Advection-based ablative material delivery

Abstract

In some examples, an apparatus may include an advection flow structure including a pathway to deliver an ablated sample from an ablated region to an ionized region by advection through a gas flow.

Description

Cross-reference to related applications

[0001] This application claims priority to co-pending U.S. Provisional Patent Application Serial No. 63 / 499,677, filed May 2, 2023, entitled “Advection-based Transport of Ablated Material,” the disclosure of which is incorporated herein by reference in its entirety. Background Technology

[0002] In techniques such as matrix-assisted laser desorption / electrospray ionization (MALDESI) mass spectrometry, laser ablation can be used for chemical analysis and imaging. In one example, MALDESI is based on the convergence of analyte particles ejected from a sample in a plume by an infrared (IR) laser with a second ion plume generated by an electrospray emitter, to produce an electrospray-like ionization from the laser-ablated surface. High-energy laser pulses can be used to remove the material of interest from the sample. In MALDESI, the ablated material can be adsorbed onto droplets originating from the electrospray. These droplets can generate ions that are analyzed by mass spectrometry. Therefore, detection may require adsorbing the ablated material onto the electrospray droplets, and those droplets, or the ions injected from them, are collected by the mass spectrometer inlet. Attached Figure Description

[0003] The features of this disclosure are shown by way of example and are not limited to the following one or more figures, wherein like reference numerals indicate like elements, in the figures:

[0004] Figure 1 shows the layout of a first embodiment of a flow-based ablation material delivery device according to an example of this disclosure, the device including a flow structure including a pathway for delivering an ablation sample from an ablation region to an ionization region via a gas flow through the flow.

[0005] Figure 2 illustrates the layout of a second embodiment of a flow-based ablation material delivery device according to an example of this disclosure, the device including an ablation shell at an ablation region, an ionization shell at an ionization region, and wherein a flow-based structure connects the ablation shell to the ionization shell via a passage.

[0006] Figure 3 illustrates the layout of a third embodiment of an advection-based ablation material delivery device according to an example of this disclosure, the device including an additional pump and a differential pressure sensor, the additional pump being separate from the mass spectrometer pump for evacuating the ionization shell, and the differential pressure sensor for controlling the differential pressure between the ablation shell and the ionization shell.

[0007] Figure 4 shows the layout of a fourth embodiment of an advection-based ablation material delivery device according to an example of this disclosure, the device including a gas flow controller at the ablation housing;

[0008] Figure 5 shows the layout of a fifth embodiment of an advection-based ablation material delivery device according to an example of this disclosure, the device including a Venturi pump for delivering an ablation sample from an ablation region to an ionization region via another gas flow.

[0009] Figure 6 illustrates the operating principle of infrared-matrix-assisted laser desorption / electrospray ionization mass spectrometry (IR-MALDESI) according to an example of this disclosure.

[0010] Figure 7 illustrates an operational configuration associated with IR-MALDESI according to an example of this disclosure;

[0011] Figure 8 shows the ESI data associated with the operational configuration of Figure 7, according to an example of this disclosure.

[0012] Figure 9 illustrates the layout of a sixth embodiment of an advection-based ablation material delivery device according to an example of this disclosure, the device including orthogonal electrospray ionization (ESI).

[0013] Figure 10 illustrates an orthogonal ESI configuration based on an example from this disclosure.

[0014] Figure 11 shows the ESI data associated with the orthogonal ESI configuration of Figure 10, according to an example of this disclosure.

[0015] Figure 12 shows the layout of a seventh embodiment of a flow-based ablation material delivery device according to an example of this disclosure, the device including a structure for guiding the flow of ablation material to collect the ablation material;

[0016] Figure 13 shows further details of the layout of a seventh embodiment of a flow-based ablation material delivery device according to an example of this disclosure, the device including the outlet of a flow pipe;

[0017] Figure 14 shows example MALDESI data of a seventh embodiment of an advection-based ablation material delivery device according to examples in this disclosure;

[0018] Figure 15 shows the layout of an eighth embodiment of a flow-based ablation material delivery device according to an example of this disclosure, the device including a Venturi pump for the flow gas powered by atomizing gas.

[0019] Figure 16A shows further details of a Venturi pump for advection gas powered by atomizing gas, as exemplified in this disclosure.

[0020] Figure 16B shows an enlarged view of a Venturi pump as an example according to this disclosure.

