methods may facilitate ionizing sample material entrained in a gas stream and / or delivering such sample material to the ion analyzer in a manner that enhances delivery efficiency. [TP385906CNSEC1]

[0018] Specifically, and as described in more detail below, such systems and methods can operate at low pressures (e.g., at or below atmospheric pressure) to entrain ablated sample material into a laminar flow, which can facilitate turbulence-free mixing with ionized material. Such systems and methods can also use various gas inlets (including passive and / or regulated gas inlets) to entrain ablated sample material into a flow flowing to an ion analyzer with little and / or minimal loss of sample material.

[0019] In recent years, gas flow assisted ion sources for mass spectrometry have become popular, such as in the form of laser ablation electrospray ionization (e.g., MALDESI), gas flow assisted desorption electrospray ionization (AFA DESI), atmospheric pressure plasma assisted laser desorption and ionization (AP PALDI), atmospheric pressure chemical ionization (APCI), and thermal desorption using APCI. Such techniques typically entrain the aerosol formed at the tissue sample into a gas flow driven by a venturi pump or an additional vacuum pump, and subject the sample to post-ionization before entering a mass spectrometer (MS). Due to the high ion loss between the sample and the MS, the sensitivity of such ion sources remains low.

[0020] Many ion sources operate to direct the pumped gas flow as close to the MS inlet as possible, relying on suction through an MS transfer tube or open orifice. Such an approach is simple, but limits the distance from the device to the sample and the flow rate in the system, thus limiting the minimum sample size and particle size of the nebulized sample.

[0021] In addition, many existing systems rely on suction and / or vacuum sources to draw ablated sample material toward the MS inlet. In such systems, the suction source also diverts a portion of the ablated sample material away from the MS inlet and into the suction source, resulting in loss of sample material and disturbance of the flow of ablated sample material into the MS inlet.

[0022] In contrast, the sample probe system according to the present disclosure can enhance ionization and transport efficiency by first entraining the sample aerosol into the sample transfer assembly at a high average velocity, reducing the thickness of the boundary layer within the sample transfer assembly. Such a system can also produce turbulence-free mixing of the sample aerosol with the ionized material produced by the ion source.

[0023] Specifically, and as described in more detail below, a sample probe system according to the present disclosure may include one or more gas inlets disposed upstream of an analyzer inlet of an ion analyzer (e.g., a mass spectrometer) and configured to receive a corresponding gas flow for delivering ablated material to the analyzer inlet. Compared to existing systems in which a portion of the sample material flow is diverted away from the analyzer inlet by a suction source, one or more gas inlets may receive a flow that flows into the analyzer inlet at least substantially in its entirety. In this way, all gas flows for delivering ablated sample material are no higher than the flow entering the analyzer inlet. In other words, the mass flow entering the analyzer inlet may be equal to or greater than the mass flow for entraining ablated sample material. Therefore, a sample probe system according to the present disclosure may be operable to suck all flows of the delivered ablated sample material and an additional optional flow for focusing the flow of the ablated sample material into the analyzer inlet. Therefore, a sample probe system according to the present disclosure may be operable to deliver ablated sample material to the ion analyzer in a controlled manner and with a high degree of delivery efficiency.

[0024] Figure 1A An example of a sample probe system 1000, which may also be referred to as an ion source 1000, is shown. Figure 1A As shown, the sample probe system 1000 includes a sample transfer assembly 1100 configured to receive ablated material 1008 discharged from the sample 1002 and to transfer the ablated material 1008 to the ion analyzer 1400. The ablated material 1008 may include and / or may be aerosolized particles discharged from the sample 1002. Therefore, the ablated material 1008 may additionally or alternatively be referred to as sample aerosol 1008. The sample 1002 may include and / or may be any of a variety of materials to be analyzed by the ion analyzer 1400. Specifically, the sample 1002 may include and / or may be an organic and / or biological sample, such as a tissue or a living cell.

[0025] As described in more detail below, the sample probe system 1000 is generally configured to transport ablated material 1008 through the sample transfer assembly 1100 by entraining the ablated material 1008 in one or more gas streams introduced into the sample transfer assembly 1100. Therefore, references herein to a flow of ablated material 1008 through the sample transfer assembly 1100 may also be understood to refer to a flow of gas carrying the ablated material 1008 through the sample transfer assembly. Figure 1A As shown, the flow of ablated material 1008 and / or accompanying gas through sample transfer assembly 1100 can be referred to as sample material flow 1018 .

[0026] The ion analyzer 1400 may include and / or may be any of a variety of systems and devices, such as a mass spectrometer. As a more specific example, the ion analyzer 1400 may include and / or may be a time-of-flight (TOF) mass spectrometer, an Orbitrap TM Mass spectrometer, linear ion trap mass spectrometer, quadrupole mass spectrometer, quadrupole ion trap mass spectrometer, sector magnetic mass spectrometer, and / or Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. However, this is not required for all examples, and in addition within the scope of the present disclosure, ion analyzer 1400 can be any other suitable system and / or device, examples of which include optical spectrometers, PCR machines and / or sequencing machines.

[0027] The sample transfer assembly 1100 includes a sample transfer conduit 1160 configured to deliver the ablated material 1008 to the analyzer inlet 1402 of the ion analyzer 1400. Figure 1A In the example of the present invention, the sample transfer assembly 1100 additionally includes a sampling capillary 1120 configured to receive the ablated material 1008 and transfer the ablated material 1008 to the sample transfer conduit 1160. Specifically, in this example, the sampling capillary 1120 is positioned adjacent to the sample 1002 to receive the ablated material.

[0028] The ablated material 1008 is removed from the sample container and conveyed to the sample transfer conduit 1160 , which in turn conveys the ablated material 1008 to the ion analyzer 1400 .

[0029] The sample probe system 1000 is generally configured to ionize the ablated material 1008 so that the ablated material 1008 is transferred to the ion analyzer 1400 in an ionized state. Specifically, in various examples, the ablated material 1008 is ionized by and / or within the sample transfer assembly. For example, Figure 1A As shown, the sample probe system 1000 can include an ionization unit 1040 configured to ionize the ablated material 1008. In some examples, the ionization unit 1040 is configured to introduce an ionization material 1046 into the flow of the ablated material 1008, such as within the sample transfer conduit 1160, so that the ablated material 1008 is ionized via charge transfer with the ionization material 1046.

[0030] The sample probe system 1000 can be configured to produce the ablated material 1008 in any of a variety of ways. For example, and as Figure 1AAs shown, the sample probe system 1000 may include an optical assembly 1020 having a laser source 1022 configured to direct a laser beam 1024 to a target region 1004 of the sample 1002. In this manner, the laser source 1022 may be operable to ablate and / or atomize the sample 1002 within the target region 1004.

[0031] like Figure 1A As shown, the optical assembly 1020 can be configured to direct the laser beam 1024 to a side of the sample 1002 opposite to a side of the sampling capillary 1120 that receives the ablated material 1008. For example, the sample probe system 1000 can include a sample stage 1010 having a first side 1012 and a second side 1014 opposite to the first side 1012. The first side 1012 can be configured for placing the sample 1002 thereon, and the optical assembly 1020 can be configured to direct the laser beam 1024 to the second side 1014 of the sample stage 1010. Such a configuration can facilitate positioning the sampling capillary 1120 arbitrarily close to the sample 1002 without spatial constraints imposed by the optical assembly 1020. Although the present disclosure generally relates to examples in which the laser beam 1024 and the sampling capillary 1120 approach the sample 1002 from opposite sides of the sample stage 1010, this is not required for all examples, and it should be understood that same-side ablation is also possible.

[0032] Laser source 1022 may include and / or may be any of a variety of laser sources operable to ablate sample 1002, as described herein. For example, laser source 1022 may include and / or may be a femtosecond laser source, and / or laser beam 1024 may include and / or may be an infrared laser beam. In some examples, laser source 1022 may be configured to provide a total of 1000 MW of carbon dioxide per cubic micrometer (μm). 3 ) of sample 1002 delivers a pulse energy of about 1 nanojoule (nJ) to about 10 microjoules (μJ).

[0033] The target area 1004 of the sample 1002 targeted by the laser beam 1024 can have any of a variety of sizes. As an example, the diameter of the target area 1004 can be at least 1 μm, at least 5 μm, at least 10 μm, at least 15 μm, at least 20 μm, at least 30 μm, at most 50 μm, at most 25 μm, at most [TP385906CNSEC1]

[0034] 17 μm or more, 12 μm or more, 7 μm or more, 2 μm or more, 1-7 μm, 5-12 μm, 10-17 μm, 15-25 μm, and / or 20-50 μm or more. Additionally or alternatively, the volume of target area 1004 may be at least 2 μm or more. 3 , at least 5μm 3 , at least 10μm 3 , at least 50μm3 , at least 100μm 3 , at least 300μm 3 , up to 500μm 3 , up to 200μm 3 , up to 70μm 3 , up to 20μm 3 , up to 7μm 3 , up to 3μm 3 , 2-7μm 3 、5-20μm 3 、10-70μm 3 、50-200μm 3 and / or 100-500 μm 3 .

[0035] In some examples, and as Figure 1A As shown, optical assembly 1020 may additionally include a sample imaging device 1032 configured to image a portion of sample 1002. In some such examples, sample imaging device 1032 may be configured to image sample 1002 along a direction similar to the direction in which laser beam 1024 approaches sample 1002. For example, optical assembly 1020 may be configured to direct laser beam 1024 to sample 1002 at least partially along beam axis 1026, and sample imaging device 1032 may be configured to receive light from sample 1002 at least partially along beam axis 1026.

[0036] like Figure 1A As shown, optical assembly 1020 may include one or more mirrors 1028, such as to direct laser beam 1024 toward sample 1002 and / or to direct light from sample 1002 away from beam axis 1026. In some examples, optical assembly 1020 additionally includes objective 1030 configured to collect light from sample 1002 for imaging by sample imaging device 1032.

[0037] Additional examples of optical assemblies and / or components thereof suitable for use with the examples taught herein are disclosed in PCT Patent Application Publication No. WO2021 / 1048555 and U.S. Patent Application Publication No. 2022 / 0399197, the entire disclosures of which are incorporated herein by reference.

[0038] The sample probe system 1000 can incorporate the ionization unit 1040 in any of a variety of ways. For example, in Figure 1AIn an example of the present invention, the sample probe system 1000 is configured such that the ablated material 1008 is mixed with the ionized material 1046 within the sample transfer conduit 1160 to ionize the ablated material 1008. In this manner, the ionization unit 1040 can be operated to generate a flow of ionized sample particles 1166 flowing to the ion analyzer 1400. In such examples, the sample transfer conduit 1160 can be described as including a charge transfer region 1164, in which the ablated material 1008 is mixed with the ionized material 1046. In some examples, the sample material flow 1018 can be described as including the ionized sample particles 1166 and / or the ionized material 1046.

[0039] In some examples, and as Figure 1A As shown, the sample transfer assembly 1100 can additionally include a sample transfer conduit heater 1168 thermally coupled to the sample transfer conduit 1160. The sample transfer conduit heater 1168 can be configured to adjust the temperature of the sample transfer conduit 1160 and / or the charge transfer region 1164, such as to adjust and / or enhance the ionization rate of the ablated material 1008 within the charge transfer region 1164. In some examples, and as shown in FIG. Figure 1A As shown in the sample transfer pipe heater 1168 straight [TP385906CNSEC1]

[0040] The sample transfer line heater 1168 may be directly coupled to the sample transfer line 1160 (e.g., wrapped around it), such as to heat the sample transfer line 1160 via conductive heat transfer. In other examples, the sample transfer line heater 1168 may be spaced apart from the sample transfer line 1160, such as to heat the sample transfer line 1160 via convection and / or radiant heat transfer, and / or may be thermally coupled to the sample transfer line 1160 via one or more intermediate components.

[0041] In the present disclosure, the term "ionized sample particles" generally refers to ablated material 1008 that has been ionized (such as by ionization unit 1040). Therefore, references herein to ablated material 1008 may be understood to include ionized sample particles 1166 formed by ionizing ablated material 1008. Similarly, references herein to ionized sample particles 1166 may be understood to include ablated material 1008 (e.g., after ionization).

[0042] Figure 1AAn example is shown in which the ionization unit 1040 includes and / or is an electrospray needle 1042, and in which the ionized material 1046 includes and / or is a spray of electrospray droplets 1048 generated by the electrospray needle 1042. However, this is not required for all examples, and it is also within the scope of the present disclosure that the ionization unit 1040 may additionally or alternatively include and / or be any of a variety of ionization units known in the art of ion analysis. As an example, the ionization unit 1040 may also include and / or be an atmospheric pressure chemical ionization (APCI) source, a low temperature plasma source, a glow discharge source, a dielectric barrier discharge source, a high energy photon source, a high energy electron source, etc. As an example, Figure 1A Additionally shown is an example where the ionization unit 1040 includes and / or is a corona discharge needle 1044 of an APCI source.

[0043] The sample probe system 1000 can be configured to entrain the ablated material 1008 into the sample material flow 1018 through the sample transfer assembly 1100 in any of a variety of ways. The sample probe system 1000 generally includes one or more gas inlets operable to introduce a corresponding gas flow into the sample transfer assembly 1100 to draw the ablated material 1008 into the sample transfer assembly 1100 and / or direct the flow of the ablated material 1008 through the sample transfer assembly 1100.

[0044] Specifically, and as Figure 1A As shown, the sample probe system 1000 includes a first gas inlet 1200 configured to receive a first gas flow 1202, at least a portion of which flows into an analyzer inlet 1402. The first gas flow 1202 can be drawn through the first gas inlet 1200 in any of a variety of ways. For example, and as Figure 1A As shown in FIG. 1 , the ion analyzer 1400 can be configured to generate a moving gas flow 1404 (e.g., generated downstream of the analyzer inlet 1402) that operates to draw a gas flow into the analyzer inlet 1402, thereby inducing the first gas flow 1202 to flow through the first gas inlet 1200 and into the analyzer inlet 1402. Specifically, the moving gas flow 1404 can generate a pressure substantially below atmospheric pressure within the analyzer adapter unit 1170 [TP385906CNSEC1]

[0045] force, thereby drawing gas into the analyzer inlet 1402 via the first gas inlet 1200 and / or via the sample transfer conduit 1160 .

