In-line reaction system with gas removal

Abstract

A fluid reaction system includes a first reactant source containing a first liquid reactant, a multiple-port fluid valve having a first port fluidically connected to the first reactant source, a channel, a pumping system for pumping a first volume of the first liquid reactant through the valve into the channel, the pumping system further being adapted to pump a gas volume into contact with the first volume in the channel, such that the first volume of the first liquid reactant is motivatable through the channel by the gas volume as directed by the pumping system, a degasser having a degassing chamber and a separation membrane disposed in the degassing chamber to define a retentate side fluidically connected with the channel, and a permeate side, the separation membrane being permeable to gas but impermeable to liquid.

Description

IN-LINE REACTION SYSTEM WITH GAS REMOVALBACKGROUND

[0001] Chemical and biological analyses typically require preparing a sample prior to instrumental analysis, such as high performance liquid chromatography, matrix-assisted laser desorption ionization, mass spectrometry, and ion mobility. In many applications, samples are manually prepared for analysis using methods such as pipetting, vortex mixing, and centrifugation. In other applications, samples are robotically prepared using expensive equipment to speed up this manual preparation process. Both manual and robotic preparation methods can be inaccurate and inefficient as these methods expose the sample to the environment, potentially allowing contamination to enter the sample volume. Exposing the sample to the environment also permits evaporation to occur. Contamination and evaporation cause inaccuracies in downstream analyses.

[0002] Accordingly, it is desirable to provide an in-line reaction system capable of forming a reaction mixture. In-line reaction systems have employed both gas-segmented and non-gas-segmented displacement for fluid movement within, for example, a sample preparation system. With few exceptions, volumetric displacement accuracy is essential, particularly in systems described as “flow injection analysis systems”, “segmented flow analysis systems”, and “programmable flow injection systems”. Many in-line reaction systems can themselves create positional inaccuracies and incomplete reactions by being susceptible to unplanned segmented liquid mixtures. The segmentation may be the result of gas bubble formation within the liquid reactant volume, due to outgassing from pressure and / or temperature changes, and from gas byproducts from the reaction. Segmentation may also be initially desired to bring reactants into a reaction zone, and thereafter mix the initially separated reactants. Therefore, it is desired to provide an in-line reaction system that is capable of removing gases / gas bubbles that may separate reactants and / or reaction products in order to provide accurate and uncontaminated sample volumes to downstream systems such as analytical equipment, as well as to ensure complete reactions among the liquid reactants.SUMMARY

[0003] According to one aspect, a fluid reaction system includes a first reactant source containing a first liquid reactant, a multiple-port fluid valve having a first port fluidicallyconnected to the first reactant source, a channel, a pumping system for pumping a first volume of the first liquid reactant through the valve into the channel, the pumping system further being adapted to pump a gas volume into contact with the first volume in the channel, such that the first volume of the first liquid reactant is motivatable through the channel by the gas volume as directed by the pumping system, a degasser having a degassing chamber and a separation membrane disposed in the degassing chamber to define a retentate side fluidically connected with the channel, and a permeate side, the separation membrane being permeable to gas but impermeable to liquid, the degasser further including an evacuation pump for evacuating the permeate side of the degassing chamber, and a heat applicator for elevating a temperature of the first volume to at least 40 °C in one or more of the channel and the retentate side of the chamber.

[0004] According to another aspect, a method for conditioning fluid in a reaction system having a channel, a heat applicator for applying heat to a reaction zone of the channel, and a degasser having a degassing chamber and a separation membrane disposed in the degassing chamber to define a retentate side in fluid communication with the channel, and a permeate side in fluid communication with an evacuation pump includes (a) forming a gas-bounded liquid reaction volume in the channel, wherein the liquid reaction volume is bounded on at least one axial end by a gas volume within the channel; (b) applying a positive or negative pressure to the gas volume to motivate the liquid reaction volume to the reaction zone; (c) operating the heat applicator to elevate the temperature of the liquid reaction volume to an extent sufficient to cause at least one of outgassing and formation of a reaction gas from the liquid reaction volume; and (d) operating the evacuation pump to establish a pressure gradient across the separation membrane that is sufficient to promote permeation of the reaction gas through the separation membrane to the permeate side of the chamber.