[0021] Figure 17A illustrates the layout of a ninth embodiment of an advection-based ablation material delivery device according to an example of this disclosure, the device including an extractor structure for collecting the ablation plume using advection gas; and

[0022] Figure 17B shows further details of the layout of a ninth embodiment of an advection-based ablation material delivery device according to an example of this disclosure, the device including an extractor structure for collecting the ablation plume using advection gas. Detailed Implementation

[0023] For simplicity and illustrative purposes, this disclosure is described primarily through examples. Numerous specific details are set forth in the following description to provide a thorough understanding of this disclosure. However, it will be readily apparent that this disclosure can be practiced without being limited to these specific details. In other instances, some methods and structures have not been described in detail to avoid unnecessarily obscuring this disclosure.

[0024] Throughout this disclosure, the terms “a” and “an” are intended to mean at least one of a particular element. As used herein, the term “includes” means including but not limited to, and the term “including” means including but not limited to. The term “based on” means at least partially based on.

[0025] This document discloses an apparatus and a method for advection-based ablation material delivery. With the apparatus and method disclosed herein, sample vapor or aerosol can be delivered from an ablation zone to a separate ionization zone via advection (e.g., entrainment by a gas flow). The width and length of the delivery channel, as well as the gas flow rate, can be controlled to ensure efficient and rapid sample delivery with relatively minimal interference to ionization and charge collection.

[0026] Regarding advection-based ablation material delivery as disclosed herein, in matrix-assisted laser desorption / electrospray ionization (MALDESI) mass spectrometry, detection may require ablation material adsorbed onto electrospray droplets, and those droplets, or ions injected from them, to be collected by the mass spectrometer inlet. In this regard, close proximity of the electrospray, sample, and mass spectrometer inlet may be required to increase the probability of each of these steps occurring. However, optimal environmental conditions (such as temperature, gas velocity, and electric field) for sample storage, ablation material delivery, ionization, and collection by the MS inlet may vary. In this respect, proximity may require large spatial gradients or suboptimal conditions. This impairment can adversely affect sensitivity, analysis speed, or residue. Furthermore, by forcing the sample close to the electrospray and MS inlet, instrument reproducibility, safety, power consumption, ease of use, cost, robustness, and flexibility may also be compromised.

[0027] To at least address the aforementioned sensitivity concerns, the ablation plume can be collimated using a tapered capillary containing the sample. However, since the residence time can be relatively long compared to the diffusion time, this collimation using a tapered capillary may not be very effective in reducing losses to the wall. Liquid samples may be drawn into the capillary, which could limit the velocity, cause residue, and may not be suitable for solid samples.

[0028] In some cases, nano-desorption electrospray ionization (NanoDESI) can completely avoid gas-phase diffusion by dissolving the sample in a liquid and then electrospraying the solution. This can limit speed and spatial resolution. Furthermore, applying nanoDESI to liquid samples in well plates for high-throughput analysis may include drawbacks related to residue and speed limitations.

[0029] The apparatus and method disclosed herein address at least the aforementioned drawbacks and additional aspects by providing efficient transport of ablated sample material to a remote ionization region (which resolves several constraints imposed by co-location). Removing these constraints provides improvements in sensitivity, speed, residue, stability, and noise.

[0030] In other examples, it may be preferable not to alter the sample in any way prior to ablation. Proximity between the ESI and the sample can compromise this objective. For instance, ESI may require evaporation, thus supplying heat and dry gas. When the sample and ESI source are relatively close, the heat and dry gas may cause the sample to evaporate before ablation, potentially leading to unreproducibility and measurement errors. In this regard, the apparatus and methods disclosed herein provide independent optimization of both sample and ESI temperatures.

[0031] In a further example, regarding gas composition, humidity can aid ablation for some samples. Furthermore, living cells require oxygen, but optimal ionization may require a different gas composition. In this regard, the apparatus and methods disclosed herein address residues or degradation between samples by providing control over the sample environment.

[0032] Furthermore, the transport of ablation material to charged droplets can be inefficient or relatively slow. In some cases, diffusion or uncontrolled advection may be achieved, and sensitivity can be improved by using controlled advection. For typical gas velocity and distance values ​​between the sample and ESI, advection may be relatively faster than diffusion. Shorter transport times can reduce sample dilution caused by diffusion, which can disperse the sample in all directions. By entraining the ablation sample in a controlled gas flow, the apparatus and methods disclosed herein provide independent optimization of the conditions for ablation, electrospraying, and MS capture. For example, in addition to evaporating the sample before ablation, the dry gas flow may also guide the ablation material away from the MS inlet via the counter-effect of advection. In this regard, the apparatus and methods disclosed herein provide independent selection of the gas velocities for collecting the ablation material and the dry gas.