[0046] The first gas inlet 1200 is disposed downstream of the sample transfer conduit 1160 and thus at least partially induces a gas flow through the sample transfer conduit 1160 toward the analyzer inlet 1402. The gas flow exiting the sample transfer conduit 1160 carries the ablated material 1108 (e.g., in the form of ionized sample particles 1166), which flows into the analyzer inlet 1402 along with the first gas flow 1202. Such a configuration may be advantageous in directing the flow of ablated material 1108 and / or ionized sample particles 1166 into the analyzer inlet 1402 with a high degree of efficiency. In general, the various gas flows are controlled by the cross-sectional area and pressure differentials in the corresponding portions of the system.

[0047] As used herein, terms such as "first," "second," "third," etc., used to mark components and / or features of the sample probe system 1000 (e.g., the first gas inlet 1200) should be understood as marking different and / or separate components and / or features, without suggesting or requiring a corresponding order and / or priority between such components and / or features.

[0048] As used herein, the term "efficiency" used to characterize the transport of ablated material 1108 and / or ionized sample particles 1166 generally refers to the proportion of ablated material 1108 that is drawn into the sample transfer assembly 1100 and subsequently received by the ionization unit 1040. As an example, the sample probe system 1000 can be configured such that the first gas flow 1202 at least partially entrains the ablated material 1008 and / or ionized sample particles 1166 to flow into the analyzer inlet 1402 such that at least 50% of the ablated material 1008 that enters the sample transfer conduit 1160 continues to flow into the analyzer inlet 1402. As a more specific example, the sample probe system 100 can be configured such that the proportion of ablated material 1008 that enters the sample transfer conduit 1160 and continues to flow into the analyzer inlet 1402 is at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, 50-99%, 60-99%, 70-99%, 80-99% and / or 90-99%.

[0049] In contrast, other ion transfer systems operate to flow ablated and / or ionized sample material into the analyzer inlet by drawing the motive flow away from the region between the ion transfer tube and the analyzer inlet (e.g., with a vacuum), thereby discarding a portion of the sample material through the motive flow and potentially interfering with ion transport in the process. Because motive gas flow 1404 is initiated downstream of analyzer inlet 1402 to cause first gas flow 1202 to flow into analyzer inlet 1402, sample probe systems according to the present disclosure thereby achieve ion transfer with enhanced efficiency relative to other systems.

[0050] The sample probe system according to the present disclosure may additionally be configured to enhance its ion transfer efficiency via control and / or configuration of flow and / or mixing dynamics within the sample transfer assembly 1100. For example, [TP385906CNSEC1]

[0051] The sample probe system 1000 can be configured to cause the ablated material 1008 to flow primarily and / or exclusively through the sampling capillary 1120 and / or through the sample transfer conduit 1160 in a laminar flow distribution. Specifically, in some examples, the sample probe system 1000 can be configured such that during operational use of the sample transfer system 1000, the sample material flow 1018 is constrained to flow at a Reynolds number that does not exceed the laminar-turbulent transition of the flow within some or all conduits of the system. For example, the sample probe system 1000 can be configured such that the Reynolds number associated with the sample material flow 1018 is less than 2300. The sample material flow 1018 can also be configured to reduce the extent to which the ablated material 1008 interacts with and / or adheres to the inner walls of the sampling capillary 1120 and / or the sample transfer conduit 1160 in a manner that may reduce the transfer efficiency of the sample probe system 1000.

[0052] In some examples, such flow characteristics are based at least in part on the geometric configuration of the components of sample transfer assembly 1100. For example, and as Figure 1A As shown, the sampling capillary 1120 and the sample transfer conduit 1160 (and / or their central axes) can be angled relative to each other at a capillary intersection angle 1156 of approximately 90°. Specifically, such a configuration can facilitate injecting the flow of ablated material 1008 into the flow of ionized material 1046 in a manner that promotes mixing of the ablated material 1008 and the ionized material 1046 while at least substantially maintaining laminar flow through the sample transfer conduit 1160 and / or through the charge transfer region 1164.

[0053] Additionally, the various flow characteristics through the sample transfer assembly 1100 can be based at least in part on the various dimensions of the components of the sample transfer assembly 1100. For example, and as Figure 1A As shown, the sampling capillary 1120 can have a sampling capillary inner diameter 1124 selected and / or configured to produce desired flow characteristics of the ablated material 1008 within the sampling capillary 1120. As an example, the sampling capillary inner diameter 1124 can be at least 0.5 millimeters (mm), at least 1 mm, at least 1.5 mm, at least 2 mm, at least 3 mm, at most 5 mm, at most 2.5 mm, at most 1.7 mm, at most 1.2 mm, at most 0.7 mm, 0.5-1.7 mm, 1-2.5 mm, and / or 1.5-5 mm.

[0054] In some examples, the sampling capillary inner diameter 1124 is significantly larger than the inner diameter of the target area 1004, which can be, for example, about 1-50 micrometers (μm). Specifically, given the small spot size of the target area 1004 relative to the sampling capillary inner diameter 1124, the sampling capillary 1120 having a sampling capillary inner diameter 1124 that is several orders of magnitude larger than the spot size can effectively receive the ablated material 1008 generated at the target area 1004 while maintaining a relatively low flow rate within the sampling capillary 1120. For example, the flow rate within the sampling capillary 1120 can be less than about 5-15 meters per second (m / s), resulting in a gas flow rate that is low enough (e.g., less than about 30 milliliters per second (mL / s)) to entrain sample particles with a diameter greater than 100 nanometers (nm) in laminar flow. In contrast, the inlet flow of commercially available systems routinely reaches [TP385906CNSEC1]

[0055] Above flow rates of 120 mL / s, this can limit the maximum size of sample particles that can be entrained in the laminar flow within the ion source.

[0056] Due to the relatively low flow rates associated with laminar flow in a sample probe system according to the present disclosure, such a system may introduce one or more gas inflows into the sample probe system and direct such flows into the analyzer inlet 1402. Examples of such gas inflows include the first gas flow 1202, the second and / or third gas flows described below, focused and / or falling gas flows, etc. Such flows may be directed into the analyzer inlet 1402 without using an aspiration pump that diverts the flow away from the analyzer inlet 1402 and / or without adjusting the analyzer inlet 1402. Thus, the mass flow can be balanced in a manner that achieves efficient transfer of the ablated material 1008 to the analyzer inlet 1402. The versatility in the balanced flow rates as described herein may also allow for the use of higher flow rates in the sampling capillary 1120 to entrain particles having sizes on the order of single nanometers.

[0057] In the present disclosure, the term "flow rate" used to describe the flow of gas and / or material (e.g., ablated material 1008) may be understood to mean any of a variety of quantities. For example, in some cases, the term "flow rate" may refer to the velocity (e.g., average velocity) of gas and / or material entrained in the gas at a selected location within the sample transfer assembly 1100. In such cases, the flow rate may be expressed in units of distance per time interval. In other cases, the term "flow rate" may refer to the volumetric flow rate of gas and / or entrained material through a portion of the sample transfer assembly 1100 (e.g., through a selected cross-sectional area of ​​a conduit of the sample transfer assembly 1100), and thus may be expressed in units of volume per unit time. In still other cases, the term "flow rate" may refer to the mass flow rate of gas and / or entrained material through a portion of the sample transfer assembly 1100 (e.g., through a selected cross-sectional area of ​​a conduit of the sample transfer assembly 1100), and thus may be expressed in units of mass per unit time.

[0058] As another example, and if Figure 1A As shown, the sampling capillary 1120 may include a sampling capillary inlet 1128 separated from the sample 1002 by a sample separation distance 1132, which is selected and / or configured to produce desired flow characteristics of the ablated material 1008 entering the sampling capillary 1120. As an example, the sample separation distance 1132 may be at least 0.1 mm, at least 0.5 mm, at least 1 mm, at least 1.5 mm, at least 2 mm, at least 3 mm, at most 5 mm, at most 2.5 mm, at most 1.7 mm, at most 1.2 mm, at most 0.7 mm, at most 0.2 mm, 0.1-0.7 mm, 0.5-1.2 mm, 1-1.7 mm, 1.5-2.5 mm, and / or 2-5 mm. As discussed in more detail below, the sample separation distance 1132 may be configured and / or varied to adjust the dynamics of the flow entering the sampling capillary inlet 1128.

[0059] [TP385906CNSEC1]

[0060] One or more characteristics of the sample transfer conduit 1160 may also be selected and / or configured to produce desired flow characteristics of the ablated material 1008 and / or ionized material 1046. For example, and as Figure 1A As shown, the sample transfer channel inner diameter 1162 of the sample transfer channel 1160 may be at least 0.5 mm, at least 1 mm, at least 1.5 mm, at least 2 mm, at least 3 mm, at most 5 mm, at most 2.5 mm, at most 1.7 mm, at most 1.2 mm, at most 0.7 mm, 0.5-1.2 mm, 1-1.7 mm, 1.5-2.5 mm and / or 2-5 mm.

[0061] The sample probe system 1000 can be configured so that the gas flow rate entering the sample transfer assembly 1100 can be controlled in any of a variety of ways. In some examples, and as Figure 1A , the sample probe system 1000 includes a first regulator mechanism 1204 configured to selectively adjust a first flow rate of a first gas stream 1202 flowing to and / or through the first gas inlet 1200. In such examples, selective adjustment of the first flow rate may be advantageous for controlling one or more characteristics of the flow of ablated material 1008 entering the analyzer inlet 1402. For example, selectively increasing the first flow rate by the first regulator mechanism 1204 may operate to reduce the flow rate of the ablated material 1008 exiting the sample transfer conduit 1160.

[0062] The sample probe system 1000 may also include additional gas inlets for inducing and / or entraining a flow 1018 of sample material through the sample transfer assembly 1100. For example, and as Figure 1A As shown, the sample probe system 1000 may include a second gas inlet 1300 configured to receive a second gas flow 1302 flowing into the sample transfer conduit 1160. Figure 1A In the example of FIG. 1 , the second gas inlet 1300 is disposed upstream of the sample transfer conduit 1160, and thus upstream of the charge transfer region 1164 within the sample transfer conduit 1160. Similar to the first gas flow 1202, the second gas flow 1302 may be induced to flow through the second gas inlet 1300 by one or more gas flows downstream of the second gas inlet (such as by the motive gas flow 1404 and / or by the first gas flow 1202).

[0063] In some examples, and as Figure 1A , the sample probe system 1000 includes a second regulator mechanism 1304 configured to selectively regulate a second flow rate at which the second gas stream 1302 flows to and / or through the second gas inlet 1300. In such examples, selective regulation of the second flow rate may be advantageous for controlling one or more characteristics of the ionization of the ablated material 1008. For example, selectively increasing the second flow rate may increase the flow rate of the ionized material 1046 entering the sample transfer conduit 1160 and / or the charge transfer region 1164, but may also undesirably introduce turbulence into the dynamics of the mixing of the ablated material 1008 and the ionized material 1046.

[0064] When present, each of the first regulator mechanism 1204 and the second regulator mechanism 1304 may include and / or may be any suitable mechanism, examples of which include a valve-based regulator, a variable orifice regulator, a diaphragm-based regulator, etc. In some examples, the first regulator mechanism 1204 and / or [TP385906CNSEC1]

[0065] The second regulator mechanism 1304 may be selectively, actively, and / or dynamically controlled via any suitable combination of manual and / or automatic inputs, as described in greater detail below.

[0066] The sample probe system 1000 can additionally be described as operating to draw the third gas flow 1134 into the sample transfer assembly 1100 as the ablated material 1008 is drawn into the sample transfer assembly 1100. For example, and as Figure 1A As shown, the third gas stream 1134 can flow into the sampling capillary inlet 1128 to entrain the ablated material 1008 for flow within the sample transfer assembly 1100. In this manner, the sampling capillary inlet 1128 can be described as representing a gas inlet of the sample transfer assembly 1100. Similar to the first gas stream 1202 and / or the second gas stream 1302, the third gas stream 1134 can be induced to flow through the sampling capillary inlet 1128 by one or more gas streams downstream of the sampling capillary inlet 1128, such as by the motive gas stream 1404, by the first gas stream 1202, and / or by the second gas stream 1302.

[0067] In some examples, the sample probe system 1000 can be configured to selectively adjust the third flow rate of the third gas stream 1134 into the sampling capillary 1120, such as by controlling the position of the sampling capillary 1120 relative to the sample 1002. For example, and as Figure 1AAs shown, the sample probe system 1000 may include a capillary positioning stage 1016 configured to selectively control the position of the sampling capillary 1120 relative to the sample 1002, such as by translating and / or rotating the sampling capillary 1120 relative to the sample 1002. In this manner, the capillary positioning stage 1016 may be configured to selectively change the sample separation distance 1132 between the sampling capillary inlet 1128 and the sample 1002, which in turn may be operable to adjust a third flow rate of a third gas stream 1134 entering the sampling capillary 1120. For example, translating the sampling capillary 1120 via the capillary positioning stage 1016 to increase the sample separation distance 1132 may be operable to increase the third flow rate, but may also limit the proportion of the ablated material 1008 discharged from the sample 1002 that is entrained to flow within the sample transfer assembly 1100. In various examples, it may be desirable to increase the third flow rate to increase the flow rate of the ablated material 1008 through the sampling capillary 1120, thereby reducing the travel time along the sampling capillary 1120. Additionally or alternatively, it may be desirable for the third flow rate to be high enough to effectively expel the flow of ablated material 1008 into the flow of ionized material 1046, thereby facilitating efficient mixing of the ablated material 1008 and the ionized material 1046.

[0068] Figure 1B The sample capillary inlet 1128 is shown in FIG. Figure 1A A portion of the sample probe system 1000. In some examples, and as Figure 1B As shown, the lateral position of the sampling capillary inlet 1128 relative to the sample 1002 and / or relative to the beam axis 1026 of the laser beam 1024 can also be adjusted to enhance the flow properties of the ablated material 1008 entering the sampling capillary 1120. For example, the sampling capillary 1120 can extend along a sampling capillary central axis 1122 and define the sampling capillary center [TP385906CNSEC1]

[0069] axis, and the beam axis 1026 and / or the target area 1004 of the sample 1002 can be spaced apart from the sampling capillary central axis 1122 by a lateral beam offset 1025 .

