Method of Mass Analysis - Controlling Viscosity of Solvent for OPP Operation
20230028264 · 2023-01-26
Inventors
Cpc classification
B01L3/022
PERFORMING OPERATIONS; TRANSPORTING
B01L3/0268
PERFORMING OPERATIONS; TRANSPORTING
B01L3/50851
PERFORMING OPERATIONS; TRANSPORTING
B01L3/0279
PERFORMING OPERATIONS; TRANSPORTING
International classification
B01L3/00
PERFORMING OPERATIONS; TRANSPORTING
Abstract
A droplet (415) is ejected from a surface (411) of a fluid sample containing an analyte using an ejector (420). A solvent is pumped into a solvent inlet (432) of an open port probe (OPP) (430) spaced apart from the surface using a pump (438). The solvent is pumped to send it from the solvent inlet (432) to a tip (431) of the OPP (430) through a solvent capillary (434) of the OPP (430), receive the droplet (415) at the tip (431) where the droplet is combined with the solvent to form an analyte-solvent dilution, and transport the dilution from the tip (431) to an output (435) of the OPP (430) through a sample capillary (436) of the OPP (430). The solvent is heated to a temperature above a threshold temperature using a heating element (437). The solvent is heated to reduce the viscosity of the solvent below a threshold viscosity and maintain the viscosity below the threshold viscosity as the dilution is transported from the tip (431) to the outlet (435).
Claims
1. A system for transporting an analyte in a fluid sample to an analytical instrument and controlling the viscosity of the fluid sample, comprising: (a) a reservoir housing a fluid sample containing an analyte, the fluid sample having a fluid surface; (b) an ejector that ejects a droplet of the fluid sample from the fluid surface; and (c) a continuous flow open port probe (OPP) spaced apart from the fluid surface, comprising (i) a sampling tip for receiving the ejected droplet of the fluid sample, (ii) a solvent inlet for receiving a solvent from a solvent source, (iii) a solvent transport capillary for transporting the solvent from the solvent inlet to the sampling tip, where the ejected droplet combines with the solvent to form an analyte-solvent dilution, (iv) a sample outlet through which the analyte-solvent dilution is directed away from the OPP to an analytical instrument, (v) a sample transport capillary for transporting the analyte-solvent dilution from the sampling tip to the sample outlet, wherein the sample transport capillary and the solvent transport capillary are in fluid communication at the sampling tip, and (vi) a heating element that heats the solvent to a temperature above a threshold temperature in order to reduce a viscosity of the solvent below a threshold viscosity and maintain the viscosity of the solvent below the threshold viscosity as the analyte-solvent dilution is transported from the sampling tip to the sample outlet.
2. The system of claim 1, wherein the heating element is located before, surrounding, or in line with the solvent inlet.
3. The system of claim 1, wherein the heating element is located before, surrounding, or in line with the solvent transport capillary.
4. The system of claim 1, wherein a second heating element is located surrounding the sample transport capillary to maintain the viscosity of the solvent below the threshold viscosity as the analyte-solvent dilution is transported from the sampling tip to the sample outlet.
5. The system of claim 1, further including a solvent pump operably connected to and in fluid communication with the solvent inlet for controlling solvent flow rate within the solvent transport capillary.
6. The system of claim 1, wherein the heating element is located in or surrounding the solvent pump.
7. The system of claim 1, wherein the solvent comprises water (H.sub.2O).
8. The system of claim 1, wherein the solvent comprises at least 50 percent water (H.sub.2O).
9. The system of claim 1, wherein the solvent comprises isopropyl alcohol (IPA).
10. The system of claim 1, wherein the solvent comprises methanol (MeOH).
11. The system of claim 1, wherein the solvent comprises acetonitrile (ACN)
12. The system of claim 1, further including a gas inlet through which a nebulizing gas flows from a gas source to the sample outlet so that the analyte-solvent dilution is drawn out of the sample outlet by the Venturi effect caused by the flow of the nebulizing gas and a gas pressure regulator operably connected to the gas inlet to control the nebulizing gas flow, wherein the nebulizing gas flow is held constant by the gas pressure regulator as the solvent is heated by the heating element in order to increase the flow of the analyte-solvent dilution through the sample transport capillary.
13. The system of claim 1, wherein the nebulizing gas flow is reduced by the gas pressure regulator as the solvent is heated by the heating element in order to maintain a constant flow of the analyte-solvent dilution through the sample transport capillary.