[0033] In other examples, the delivery of charged particles (e.g., charged droplets or ions) to the MS inlet may depend on an electric field. The presence of the sample and its holder may alter said electric field, making it impossible for charges to be efficiently drawn into the MS. The apparatus and methods disclosed herein can provide independent optimization and control of the electric field, regardless of sample properties. Separation can prevent ESI from charging insulating samples. Furthermore, the sample stream can be introduced into the electrospray plume at locations where adsorption, ionization, and collection are likely to occur. This ability to select the introduction location of the ablation sample in the electrospray can be particularly important, taking into account the effects of advection flow on the electrospray itself and the optimal droplet size for adsorption.

[0034] The improvements in sensitivity discussed above can also provide benefits related to stability or reproducibility. Gas velocity, temperature, and electric field can change slowly due to a variety of different mechanisms. The sample may redirect the gas, absorb heat, evaporate, and become charged if it is insulating. Furthermore, these instabilities can depend on the sample holder, liquid level, surface roughness, solvent, and any matrix. When analyzing diverse samples, these dependencies can negatively impact reproducibility. Separating the sample and the ESI region can promote the stability of key parameters.

[0035] Many sample loss mechanisms can also fluctuate on even shorter timescales, comparable to the measurement duration, and thus contribute to measurement noise. In this regard, the apparatus and method disclosed herein provide improvements in measurement noise by stabilizing rapidly fluctuating parameters. An example of relatively rapidly fluctuating parameters is gas velocity in turbulent flow. The gas velocity field used for advection can be laminar and in a steady state, while the gas velocity in the ESI region can be turbulent.

[0036] The apparatus and methods disclosed herein offer improvements in speed and residue because they can use controlled advection instead of diffusion or uncontrolled advection. Dependence can slow down the rate of measurement. Diffusion can mix materials from different samples, thus leading to residue, which can also be negatively affected by uncontrolled gas flows (e.g., eddies that recycle ablated material).

[0037] The apparatus and methods disclosed herein further provide improvements in sensitivity, speed, residual effects, measurement error, robustness, and ease of use. Additionally, the apparatus and methods disclosed herein simplify the addition of MALDESI to ESI instruments with minimal modifications to the ESI source.

[0038] While the foregoing discussion of the apparatus and methods disclosed herein refers to MALESI-MS, these concepts can be applied to any instrument using ablation and chemical analysis.

[0039] According to another aspect of the apparatus and methods disclosed herein, in some cases, the electrospray emitter can be directly pointed at the mass spectrometer inlet. In other cases, there is a reverse flow of drying gas. This geometry can be detrimental because a large number of undesolvated droplets from the ESI emitter may enter the mass spectrometer inlet, leading to increased noise and signal instability. Furthermore, the reverse flow of drying gas may disperse desolvated droplets or ions before they interact with the laser-ablated analyte, thereby reducing sensitivity.

[0040] To at least address the aforementioned drawbacks of operating an electrospray emitter directly pointed at the mass spectrometer inlet, by moving the ESI emitter 90° so that it sprays orthogonally to the MS inlet, the ESI plume can still interact with the laser ablation plume, thereby generating charged particles that can be electrostatically drawn into the MS inlet. In this regard, the ESI emitter can be moved from 30° to 170°, and is preferably positioned at 90°. Any drying gas exiting the MS inlet can be used to dry the ESI droplets without interfering with the formation of the original ESI plume. Voltage can be applied to both the ESI emitter and the MS inlet to shape the field and manipulate both the ESI ions and the resulting sample ions.

[0041] The apparatus and methods disclosed herein further provide decoupling of heating and drying from the electrospray ionization process. The apparatus and methods disclosed herein provide electrospray ion generation for the IR-MALDESI process with reduced noise and higher ionization efficiency, while decoupling the desolvation process from the electrospray ion production process.

[0042] According to the examples disclosed herein, an apparatus may include a lateral flow structure comprising a pathway for transporting an ablation sample from an ablation region to an ionization region via a gas flow through lateral flow.