[0070] Offsetting the sampling capillary central axis 1122 from the beam axis 1026 by the lateral beam offset 1025 in this manner can facilitate generating a plume of ablated material 1008 in a region where entrainment into the third gas stream 1134 is enhanced and / or maximized. Specifically, and as Figure 1BAs shown in , the third gas stream 1134 can flow into the sampling capillary inlet 1128 along the sampling capillary central axis 1122 and / or at a velocity profile that creates a stagnant region 1136 near the sample 1002. When ablated material 1008 is generated within the stagnant region 1136, such material may not be effectively drawn into the sampling capillary 1120 by the third gas stream 1134. Alternatively, shifting the beam axis 1026 from the sampling capillary central axis 1122 by a transverse beam offset 1025 can result in the generation of ablated material 1008 in a region of relatively high velocity of the third gas stream 1134 entering the sampling capillary 1120.

[0071] The lateral beam offset 1025 can take any of a variety of values, such as can be based at least in part on the size of the sampling capillary 1120. As an example, the lateral beam offset 1025 can be at least 0.2 mm, at least 0.5 mm, at least 1.0 mm, at most 1.5 mm, at most 0.7 mm, at most 0.3 mm, 0.2-0.7 mm, and / or 0.5-1.5 mm. Additionally or alternatively, the lateral beam offset 1025 can be at least 10% of the sampling capillary inner diameter 1024, at least 20% of the sampling capillary inner diameter 1024, at least 30% of the sampling capillary inner diameter 1024, at least 40% of the sampling capillary inner diameter 1024, at most 45% of the sampling capillary inner diameter 1024, at most 35% of the sampling capillary inner diameter 1024, at most 25% of the sampling capillary inner diameter 1024, at most 15% of the sampling capillary inner diameter 1024, 10-25% of the sampling capillary inner diameter 1024, 20-35% of the sampling capillary inner diameter 1024, and / or 25-45% of the sampling capillary inner diameter 1024.

[0072] By directing the laser beam 1024 to the target area 1004 in an area of ​​bulk gas flow, the ablated material 1008 can be effectively separated from the sample 1002 and drawn into the sampling capillary 1120 via the Coanda effect. In contrast, positioning the sampling capillary 1120 so that the sampling capillary central axis 1122 is co-linear with the beam axis 1026 can result in the generation of an ablation plume in an area of ​​relative stagnation or eddy flow of the third gas flow 1134, which can reduce and / or hinder the flow of the ablated material 1008 into the sampling capillary 1120.

[0073] In general, the flow rate of each gas stream entering the sample transfer assembly 1100 can be based at least in part on the flow rate of one or more other gas streams entering the sample transfer assembly 1100. Thus, the control of the flow dynamics of the ablated material 1008 and / or ionized sample particles 1166 within the sample transfer assembly 1100 can be controlled by the flow rate of each gas stream entering the sample transfer assembly 1100.

[0074] Control of the efficiency of delivery of the ablated material 1008 to the ion analyzer 1400 may require active and / or iterative adjustment of the first flow rate, the second flow rate, and / or the third flow rate as described herein.

[0075] In this manner, the values ​​of the first flow rate, the second flow rate, and / or the third flow rate can be balanced relative to one another (e.g., independently adjusted) to enhance efficient transfer of the ablated material 1008 to the analyzer inlet 1402. Additionally or alternatively, these flow rates can be balanced and / or adjusted to account for additional gas flows in the sample transfer assembly 1100, such as gas flows associated with the ionization cell 1040, gas flows associated with additional inlets, gas flows near the analyzer inlet 1402 (e.g., curtain gas flows and / or sheath gas flows), etc.

[0076] Thus, in some examples, the operational configuration of the sample probe system 1000 may be characterized at least in part in terms of the relative flow rates of the gas flows therein, which in turn may be related to the characteristic size of particles most efficiently transported in such a configuration. As an example, operating the sample probe system 1000 such that the mixing ratio of the second flow rate to the third flow rate is about 11:1 may facilitate efficient transport of ablated material 1008 in the form of particles having a size less than about 100 nm. Alternatively, operating the sample probe system 1000 at a lower mixing ratio may facilitate efficient transport of ablated material 1008 in the form of particles having a size in the range of about 1-10 nm.

[0077] In various examples, control of the flow dynamics of the ablated material 1008 through the sample transfer assembly 1100 can facilitate concentric flow of the ablated material 1008 through and / or out of the sample transfer assembly 1100. For example, such concentric flow can be achieved and / or enhanced by configuring the internal dimensions of the sample transfer assembly 1100 and / or the flow rate through the sample transfer assembly 1100 to promote laminar flow of the ablated material 1008. Specifically, mixing the ablated material 1008 with the ionized material 1046 in a laminar flow can avoid mixing via diffusion and / or turbulence that can otherwise result in uncontrollable loss of the ablated material 1008, for example, due to collisions with walls and significant amounts of flow being trapped in eddies of the analyzer adapter unit 1170. Such turbulent mixing can also undesirably result in peak tailing in the signal generated by the ion analyzer 1400. In addition, the relative gas flow rates through the sample transfer assembly 1100 can be adjusted to increase or decrease the concentration of ablated material 1008 toward the center and away from the walls of the sample transfer conduit 1160. By concentrating the ablated material 1008 toward the center of the sample transfer conduit 1160, the loss of ablated material 1008 at the transition between the sample transfer conduit 1160 and the analyzer inlet 1402 is reduced. Specifically, the second gas flow 1302 can form a sheath around the core flow of ablated material 1008 within the sample transfer conduit 1160, thereby limiting the collision of the ablated material 1008 with the walls of the sample transfer conduit 1160 and directing the ablated material 1008 toward the analyzer inlet 1402.

[0078] [TP385906CNSEC1]

[0079] Such concentric flow exiting the sample transfer assembly 1100 may also facilitate directing the sample material flow 1018 directly into the analyzer inlet 1402 in a manner that reduces the loss of ablated material 1008. In some examples, the analyzer inlet 1402 may be shaped and / or otherwise configured to accept a flow of ablated material 1008 from various directions. For example, and as Figure 1A As shown, the analyzer inlet 1402 may have a flared and / or trumpet shape to direct the ablated material 1008 to the ion analyzer 1400 even when the flow of the ablated material 1008 is not completely concentric with the analyzer inlet 1402 .

[0080] When present, the capillary positioning stage 1016 may include and / or may be any suitable mechanism, such as a moving stage (e.g., a translation stage and / or a rotation stage). In some examples, at least a portion of the sampling capillary 1120 and / or the sample transfer assembly 1100 is supported relative to the sample 1002 by the capillary positioning stage 1016.

[0081] In some examples, additionally or alternatively, the position of the sampling capillary 1120 and / or the sample transfer assembly 1100 relative to the sample 1002 and / or the sample stage 1010 can be controlled by moving the sample 1002 and / or the sample stage 1010 relative to the sample transfer assembly 1100. For example, the sample stage 1010 can be supported by a motion (e.g., translation and / or rotation) stage and / or can include a motion stage configured to selectively position the sample 1002 relative to the sample transfer assembly 1100 and / or the sampling capillary 1120. In some examples, the sample stage 1010 and / or an associated motion stage can be used to move the sample 1002 relative to the laser beam 1024 to scan (e.g., raster scan) the laser beam 1024 across an area of ​​the sample 1002.

[0082] When present, each of the first gas stream 1202, the second gas stream 1302, and the third gas stream 1134 can include and / or can be any of a variety of gases. In some examples, such as when the sample 1002 includes a biological and / or organic sample, it may be desirable to use a biologically inert, biocompatible, and / or oxygen-free gas (such as nitrogen and / or a noble gas) as the first gas stream 1202, the second gas stream 1302, and / or the third gas stream 1134.

[0083] The sampling capillary 1120 can be configured to deliver the ablated material 1008 to the sample transfer conduit 1160 in any of a variety of ways. Figure 1A In the example of, and as described in more detail below, the sampling capillary 1120 delivers the ablated material 1008 to the sample transfer conduit 1160 via various intermediate components. In other examples, the sampling capillary 1120 can be configured to deliver the ablated material 1008 directly to the sample transfer conduit 1160.

[0084] In various examples, the sample transfer assembly 1100 may be described as including a sample transfer conduit 1150 including a sample transfer channel 1160 and a sampling conduit 1110 including a sampling capillary 1120. In such examples, the sampling capillary 1120 may be described as providing a sample [TP385906CNSEC1]

[0085] The transfer conduit 1150 and / or the sample transfer conduit 1160 deliver the ablated material 1008. Similarly, in such examples, the sample transfer conduit 1150 may be described as receiving the ablated material 1008 from the sampling conduit 1110 and / or from the sampling capillary 1120. In various examples, and as Figure 1A As shown, the sampling conduit 1110 can be directly coupled to the sample transfer conduit 1150.

[0086] like Figure 1AAs shown, the sample transfer conduit 1150 may include a sample transfer conduit first inlet 1152, a sample transfer conduit second inlet 1154, and a sample transfer conduit outlet 1130. In this example, each of the sample transfer conduit first inlet 1152 and the sample transfer conduit second inlet 1154 may be described as representing an inlet and / or an inlet of the sample transfer conduit 1160. The sample transfer conduit outlet 1130 may be configured to discharge the ablated material 1008 (e.g., in the form of ionized sample particles 1166) to the analyzer inlet 1402.

[0087] The sample transfer conduit first inlet 1152 can be configured to receive the ionized material 1046 and / or the second gas stream 1302, while the sample transfer conduit second inlet 1154 can be configured to receive the ablated material 1008, such as receiving the ablated material from the sampling conduit 1110 and / or the sampling capillary 1120. Figure 1A In the example of FIG. 1 , the sampling conduit 1110 is directly coupled to the sample transfer conduit second inlet 1154 and is angled relative to the sample transfer conduit 1150 at a capillary intersection angle 1156. More specifically, in this example, the sampling conduit 1110 includes a sampling conduit outlet 1112 that is coupled to the sample transfer conduit 1150 at the capillary intersection angle 1156 at the sample transfer conduit second inlet 1154. In other examples, the sampling capillary 1120 can be coupled (e.g., directly coupled) to the sample transfer conduit second inlet 1154.

[0088] exist Figure 1A In the example of the present invention, the sample transfer assembly 1100 additionally includes a capillary coupling unit 1140 that fluidly couples the sampling capillary 1120 and the sample transfer conduit 1160 to each other. In other words, the sampling capillary 1120 and the sample transfer conduit 1160 are fluidly coupled to each other via the capillary coupling unit 1140. In this example, the capillary coupling unit 1140 includes and / or defines a portion of the sampling conduit 1110 and the sample transfer conduit 1150. Specifically, the capillary coupling unit 1140 includes a portion of the sampling conduit 1110 extending between the sampling capillary 1120 and the sample transfer conduit 1150 and a portion of the sample transfer conduit 1150 extending between the sample conduit 1110 and the sample transfer conduit 1160. The capillary coupling unit 1140 also defines a first sample transfer conduit inlet 1152 and a second sample transfer conduit inlet 1154.

[0089] The capillary coupling unit 1140 can be coupled to the sampling capillary 1120 in any suitable manner. For example, the capillary coupling unit 1140 can include a sampling capillary interface 1144 that couples the sampling capillary 1120 to the capillary coupling unit 1140. In some such examples, the sampling capillary interface 1144 is connected to the sampling capillary 1120.

[0090] A portion of the sampling capillary 1120 is received, such as by inserting the sampling capillary 1120 into the capillary engagement unit 1140 at the sampling capillary interface 1144 .

[0091] Additionally or alternatively, the sampling capillary 1120 may be removably coupled to the sampling capillary interface 1144. Specifically, in some examples, the sample probe system 1000 may be configured such that the sampling capillary 1120 may be selected from a plurality of sampling capillaries 1120 of different sizes (e.g., different sampling capillary inner diameters 1124), such as based on the properties of the sample 1002 under investigation, and selectively coupled to the capillary engagement unit 1140 for analysis of the sample 1002. In such examples, the sampling capillary 1120 may be coupled to the sampling capillary interface 1144 via any of a variety of releasable couplings, examples of which include threaded couplings, pin lock couplings, bayonet lock couplings, ferrule lock couplings, and the like. In some examples, each of the plurality of sampling capillaries 1120 may be characterized by the same or similar sampling capillary outer diameter 1126, which in turn may represent a diameter configured to operably engage the sampling capillary interface 1144. In this manner, any of the plurality of sampling capillaries 1120 may be operably coupled to the sampling capillary interface 1144 in a similar manner, regardless of their respective interior dimensions.

[0092] Similarly, the capillary engagement unit 1140 can be coupled to the sample transfer conduit 1160 in any suitable manner. For example, the capillary engagement unit 1140 can include an upstream sample transfer conduit interface 1146 that couples the sample transfer conduit 1160 to the capillary engagement unit 1140. In some such examples, the upstream sample transfer conduit interface 1146 receives a portion of the sample transfer conduit 1160, such as by inserting the sample transfer conduit 1160 into the capillary engagement unit 1140 at the upstream sample transfer conduit interface 1146.

[0093] Additionally or alternatively, the sample transfer conduit 1160 can be removably coupled to the upstream sample transfer conduit interface 1146. In such examples, the sample transfer conduit 1160 can be coupled to the upstream sample transfer conduit interface 1146 via any of a variety of releasable couplings, examples of which include threaded couplings, pin lock couplings, bayonet lock couplings, ferrule lock couplings, and the like.

[0094] In some examples, and as Figure 1A As shown, the sample transfer conduit 1160 is coupled to the upstream sample transfer conduit interface 1146 via an upstream sample transfer conduit adapter 1148. For example, the upstream sample transfer conduit adapter 1148 may be removably coupled to the sample transfer conduit 1160 and / or the upstream sample transfer conduit interface 1146, such as via a threaded coupling, a pin lock coupling, a bayonet lock coupling, a ferrule lock coupling, etc. In other examples, the upstream sample transfer conduit adapter 1148 may be fixedly coupled to the capillary engagement unit 1140.

[0095] [TP385906CNSEC1]

[0096] exist Figure 1A In an example of the present invention, the capillary junction unit 1140 includes a second gas inlet 1300 such that a second gas stream 1302 flows into the sample transfer conduit 1150 and the sample transfer channel 1160 via the capillary junction unit 1140. In such an example, the second gas inlet 1300 may additionally or alternatively be described as a capillary junction gas inlet 1300, and / or the second gas stream 1302 may additionally or alternatively be described as a capillary junction unit gas stream 1302. Similarly, the second regulator mechanism 1304 may additionally or alternatively be described as an upstream inlet regulator mechanism 1304.