14. A method for transporting an analyte in a fluid sample to an analytical instrument and controlling the viscosity of the fluid sample, comprising: ejecting a droplet from a fluid surface of a fluid sample containing an analyte that is housed in a reservoir using an ejector; pumping a solvent from a solvent source into a solvent inlet of a continuous flow open port probe (OPP) spaced apart from the fluid surface using a solvent pump in order to transport the solvent from the solvent inlet to a sampling tip of the OPP through a solvent transport capillary of the OPP, receive the ejected droplet at the sampling tip where the ejected droplet is combined with the solvent to form an analyte-solvent dilution, and transport the analyte-solvent dilution from the sampling tip to a sample output of the OPP through a sample transport capillary of the OPP; and heating the solvent to a temperature above a threshold temperature using a heating element in order to reduce a viscosity of the solvent below a threshold viscosity and maintain the viscosity of the solvent below the threshold viscosity as the analyte-solvent dilution is transported from the sampling tip to the sample outlet.
15. A computer program product, comprising a non-transitory and tangible computer-readable storage medium whose contents include a program with instructions being executed on a processor so as to perform a method for transporting an analyte in a fluid sample to an analytical instrument and controlling the viscosity of the fluid sample, the method comprising: providing a system, wherein the system comprises one or more distinct software modules, and wherein the distinct software modules comprise a control module; instructing an ejector to eject a droplet from a fluid surface of a fluid sample containing an analyte that is housed in a reservoir; instructing a solvent pump to pump a solvent from a solvent source into a solvent inlet of a continuous flow open port probe (OPP) spaced apart from the fluid surface in order to transport the solvent from the solvent inlet to a sampling tip of the OPP through a solvent transport capillary of the OPP, receive the ejected droplet at the sampling tip where the ejected droplet is combined with the solvent to form an analyte-solvent dilution, and transport the analyte-solvent dilution from the sampling tip to a sample output of the OPP through a sample transport capillary of the OPP; and instructing a heating element to heat the solvent to a temperature above a threshold temperature in order to reduce a viscosity of the solvent below a threshold viscosity and maintain the viscosity of the solvent below the threshold viscosity as the analyte-solvent dilution is transported from the sampling tip to the sample outlet.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0042] The skilled artisan will understand that the drawings, described below, are for illustration purposes only. The drawings are not intended to limit the scope of the present teachings in any way.
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[0050]
[0051] Before one or more embodiments of the present teachings are described in detail, one skilled in the art will appreciate that the present teachings are not limited in their application to the details of construction, the arrangements of components, and the arrangement of steps set forth in the following detailed description or illustrated in the drawings. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting.
DESCRIPTION OF VARIOUS EMBODIMENTS
Computer-Implemented System
[0052]
[0053] Computer system 200 may be coupled via bus 202 to a display 212, such as a cathode ray tube (CRT) or liquid crystal display (LCD), for displaying information to a computer user. An input device 214, including alphanumeric and other keys, is coupled to bus 202 for communicating information and command selections to processor 204. Another type of user input device is cursor control 216, such as a mouse, a trackball or cursor direction keys for communicating direction information and command selections to processor 204 and for controlling cursor movement on display 212. This input device typically has two degrees of freedom in two axes, a first axis (i.e., x) and a second axis (i.e., y), that allows the device to specify positions in a plane.
[0054] A computer system 200 can perform the present teachings. Consistent with certain implementations of the present teachings, results are provided by computer system 200 in response to processor 204 executing one or more sequences of one or more instructions contained in memory 206. Such instructions may be read into memory 206 from another computer-readable medium, such as storage device 210. Execution of the sequences of instructions contained in memory 206 causes processor 204 to perform the process described herein. Alternatively, hard-wired circuitry may be used in place of or in combination with software instructions to implement the present teachings. Thus, implementations of the present teachings are not limited to any specific combination of hardware circuitry and software.
[0055] In various embodiments, computer system 200 can be connected to one or more other computer systems, like computer system 200, across a network to form a networked system. The network can include a private network or a public network such as the Internet. In the networked system, one or more computer systems can store and serve the data to other computer systems. The one or more computer systems that store and serve the data can be referred to as servers or the cloud, in a cloud computing scenario. The one or more computer systems can include one or more web servers, for example. The other computer systems that send and receive data to and from the servers or the cloud can be referred to as client or cloud devices, for example.