[0043] For the aforementioned equipment, the advection flow structure may include a pipe, wherein the pipe includes a passage.

[0044] For the aforementioned device, the length of the passage can be determined to reduce losses caused by the ablation of the sample diffusing into the walls of the advection flow structure.

[0045] The aforementioned device may include an ablation shell at the ablation region and an ionization shell at the ionization region. A lateral flow structure may connect the ablation shell to the ionization shell via a passage.

[0046] For the aforementioned device, the ablation shell may include an ablation shell pressure, which is greater than the ionization shell pressure of the ionization shell.

[0047] The aforementioned device may further include a pressure generator operatively connected to the ablation housing to generate an ablation housing pressure greater than the ionization housing pressure of the ionization housing.

[0048] The aforementioned apparatus may further include a mass spectrometer connected to the ionization enclosure. The mass spectrometer may include a mass spectrometer pump for evacuating the ionization enclosure.

[0049] The aforementioned device may further include an additional pump, separate from the mass spectrometer pump, for evacuating the ionization shell. A differential pressure sensor can control the differential pressure between the ablation shell and the ionization shell.

[0050] The aforementioned device may further include a Venturi pump for transporting the ablation sample from the ablation region to the ionization region via another gas flow.

[0051] The aforementioned apparatus may further include an electrospray ionization (ESI) emitter for emitting ions to collide with analyte particles ejected from a laminar flow structure. A mass spectrometer (MS) including an MS inlet can receive ions subjected to electrospray ionization by the ESI emitter. The MS inlet may be orthogonally positioned relative to the ESI emitter.

[0052] Based on the examples disclosed herein, an apparatus may include an ablation shell at an ablation region and / or an ionization shell at an ionization region. Advection flow structures may include pathways for transporting an ablation sample from the ablation region to the ionization region via advection.

[0053] According to the examples disclosed herein, one method may include using advection to transport an ablation sample from the ablation region through a pathway of an advection flow structure to the ionization region.

[0054] In the above method, the ablation region may include an ablation shell, and the ionization region may include an ionization shell. The method may further include transporting the ablation sample from the ablation shell through a passage to the ionization shell.

[0055] The above method may further include maintaining the ablation shell at an ablation shell pressure greater than the ionization shell pressure of the ionization shell.

[0056] The above method may further include generating an ablation shell pressure by a pressure generator operatively connected to the ablation shell, the ablation shell pressure being greater than the ionization shell pressure of the ionization shell.

[0057] The above method may further include receiving ions ionized by electrospray-like ionization from the ionization shell through the MS inlet of a mass spectrometer (MS).

[0058] The above method may further include evacuating the ionized casing via an MS pump.

[0059] The above method may further include evacuating the ionized housing by a separate pump, which is separate from the MS pump.

[0060] The above method may further include emitting ions using an electrospray ionization (ESI) emitter to collide with analyte particles ejected from a laminar flow structure, and receiving the ions subjected to the electrospray ionization by the ESI emitter through the MS inlet of a mass spectrometer (MS). The MS inlet may be orthogonally positioned relative to the ESI emitter.

[0061] Figure 1 illustrates the layout of a first embodiment of a flow-based ablation material delivery device (hereinafter also referred to as “device 100”) according to an example of this disclosure, the device including a flow structure comprising a pathway for delivering an ablation sample from an ablation region to an ionization region via a gas flow through the flow.

[0062] Referring to Figure 1, the device 100 may include a lateral flow structure 102, which includes a passage 104 for conveying an ablation sample 106 from an ablation region 108 to an ionization region 110 via the advection of a gas flow. The lateral flow structure may include a tube 112, which includes the passage 104. According to the examples disclosed herein, the length of the passage 104 may be determined to reduce losses due to diffusion of the ablation sample into the walls 114 of the lateral flow structure.

[0063] Referring again to Figure 1, the ablation sample 106 can be transported via a controlled gas flow through advection (e.g., entrainment). The geometry of the gas flow and advection flow structure 102 can be selected to minimize losses from diffusion and turbulence.

[0064] Flow rate The tube length l of tube 112 can be selected to reduce losses due to diffusion to the wall. In some cases, the sample of interest is non-volatile and can adhere to the wall of tube 112 upon contact. If the distance diffused during the time the material spends in the tube (e.g., residence time) is small relative to the tube diameter, the losses can be relatively small.