[0005] According to another aspect, a method for conditioning fluid in a reaction system having a channel and a degasser having a degassing chamber and a separation membrane disposed in the degassing chamber to define a retentate side in fluid communication with the channel, and a permeate side in fluid communication with an evacuation pump includes (a) forming a gas-bounded liquid reaction volume in the channel, wherein the liquid reaction volume includes a first liquid reactant and a second reactant that together produce a reaction gas when mixed at reaction conditions, the liquid reaction volume being motivatable through the channel under a force applied through a gas volume bounding at least one axial end of the liquid reaction volume; (b) establishing the reaction conditions at the liquid reaction volume;(c) applying a first pressure to the gas volume to motivate the liquid reaction volume along the channel to the retentate side of the degassing chamber; and (d) operating the evacuation pump to establish a pressure gradient across the separation membrane that is sufficient to promote permeation of the reaction gas through the separation membrane to the permeate side of the chamber.

[0006] According to another aspect, a method for conditioning fluid in a reaction system having a channel and a degasser having a degassing chamber and a separation membrane disposed in the degassing chamber to define a retentate side in fluid communication with the channel, and a permeate side in fluid communication with an evacuation pump includes (a) forming a gas-bounded liquid reaction volume in the channel, wherein the liquid reaction volume includes a first liquid reactant separated from a second liquid reactant by a separating gas volume, wherein the first and second liquid reactants are reactable with one another at reaction conditions, the liquid reaction volume being motivatable through the channel under a force applied through a terminal gas volume bounding at least one axial end of the liquid reaction volume; (b) applying a first pressure to the terminal gas volume to motivate the liquid reaction volume along the channel to the retentate side of the degassing chamber; and (c) operating the evacuation pump to establish a pressure gradient across the separation membrane that is sufficient to promote permeation of gas in the separating gas volume through the separation membrane to the permeate side of the chamber.BRIEF DESCRIPTION OF DRAWINGS

[0007] This written disclosure describes illustrative embodiments that are non-limiting and non-exhaustive. Reference is made to illustrative embodiments that are depicted in the figures, in which:

[0008] FIG. 1 illustrates reaction system 100, according to some embodiments.

[0009] FIG. 2A illustrates degasser 160 for reaction system 100, according to some embodiments.

[0010] FIG. 2B illustrates a cross-sectional view of degassing chamber 210 with a separation membrane 220, according to some embodiments.

[0011] FIG. 2C illustrates a cross-sectional view of degassing chamber 210 with a separation membrane 220, according to some embodiments.

[0012] FIG. 3A illustrates reaction system 300, according to some embodiments.

[0013] FIG. 3B illustrates reaction system 375, according to some embodiments.

[0014] FIG. 4 illustrates a reaction zone 400 for reaction systems 100, 300, and / or 375, according to some embodiments.

[0015] FIG. 5 illustrates degasser 360 for reaction systems 300 and / or 375, according to some embodiments.

[0016] FIG. 6 illustrates controller system 250 for reaction systems 100, 300, and / or 375, according to some embodiments.

[0017] FIG. 7A illustrates fluid position 700 in any reaction system of the present disclosure, according to some embodiments.

[0018] FIG. 7B illustrates fluid position 725 in any reaction system of the present disclosure, according to some embodiments.

[0019] FIG. 7C illustrates fluid position 750 in any reaction system of the present disclosure, according to some embodiments.

[0020] FIG. 7D illustrates reactants in a reaction volume initially separated by a gas in a reaction zone.

[0021] FIG. 7E illustrates the reaction volume of FIG. 7D subsequent to degassing.

[0022] FIG. 7F illustrates a reaction product formed from a reaction of the reactants ofFIG. 7D in the reaction zone.

[0023] FIG. 8 illustrates method 800 for conditioning fluid in a reaction system, according to some embodiments.

[0024] FIG. 9 illustrates method 900 for conditioning fluid in a reaction system, according to some embodiments.

[0025] FIG. 10 illustrates an isometric view of degasser system 1000, according to some embodiments.

[0026] FIG. 11 illustrates a side view of degasser system 1000, according to some embodiments.

[0027] FIG. 12 illustrates an isometric view of degasser system 1200, according to some embodiments.