[0097] exist Figure 1A In the example of the capillary engagement unit 1140, the second gas inlet 1300 is in the form of an inlet extending through a structure that at least partially encloses one or more conduits that fluidly couple the sampling capillary 1120 and the sample transfer conduit 1160 to each other. However, this is not required in all examples, and further within the scope of the present disclosure, the second gas inlet 1300 may be a portion of a conduit coupled to and / or coextensive with the sample transfer conduit 1160. For example, the sample transfer conduit first inlet 1152 may represent and / or form the second gas inlet 1300 of the sample probe system 1000.

[0098] exist Figure 1A In the example of , the capillary junction unit 1140 additionally includes and / or supports at least a portion of the ionization unit 1040, such as an electrospray needle 1042 or a corona discharge needle 1044. Specifically, in this example, the capillary junction unit 1140 defines an inner chamber 1142, so that the ionization unit 1040 is at least partially received within the inner chamber 1142.

[0099] In addition, Figure 1AIn some examples, the capillary positioning stage 1016 is directly coupled to and / or supports the capillary engagement unit 1140. In this manner, the capillary positioning stage 1016 is operable to control the position of the sampling capillary inlet 1128 relative to the sample 1002 by moving the capillary engagement unit 1140 relative to the sample 1002. In other examples, the capillary positioning stage 1016 may be directly coupled to and / or may support the sampling capillary 1120.

[0100] although Figure 1A An example is shown in which the sampling capillary 1120 and the sample transfer conduit 1160 are coupled to each other via the capillary coupling unit 1140, but this is not required for all examples. For example, it is also within the scope of the present disclosure that the sampling capillary 1120 and / or the sampling conduit 1110 can be directly coupled to the sample transfer conduit 1160. In such an example, the sample transfer conduit 1160 can be described as including a sample transfer conduit first inlet 1152 and / or a sample transfer conduit second inlet 1154.

[0101] exist Figure 1A In the example of , the sample transfer assembly 1100 also includes an analyzer adapter unit 1170, which is configured to allow the sample material flow 1018 (e.g., ablated material 1008 and / or ionized sample particles 1166) to be transferred from the sample transfer conduit 1150 and / or the sample transfer conduit 1160 to the analyzer inlet 1402 via the analyzer adapter unit 1170. Figure 1A [TP385906CNSEC1]

[0102] In this example, the analyzer adapter unit 1170 includes and / or defines the first gas inlet 1200. Thus, the analyzer adapter unit 1170 can at least partially direct the first gas flow 1202 to flow into the analyzer inlet 1402, such as by restricting the first gas flow 1202 from flowing away from the analyzer inlet 1402.

[0103] The sample transfer conduit 1160 may be coupled to the analyzer adapter unit 1170 in any of a variety of ways. For example, the sample transfer conduit 1160 may be directly coupled to the analyzer adapter unit 1170. Additionally or alternatively, the analyzer adapter unit 1170 may include a downstream sample transfer conduit interface 1172 that couples the sample transfer conduit 1160 to the analyzer adapter unit 1170. In some such examples, the downstream sample transfer conduit interface 1172 receives a portion of the sample transfer conduit 1160, such as by inserting the sample transfer conduit 1160 into the analyzer adapter unit 1170 at the downstream sample transfer conduit interface 1172.

[0104] Additionally or alternatively, the sample transfer conduit 1160 can be removably coupled to the downstream sample transfer conduit interface 1172. In such examples, the sample transfer conduit 1160 can be coupled to the downstream sample transfer conduit interface 1172 via any of a variety of releasable couplings, examples of which include threaded couplings, pin lock couplings, bayonet lock couplings, ferrule lock couplings, and the like.

[0105] In some examples, and as Figure 1A As shown, the sample transfer conduit 1160 is coupled to the downstream sample transfer conduit interface 1172 via a downstream sample transfer conduit adapter 1174. For example, the downstream sample transfer conduit adapter 1174 can be removably coupled to the sample transfer conduit 1160 and / or the downstream sample transfer conduit interface 1172, such as via a threaded coupling, a pin lock coupling, a bayonet lock coupling, a ferrule lock coupling, etc. In other examples, the downstream sample transfer conduit adapter 1174 can be fixedly coupled to the analyzer adapter unit 1170.

[0106] exist Figure 1A In some examples, the analyzer adapter unit 1170 includes an analyzer transfer capillary 1180 that is configured to receive the sample material flow 1018 from the sample transfer conduit 1160 and convey the sample material flow 1018 to the analyzer inlet 1402. In such examples, the sample transfer conduit 1150 may be described as including the analyzer transfer capillary 1180. Specifically, in some examples, the analyzer transfer capillary 1180 may be described as representing a portion of the sample transfer conduit 1150 extending within the analyzer adapter unit 1170. Additionally or alternatively, the analyzer transfer capillary 1180 may be described as defining a sample transfer conduit outlet 1158 of the sample transfer conduit 1150. In some examples, the analyzer transfer capillary 1180 is fixedly coupled to at least a portion of the analyzer adapter unit 1170, such as to the downstream sample transfer conduit interface 1172 and / or the downstream sample transfer conduit adapter 1174.

[0107] [TP385906CNSEC1]

[0108] In some examples, the analyzer adapter unit 1170 can be configured to allow movement and / or repositioning of the analyzer transfer capillary 1180 relative to the analyzer inlet 1402. For example, the analyzer adapter unit 1170 can include a body portion 1176 that is fixed relative to the analyzer inlet 1402, and the downstream sample transfer tubing interface 1172 and / or the analyzer transfer capillary 1180 can be movably coupled to the body portion 1176.

[0109] Specifically, in Figure 1AIn an example of the analyzer adapter unit 1170, the analyzer adapter unit 1170 includes a coupling member 1178 via which the downstream sample transfer conduit interface 1172 is coupled to the body portion 1176. The coupling member 1178 can be configured to allow the sample transfer conduit interface 1172 (and therefore at least a portion of the sample transfer conduit 1150) to translate in one or more directions relative to the body portion 1176. In this manner, the coupling member 1178 can allow the position of the sampling conduit 1110, the sample transfer conduit 1150, and / or their components to be adjusted relative to the sample 1002 while the body portion 1176 and the analyzer inlet 1402 remain fixed relative to the sample 1002. When present, the coupling member 1178 can include and / or can be any suitable component and / or material, examples of which include membranes, gaskets, flexible seals, etc. In some examples, the coupling member 1178 desirably provides a thermal barrier between the heated analyzer transfer capillary 1180 and the relatively cool body portion 1176 of the analyzer adapter unit 1170.

[0110] Although Figure 1A An example is shown in which the sample material flow 1018 is transferred to the analyzer inlet 1402 via the analyzer adapter unit 1170, but this is not required for all examples. For example, it is also within the scope of the present disclosure that the sample transfer conduit 1160 directly faces the analyzer inlet 1402. In such an example, the sample transfer conduit 1160 can be described as including a sample transfer conduit outlet 1158.

[0111] In some examples, and as Figure 1A As shown, the sample probe system 1000 additionally includes a controller 1500 that is programmed and / or configured to control one or more components of the sample probe system 1000. For example, the controller 1500 may be programmed and / or configured to control the generation of a laser beam 1024 by a laser source 1022 and / or receive an image of a portion of the sample 1002 from a sample imaging device 1032.

[0112] Additionally or alternatively, the controller 1500 may be operable to directly or indirectly control one or more properties of the flow of gas and / or ablated material 1008 through the sample transfer assembly 1100. For example, the controller 1500 may be programmed and / or configured to control the first regulator mechanism 1204 to adjust a first flow rate of the first gas flow 1202 and / or control the second regulator mechanism 1304 to adjust a second flow rate of the second gas flow 1302. Similarly, the controller 1500 may be programmed and / or configured to control the capillary positioning stage 1016 to adjust a third flow rate of the third gas flow 1134 entering the sampling capillary 1120, such as by changing the sample separation distance 1132 and / or the separation between the beam axis 1026 and the sampling capillary central axis 1122.

[0113] [TP385906CNSEC1]

[0114] The controller 1500 may also communicate with the ion analyzer 1400, such as to receive an indication of a signal strength corresponding to an amount of ablated material 1008 received by the analyzer inlet 1402. Such signal strength may, in turn, correspond to and / or be indicative of a delivery efficiency of the sample probe system 1000 in delivering ablated material 1008 from the sample 1002 to the analyzer inlet 1402.

[0115] The controller 1500 may be programmed and / or configured to communicate with any other components of the sample probe system 1000 in any suitable manner, such as via wired and / or wireless connections.

[0116] As discussed above, the delivery efficiency of the sample probe system 1000 may depend at least in part on various selectively variable flow characteristics within the sample transfer assembly 1100 and / or the flow rate of the gas entering the sample transfer assembly 1100. The controller 1500 may therefore be able to actively and / or automatically enhance the delivery efficiency of the sample probe system 1000. For example, the controller 1500 may be programmed and / or configured to indicate to the user the delivery efficiency corresponding to a particular configuration of the sample probe system 1000, and the user may selectively adjust the configuration of the sample probe system 1000 to change and / or enhance the delivery efficiency. Specifically, the user may adjust the configuration of the sample probe system 1000 by changing the first flow rate, the second flow rate, and / or the third flow rate in any manner described herein (such as via the controller 1500).

[0117] Additionally or alternatively, the controller 1500 may be programmed and / or configured to automatically adjust the configuration of the sample probe system 1000 to change and / or enhance the efficiency of transport of the ablated material 1008 through the sample transfer assembly 1100. For example, the controller 1500 may receive an indication of the transport efficiency from the ion analyzer 1400 and may automatically adjust the first flow rate, the second flow rate, and / or the third flow rate in any manner described herein to enhance the transport efficiency.

[0118] Figure 2 Another example of a sample probe system 2000 is shown. Figure 2 The sample probe system 2000 is substantially similar to Figure 1A The sample probe system 1000, except as described herein. Figures 1A to 2 In particular, all illustrated components of sample probe system 2000, labeled or unlabeled, may share any suitable features, characteristics, properties, etc. with corresponding components of sample probe system 1000, except as discussed below. Figure 2For those parts marked in FIG. 2, parts marked with reference numerals of the form "2XXX" are intended to be the same as those marked in FIG. Figure 1A Components marked with reference numerals of the form "1XXX" correspond to the components marked with reference numerals of the form "1XXX". For example, Figure 2 The optical components 2020 correspond to Figure 1A The optical component 1020 may be at least substantially identical thereto.

[0119] and Figure 1A Compared to the sample probe system 1000 of FIG. 1 , the sample probe system 2000 lacks a separate sampling conduit, a separate sampling capillary, or a capillary coupling unit. Figure 2 In the example of FIG. 2 , the sample probe system 2000 includes a sample transfer assembly 2100 having a sample transfer conduit 2150 that receives ablated material 2008 directly from a sample 2002. [TP385906CNSEC1] of the sample transfer conduit 2150

[0120] The features may be the sample transfer conduit inner diameter 2124 and / or the sample transfer conduit outer diameter 2126, which may be similar to those described herein. Figure 1A The sampling capillary 1120 and / or the sample transfer conduit 1160 may have values ​​similar to those disclosed.

[0121] exist Figure 2 In the example of FIG. 2 , the sample transfer conduit 2150 includes a sample transfer conduit inlet 2128 and extends away from the sample transfer conduit inlet 2128 along the sample transfer conduit central axis 2122. The sample transfer conduit inlet 2128 and the sample transfer conduit central axis 2122 can be described as corresponding to Figure 1A The sampling capillary inlet 1128 and the sampling capillary central axis 1122 are shown.

[0122] Figure 2 The various parts of the sample transfer conduit 2150 may be similar to Figure 1A The corresponding components of the sample transfer assembly 1100 are described and / or named. For example, and as Figure 2 As shown, the portion of the sample transfer conduit 2150 near the sample transfer conduit inlet 2128 can be described as the sampling conduit 2110 and / or the sampling capillary 2120. Similarly, the portion of the sample transfer conduit 2150 downstream of the sampling conduit 2110 can be described as the sample transfer conduit 2150 and / or the sample transfer conduit 1260. Additionally or alternatively, Figure 2 The sample transfer conduit inlet 2128 can be described as being similar to Figure 1A to Figure 1B The sampling capillary inlet 1128 of the sample transfer assembly 2100 and / or may be described as representing a gas inlet of the sample transfer assembly 2100.

[0123] exist Figure 2In the example of FIG. 2 , the sample transfer conduit 2150 is curved between the sample 2002 and the analyzer inlet 2402. However, this is not required in all examples, and it is also within the scope of the present disclosure that the sample transfer conduit 2150 can be at least substantially straight between the sample 2002 and the analyzer inlet 2402.

[0124] In addition, Figure 2 In the example of , the ionization unit 2040 is at least partially received within the analyzer adapter unit 2170. Specifically, in this example, the ionization unit 2040 includes a corona discharge needle 2044 positioned at least partially within the analyzer adapter unit 2170. When the ablated material 2008 exits the sample transfer conduit 2150 within the analyzer adapter unit 2170, the ionization unit 2040 thus operates to ionize the ablated material 2008 via APCI. Other ionization devices known in the art may be used, such as electrospray, dielectric barrier discharge, etc. It should be understood that Figure 1A and Figure 2 The examples are non-limiting, and any suitable form of ionization unit 1040 / 2040 may be used. Figure 1A and Figure 2 For example, Figure 1A The ionization unit 1040 may additionally or alternatively be Figure 2 It is also within the scope of the present disclosure that the illustrated approach is at least partially received within the analyzer adapter unit 1170. Additionally, it should be understood that each of the ionization unit 1040 and the ionization unit 2040 may include and / or may be any suitable ionization device disclosed herein and / or known in the art.

[0125] and Figure 1A Compared to the sample probe system 1000 of FIG. 1 , the sample probe system 2000 also lacks a capillary junction gas inlet in the sample transfer assembly 2100 for introducing a gas flow between the sample transfer conduit inlet 2128 and the sample transfer conduit outlet 2158. However, similar to Figure 1A Sample probe system [TP385906CNSEC1]

[0126] 1000, various properties of the flow of ablated material 1008 through the sample transfer conduit 2150 can be controlled by adjusting the first flow rate of the first gas flow 2202 through the first gas inlet 2204, as described above with reference to the first gas flow 1202. Similarly, various properties of the flow of ablated material 1008 through the sample transfer conduit 2150 can be controlled by adjusting the sample flow rate of the sample gas flow 2134 entering the sample transfer conduit inlet 2128, as described above with reference to the third gas flow 1134.