[0065] The ratio of diffusion time to residence time can be derived from... Given, where φ is the diffusion constant. Using the piston flow approximation for the flow, the characteristic flow rate in pipe 112 can be obtained from... = 2 μL limit. When the flow is... When the flow rate is increased several times, diffusion losses can be reduced. Further increases in flow rate exceeding... It may offer minimal benefit, and could be detrimental if the flow becomes turbulent. Several times greater than The flow rate can be optimized because it can reduce diffusion losses while avoiding turbulence, unrealistically large pressure differences, and interference in the ESI region.

[0066] The aforementioned principle can also be applied to implementations that do not use pipes. In such implementations, the loss can enter the free space opposite to the wall of pipe 112.

[0067] The use of tube 112 can be advantageous in terms of gas flow control, area isolation, robustness against external disturbances, and prevention of residues caused by gas circulation.

[0068] Example values ​​for parameters that can be used in MALDESI instruments may include a tube 112 with a length l = 40 mm and an inner diameter d = 6 mm. Particles may include a diffusion constant φ = 0.2 cm⁻¹. 2 / s, which is typical for small molecules in air at normal temperature and pressure. However, large molecules and aerosol droplets can include even lower diffusion constants. The characteristic flux can be specified as... = 5cm 3 / s. From the Poiseuille flow, the pressure drop across the pipe can be roughly estimated at 0.12 Pa. The actual pressure drop is likely much larger because the flow is not fully developed and could be several times greater. Run it.

[0069] Flow can be generated in several ways. For example, a first technique may include generating and controlling a pressure difference between the two housings (e.g., as disclosed herein with respect to Figure 2). Gas will flow from the ablation zone 108 to the ionization zone 110 when the pressure in the ablation zone (108; P1) is greater than the pressure in the ionization zone (110; P2). A preferred value for the pressure difference can be determined empirically, by calculation or calibration of the tube's conductivity. Control of the pressure difference can be achieved using various control schemes, such as mechanical regulators and electronic control systems.

[0070] Figure 2 illustrates the layout of a second embodiment of a flow-based ablation material delivery device (hereinafter also referred to as “device 200”) according to an example of this disclosure, the device including an ablation shell at an ablation region, an ionization shell at an ionization region, and wherein a flow-based structure connects the ablation shell to the ionization shell via a passage.

[0071] Referring to FIG. 2, device 200 may include an ablation shell 214 at the ablation region and an ionization shell 202 at the ionization region. Advection flow structure 102 may connect ablation shell 214 to ionization shell 202 via passage 104. According to the examples disclosed herein, ablation shell 214 may include an ablation shell pressure 206 (e.g., P1) greater than the ionization shell pressure 208 (e.g., P2) of ionization shell 202. Pressure generator 204 (e.g., gas source) may be operatively connected to ablation shell 214 to generate an ablation shell pressure 206 greater than the ionization shell pressure 208 of ionization shell 202. Mass spectrometer 210 may be connected to ionization shell 202. According to the examples disclosed herein, mass spectrometer 210 may include a mass spectrometer pump 212 for evacuating ionization shell 202.

[0072] Referring again to Figure 2, the pressure difference (P1 and P2) can be generated by pressurizing the ablation shell 214, pumping the ionization shell 202, or both. The pressurized gas can have a controlled composition (e.g., humidity, oxygen, CO2 concentration, etc.) and temperature. Excess pressurized gas can be evacuated. Evacuation of the ionization shell 202 can be performed using a pump from the mass spectrometer (e.g., 212) or a separate pump. In some cases, the total gas flow rate of the ESI (e.g., nebulized gas, dry gas, solvent vapor, etc.) may exceed the gas flow rate into the MS inlet, and a separate pump may be required.

[0073] Figure 3 illustrates the layout of a third embodiment of an advection-based ablation material delivery device (hereinafter also referred to as “device 300”) according to an example of this disclosure, the device including an additional pump and a differential pressure sensor, the additional pump being separate from the mass spectrometer pump for evacuating the ionization shell, and the differential pressure sensor for controlling the differential pressure between the ablation shell and the ionization shell.

[0074] Referring to Figure 3, a separate pump 302, independent of the mass spectrometer pump 212, can evacuate the ionization housing 308. A differential pressure sensor 304 can control the differential pressure between the ablation housing 310 and the ionization housing 308.