[0028] FIG. 13 illustrates a side view of degasser system 1200, according to some embodiments.DETAILED DESCRIPTION

[0029] Embodiments of the present disclosure provide novel systems and methods for in-line reactions with gas removal. Often, preparing samples for analytical equipment requires manual mixing of sample and reagent components. Manual mixing may include manual pipetting of reagents and a separate centrifugation step. These methods for preparing samples typically suffer from exposure to the atmosphere and contamination, in addition to being inefficient processes. Further, highly precise analytical equipment requires accurate sample volumes and reaction mixtures. When reactants are chemically reacted, unknown volumes of outgas may segment the reaction products. The nature of outgassing may be random and may affect positional accuracy of the reaction products. The systems and methods of the present disclosure provide precise sample volumes to downstream equipment by degassing the in-line reaction system prior to, during, and / or after the reaction. These systems and methods are capable of efficiently degassing the fluid(s) in an in-line reaction system, preventing exposure to external contamination.

[0030] FIG. 1 illustrates reaction system 100, according to some embodiments. Reaction system 100 may include a first reactant source 110, a second reactant source 120, a pumping system 130, a valve 140, a vessel 150, a degasser 160, optional vent 170, and outlet 180. First reactant source 110 and second reactant source 120 may include samples, reagents, reactants, and / or solvents that may be combined and / or reacted with one another to obtain a product for instrumental analysis. Instrumental analysis may include high performance liquid chromatography, matrix assisted laser desorption ionization, mass spectrometry, and ion mobility. Pumping system 130 may include first pump 132 and second pump 134. Outlet 180 of reaction system 100 directs samples to the instrumental analysis. In some embodiments, products from the reaction conducted in reaction system 100 may be directed through outlet 180 to an instrumental analysis stage.

[0031] First reactant source 110 and / or second reactant source 120 may include one or more undigested proteins sufficient for chemical or enzyme reactions with one another. In one example, first reactant source 110 and second reactant source 120 include a first liquid reactant, such as an enzyme, and a second liquid reactant, such as a target protein to be digested by the enzyme into reaction byproducts, like one or more peptides. Reaction system 100 may be an in-line / flow-through system sufficient to reduce reaction contamination and exposure toatmosphere. Accordingly, the first liquid reactant and second liquid reactant may be mixed and chemically or enzymatically reacted in the same vessel.

[0032] Pumping system 130 may include one or more fluid pumps. For example, pumping system 130 may include first pump 132 and second pump 134. First pump 132 may include an inlet from first reactant source 110 and second pump 134 may include an inlet from second reactant source 120. As shown in FIG. 1, first pump 132 and second pump 134 are upstream of valve 140. In an alternative embodiment, one or more of first pump 132 and second pump 134 is downstream of valve 140. In one example, pumping system 130 is in fluidic connection with first reactant source 110 and second reactant source 120. Accordingly, first pump 132 may fluidically connect first reactant source 110 to valve 140, and second pump 134 may fluidically connect second reactant source 120 to valve 140.

[0033] Pumping system 130 is preferably configured to accurately measure and dispense reagents and discrete gas volumes, such as gas plugs or gas bubbles into reaction system 100. The discrete gas volumes may be employed as liquid volume containment means, wherein pumping system 130 may operably apply positive or negative force to the discrete gas volume to motivate the at least partially contained liquid volume along one or more flow paths in reaction system 100. For example, pumping system 130 may apply positive and / or negative pressure to one or more fluids in reaction system 100. In one example, pumping system 130 includes one or more syringe pumps. For example, a syringe pump is capable of mixing reagents and samples in a vessel using a back and forth movement of the pump piston. The ability to accurately position a sample and reagent and mix the sample and reagent in a vessel prevents exposure to the atmosphere, reducing losses of the sample through evaporation. Further, a syringe pump is capable of accurately positioning samples and reagents in a particular position in a downstream vessel using displacement gas.

[0034] Valve 140 may be a multiple-port fluid valve and may be fluidically connected to pumping system 130. Valve 140 and pumping system 130 may be fluidically connected by a conduit sufficient to transfer fluid(s). In one example, valve 140 includes a first port fluidically connected to first reactant source 110. Accordingly, valve 140 may be fluidically connected to a first pump. In another example, valve 140 includes a second port fluidically connected to second reactant source 120. Accordingly, valve 140 may be fluidically connected to a second pump. In some embodiments, pumping system 130 may be downstream from valve 140, wherein first reactant source 110 and second reactant source 120 may be “pulled” through valve 140, while a reaction product may be oppositely “pushed” through valve 140 toward outlet180. In some embodiments, valve 140 may be a shear valve. Valve 140 may mix fluids from first reactant source 110 and second reactant source 120 sufficient to create a liquid reactant mixture. Further, valve 140 may be directly connected to one or more sealed reagent containers through one or more valve ports.