[0127] FIG. 3A to FIG. 3CVarious aspects of a sample transfer assembly 3100 are shown, which may be described as representing Figure 1A An example of a sample transfer assembly 1100. Thus, in Figure 1A to Figure 1B and FIG. 3A to FIG. 3C In particular, all illustrated components of sample transfer assembly 3100, labeled or unlabeled, may share any suitable features, characteristics, properties, etc. with corresponding components of sample transfer assembly 1100, except as discussed below. FIG. 3A to FIG. 3C For those parts marked in the Figure 1A Components marked with reference numerals of the form "1XXX" correspond to the components marked with reference numerals of the form "1XXX". For example, FIG. 3A to FIG. 3C The analyzer adapter unit 3170 corresponds to Figure 1A Analyzer adapter unit 1170.

[0128] exist FIG. 3A to FIG. 3C In the example of FIG. 31 , the sample transfer conduit 3160 is coupled to the upstream sample transfer conduit interface 3146 via the upstream sample transfer conduit adapter 3148, which allows the sample transfer conduit 3160 to be removed from the capillary junction unit 3140. Similarly, in this example, the sample transfer conduit 3160 is coupled to the downstream sample transfer conduit interface 3172 via the downstream sample transfer conduit adapter 3174, which allows the sample transfer conduit 3160 to be removed from the analyzer adapter unit 3170. The sampling capillary 1120 is removably attached to the capillary junction unit 3140 at the sampling capillary interface 3144. The ionization unit 3040 includes an electrospray needle 3042 extending within an inner chamber 3142 of the capillary junction unit 3140. FIG. 3A to FIG. 3C Additional aspects of the sample transfer assembly 3100 may be referenced Figure 1A The foregoing discussion of the corresponding components of the sample transfer assembly 1100 is understood.

[0129] Figure 4 is a description of the ablated and ionized sample material (e.g. Figure 1A ablated material 1008 and / or ionized sample particles 1166) are transferred to an analyzer inlet (e.g., Figure 1A Flow chart of an example of a method 400 of an ion analyzer 1400 having an analyzer inlet 1402. In the following discussion, in the context of the method 400, the term corresponding to Figure 1A The various components are described using the terms of the components shown in and discussed above. Therefore, such components described herein with reference to method 400 may be understood to correspond to and / or represent the components described above with reference to Figure 1A Such components may also correspond to the components described above. Figure 2 and / or FIG. 3A to FIG. 3C The parts shown in .

[0130] [TP385906CNSEC1]

[0131] like Figure 4 As shown, method 400 includes ablating a sample at 410 to produce ablated material, and entraining the ablated material in a sample material flow at 420. The sample material flow includes the ablated material and flows within a sample transfer assembly. Method 400 also includes ionizing the ablated material at 440 to produce ionized sample particles, and transmitting the ionized sample particles to an analyzer inlet of an ion analyzer at 450. As described herein, entraining the ablated material in the sample material flow at 420 includes causing a downstream inlet gas flow (e.g., Figure 1A A first gas stream 1202) is flowed into the analyzer inlet to at least partially induce a flow of sample material.

[0132] In some examples, entraining the ablated material in the sample material flow at 420 includes receiving the ablated material into a sampling conduit of a sample transfer assembly, and ionizing the ablated material is performed within the sample transfer conduit of the sample transfer assembly at 440. In some such examples, entraining the ablated material in the sample material flow at 420 is performed such that the sample material flow is at least substantially laminar within the sampling conduit and / or the sample transfer conduit.

[0133] Ablating the sample at 410 can be performed in any suitable manner. For example, ablating the sample at 410 can include ablating and / or atomizing the sample with a laser source, such as a laser source that directs a laser beam to a side of the sample opposite to a side where ablated material flows to a sample transfer assembly. In some examples, ablating the sample at 410 includes ablating with femtosecond laser pulses generated by a laser source and directed to the sample.

[0134] Entraining the ablated material in the sample material flow at 420 may be performed in any suitable manner. For example, entraining the ablated material in the sample material flow at 420 may include causing a sampling capillary gas flow (e.g., Figure 1A The third gas stream 1134 of the sampling conduit flows into the sampling capillary of the sampling conduit. In some such examples, flowing the sampling capillary gas stream at 426 is performed passively. For example, the sampling capillary gas stream can be drawn into the sampling capillary by one or more gas streams initiated downstream of the sampling capillary.

[0135] In some examples, method 400 may include adjusting a flow rate of the sampling capillary gas flow at 428. For example, adjusting the flow rate of the sampling capillary gas flow at 428 may include adjusting a sample separation distance between the sampling capillary and the sample.

[0136] In some examples, additionally or alternatively, entraining the ablated material in the sample material flow at 420 includes causing a sample transfer conduit gas flow (eg, Figure 1A The second gas stream 1302 of the sample transfer assembly flows into a sample transfer conduit of the sample transfer assembly. In some such examples, flowing the sample transfer conduit gas stream at 430 is performed passively. For example, the sample transfer conduit gas stream can be drawn into the sample transfer conduit by one or more gas streams initiated downstream of the sample transfer conduit [TP385906CNSEC1].

[0137] In some examples, method 400 may include adjusting a flow rate of a sample transfer conduit gas flow at 432. For example, a sample transfer assembly may include a sample transfer conduit upstream gas inlet (e.g., Figure 1A A second gas inlet 1300) and an upstream inlet regulator mechanism (e.g., Figure 1A 1304). Thus, adjusting the flow rate of the sample transfer conduit gas flow at 432 may be performed at least in part with the upstream inlet regulator air mechanism. For example, adjusting the flow rate of the sample transfer conduit gas flow at 432 may be performed at least in part by a controller that transmits commands to the upstream inlet regulator mechanism, such as in response to user input and / or based on an automated routine.

[0138] Flowing the downstream inlet gas stream at 422 may be performed in any suitable manner. In some examples, flowing the downstream inlet gas stream at 422 may be performed passively. For example, the downstream inlet gas stream may be drawn into the analyzer inlet by one or more gas streams initiated downstream of the analyzer gas inlet. Specifically, in some examples, entraining the ablated material in the sample material stream at 420 includes generating a motive gas stream downstream of the analyzer inlet at 434. The motive gas stream may be generated, at least in part, by the ion analyzer.

[0139] Generating the motive gas flow at 434 may be operable to induce flow of the downstream inlet gas flow, the sample transfer conduit gas flow, and / or the sampling capillary gas flow. In this manner, actively generating the motive gas flow at 434 may result in passively generating at least a portion of the downstream inlet gas flow, the sample transfer conduit gas flow, and / or the sampling capillary gas flow.

[0140] In some examples, method 400 may include adjusting a flow rate of the downstream inlet gas flow at 424. For example, the sample transfer assembly may include a sample transfer conduit downstream gas inlet (eg, Figure 1AThe embodiment of the present invention is a first gas inlet 1200 of the embodiment of the present invention and a downstream inlet regulator mechanism (e.g., first regulator mechanism 1204) configured to selectively adjust the flow rate of the downstream inlet gas flow. Therefore, adjusting the flow rate of the downstream inlet gas flow at 424 can be at least partially performed with the downstream inlet regulator mechanism. For example, adjusting the flow rate of the downstream inlet gas flow at 424 can be at least partially performed by a controller, such as in response to user input and / or based on an automatic routine to transmit commands to the downstream inlet regulator mechanism.

[0141] Ionizing the ablated material at 440 may be performed in any suitable manner. As an example, ionizing the ablated material at 440 may include mixing the ablated material with an ionized material (such as ionized material produced by an ionization unit). As a more specific example, the ionized material may include and / or be generated by electrospray [TP385906CNSEC1]

[0142] Additionally or alternatively, the ionized material may be generated by an ionization unit that includes and / or is an APCI source, a low temperature plasma source, a glow discharge source, a dielectric barrier discharge source, a high energy photon source, and / or a high energy electron source.

[0143] In some examples, the sample transfer assembly includes a sample transfer conduit, and ionizing the ablated material is performed within the sample transfer conduit (e.g., within a charge transfer region of the sample transfer conduit) at 440. In such examples, method 400 may additionally include entraining a flow of ionized material within the sample transfer conduit to mix with the ablated material within the sample transfer conduit.

[0144] In some other examples, ionizing the ablated material at 440 can be performed downstream of the sample transfer conduit. For example, the sample transfer assembly can include an analyzer adapter unit configured such that the ablated material is transferred from the sample transfer conduit to the analyzer inlet via the analyzer adapter unit, and ionizing the ablated material at 440 can be performed within the analyzer adapter unit.

[0145] Figure 5 The following discussion is intended to provide a brief, general description of an exemplary computing environment in which the disclosed technology may be implemented. For example, Figure 5 One or more aspects of the computing system may represent and / or correspond to Figure 1A The controller 1500 and / or Figure 2 Controller 2500. Specifically, some or all of the computing environment may be used with the methods and apparatus described above to, for example, position a sample probe system relative to a sample, control an optical component of the sample probe system, control an ionization unit of the sample probe assembly, regulate one or more gas flows through the sample probe system, and / or perform any portion of the methods described above.

[0146] Although not required, the disclosed technology is described in the general context of computer executable instructions executed by a personal computer (PC), such as program modules. Typically, program modules include routines, programs, objects, components, data structures, etc. that perform specific tasks or implement specific abstract data types. In addition, the disclosed technology can be implemented with other computer system configurations including: handheld devices, tablet computers, multiprocessor systems, microprocessor-based or programmable consumer electronics, network PCs, microcomputers, mainframe computers, virtual machines, containerized applications, etc. The disclosed technology can also be practiced in a distributed computing environment where remote processing devices linked through a communication network perform tasks. In a distributed computing environment, program modules can be located in both local memory storage devices and remote memory storage devices. In some cases, such processing is provided in a CPM system. The disclosed system can be used to control image acquisition, and provide a user interface and act as an image processor.

[0147] refer to Figure 5 , an exemplary system for implementing the disclosed technology includes a general-purpose computing device in the form of an exemplary PC 500, which includes one or more processing units 502, a system [TP385906CNSEC1]

[0148] Memory 504 and a system bus 506 that couples various system components including system memory 504 to one or more processing units 502. System bus 506 may be any of several types of bus structures including a memory bus or memory controller, a peripheral bus, and a local bus using any of a variety of bus architectures. Exemplary system memory 504 includes read-only memory (ROM) 508 and random access memory (RAM) 510. A basic input / output system (BIOS) 512, containing the basic routines that help transfer information between elements within PC 500, is stored in ROM 508. PC 500 may represent and / or correspond to Figure 1A Controller 1500.

[0149] The exemplary PC 500 also includes one or more storage devices 530, such as a hard disk drive for reading from and writing to a hard disk, a disk drive for reading from or writing to a removable disk, and an optical drive for reading from or writing to a removable optical disk (such as a CD-ROM or other optical media). Such storage devices can be connected to the system bus 506 via a hard disk drive interface, a disk drive interface, and an optical drive interface, respectively. The drive and its associated computer-readable medium provide non-volatile storage of computer-readable instructions, data structures, program modules, and other data for the PC 500. Other types of computer-readable media capable of storing data accessible by the PC, such as magnetic tape cassettes, flash memory cards, solid-state drives, digital video disks, CDs, DVDs, RAM, ROM, etc., can also be used in the exemplary operating environment. Multiple program modules can be stored in the storage device 530 including the following items: an operating system, multiple operating systems, virtual operating systems, one or more application programs, other program modules, and / or program data.

[0150] The exemplary PC 500 may include various devices configured for user interface. For example, a user may enter commands and information into the PC 500 via one or more input devices 540 such as a keyboard and / or a pointing device such as a mouse. For example, a user may enter a command to start image acquisition and / or start one or more methods disclosed herein. Other input devices may include a digital camera, a microphone, a joystick, a game pad, a button, a dial, a satellite dish, a scanner, etc. These and other input devices are often connected to one or more processing units 502 via a serial port interface coupled to the system bus 506, but may be connected via other interfaces such as a parallel port, a game port, a universal serial bus (USB), or a wired or wireless network connection. A monitor 546 or other type of display device is also connected to the system bus 506 via an interface such as a video adapter, and may display one or more images of a sample or specimen before, after, and / or during the execution of one or more methods disclosed herein. The monitor 1246 may also be used to select a segment or specific image alignment and alignment procedure for processing, [TP385906CNSEC1]

[0151] Such as correlation, feature identification and preview area selection or other image selection. Other peripheral output devices may be included, such as speakers and printers (not shown).

[0152] PC 500 can operate in a networked environment using logical connections to one or more remote computers, such as remote computer 560. In some examples, one or more network or communication connections 550 are included. Remote computer 560 can be another PC, a server, a router, a network PC and / or a peer device or other common network node, and typically includes many or all of the elements described above with respect to PC 500, although in some embodiments, the remote computer 560 may be a PC, a server, a router, a network PC, and / or a peer device or other common network node. Figure 5 Only memory storage device 562 is shown. Personal computer 500 and / or remote computer 560 can be connected to a local area network (LAN) and / or a wide area network (WAN). Such networking environments are common in offices, enterprise-wide computer networks, intranets and the Internet.

[0153] like Figure 5 As shown, the memory 590 (or portions of the memory or other memory) may store processor-executable instructions for sample ablation, for gas flow regulation, for sample ionization, and / or for any other process described herein. For example, such processor-executable instructions may cause the PC 500 and / or another component (e.g., Figure 1A Sample Probe System 1000, Figure 2 The Sample Probe System 2000 and / or FIG. 3A to FIG. 3C Any suitable component of the sample probe system 3000 of the present invention) can perform any method disclosed herein. In addition, the memory 590 can include processor-executable instructions for setting cross-correlation, image alignment such as image rotation and translation, selection of reference images and regions of interest, and / or recording platform coordinates for alignment. In some examples, the processor-executable instructions can generate displayed images that show segment identification, processing of preview images, and / or acquisition of additional images.

[0154] General considerations

[0155] As used in this application and in the claims, the singular forms "a", "an", and "the" include the plural forms unless the context clearly dictates otherwise. In addition, the term "comprising" means "including". Furthermore, the term "coupled" does not exclude the presence of intervening elements between the coupled items.

[0156] Unless otherwise indicated, the term "substantially" as used herein refers to the listed values ​​and / or properties and any values ​​and / or properties that are at least 75% of the listed values ​​and / or properties. Equivalently, the term "substantially" refers to the listed values ​​and / or properties and any values ​​and / or properties that differ from the listed values ​​and / or properties by at most 25%. For example, "substantially equal" refers to completely equal amounts, as well as amounts that differ from each other by at most 25%.