[0075] Referring again to Figure 3, in some examples disclosed herein, the ionization housing 308 can be pumped via both the MS inlet and the additional pump 302. This can be applied when adding a MALDESI to an existing ESI instrument. In some cases, gases from the ESI source (including solvent vapors) can be pumped through the exhaust port. This implementation can use a differential pressure sensor 304, a continuously variable valve 306, and a control system (not shown) to control the pressure difference between the ablation housing 310 and the ionization housing 308. By stabilizing the differential pressure, advection flow can also be stabilized. In the examples of Figure 3, the flow can be nonlinear in the pressure difference. In other examples, the ablation housing 310 can utilize a controlled gas that is pressurized slightly above atmospheric pressure.

[0076] Figure 4 illustrates the layout of a fourth embodiment of an advection-based ablation material delivery device (hereinafter also referred to as “device 400”) according to an example of this disclosure, the device including a gas flow controller at the ablation housing.

[0077] Referring to Figure 4, compared to the example in Figure 3, for device 400, a gas flow controller 402 may be located at the ablation housing 404. Additionally, the ionization housing 406 may include an exhaust port 408. The gas flow controller 402 and the exhaust port 408 can provide a specified pressure difference for maintaining the ablation housing 404 and the ionization housing 406.

[0078] Figure 5 illustrates the layout of a fifth embodiment of an advection-based ablation material delivery device (hereinafter also referred to as “device 500”) according to an example of this disclosure, the device including a Venturi pump for delivering an ablation sample from an ablation region to an ionization region via another gas flow.

[0079] Referring to Figure 5, a Venturi pump 502 can be used to transport the ablation sample 504 from the ablation region 506 to the ionization region 508 via another gas flow. In this regard, in some cases, closing both regions may not be practical, and the flow can be generated by the Venturi pump 502, a fan, or a jet. The Venturi pump can accelerate the gas used for advection by introducing a second gas flow (e.g., a driving gas) at high speed in the advection direction. As the driving flow decelerates, it can entrain gas to produce advection flow. An approximation of the maximum pressure difference that can be generated can be specified by Bernoulli's equation. To minimize dilution, the area of ​​the jet can be relatively small compared to the cross-sectional area of ​​the tube 510.

[0080] Instead of the Venturi pump 502, other devices can be used to generate advection flow in open environments. Similar to the Venturi pump 502, other high-velocity streams can entrain secondary flows for sample advection. For example, countercurrent drying gas coaxial with the MS inlet can entrain secondary flows. Similarly, electrospray ionization (ESI) itself can entrain gas in its wake. This wake can be generated by atomizing gas or by accelerating the gas through charged droplets. Fans can also be used to generate flow in open environments. Other techniques for actuating flow can include acoustic flow and natural convection.

[0081] Figure 6 illustrates the operating principle of infrared-matrix-assisted laser desorption / electrospray ionization mass spectrometry (IR-MALDESI) according to an example of this disclosure.

[0082] Referring to Figure 6, MALDESI is based on the convergence of analyte particles ejected from the sample in a plume 606 by an IR laser 600 and a second ion plume generated by an electrospray emitter 602 to generate an electrospray-like ionization 604 from the laser-ablated surface. The resulting charged particles can be electrostatically drawn into the MS inlet 608.

[0083] Figure 7 illustrates an operational configuration associated with IR-MALDESI, based on an example from this disclosure.

[0084] Referring to Figure 7, the orientation of the electrospray emitter 702, laser 704, and MS inlet 706 is shown for the operational configuration of system 700. In the example of Figure 7, system 700 can operate in electrospray ionization (ESI) mode, where the ESI liquid flow rate is 1.5 μL / min. The ESI liquid may contain compounds that generate tracking ions with m / z of 121 and m / z of 922 to monitor ESI intensity and stability.

[0085] Figure 8 shows the ESI data associated with the operational configuration of Figure 7, according to an example of this disclosure.

[0086] Referring to Figure 8, as the dry gas flow rate leaving the MS inlet increases from 1 L / min to 9 L / min, the electrospray plume, as shown by the image at 800, and the ESI signal, as shown by the EIC at 802 m / z 121 and 804 m / z 922, become increasingly noisy as the signal strength decreases.

[0087] Figure 9 illustrates the layout of a sixth embodiment of a flow-based ablation material delivery device (hereinafter also referred to as “device 900”) according to an example of this disclosure, the device comprising orthogonal ESI.