[0035] Vessel 150 may define a channel that may be fluidically connected with one or more of pumping system 130 and valve 140. Additionally, or alternatively, vessel 150 may be directly connected to valve 140. In one example, the channel may include a lumen and / or bore of a tube. One or more portions of the tube may be gas-permeable and liquid-impermeable to facilitate degassing of fluids through Fick’s law of diffusion, wherein an environment on a permeate side of the tube wall having a lower concentration of the target gas than that in the fluid causes diffusion by the target gas through the wall of the tube. Example materials for fabricating a gas-permeable, liquid-impermeable barrier include fluoropolymers and silicones. In some embodiments, the gas-permeable, liquid-impermeable barrier may be non-porous, such that gas transfer / permeation through the barrier occurs through a sorption diffusion mechanism, rather than free transport through continuous pores. In an example, vessel 150 extends from valve 140 to optional vent 170. The channel of vessel 150 may be configured to convey fluid(s) transferred through valve 140. These fluid(s) may include the liquid reactant mixture and one or more gases. In some embodiments, the liquid reactants may be initially separated for combination and reaction in a reaction zone of reaction system 100. In some embodiments, vessel 150 may be a body or substrate in which a channel is formed to convey fluid. At least a portion of the channel may be bound by a gas-permeable, liquid-impermeable barrier. In some embodiments, the barrier is a semi-permeable membrane. The semi -permeable membrane may be porous or, in some embodiments, non-porous.

[0036] Pumping system 130 may pump a first volume of the first liquid reactant through valve 140 into the lumen. Pumping system 130 may further pump a gas volume into contact with the first volume in the lumen, such that the first volume of the first liquid reactant is motivatable through the lumen by the gas volume as directed by pumping system 130. The gas volume may comprise a gas plug or gas bubble that permits accurate motivation of the liquid volume through the lumen by applying a positive or negative fluid force (such as compressed air or negative pressure) to the gas volume. Pumping system 130 may be adapted to pump a second volume of the second liquid reactant through valve 140 into the lumen. In some embodiments, the second volume of the second liquid reactant may be placed into contact with the first volume to form the liquid reactant mixture. In other embodiments, a gas volume mayinitially separate the first liquid volume from the second liquid volume. Pumping system 130 may be adapted to pump the gas volume such that the liquid reactant mixture or the first and second liquid volumes are motivatable through the lumen by the bounding gas volume as directed by pumping system 130. The liquid volume or volumes may be a gas-bounded to facilitate pumping through the lumen as coherent liquid volumes. For example, the liquid reactant mixture may be bounded on at least one axial end by a gas volume within the lumen. The liquid reactant mixture may be bounded on two axial ends by first and second discrete gas volumes within the lumen. The liquid reactant mixture may be bounded radially by a vessel wall defining the lumen.

[0037] At least a portion of vessel 150 may extend within and / or through degasser 160. In some embodiments, at least a portion of the channel defined by vessel 150 may extend within and / or through degasser 160. In some embodiments, degasser 160 may be formed by a combination of one or more of a membrane and vessel together encompassing at least a portion of the channel. Accordingly, the liquid reactant volumes may react within, and be degassed within, degasser 160. In one example, vessel 150 includes a coiled fluid conduit within degasser 160. Reaction system 100 may optionally include vent 170. Vent 170 may include a filter for filtering dust, particles, and / or biocontamination. For example, filters with pore sizes smaller than 0.5 microns may be utilized in vent 170. In one example, vent 170 is downstream of degasser 160. In another example, vent 170 is in fluidic communication with valve 140.