[0157] The systems, devices, and methods described herein should not be construed as limiting in any way. On the contrary, the present disclosure is directed to all novel and non-obvious features and aspects of the various disclosed examples, whether individually or in various combinations and sub-combinations formed with each other. Disclosed systems, methods [TP385906CNSEC1]

[0158] The disclosed systems, methods and devices are not limited to any specific aspect or feature or combination thereof, nor do the disclosed systems, methods and devices require any one or more specific advantages or solutions to problems. Any operating theory is for ease of explanation, but the disclosed systems, methods and devices are not limited to such operating theories.

[0159] Although the operations of some of the disclosed methods are described in a particular sequential order for ease of presentation, it should be understood that this manner of description includes rearrangement unless a particular order is required by the specific language described below. For example, the operations described in sequence may be rearranged or performed simultaneously in some cases. In addition, for simplicity, the accompanying drawings may not show the various ways in which the disclosed systems, methods, and devices can be used in conjunction with other systems, methods, and devices. In addition, the specification sometimes uses terms like "produce" and "provide" to describe the disclosed methods. These terms are high-level abstractions of the actual operations performed. The actual operations corresponding to these terms will vary depending on the specific implementation and can be easily discerned by those skilled in the art.

[0160] In some examples, values, procedures, etc. may be characterized by qualifying terms such as "lowest," "best," "minimum," "extreme," etc. It should be understood that such descriptions are intended to indicate that a selection may be made among a number of functional alternatives used, and that such selection is not necessarily better, lesser, or otherwise preferred than other selections.

[0161] Innovations may be described in the general context of computer executable instructions, such as those instructions included in a program module and executed in a computing system on a target real or virtual processor. In general, a program module or component includes a routine, program, library, object, class, component, data structure, etc. that performs a specific task or implements a specific abstract data type. The functions of the program module may be combined or split between program modules as needed in various examples. Computer executable instructions for program modules may be executed in a local or distributed computing system. In general, a computing system or computing device may be local or distributed, and may include any combination of dedicated hardware and / or general hardware with software that implements the functions described herein, and examples of the computing system or computing device include personal computers, handheld devices, tablet computers, multiprocessor systems, microprocessor-based or programmable consumer electronics, network PCs, minicomputers, mainframe computers, virtual machines, containerized applications, etc.

[0162] In various examples described herein, a module (e.g., component or engine) may be "programmed" and / or "coded" to perform certain operations or provide certain functionality, thereby indicating that computer executable instructions for the module may be executed to perform such operations, cause such operations to be performed, or otherwise provide such functionality. Although the functionality described with respect to a software component, module, or engine may be performed as a discrete software unit (e.g., procedure, function, class method), it need not be performed as a separate software unit.

[0163] That is, the functionality may be incorporated into a larger or more general program, such as one or more lines of code in the larger or more general program.

[0164] The algorithm described may, for example, be embodied as software or firmware instructions executed by a digital computer. For example, any of the disclosed methods may be performed by one or more of a computer or other computing hardware that is part of a microscopy and / or ion analysis tool. The computer may be a computer system comprising one or more processors (processing devices) and a tangible, non-transitory computer-readable medium (e.g., one or more optical media disks, volatile memory devices (such as DRAM or SRAM), or non-volatile memory or storage devices (such as hard disk drives, NVRAM, and solid-state drives (e.g., flash drives)). The one or more processors may execute computer-executable instructions stored on one or more tangible, non-transitory computer-readable media, and thereby perform any of the disclosed techniques. For example, software for performing any of the disclosed examples may be stored as computer-executable instructions on the one or more volatile, non-transitory computer-readable media, which, when executed by the one or more processors, cause the one or more processors to perform any of the disclosed techniques or subsets of techniques.

[0165] Additional Embodiments of the Disclosed Technology

[0166] The principles of the disclosed technology have been described and illustrated with reference to the illustrated examples, and it should be appreciated that the illustrated examples may be modified in arrangement and detail without departing from such principles. For example, the example elements executed in software may be implemented in hardware, and vice versa. In addition, the techniques from any example may be combined with the techniques described in any one or more of the other examples. It should be understood that processes and functions such as those described with reference to the illustrated examples may be implemented in a single hardware or software module, or separate modules may be provided. The above specific arrangements are provided for ease of description, and other arrangements may be used.

[0167] Embodiment 1. A system, the system comprising: a sample transfer component, the sample transfer component being configured to receive ablated material discharged from a sample and convey the ablated material to an ion analyzer, wherein the sample transfer component comprises: a sample transfer conduit, the sample transfer conduit being configured to convey the ablated material to an analyzer inlet of the ion analyzer; and one or more gas inlets, the one or more gas inlets being arranged upstream of the analyzer inlet, each gas inlet being configured to receive a corresponding gas flow flowing toward the analyzer inlet and conveying the ablated material toward the analyzer inlet, wherein the sample transfer component is configured so that the mass flow rate entering the analyzer inlet is equal to or greater than the total mass flow rate of the gas flow entering the one or more gas inlets.

[0168] [TP385906CNSEC1]

[0169] Embodiment 2. A system according to any embodiment herein (particularly Embodiment 1), wherein the one or more gas inlets include a first gas inlet disposed downstream of at least a portion of the sample transfer conduit, and wherein the first gas inlet is configured to receive a first gas flow flowing into the analyzer inlet.

[0170] Embodiment 3. A system according to any embodiment described herein (particularly any one of Embodiments 1 to 2), wherein the system is configured so that the first gas flow at least partially entrains the ablated material to flow into the analyzer inlet, so that the proportion of the ablated material entering the sample transfer conduit and continuing to flow to the analyzer inlet is at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, 50-99%, 60-99%, 70-99%, 80-99% or 90-99% or one or more of the above.

[0171] Embodiment 4. A system according to any embodiment herein (particularly any one of embodiments 1 to 5), wherein the system is configured such that the ablated material is mixed with the ionized material within the sample transfer conduit to produce an ionized sample particle flow.

[0172] Embodiment 5. A system according to any embodiment described herein (particularly any one of embodiments 1 to 4), wherein the one or more gas inlets include a second gas inlet, which is arranged upstream of at least a portion of the sample transfer pipeline and is configured to receive a second gas flow flowing into the sample transfer pipeline.

[0173] Embodiment 6. A system according to any embodiment described herein (particularly Embodiment 5), wherein the sample transfer conduit includes a charge transfer region, wherein the ablated material is mixed with an ionized material to ionize the ablated material to produce an ionized sample flow, and wherein the second gas inlet is arranged upstream of the charge transfer region.

[0174] Embodiment 7. A system according to any embodiment herein (particularly any one of embodiments 1 to 6), wherein the sample transfer component comprises a sampling capillary configured to receive the ablated material and transfer the ablated material to the sample transfer conduit.

[0175] Embodiment 8. A system according to any embodiment herein, in particular Embodiment 7, wherein the one or more gas inlets include a sampling capillary inlet of the sampling capillary configured to receive a third gas flow flowing into the sampling capillary.

[0176] Embodiment 9. The system according to any embodiment herein, in particular embodiment 8, wherein the sampling capillary is configured to receive the ablated material via the sampling capillary inlet.

[0177] [TP385906CNSEC1]

[0178] Embodiment 10. The system according to any embodiment herein, in particular any one of embodiments 7 to 9, wherein the sampling capillary and the sample transfer conduit are angled relative to each other at a capillary crossing angle of approximately 90°.

[0179] Embodiment 11. A method according to any embodiment herein (especially any one of embodiments 7 to 10), wherein the inner diameter of the sampling capillary of the sampling capillary is one or more of at least 0.5 millimeters (mm), at least 1 mm, at least 1.5 mm, at least 2 mm, at least 3 mm, at most 5 mm, at most 2.5 mm, at most 1.7 mm, at most 1.2 mm, at most 0.7 mm, 0.5-1.7 mm, 1-2.5 mm or 1.5-5 mm.

[0180] Embodiment 12. A method according to any embodiment herein (especially any one of Embodiments 7 to 11), wherein the system is configured so that the sampling capillary inlet of the sampling capillary is separated from the sample by a sample separation distance, and the sample separation distance is at least 0.1 mm, at least 0.5 mm, at least 1 mm, at least 1.5 mm, at least 2 mm, at least 3 mm, at most 5 mm, at most 2.5 mm, at most 1.7 mm, at most 1.2 mm, at most 0.7 mm, at most 0.2 mm, 0.1-0.7 mm, 0.5-1.2 mm, 1-1.7 mm, 1.5-2.5 mm or 2-5 mm. One or more.

[0181] Embodiment 13. The system according to any embodiment herein, in particular any one of embodiments 7 to 12, wherein the sampling capillary is configured to deliver the ablated material directly to the sample transfer conduit.

[0182] Embodiment 14. A system according to any embodiment herein (particularly any one of embodiments 7 to 13), wherein the sample transfer component includes a sample transfer conduit, the sample transfer conduit includes the sample transfer pipeline, and wherein the sampling capillary is configured to transfer the ablated material to the sample transfer conduit.

[0183] Example 15. A system according to any embodiment described herein (particularly Example 14), wherein the sample transfer conduit includes one or more of the following: a first inlet of the sample transfer conduit, the first inlet of the sample transfer conduit is configured to receive ionized material; a second inlet of the sample transfer conduit, the second inlet of the sample transfer conduit is configured to receive the ablated material; or a sample transfer conduit outlet, the sample transfer conduit outlet is configured to discharge the ablated material to the analyzer inlet.

[0184] Embodiment 16. A system according to any embodiment herein (particularly Embodiment 15), wherein the sample transfer conduit comprises one or more of the sample transfer conduit first inlet, the sample transfer conduit second inlet, or the sample transfer conduit outlet.

[0185] [TP385906CNSEC1]

[0186] Embodiment 17. The system according to any embodiment herein, in particular any one of embodiments 15 to 16, wherein the sampling capillary is coupled to, optionally directly coupled to, the sample transfer conduit second inlet.

[0187] Embodiment 18. A system according to any embodiment herein (particularly any one of Embodiments 15 to 17), wherein the sample transfer component includes a sampling conduit, the sampling conduit includes the sampling capillary, and wherein the sampling conduit is coupled to, optionally directly coupled to, the second inlet of the sample transfer conduit.

[0188] Embodiment 19. A system according to any embodiment herein (particularly any one of embodiments 14 to 18), wherein the sample transfer component comprises a sampling conduit, the sampling conduit comprises the sampling capillary, and wherein the sampling conduit is coupled to, optionally directly coupled to, the sample transfer conduit.

[0189] Embodiment 20. A system according to any embodiment herein, in particular any one of embodiments 14 to 19, wherein the sampling conduit comprises a sampling conduit outlet coupled to the sample transfer conduit at a capillary crossing angle of approximately 90°.

[0190] Embodiment 21. The system according to any embodiment herein, in particular any one of embodiments 14 to 20, wherein the sample transfer conduit is configured to receive the ablated material directly from the sample.

[0191] Embodiment 22. A system according to any embodiment herein, in particular any one of embodiments 14 to 21, wherein the sample transfer conduit is at least partially curved between the sample and the analyzer inlet.

[0192] Embodiment 23. A system according to any embodiment herein (particularly any one of embodiments 1 to 22), wherein the sample transfer component comprises a sampling capillary, and wherein the sample transfer component comprises a capillary coupling unit fluidically coupling the sampling capillary and the sample transfer conduit to each other.

[0193] Embodiment 24. A system according to any embodiment described herein (particularly Embodiment 23), wherein the sample transfer component includes a sampling conduit, the sampling conduit includes the sampling capillary, wherein the sample transfer component includes a sample transfer conduit, the sample transfer conduit includes the sample transfer channel, and wherein the capillary coupling unit includes at least a portion of one or both of the sampling conduit and the sample transfer conduit.

[0194] [TP385906CNSEC1]

[0195] Embodiment 25. The system according to any embodiment herein, in particular any one of embodiments 23 to 24, wherein the capillary junction unit comprises a sampling capillary interface coupling the sampling capillary to the capillary junction unit.

[0196] Embodiment 26. The system according to any embodiment herein, in particular embodiment 25, wherein the sampling capillary interface receives the sampling capillary.

[0197] Embodiment 27. The system according to any embodiment herein, in particular any one of embodiments 25 to 26, wherein the sampling capillary is removably coupled to the sampling capillary interface.

[0198] Embodiment 28. A system according to any embodiment herein, in particular any one of embodiments 23 to 27, wherein the capillary coupling unit comprises an upstream sample transfer channel interface coupling the sample transfer channel to the capillary coupling unit.

[0199] Embodiment 29. A system according to any embodiment herein, in particular embodiment 28, wherein the upstream sample transfer conduit interface receives the sample transfer conduit.

[0200] Embodiment 30. A system according to any embodiment herein, in particular any one of embodiments 28 to 29, wherein the sample transfer conduit is removably coupled to the upstream sample transfer conduit interface.

[0201] Embodiment 31. A system according to any embodiment herein, in particular any one of embodiments 28 to 30, wherein the sample transfer conduit is coupled to the upstream sample transfer conduit interface via an upstream sample transfer conduit adapter.

[0202] Embodiment 32. A system according to any embodiment herein, particularly Embodiment 31, wherein the upstream sample transfer conduit adapter is removably coupled to one or both of the sample transfer conduit and the upstream sample transfer conduit interface.

[0203] Embodiment 33. The system according to any embodiment herein, in particular any one of embodiments 31 to 32, wherein the upstream sample transfer tubing adapter is fixedly coupled to the capillary junction unit.

[0204] Embodiment 34. A system according to any embodiment described herein (in particular any one of embodiments 23 to 33), wherein the capillary junction unit includes a capillary junction unit gas inlet, which is arranged upstream of at least a portion of the sample transfer pipeline and is configured to receive a capillary junction unit gas flow flowing into the sample transfer pipeline.

[0205] Embodiment 35. A system according to any embodiment herein (particularly embodiment 34), wherein the capillary junction unit comprises an upstream inlet regulator mechanism, wherein the upstream inlet regulator [TP385906CNSEC1]

[0206] The mechanism is configured to selectively adjust a second flow rate of the capillary junction unit gas flow into the capillary junction unit gas inlet.

[0207] Embodiment 36. A system according to any embodiment described herein (particularly any one of embodiments 23 to 35), wherein the capillary junction unit defines an inner chamber, wherein the system further comprises an ionization unit configured to introduce ionization material into the sample transfer conduit to ionize the ablated material, and wherein the ionization unit is at least partially received in the inner chamber.