[0088] Referring to Figure 9, an example orientation of the ESI emitter 902, MS inlet 904, and laser 906 is shown. As shown, the ESI emitter 902 can be positioned at 90º relative to the MS inlet 904, such that the ESI emitter 902 sprays orthogonally to the MS inlet 904. In this regard, the ESI emitter 902 can be positioned relative to the MS inlet 904 in the range of 30º to 170º, and preferably at 90º. With this orientation of the ESI emitter 902 and MS inlet 904, the ESI plume can interact with the laser ablation plume, thereby generating charged particles that can be electrostatically drawn into the MS inlet 904. The orthogonal orientation of the ESI emitter 902 relative to the MS inlet 904 can be implemented in conjunction with or independently of MALDESI as disclosed herein.

[0089] Figure 10 illustrates an orthogonal ESI configuration based on an example from this disclosure.

[0090] Referring to Figure 10, the ESI emitter 1000 can emit ions to interact with analyte particles ejected from the advection flow structure. The MS 1002, including the MS inlet 1004, can receive ions ionized by the electrospray-like ionization of the ESI emitter 1000. The MS inlet 1004 can be orthogonally positioned relative to the ESI emitter 1000.

[0091] Figure 11 shows the ESI data associated with the orthogonal ESI configuration of Figure 10, according to an example of this disclosure.

[0092] Referring to Figure 11, as the dry gas flow rate leaving the MS inlet increases from 1 L / min to 9 L / min, the ESI signal remains relatively stable, as shown by the EIC values ​​of 121 m / z at 1100 and 922 m / z at 1102 (compared to the example in Figure 8). Therefore, both stability and signal strength depend less on the gas flow rate shown compared to the example in Figure 8.

[0093] Figure 12 illustrates the layout of a seventh embodiment of an advection-based ablation material transport device (hereinafter also referred to as “device 1200”) according to an example of this disclosure, the device including a structure for guiding advection flow to collect ablation material.

[0094] Referring to Figure 12, device 1200 may include a structure 1202 disposed above a sample 1204, which may include a liquid sample. Structure 1202 may guide advection flow 1206, as shown. Structure 1202 facilitates the collection of ablation material by directing advection flow (e.g., via advection gas flow) as shown at 1210 into advection tube 1212. In the example of Figure 12, device 1200 may include a lens 1214 having a focal length of 75 mm, which may vary between 25 mm and 150 mm.

[0095] Figure 13 shows further details of the layout of a device 1200 according to an example of this disclosure, the device including the outlet of a duct.

[0096] Referring to Figure 13, for device 1200, the advection tube 1212 may include an outlet 1300. Device 1200 may further include an electrospray needle 1302 and an ionization chamber 1304.

[0097] Figure 14 shows example MALDESI data for device 1200 according to an example of this disclosure text.

[0098] Referring to Figure 14, for device 1200, a MALDESI response of 30 pulses / second is shown at 1400, and an average MALDESI response is shown at 1402.

[0099] Figure 15 shows the layout of an eighth embodiment of an advection-based ablation material delivery device (hereinafter also referred to as “device 1500”) according to an example of this disclosure.

[0100] Referring to Figure 15, device 1500 may include using ESI atomizing gas 1502 as the driving gas for venturi pump 1504. In this regard, venturi pump 1504 may be used for advection gas powered by atomizing gas 1502. Device 1500 may include laser beam 1506 to facilitate the collection of ablation material by directing advection flow (e.g., via advection gas flow) as shown at 1508 into advection tube 1510. Venturi pump 1504 may be used for advection gas powered by atomizing gas 1502 and mixed with ESI liquid flow 1512. Therefore, advection flow structure 1514 may include passage 1516 for transporting ablation sample 1518 from ablation region 1520 to ionization region 1522 via advection by gas flow.

[0101] Figure 16A shows further details of a Venturi pump for advection gas powered by atomizing gas, as exemplified in this disclosure. Figure 16B shows an enlarged view of a Venturi pump, as exemplified in this disclosure.

[0102] Referring to Figures 16A and 16B, the Venturi pump 1504 may include a tip 1600 for atomizing gas and liquid samples. A tube 1602 may be used for advection gas. A housing 1604 may be used for drawing in advection gas. Further, the Venturi pump 1504 may include an outlet 1606 for electrospraying and advection gas.