[0038] Vent 170 may be sufficient to maintain one or more fluids within the lumen at about atmospheric pressure. For example, atmospheric pressure may range from about 0.9 bar to about 1.1 bar. In one example, atmospheric pressure may range from about 0.95 bar to about 1.05 bar. In another example, atmospheric pressure may range from about 1 bar to about 1.02 bar. By maintaining atmospheric pressure in vessel 150, reaction system 100 can properly position the liquid reactant mixture and / or gases from pumping system 130 along vessel 150. For example, reaction system 100 can position the liquid reactant mixture within the degasser 160. In another example, the displacement gas volume from pumping system 130 does not enter the portion of vessel 150 that is within degasser 160 so that the discrete displacement (bounding) gas volume remains intact while the liquid reactant mixture may be degassed. For the purposes of calibrating controlled movement of the gas-bound liquid volume within reaction system 100, the displacement gas volume may be considered to be incompressible. Thus, applied pressure to the displacement gas volume may be considered to directly motivate the at least partially contained liquid volume. Reaction system 100 is therefore capable ofplacing the liquid reaction mixture in various positions throughout reaction system 100 without complex sensing systems. Further, exposing the reaction volume to atmospheric pressure promotes the formation of gas bubbles. This promotes gas bubbles to form and contact permeable walls at least partially surrounding the channel instead of remaining within the liquid bulk. By promoting these gas bubbles to form and contact the permeable walls of, for example, the membrane, the gas is more easily diffused out from the liquid.

[0039] Pumping system 130 may apply a negative pressure to fluid(s) in vessel 150 sufficient to pass the fluid(s) through valve 140 into outlet 180. For example, after the liquid reactants have reacted to form one or more reaction products, pumping system 130 may apply a negative pressure to a displacement gas volume bounding the reaction products sufficient to transfer the reaction products from vessel 150 to outlet 180. In one example, outlet 180 is in fluidic connection with valve 140. In another example, outlet 180 is upstream of degasser 160. In yet another example, outlet 180 is downstream of degasser 160. Additionally, reaction system 100 may operate without requiring a detergent in vessel 150. Importantly, detergents in the fluid side of the vessel may plug the membrane.

[0040] FIG. 2 A illustrates degasser 160 for reaction system 100, according to some embodiments. Degasser 160 is capable of removing gas / bubbles from the fluid volume in vessel 150. In one example, degasser 160 can remove gas that separates first and second liquid reactants in reaction zone of reaction system 100 to initiate a chemical reaction between the first and second reactants. For example, degasser 160 may be operated to remove one or more gases that separate a first liquid reactant and a second liquid reactant sufficient to initiate a chemical or enzymatic reaction between the first liquid reactant and the second liquid reactant when the liquid reactants are brought into contact with one another, and preferably mixed. In another example, degasser 160 can remove gaseous products from vessel 150. In the embodiment illustrated in FIG. 2A, channel 202 is exposed to degasser 160. Degasser 160 includes a degassing chamber 210 and a separation membrane 220. Separation membrane 220 may define a retentate side 222 and permeate side 224. Retentate side 222 may be fluidically connected with channel 202. In one example, separation membrane 220 is permeable to one or more gases, but impermeable to liquid. In some embodiments, separation membrane 220 is non-porous, yet permeable to one or more gases. Separation membrane 220 may comprise a wall of vessel 150. In some embodiments, separation membrane may form a barrier for use in combination with vessel 150 to at least partially enclose the liquid reactants in channel 202. In the illustrated embodiment, at least a portion of vessel 150 is a tube, wherein the tube wall isgas-permeable and liquid-impermeable to form separation membrane 220. Various embodiments of degassers are described in U.S. Patent Nos. 6,949,132, 7,144,443, 7,713,331, and 9,700,816, each assigned to the present assignee and herein incorporated by reference in their entireties.

[0041] Degasser 160 may further include evacuation pump 230. Evacuation pump 230 may be in fluidic connection with evacuation conduit 232 and may be in communication with one or more of vacuum sensor 234 and vacuum controller 236. Evacuation pump 230 may be sufficient to evacuate permeate side 224 of degassing chamber 210. Therefore, evacuation pump 230 may remove one or more gases permeated through membrane 220 from retentate side 222 to permeate side 224. Degassing chamber 210 may comprise a shell defining a chamber therewithin which is disposed at least a portion of vessel 150. In one example, evacuation pump 230 is fluidically connected to permeate side 224 of degassing chamber 210 through a port connected to degassing chamber 210. In another example, evacuation pump 230 includes one or more vacuum pumps. Vacuum sensor 234 may transmit a signal indicative of the vacuum in evacuation conduit 232 to vacuum controller 236. Vacuum controller 236 may operably control evacuation pump 230 based on signals transmitted from vacuum sensor 234.