[0056] The term “computer-readable medium” as used herein refers to any media that participates in providing instructions to processor 204 for execution. Such a medium may take many forms, including but not limited to, non-volatile media, volatile media, and transmission media. Non-volatile media includes, for example, optical or magnetic disks, such as storage device 210. Volatile media includes dynamic memory, such as memory 206. Transmission media includes coaxial cables, copper wire, and fiber optics, including the wires that comprise bus 202.
[0057] Common forms of computer-readable media or computer program products include, for example, a floppy disk, a flexible disk, hard disk, magnetic tape, or any other magnetic medium, a CD-ROM, digital video disc (DVD), a Blu-ray Disc, any other optical medium, a thumb drive, a memory card, a RAM, PROM, and EPROM, a FLASH-EPROM, any other memory chip or cartridge, or any other tangible medium from which a computer can read.
[0058] Various forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to processor 204 for execution. For example, the instructions may initially be carried on the magnetic disk of a remote computer. The remote computer can load the instructions into its dynamic memory and send the instructions over a telephone line using a modem. A modem local to computer system 200 can receive the data on the telephone line and use an infra-red transmitter to convert the data to an infra-red signal. An infra-red detector coupled to bus 202 can receive the data carried in the infra-red signal and place the data on bus 202. Bus 202 carries the data to memory 206, from which processor 204 retrieves and executes the instructions. The instructions received by memory 206 may optionally be stored on storage device 210 either before or after execution by processor 204.
[0059] In accordance with various embodiments, instructions configured to be executed by a processor to perform a method are stored on a computer-readable medium. The computer-readable medium can be a device that stores digital information. For example, a computer-readable medium includes a compact disc read-only memory (CD-ROM) as is known in the art for storing software. The computer-readable medium is accessed by a processor suitable for executing instructions configured to be executed.
[0060] The following descriptions of various implementations of the present teachings have been presented for purposes of illustration and description. It is not exhaustive and does not limit the present teachings to the precise form disclosed. Modifications and variations are possible in light of the above teachings or may be acquired from practicing of the present teachings. Additionally, the described implementation includes software, but the present teachings may be implemented as a combination of hardware and software or in hardware alone. The present teachings may be implemented with both object-oriented and non-object-oriented programming systems.
Controlling the Temperature of Solvents in an OPP
[0061] As described above, an OPP device currently relies on a low viscosity solvent to ensure proper operation. A low viscosity solvent allows a sample to rapidly transit the tubing of the device and balances the Venturi effect generated by the nebulizing gas.
[0062] Unfortunately, however, using higher viscosity solvents can provide some advantages for mass spectrometry and other analytical device techniques. In addition, being able to accommodate higher viscosity solvents means that the Venturi effect generated by the nebulizing gas can more easily be balanced. For example, liquid flow of lower viscosity solvents can be increased further for a fixed nebulizing gas flow. Similarly, being able to accommodate higher viscosity solvents means that nebulizing gas flow can be reduced for a fixed or desirable liquid flow rate.
[0063] As a result, additional OPP systems and methods are needed to allow solvents with higher viscosities to be used, to accommodate higher liquid flows, and to reduce gas flow requirements.
[0064] In various embodiments, the liquid viscosity of a solvent in an OPP device is altered by controlling the temperature of the transfer line and/or the liquid injection port of the OPP. By adjusting the temperature in the range of 50-60° C., for example, a number of benefits are achieved. The first benefit is allowing solvents with higher viscosities to be used.
[0065]
[0066] Plot 300 shows that the viscosities of methanol 330 and the viscosities of acetonitrile 340 are below viscosity threshold line 310 for temperatures above temperature threshold line 320. In other words, and as described above, at room temperature or above, the viscosities of methanol 330 and the viscosities of acetonitrile 340 are low enough to ensure proper operation of the OPP device.
[0067] Plot 300 also shows that the viscosities of water 350 are below viscosity threshold line 310 for at least some temperatures above temperature threshold line 320. In other words, and as also described above, at room temperature and at least some temperatures above room temperature, the viscosities of water 350 are too high to ensure proper operation of the OPP device.
[0068] Adjusting the temperature of water in the range of 50-60° C., however, places the viscosities of water 350 low enough to ensure proper operation of the OPP device. In other words, the viscosity of water is reduced by increasing its temperature. As a result, plot 300 shows that increasing the temperature of the solvent in an OPP device can allow a higher viscosity liquid such as water at a high percentage (50%) to be used as the solvent. Again, using a higher viscosity liquid like water as a solvent can improve operational stability and offer solubility for a wider range of analytes.