[0103] Figure 17A shows the layout of a ninth embodiment of an advection-based ablation material delivery device (hereinafter also referred to as "device 1700") according to an example of this disclosure, the device including an extractor structure for collecting the ablation plume using advection gas. Figure 17B shows further details of the layout of device 1700 according to an example of this disclosure.

[0104] Referring to Figure 17A, the device 1700 may include an extractor 1702 for collecting the ablation plume using advection gas. In this regard, the extractor 1702 can direct the gas flow to the vicinity of the ablation plume. The advection gas flow can be directed as shown at 1704. The laser path and sample are shown accordingly at 1706 and 1708.

[0105] Referring to Figure 17B, device 1700 may include an aperture for a laser at 1710. A lateral gas flow may be directed through lateral tube 1712.

[0106] The examples described and illustrated herein are of one kind and some of their variations. The terminology, descriptions, and figures used herein are set forth by way of illustration only and are not intended to be limiting. Many variations are possible within the spirit and scope of the subject matter and are intended to be defined by the appended claims and their equivalents, wherein, unless otherwise stated, all terms shall be understood in their broadest reasonable sense.

Claims

1. An apparatus comprising: A laminar flow structure, the laminar flow structure including a pathway for transporting an ablation sample from an ablation region to an ionization region via a gas flow through laminar flow.

2. The device according to claim 1, wherein, The advection flow structure includes a pipe, and the pipe includes the passage.

3. The device according to claim 1, wherein, The length of the passage is determined to reduce losses caused by the ablation sample diffusing into the walls of the advection flow structure.

4. The device according to claim 1, further comprising: The ablated outer shell at the ablation zone; as well as The ionization shell at the ionization region, The advection flow structure connects the ablation shell to the ionization shell via the passage.

5. The device according to claim 4, wherein, The ablation shell includes an ablation shell pressure, which is greater than the ionization shell pressure of the ionization shell.

6. The device according to claim 4, further comprising: A pressure generator operatively connected to the ablation housing to generate an ablation housing pressure greater than the ionization housing pressure of the ionization housing.

7. The device according to claim 4, further comprising: A mass spectrometer connected to the ionization shell.

8. The device according to claim 7, wherein, The mass spectrometer includes a mass spectrometer pump for evacuating the ionization shell.

9. The device according to claim 8, further comprising: An additional pump, separate from the mass spectrometer pump, is used to evacuate the ionization casing; as well as A differential pressure sensor is used to control the differential pressure between the ablation shell and the ionization shell.

10. The device according to claim 1, further comprising: A Venturi pump, used to transport the ablation sample from the ablation region to the ionization region via another gas flow.

11. The device according to claim 1, further comprising: A Venturi pump for transporting the ablation sample from the ablation region to the ionization region via electrospray ionization (ESI) atomized gas.

12. The device according to claim 1, further comprising: An extractor structure for collecting an ablation plume associated with the ablation sample using advection gas.

13. The device according to claim 1, further comprising: An electrospray ionization (ESI) emitter is used to emit ions to collide with analyte particles ejected from the advection flow structure; as well as A mass spectrometer (MS), comprising an MS inlet for receiving ions subjected to electrospray ionization by the ESI emitter, The MS inlet is orthogonally positioned relative to the ESI transmitter.

14. An apparatus comprising: At least one of the following: The ablation shell at the ablation area, or The ionized outer shell at the ionization region; as well as A laminar flow structure, the laminar flow structure including a pathway for transporting an ablation sample from the ablation region to the ionization region via laminar flow.

15. A method comprising: Advection is used to transport the ablation sample from the ablation region through the pathway of the advection flow structure to the ionization region.

16. The method according to claim 15, wherein, The ablation region includes an ablation shell, and the ionization region includes an ionization shell; the method further includes: The ablation sample is transported from the ablation shell through the passage to the ionization shell.

17. The method of claim 16, further comprising: The ablation shell is maintained at an ablation shell pressure that is greater than the ionization shell pressure of the ionization shell.

18. The method of claim 16, further comprising: Ions subjected to electrospray ionization from the ionization shell are received through the MS inlet of a mass spectrometer (MS).

19. The method of claim 18, further comprising: The ionized casing is evacuated by the MS pump of the MS.

20. The method of claim 19, further comprising: The ionized casing is evacuated by a separate pump, which is separate from the MS pump.

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