[0042] Degasser 160 may further include a heat applicator 240, wherein heat applicator 240 is communicatively connected to a heat applicator controller 242. Heat applicator controller 242 may be communicatively connected to temperature sensor 244. Temperature sensor 244 may be arranged to sense temperature within deassing chamber 210, and / or within vessel 150. Heat applicator 240 may be located within degassing chamber 210 to most efficiently apply thermal energy to the liquid reactant mixture. As illustrated in FIG. 2A, heat applicator 240 may apply heat to a reaction zone and / or heat zone of channel 202. In the illustrated embodiment of FIG. 2A, the heat zone may include the portion of channel 202 within degasser 160. Accordingly, degassing chamber 210 may also be a reaction zone for fluid in channel 202. The reaction zone may include retentate side 222, and retentate side 222 may include a portion of channel 202. Heat applicator 240 is sufficient to elevate a temperature of the first volume and / or the second volume in one or more of channel 202 and retentate side 222 of degassing chamber 210. Elevating temperature of the liquid reactant mixture may cause or accelerate a chemical reaction of the liquid reactant mixture. Elevating temperature of the liquid reactant mixture may itself be sufficient to cause outgassing of a dissolved gas from the liquid reactants or the liquid reactant mixture, all while maintaining channel 202 at about atmospheric pressure. In other embodiments, gas may evolve as a result of a chemical reaction in the liquidreactant mixture. Elevating the temperature of the liquid reactant mixture may initiate, enhance, or accelerate the chemical reaction among the liquid reactant mixture. However, outgassing from the liquid reactant mixture may occur for other reasons, including over saturation of one or more gases in the liquid reactant mixture.

[0043] In one example, heat applicator 240 may elevate a temperature of the liquid reactant mixture to at least 30 °C. In another example, heat applicator 240 may elevate a temperature of the liquid reactant mixture to at least 40 °C. In yet another example, heat applicator 240 may elevate a temperature of the liquid reactant mixture to at least 50 °C. Heat applicator controller 242 may operably control heat applicator 240 based on signals transmitted from temperature sensor 244 indicative of temperature within one or more of degassing chamber 210, permeate side 224, and channel 202. Accordingly, heat applicator controller 242 may operably control heat applicator 240 sufficient to start the chemical reaction of the liquid reactant mixture. In another embodiment, heat applicator 240 may be a pelteir device in which heat applied may be more quickly removed thereby quenching the chemical reaction. In addition, heat applicator 240 may also remove heat from ambient temperature reaction mixtures.

[0044] As illustrated in FIG. 2 A, vacuum controller 236 and heat applicator controller 242 may be communicatively connected to parent controller system 250, wherein parent controller system 250 includes processor 252 and memory 254. Memory 254 may include non- transitory memory and / or may be communicatively connected to processor 252. Parent controller system 250 may operably control one or more of evacuation pump 230 and heat applicator 240 sufficient to react two or more reactants and cause outgassing of reaction gas from the liquid reaction volume. Operating evacuation pump 230 may establish a pressure gradient across separation membrane 220 that is sufficient to promote permeation of gas, such as a reaction by product or other evolved gas through separation membrane 220 to permeate side 224 of degassing chamber 210.

[0045] FIG. 2B illustrates a cross-sectional view of vessel 150 in degassing chamber 210, according to some embodiments. As shown in FIG. 2B, channel 202 includes a lumen and / or bore of a tube. Accordingly, the cross-sectional shape of channel 202 may be substantially circular, and the cross-sectional shape of separation membrane 220 may be substantially annular. Separation membrane 220 may define a retentate side 222 and permeate side 224. In one example, retentate side 222 is entirely bounded by separation membrane 220.

[0046] FIG. 2C illustrates a cross-sectional view of channel 202 defined by a recess and / or path formed in body 260 and bounded at least in part by separation membrane 220. Separation membrane 220 separates retentate side 222 from permeate side 224. Body 260 may be a block including solid material that may, in some embodiments, be heated and / or cooled to adjust temperature in channel 202 and / or adjust temperature of fluids in channel 202. For example, heat applicator 240 may heat body 260 sufficient to heat channel 202 and / or fluids in channel 202. Heat applicator 240 may be disposed within body 260 or outside of body 260. In one example, separation membrane 220 is configured to enclose the pathway to define channel 202 such that fluid flow through channel 202 contacts separation membrane 220. In some embodiments, separation membrane 220 may be substantially planar.