[0208] Embodiment 37. A system according to any embodiment described herein (in particular any one of embodiments 1 to 36), wherein the sample transfer component includes an analyzer adapter unit, and the analyzer adapter unit is configured so that the ablated material is transferred from the sample transfer conduit to the analyzer inlet via the analyzer adapter unit.

[0209] Embodiment 38. A system according to any embodiment herein, in particular Embodiment 37, wherein the analyzer adapter unit comprises the first gas inlet.

[0210] Embodiment 39. A system according to any embodiment herein, in particular any one of embodiments 37 to 38, wherein the sample transfer conduit is directly coupled to the analyzer adapter unit.

[0211] Embodiment 40. A system according to any embodiment herein, in particular any one of embodiments 37 to 38, wherein the analyzer adapter unit comprises a downstream sample transfer conduit interface coupling the sample transfer conduit to the analyzer adapter unit.

[0212] Embodiment 41. A system according to any embodiment herein, in particular embodiment 40, wherein the downstream sample transfer conduit interface receives the sample transfer conduit.

[0213] Embodiment 42. A system according to any embodiment herein, in particular any one of embodiments 40 to 41, wherein the sample transfer conduit is removably coupled to the downstream sample transfer conduit interface.

[0214] Embodiment 43. A system according to any embodiment herein, in particular any one of embodiments 40 to 42, wherein the sample transfer conduit is coupled to the downstream sample transfer conduit interface via a downstream sample transfer conduit adapter.

[0215] Embodiment 44. A system according to any embodiment herein, in particular Embodiment 43, wherein the downstream sample transfer tubing adapter is removably coupled to one or both of the sample transfer tubing and the downstream sample transfer tubing interface.

[0216] Embodiment 45. A system according to any embodiment herein (particularly any one of embodiments 37 to 44), wherein the analyzer adapter unit comprises an analyzer transfer capillary, the sub-[TP385906CNSEC1]

[0217] An analyzer transfer capillary is configured to receive the ablated material from the sample transfer conduit and deliver the ablated material to the analyzer inlet.

[0218] Embodiment 46. The system of any embodiment herein, particularly Embodiment 45, wherein the analyzer transfer capillary is fixedly coupled to at least a portion of the analyzer adapter unit.

[0219] Embodiment 47. A system according to any embodiment herein (particularly any one of Embodiments 45 to 46), wherein the analyzer adapter unit includes a downstream sample transfer pipeline interface that couples the sample transfer pipeline to the analyzer adapter unit, and wherein the analyzer transfer capillary is fixedly coupled to the downstream sample transfer pipeline interface.

[0220] Embodiment 48. A system according to any embodiment herein (particularly any one of Embodiments 40 to 47), wherein the analyzer adapter unit includes a main body portion fixed relative to the analyzer inlet, and wherein the downstream sample transfer pipeline interface is movably coupled to the main body portion.

[0221] Example 49. A system according to any of the embodiments described herein (in particular Example 48), wherein the analyzer adapter unit includes a coupling member, and the downstream sample transfer pipeline interface is coupled to the main body via the coupling member to allow the sample transfer pipeline interface to translate in one or more directions relative to the main body.

[0222] Embodiment 50. A system according to any embodiment herein (particularly Embodiment 49), wherein the analyzer adapter unit includes an analyzer transfer capillary, which is configured to receive the ablated material from the sample transfer conduit and transfer the ablated material to the analyzer inlet, and wherein the coupling member provides a thermal barrier between the analyzer transfer capillary and the main body.

[0223] Embodiment 51. A system according to any embodiment herein, in particular Embodiment 50, wherein the coupling member comprises one or more of a membrane, a gasket, or a flexible seal.

[0224] Embodiment 52. The system according to any embodiment described herein (particularly any one of embodiments 37 to 51) further includes an ionization unit configured to ionize the ablated material, wherein the ionization unit is at least partially received within the analyzer adapter unit.

[0225] Embodiment 53. A system according to any embodiment herein, in particular Embodiment 52, wherein the ionization unit is configured to ionize the ablated material as it flows between the sample transfer conduit and the analyzer inlet.

[0226] [TP385906CNSEC1]

[0227] Embodiment 54. The system according to any embodiment herein (particularly any one of embodiments 1 to 53) further comprises an ionization unit configured to introduce ionization material into the sample transfer conduit to ionize the ablated material.

[0228] Embodiment 55. A system according to any embodiment herein, in particular Embodiment 54, wherein the ionization unit comprises an electrospray needle, and wherein the ionized material comprises charged electrospray droplets.

[0229] Embodiment 56. A system according to any embodiment described herein (especially any one of embodiments 54 to 55), wherein the ionization unit includes one or more of an atmospheric pressure chemical ionization (APCI) source, a low-temperature plasma source, a glow discharge source, a dielectric barrier discharge source, a high-energy photon source, or a high-energy electron source.

[0230] Embodiment 57. A system according to any embodiment herein, in particular any one of embodiments 54 to 56, wherein the system is configured such that the ablated material is mixed with the ionized material within the sample transfer conduit to ionize the ablated material.

[0231] Embodiment 58. The system according to any embodiment described herein (in particular any one of embodiments 1 to 57) further includes an optical component having a laser source, which is configured to direct a laser beam to a target area of ​​the sample to ablate the sample within the target area.

[0232] Embodiment 59. A system according to any embodiment herein, in particular Embodiment 58, wherein the laser source comprises a femtosecond laser.

[0233] Embodiment 60. A system according to any embodiment herein, in particular any one of embodiments 58 to 59, wherein the laser beam comprises an infrared laser beam.

[0234] Embodiment 61. A system according to any embodiment herein, in particular any one of embodiments 58 to 60, wherein the laser source is configured to generate a 3 ) of the sample delivers a pulse energy of about 1 nanojoule (nJ) to about 10 microjoules (μJ).

[0235] Embodiment 62. A system according to any embodiment herein (particularly any one of Embodiments 58 to 61), wherein the diameter of the target area is one or more of at least 1 μm, at least 5 μm, at least 10 μm, at least 15 μm, at least 20 μm, at least 30 μm, at most 50 μm, at most 25 μm, at most 17 μm, at most 12 μm, at most 7 μm, at most 2 μm, 1-7 μm, 5-12 μm, 10-17 μm, 15-25 μm or 20-50 μm.

[0236] Embodiment 63. A system according to any embodiment herein, in particular any one of embodiments 58 to 62, wherein the volume of the target area is at least 2 μm 3 , at least 5μm 3 , at least 10μm 3 , at least 50μm 3 , at least 100μm 3 , at least 300μm 3 , up to 500μm 3 , at most [TP385906CNSEC1]

[0237] 200μm 3 , up to 70μm 3 , up to 20μm 3 , up to 7μm 3 , up to 3μm 3 , 2-7μm 3 、5-20μm 3 、10-70μm3 、50-200μm 3 or 100-500μm 3 One or more of .

[0238] Embodiment 64. A system according to any embodiment herein, in particular any one of embodiments 58 to 63, wherein the optical component includes a sample imaging system configured to image a portion of the sample.

[0239] Embodiment 65. A system according to any embodiment herein (particularly Embodiment 64), wherein the optical component is configured to direct the laser beam to the sample at least partially along the beam axis, and wherein the sample imaging system is configured to receive light from the sample at least partially along the beam axis.

[0240] Embodiment 66. The system according to any embodiment described herein (particularly Embodiment 65) further includes a sampling capillary, which is configured to receive the ablated material and transfer the ablated material to the sample transfer pipeline, wherein the sampling capillary extends along and defines a sampling capillary central axis, and wherein the beam axis is spaced apart from the sampling capillary central axis by a lateral beam offset.

[0241] Embodiment 67. A system according to any embodiment described herein (particularly Embodiment 66), wherein the lateral beam offset is one or more of at least 0.2 mm, at least 0.5 mm, at least 1.0 mm, at most 1.5 mm, at most 0.7 mm, at most 0.3 mm, 0.2-0.7 mm or 0.5-1.5 mm.

[0242] Embodiment 68. A system according to any embodiment herein (in particular any one of Embodiments 66 to 67), wherein the sampling capillary has a sampling capillary inner diameter, and wherein the lateral beam offset is one or more of the following: at least 10% of the sampling capillary inner diameter, at least 20% of the sampling capillary inner diameter, at least 30% of the sampling capillary inner diameter, at least 40% of the sampling capillary inner diameter, at most 45% of the sampling capillary inner diameter, at most 35% of the sampling capillary inner diameter, at most 25% of the sampling capillary inner diameter, at most 15% of the sampling capillary inner diameter, 10-25% of the sampling capillary inner diameter, 20-35% of the sampling capillary inner diameter, or 25-45% of the sampling capillary inner diameter.

[0243] Embodiment 69. A system according to any embodiment herein (in particular any one of embodiments 64 to 68), wherein the optical component includes an objective lens configured to collect light from the sample for imaging by the sample imaging system.

[0244] Embodiment 70. A system according to any embodiment herein (particularly any one of Embodiments 58 to 69), further comprising a sample stage having a first side configured for placing the sample thereon and a second side opposite to the first side, wherein the optical component is configured to direct the laser beam to the second side of the sample stage.

[0245] Embodiment 71. The system according to any embodiment described herein (particularly any one of Embodiments 58 to 70), further includes a sampling capillary, which is configured to receive the ablated material and transfer the ablated material to the sample transfer pipeline, wherein the sampling capillary extends along and defines a sampling capillary central axis, and wherein the target area is separated from the sampling capillary central axis by a lateral beam offset.

[0246] Embodiment 72. A system according to any embodiment described herein (particularly Embodiment 71), wherein the lateral beam offset is one or more of at least 0.2 mm, at least 0.5 mm, at least 1.0 mm, at most 1.5 mm, at most 0.7 mm, at most 0.3 mm, 0.2-0.7 mm or 0.5-1.5 mm.

[0247] Embodiment 73. A system according to any embodiment herein (in particular any one of Embodiments 71 to 72), wherein the sampling capillary has a sampling capillary inner diameter, and wherein the lateral beam offset is one or more of the following: at least 10% of the sampling capillary inner diameter, at least 20% of the sampling capillary inner diameter, at least 30% of the sampling capillary inner diameter, at least 40% of the sampling capillary inner diameter, at most 45% of the sampling capillary inner diameter, at most 35% of the sampling capillary inner diameter, at most 25% of the sampling capillary inner diameter, at most 15% of the sampling capillary inner diameter, 10-25% of the sampling capillary inner diameter, 20-35% of the sampling capillary inner diameter, or 25-45% of the sampling capillary inner diameter.

[0248] Embodiment 74. A system according to any embodiment herein, in particular any one of embodiments 1 to 73, wherein the ion analyzer comprises a mass spectrometer.

[0249] Embodiment 75. A system according to any embodiment herein (particularly embodiment 74), wherein the mass spectrometer is configured as a time-of-flight (TOF) mass spectrometer, an Orbitrap TM One or more of a mass spectrometer, a linear ion trap mass spectrometer, a quadrupole mass spectrometer, a quadrupole ion trap mass spectrometer, a sector magnetic mass spectrometer, or a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer.

[0250] Embodiment 76. A system according to any embodiment herein (particularly any one of embodiments 1 to 75), wherein the ion analyzer comprises one or more of an optical spectrometer, a PCR machine and / or a sequencing machine.

[0251] Embodiment 77. A system according to any embodiment herein (particularly any one of embodiments 1 to 76), wherein the sample transfer conduit inner diameter of the sample transfer conduit is at least 0.5 mm, at least 1 mm, at least 1.5 mm, at least 2 mm, at least 3 mm, at most 5 mm, at most 2.5 mm, [TP385906CNSEC1]

[0252] One or more of at most 1.7 mm, at most 1.2 mm, at most 0.7 mm, 0.5-1.2 mm, 1-1.7 mm, 1.5-2.5 mm or 2-5 mm.

[0253] Embodiment 78. A system according to any embodiment described herein (particularly any one of embodiments 1 to 77), wherein the sample transfer component includes a sample transfer line heater, and the sample transfer line heater is configured to adjust the temperature of the sample transfer line to adjust the ionization of the ablated material.

[0254] Embodiment 79. A system according to any embodiment herein, particularly Embodiment 78, wherein the sample transfer line heater is directly coupled to the sample transfer line.

[0255] Embodiment 80. A system according to any embodiment herein, in particular any one of embodiments 1 to 79, wherein the first gas flow comprises nitrogen.

[0256] Embodiment 81. The system according to any embodiment described herein (especially any one of embodiments 1 to 80) also includes a first regulator mechanism, which is configured to selectively adjust a first flow rate of the first gas flow flowing into the first gas inlet.

[0257] Embodiment 82. A system according to any embodiment herein (particularly any one of Embodiments 1 to 81), wherein the one or more gas inlets include a second gas inlet, which is disposed upstream of at least a portion of the sample transfer conduit and is configured to receive a second gas flow flowing into the sample transfer conduit, and wherein the second gas flow includes nitrogen.

[0258] Embodiment 83. A system according to any embodiment described herein (in particular any one of Embodiments 1 to 82), wherein the one or more gas inlets include a second gas inlet, which is disposed upstream of at least a portion of the sample transfer conduit and is configured to receive a second gas flow flowing into the sample transfer conduit, and also includes a second regulator mechanism, which is configured to selectively adjust a second flow rate of the second gas flow flowing into the second gas inlet.

[0259] Embodiment 84. The system according to any embodiment described herein (in particular any one of embodiments 1 to 83) further includes a sampling capillary, which is configured to receive the ablated material and transfer the ablated material to the sample transfer pipeline, wherein the sampling capillary is configured to receive a third gas flow flowing into the sampling capillary.

[0260] Embodiment 85. A system according to any embodiment herein, particularly Embodiment 84, wherein the third gas flow comprises nitrogen.

[0261] [TP385906CNSEC1]

[0262] Embodiment 86. The system according to any embodiment described herein (in particular any one of Embodiments 84 to 85) further includes a capillary positioning stage, which is configured to selectively control the position of the sampling capillary relative to the sample, wherein the capillary positioning stage is configured to selectively change the sample separation distance between the sampling capillary inlet of the sampling capillary and the sample to adjust a third flow rate of the third gas flow into the sampling capillary.

[0263] Embodiment 87. The system according to any embodiment herein, in particular Embodiment 86, wherein the sampling capillary is supported by the capillary positioning stage.

[0264] Embodiment 88. The system according to any embodiment herein, in particular any one of embodiments 86 to 87, wherein the sampling capillary is directly coupled to the capillary positioning stage.