[0069] Another benefit of adjusting the temperature of the solvent in an OPP device to a range of 50-60° C. is the ability to accommodate higher liquid flows. As shown in plot 300, adjusting the temperature of methanol or acetonitrile in the range of 50-60° C. further lowers the viscosities of methanol 330 and the viscosities of acetonitrile 340 below viscosity threshold line 310. This means that the flow rates of methanol or acetonitrile can be increased even when the nebulizer gas flow stays constant.
[0070]
[0071] Returning to
[0072] As described above, increasing the flow rate of the analyte-solvent dilution is advantageous for mass spectrometry or any analytical technique. Increasing the flow rate of the analyte-solvent dilution means more samples can be analyzed in the same amount of time.
[0073] A third benefit of adjusting the temperature of the solvent in an OPP device to a range of 50-60° C. is the ability to reduce the flow rate of the nebulizing gas. As just described with reference to
[0074] An additional side benefit of adjusting the temperature of the solvent in an OPP device to a range of 50-60° C. is ensuring line cleanliness for applications where analyte could be “sticky.” In other words, some analytes can stick to the walls of sample transport capillary 61 if the viscosity of the solvent is high enough and the flow rate of the analyte-solvent dilution is slow enough. Increasing either or both of the viscosity of the solvent and the flow rate of the analyte-solvent dilution can help prevent this problem.
[0075] In various embodiments, the temperature of the solvent in an OPP device is increased by applying heat to the solvent through the use of a heating element. The heating element can be, but is not limited to, a resistance-type heating element, such as nichrome wire.
[0076] The heating element is located within the OPP system in order to heat the solvent so that the solvent reaches a desired temperature to reduce the viscosity below a desired viscosity level before the solvent receives the analyte sample. The heating element is also located within the OPP system in order to heat the solvent so that the solvent maintains the desired temperature to reduce the viscosity below the desired viscosity level for the entire time the analyte-solvent dilution is transported through the OPP device. In other words, the heating element is placed to heat the solvent above a certain temperature level before the analyte is introduced and have the analyte-solvent dilution maintain a temperature above that temperature level for the entire time the analyte-solvent dilution is transported through the OPP device. In this way, the viscosity of the analyte-solvent dilution is maintained below a certain viscosity level or threshold while the analyte-solvent dilution passes through the OPP device.
[0077] Returning to
[0078] In another embodiment, a heating element is placed to heat the solvent in solvent transport capillary 59. For example, a heating element or heating sleeve can be placed before, surrounding, or in line with transport capillary 59. In this embodiment, the solvent is heated before it receives the sample and the sample is transported through sample transport capillary 61. The heating element heats the solvent so that it maintains a lower viscosity through sample transport capillary 61.
[0079] Returning to
System for Transporting an Analyte to an Instrument
[0080]
[0081] Reservoir 410 houses a fluid sample containing an analyte. The fluid sample has fluid surface 411. Reservoir 410 is, for example, a microtiter plate well. Ejector 420 ejects droplet 415 of the fluid sample from fluid surface 411. Ejector 420 is, for example, an ADE. OPP 430 is spaced apart from fluid surface 411.
[0082] OPP 430 includes sampling tip 431 for receiving ejected droplet 415 of the fluid sample. OPP 430 includes solvent inlet 432 for receiving a solvent from solvent source or reservoir 433. OPP 430 includes solvent transport capillary 434 for transporting the solvent from solvent inlet 432 to sampling tip 431, where ejected droplet 415 combines with the solvent to form an analyte-solvent dilution. OPP 430 includes sample outlet 435 through which the analyte-solvent dilution is directed away from OPP 430 to an analytical instrument (not shown).
[0083] OPP 430 includes sample transport capillary 436 for transporting the analyte-solvent dilution from sampling tip 431 to sample outlet 435. Sample transport capillary 436 and solvent transport capillary 434 are in fluid communication at sampling tip 431. Finally, OPP 430 includes heating element 437 that heats the solvent to a temperature above a threshold temperature in order to reduce a viscosity of the solvent below a threshold viscosity. This maintains the viscosity of the solvent below a threshold viscosity as the analyte-solvent dilution is transported from sampling tip 431 to sample outlet 435.
[0084] As shown in
[0085] As shown in
[0086] In various embodiments not shown, the heating element can be located before, surrounding, or in line with solvent transport capillary 434.