[0265] Embodiment 89. A system according to any embodiment herein (particularly any one of Embodiments 86 to 87), wherein the sample transfer component includes a capillary coupling unit that fluidically couples the sampling capillary and the sample transfer channel to each other, and wherein the capillary coupling unit is directly coupled to the capillary positioning stage.

[0266] Embodiment 90. A method comprising one or more of: ablating a sample to produce ablated material; entraining the ablated material in a sample material flow, the sample material flow comprising the ablated material and flowing within a sample transfer assembly; ionizing the ablated material to produce ionized sample particles; or transmitting the ionized sample particles to an analyzer inlet of an ion analyzer, wherein entraining the ablated material in the sample material flow comprises flowing a downstream inlet gas flow to the analyzer inlet to at least partially induce the sample material flow.

[0267] Embodiment 91. A method according to any embodiment herein, in particular Embodiment 90, wherein entraining the ablated material in the sample material flow is performed such that the sample material flow is laminar within at least a portion of the sample transfer assembly.

[0268] Example 92. A method according to any embodiment herein (in particular any one of Embodiments 90 to 91), wherein the sample transfer assembly includes a sampling conduit and a sample transfer conduit, wherein entraining the ablated material in the sample flow includes receiving the ablated material into the sampling conduit, and wherein ionizing the ablated material is performed within the sample transfer conduit.

[0269] Embodiment 93. A method according to any embodiment herein (particularly Embodiment 92), wherein entraining the ablated material in the sample material flow is performed so that the sample material flow is laminar within one or both of the sampling conduit and the sample transfer conduit.

[0270] [TP385906CNSEC1]

[0271] Embodiment 94. A method according to any embodiment herein (particularly any one of Embodiments 92 to 93), wherein the sampling conduit comprises a sampling capillary, and wherein entraining the ablated material in the sample flow comprises flowing a sampling capillary gas flow into the sampling capillary.

[0272] Embodiment 95. The method according to any embodiment herein, in particular Embodiment 94, wherein said flowing the sampling capillary gas flow into the sampling capillary is performed passively.

[0273] Embodiment 96. The method according to any embodiment described herein (especially any one of embodiments 94 to 95) further comprises adjusting the flow rate of the sampling capillary gas flow.

[0274] Embodiment 97. The method according to any embodiment herein, in particular Embodiment 96, wherein adjusting the flow rate of the sampling capillary gas flow comprises adjusting a sample separation distance between the sampling capillary and the sample.

[0275] Embodiment 98. A method according to any embodiment herein (particularly any one of embodiments 90 to 97), wherein the sample transfer component includes a sample transfer conduit, and wherein entraining the ablated material in the sample flow includes flowing a sample transfer conduit gas flow into the sample transfer conduit.

[0276] Embodiment 99. A method according to any embodiment herein, in particular Embodiment 98, wherein said causing the sample transfer conduit gas flow to flow into the sample transfer conduit is performed passively.

[0277] Embodiment 100. The method according to any embodiment described herein (particularly any one of embodiments 98 to 99), further comprising adjusting the flow rate of the gas flow in the sample transfer conduit.

[0278] Embodiment 101. A method according to any embodiment herein (particularly Embodiment 100), wherein the sample transfer component includes a sample transfer conduit upstream gas inlet configured to receive the sample transfer conduit gas flow and an upstream inlet regulator mechanism configured to selectively adjust the flow rate of the sample transfer conduit gas flow, and wherein the adjustment of the flow rate of the sample transfer conduit gas flow is performed by the upstream inlet regulator mechanism, optionally by a controller that sends a command to the upstream inlet regulator mechanism.

[0279] Embodiment 102. A method according to any embodiment herein, in particular any one of Embodiments 90 to 101, wherein flowing the downstream inlet gas flow into the analyzer inlet is performed passively.

[0280] Embodiment 103. The method according to any embodiment described herein (especially any one of embodiments 90 to 102) further includes adjusting the flow rate of the downstream inlet gas flow.

[0281] [TP385906CNSEC1]

[0282] Embodiment 104. A method according to any embodiment herein (particularly Embodiment 103), wherein the sample transfer component includes a downstream gas inlet of a sample transfer conduit configured to receive the downstream inlet gas flow and a downstream inlet regulator mechanism configured to selectively adjust the flow rate of the downstream inlet gas flow, and wherein the adjustment of the flow rate of the downstream inlet gas flow is performed by the downstream inlet regulator mechanism, optionally by a controller that sends a command to the downstream inlet regulator mechanism.

[0283] Embodiment 105. A method according to any embodiment herein (particularly any one of embodiments 90 to 104), wherein the sample transfer assembly comprises a sample transfer conduit, and wherein the ionizing of the ablated material is performed within the sample transfer conduit.

[0284] Embodiment 106. The method according to any embodiment herein, in particular Embodiment 105, wherein ionizing the ablated material comprises mixing the ablated material with an ionized material.

[0285] Embodiment 107. A method according to any embodiment herein, in particular embodiment 106, wherein the ionized material comprises electrospray droplets generated by an electrospray needle.

[0286] Embodiment 108. A method according to any embodiment described herein (especially any one of embodiments 106 to 107), wherein the ionized material is produced by an ionization unit, the ionization unit comprising one or more of an atmospheric pressure chemical ionization (APCI) source, a low temperature plasma source, a glow discharge source, a dielectric barrier discharge source, a high-energy photon source, or a high-energy electron source.

[0287] Embodiment 109. A method according to any embodiment herein (particularly any one of embodiments 90 to 108), wherein the sample transfer component includes a sample transfer conduit, and wherein the ionizing of the ablated material is performed downstream of the sample transfer conduit.

[0288] Embodiment 110. A method according to any embodiment herein (in particular any one of embodiments 90 to 108), wherein the sample transfer component includes an analyzer adapter unit, the analyzer adapter unit is configured such that the ablated material is transferred from the sample transfer conduit to the analyzer inlet via the analyzer adapter unit, and wherein the ionization of the ablated material is performed within the analyzer adapter unit.

[0289] Embodiment 111. The method according to any embodiment herein, in particular any one of embodiments 90 to 110, wherein ablating the sample comprises ablating by a laser source.

[0290] Embodiment 112. A method according to any embodiment herein, particularly Embodiment 111, wherein the laser source directs a laser beam to a side of the sample opposite to a side where the ablated material flows into the sample transfer assembly.

[0291] [TP385906CNSEC1]

[0292] Embodiment 113. A method according to any embodiment herein, particularly Embodiment 111, wherein the laser source directs a laser beam to the same side of the sample as the side on which the ablated material flows into the sample transfer assembly.

[0293] Embodiment 114. The method according to any embodiment herein, in particular any one of embodiments 111 to 113, wherein ablating the sample by the laser source comprises ablating by femtosecond laser pulses.

[0294] Embodiment 115. A method according to any embodiment herein, in particular any one of embodiments 90 to 114, wherein entraining the ablated material comprises generating a motive gas flow downstream of the analyzer inlet.

[0295] Embodiment 116. A method according to any embodiment herein, in particular Embodiment 115, wherein the motive gas flow is at least partially generated by the ion analyzer.

[0296] Embodiment 117. A method according to any embodiment described herein, in particular any one of embodiments 115 to 116, wherein the motive gas flow at least partially induces the downstream inlet gas flow.

[0297] Embodiment 118. A method according to any embodiment herein (particularly any one of Embodiments 115 to 117), wherein the sample transfer component includes a sample transfer conduit, wherein entraining the ablated material in the sample flow includes flowing a sample transfer conduit gas flow into the sample transfer conduit, and wherein the moving gas flow at least partially induces the sample transfer conduit gas flow.

[0298] Embodiment 119. A method according to any embodiment herein (particularly any one of Embodiments 115 to 118), wherein the sampling conduit comprises a sampling capillary, wherein entraining the ablated material in the sample flow comprises flowing a sampling capillary gas flow into the sampling capillary, and wherein the moving gas flow at least partially induces the sampling capillary gas flow.

[0299] Embodiment 120. A computer-readable medium, comprising stored processor-executable instructions, which, when executed by a processor, cause the processor to perform a method according to any one of Embodiments 1 to 119.

[0300] In view of the many possible embodiments in which the principles of the disclosed technology can be applied, it should be recognized that the embodiments shown are only preferred embodiments and should not be taken as limiting the scope of the disclosed technology. Rather, the scope is defined by the appended claims. Therefore, we claim protection for all that falls within the scope of these claims.

Claims

1. A system, comprising: a sample transfer assembly configured to receive ablated material discharged from the sample and to transfer the ablated material to an ion analyzer, wherein the sample transfer assembly comprises: a sample transfer conduit configured to deliver the ablated material to an analyzer inlet of the ion analyzer; and one or more gas inlets disposed upstream of the analyzer inlet, each gas inlet configured to receive a respective gas flow flowing toward the analyzer inlet and conveying the ablated material toward the analyzer inlet, The sample transfer assembly is configured such that a mass flow rate into the analyzer inlet is equal to or greater than a total mass flow rate of the gas flow into the one or more gas inlets.

2. The system of claim 1 , wherein the one or more gas inlets include a first gas inlet disposed downstream of at least a portion of the sample transfer conduit, and wherein the first gas inlet is configured to receive a first gas flow flowing into the analyzer inlet.

3. The system of claim 1 , wherein the one or more gas inlets include a second gas inlet disposed upstream of at least a portion of the sample transfer conduit and configured to receive a second gas flow into the sample transfer conduit.

4. The system of claim 1 , wherein the sample transfer assembly comprises a sampling capillary configured to receive the ablated material and transfer the ablated material to the sample transfer conduit, wherein the one or more gas inlets comprise a sampling capillary inlet of the sampling capillary configured to receive a third gas flow flowing into the sampling capillary, and wherein the sampling capillary is configured to receive the ablated material via the sampling capillary inlet.

5. The system of claim 4, wherein the sampling capillary and the sample transfer conduit are angled relative to each other at a capillary crossing angle of approximately 90°. 6 . The system of claim 4 , wherein the sample transfer assembly comprises a capillary coupling unit that fluidically couples the sampling capillary and the sample transfer conduit to each other.

7. The system of claim 6, wherein the capillary junction unit comprises a second gas inlet of the one or more gas inlets, the second gas inlet being disposed upstream of at least a portion of the sample transfer conduit and configured to receive a second gas flow flowing into the sample transfer conduit.

8. The system of claim 6, wherein the capillary junction unit defines an inner chamber, wherein the system further comprises an ionization unit configured to introduce ionization material into the sample transfer conduit to ionize the ablated material, and wherein the ionization unit is at least partially received in the inner chamber.

9. The system of claim 8, wherein the ionization unit comprises an electrospray needle.

10. A system according to claim 1, wherein the one or more gas inlets include a first gas inlet disposed downstream of at least a portion of the sample transfer conduit, wherein the sample transfer assembly includes an analyzer adapter unit, the analyzer adapter unit is configured such that the ablated material is transferred from the sample transfer conduit to the analyzer inlet via the analyzer adapter unit, and wherein the analyzer adapter unit includes the first gas inlet.

11. The system of claim 10, further comprising an ionization cell configured to ionize the ablated material, wherein the ionization cell is at least partially received within the analyzer adapter unit.

12. The system of claim 1, further comprising: an optical assembly having a laser source, the optical assembly configured to direct a laser beam to a target region of the sample to ablate the sample within the target region; and a sample stage having a first side configured for placing the sample thereon and a second side opposite the first side, The optical assembly is configured to direct the laser beam to the second side of the sample stage.

13. A method comprising: [TP385906CNSEC1] ablating the sample to produce ablated material; entraining the ablated material in a sample material stream, the sample material stream including the ablated material and flowing within a sample transfer assembly; ionizing the ablated material to produce ionized sample particles; as well as delivering the ionized sample particles to an analyzer inlet of an ion analyzer such that a mass flow rate into the analyzer inlet is equal to or greater than a mass flow rate of the sample material flow, wherein entraining the ablated material in the sample flow comprises flowing a downstream inlet gas flow into the analyzer inlet to at least partially induce the sample material flow, and wherein entraining the ablated material in the sample material flow is performed such that the sample material flow is laminar within at least a portion of the sample transfer assembly.

14. The method of claim 13, wherein the sample transfer assembly comprises a sample transfer conduit downstream gas inlet configured to receive the downstream inlet gas flow and a downstream inlet regulator mechanism configured to selectively adjust a flow rate of the downstream inlet gas flow, and wherein the method further comprises adjusting the flow rate of the downstream inlet gas flow with the downstream inlet regulator mechanism.

15. The method of claim 13, wherein the sample transfer assembly comprises a sampling capillary, wherein the entraining the ablated material in the sample flow comprises flowing a sampling capillary gas flow into the sampling capillary, and wherein the method further comprises adjusting a flow rate of the sampling capillary gas flow by adjusting a sample separation distance between the sampling capillary and the sample.

16. The method of claim 13, further comprising adjusting a flow rate of the downstream inlet gas flow.

17. The method of claim 13, wherein the sample transfer assembly comprises a sample transfer conduit, and wherein the ionizing the ablated material is performed within the sample transfer conduit.

18. The method of claim 13, wherein the sample transfer assembly comprises a sample transfer conduit, and wherein the ionizing the ablated material is performed downstream of the sample transfer conduit.

19. A computer-readable medium comprising stored processor-executable instructions which, when executed by a processor, cause the processor to: [TP385906CNSEC1] adjusting a flow rate of a sample material flow induced to flow within a sample transfer assembly by at least a sampling capillary gas flow and a downstream inlet gas flow such that the sample material flow is laminar within at least a portion of the sample transfer assembly, wherein the sample material flow comprises ablated material that is ablated from a sample and entrained into the sample material flow and directed into an analyzer inlet of an ion analyzer, and wherein adjusting the flow rate is performed such that the mass flow rate entering the analyzer inlet is equal to or greater than the total mass flow rate of the sampling capillary gas flow and the downstream inlet gas flow.

20. The computer-readable medium of claim 19, wherein the processor-executable instructions, when executed by the processor, further cause the processor to perform one or both of the following operations: (i) adjusting the flow rate of the sample material flow by sending a command to a mobile station to adjust the sample separation distance between the sample capillary and the sample; and (i) adjusting the flow rate of the downstream inlet gas flow by sending a command to a downstream inlet regulator mechanism, the downstream inlet regulator mechanism selectively regulating the flow rate of the downstream inlet gas flow through the downstream gas inlet of the sample transfer conduit.

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