[0087] In various embodiments not shown, a second heating element (not shown) is located surrounding sample transport capillary 436. A second heating element is used in addition to heating element 437, for example, to maintain the viscosity of the solvent below the threshold viscosity as the analyte-solvent dilution is transported from sampling tip 431 to sample outlet 435.
[0088] In various embodiments, the system of
[0089] In various embodiments not shown, the heating element is located in or surrounding solvent pump 438.
[0090] In various embodiments, solvents with higher viscosities are used. For example, the solvent can include water (H.sub.2O), at least 50 percent water (H.sub.2O), or isopropyl alcohol (IPA).
[0091] In various embodiments, the solvent includes methanol (MeOH), or acetonitrile (ACN).
[0092] In various embodiments, the system of
[0093] In various embodiments, the nebulizing gas flow is held constant as the solvent is heated in order to accommodate higher liquid flows. For example, the nebulizing gas flow is held constant by gas pressure regulator 441 as the solvent is heated by heating element 437 in order to increase the flow of the analyte-solvent dilution through sample transport capillary 436.
[0094] In various embodiments, the flow of the analyte-solvent dilution is held constant as the solvent is heated in order to reduce gas flow requirements. For example, the nebulizing gas flow is reduced by gas pressure regulator 441 as the solvent is heated by heating element 437 in order to maintain a constant flow of the analyte-solvent dilution through sample transport capillary 436.
[0095] In various embodiments, processor 450 is used to control or provide instructions to ejector 420, solvent pump 438, and gas pressure regulator 441. Processor 450 controls or provides instructions by, for example, controlling one or more voltage, current, or pressure sources (not shown). Processor 450 can be a separate device as shown in
Method for Transporting an Analyte to an Instrument
[0096]
[0097] In step 510 of method 500, a droplet is ejected from a fluid surface of a fluid sample containing an analyte using an ejector. The fluid sample is housed in a reservoir.
[0098] In step 520, a solvent is pumped from a solvent source into a solvent inlet of a continuous flow OPP spaced apart from the fluid surface using a solvent pump. The solvent is pumped in order to transport the solvent from the solvent inlet to a sampling tip of the OPP through a solvent transport capillary of the OPP, receive the ejected droplet at the sampling tip where the ejected droplet is combined with the solvent to form an analyte-solvent dilution, and transport the analyte-solvent dilution from the sampling tip to a sample output of the OPP through a sample transport capillary of the OPP.
[0099] In step 530, the solvent is heated to a temperature above a threshold temperature using a heating element. The solvent is heated in order to reduce the viscosity of the solvent below a threshold viscosity and maintain the viscosity of the solvent below the threshold viscosity as the analyte-solvent dilution is transported from the sampling tip to the sample outlet.
Computer Program Product for Transporting an Analyte to an Instrument
[0100] In various embodiments, computer program products include a tangible computer-readable storage medium whose contents include a program with instructions being executed on a processor so as to perform a method for transporting an analyte in a fluid sample to an analytical instrument and controlling the viscosity of the fluid sample. This method is performed by a system that includes one or more distinct software modules.
[0101]
[0102] Control module 610 instructs an ejector to eject a droplet from a fluid surface of a fluid sample containing an analyte. The fluid sample is housed in a reservoir. Control module 610 instructs a solvent pump to pump a solvent from a solvent source into a solvent inlet of a continuous flow OPP spaced apart from the fluid surface. The solvent is pumped in order to transport the solvent from the solvent inlet to a sampling tip of the OPP through a solvent transport capillary of the OPP, receive the ejected droplet at the sampling tip where the ejected droplet is combined with the solvent to form an analyte-solvent dilution, and transport the analyte-solvent dilution from the sampling tip to a sample output of the OPP through a sample transport capillary of the OPP. Finally, control module 610 instructs a heating element to heat the solvent to a temperature above a threshold temperature. The solvent is heated in order to reduce the viscosity of the solvent below a threshold viscosity and maintain the viscosity of the solvent below the threshold viscosity as the analyte-solvent dilution is transported from the sampling tip to the sample outlet.
[0103] Further, in describing various embodiments, the specification may have presented a method and/or process as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth herein, the method or process should not be limited to the particular sequence of steps described. As one of ordinary skill in the art would appreciate, other sequences of steps may be possible. Therefore, the particular order of the steps set forth in the specification should not be construed as limitations on the claims. In addition, the claims directed to the method and/or process should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the sequences may be varied and still remain within the spirit and scope of the various embodiments.