[0047] Importantly, reaction system 100 is capable of forming a liquid reactant mixture from two or more fluid sources, initiating a chemical reaction between the components in the liquid reactant mixture, and removing gas, such as chemical reaction outgas in an in-line reaction system. By utilizing a degassing chamber in fluidic connection with an evacuation pump, gas / bubbles may be removed from the fluid vessel prior to, during, and / or after the chemical reaction. Further, by removing reaction outgas from vessel 150, the system is capable of maintaining a known total liquid volume at least partially bound by the gas displacement volume, as described above. As a result, the system may be operated as though the total liquid volume is unchanged throughout the transfer, mixture, and reaction process. The position of the liquid volume may therefore be accurately predicted merely from displacement of the pump, particularly in the case of a positive displacement pump such as a syringe pump. The liquid reaction products may accordingly be transferred to various portions of the system, such as the reaction zone, the degassing zone, and downstream systems with accurate delivery positions and accurate volumes.

[0048] FIG. 3A illustrates reaction system 300, according to some embodiments. Reaction system 300 includes a first reactant source 110, second reactant source 120, pumping system 130, valve 140, vessel 150, heat applicator 240, degasser 360, optional vent 170, and outlet 180. In contrast to reaction system 100 where the reaction occurs within degasser 160, FIG. 3A illustrates that heat applicator 240 and degasser 360 may be fluidically connected in a series orientation. Accordingly, a reaction of the liquid reactant mixture may be driven prior to a degassing procedure. As shown, degasser 360 may be downstream of heat applicator 240 and is capable of removing gases / bubbles from vessel 150. In this embodiment, the location of heat applicator 240 serves as the reaction zone for the system. The embodiments of FIGs 1 and 2,by contrast, illustrated the reaction zone as within the degasser. The present invention contemplates those and other scenarios, including a reaction zone without a heat applicator, and separate from a degassing zone.

[0049] Pumping system 130 may be capable of motivating a first liquid reactant and a second liquid reactant in a back-and-forth motion within the channel to promote mixing sufficient to form the liquid reactant mixture, and to promote, initiate, and / or accelerate a chemical reaction among the liquid reactant mixture. In some embodiments, the pumping action upon the first and second liquid reactants may take place subsequent to removal by degassing of a separating gas plug between the first and second liquid reactants. Pumping system 130 is capable of positioning the liquid reactant mixture near / in heat applicator 240 sufficient to initiate a chemical reaction between components in the liquid reactant mixture in embodiments requiring application of external heat. Pumping system 130 may utilize displacement gas to position the liquid reactant mixture near / in heat applicator 240. This chemical reaction may produce one or more liquid reaction products, and outgassing from the chemical reaction may occur. Pumping system 130 is then capable of motivating reaction products and the outgas downstream to degasser 360 using displacement gas. In one example, the displacement gas includes air and / or non-miscible fluids. In another example, the displacement gas remains in contact with the leading edge of liquid in vessel 150 regardless of the amount of outgassing which may segment the liquid during the chemical reactions or heating.

[0050] FIG. 3B illustrates reaction system 375, according to some embodiments. Reaction system 375 includes a first reactant source 110, second reactant source 120, pumping system 130, valve 140, vessel 150, heat applicator 240, degasser 360, optional vent 170, and outlet 180. FIG. 3B illustrates that reaction system 375 includes outlet 180 downstream from degasser 360. Accordingly, pumping system 130 may apply a positive pressure to one or more liquid reaction products to transfer the products through degasser 360 and into outlet 180.

[0051] FIG. 4 illustrates reaction zone 400 for reaction systems 100, 300, and / or 375, according to some embodiments. Reaction zone 400 may include at least a portion of channel 202 and optionally a heat applicator, such as heat applicator 240. Reaction zone 400 may include the portion of channel 202 that has heat adjustment by heat applicator 240. Heat applicator 240 may be communicatively connected to heat applicator controller 242. Heat applicator controller 242 may be communicatively connected to temperature sensor 244 and / or parent controller system 250. Reaction conditions may be established when the liquid reactionvolume is in reaction zone 400. For example, heat applicator 240 may apply heat to the liquid reaction mixture in reaction zone 400 to elevate temperature of the liquid reaction mixture to an extent sufficient to cause production of a reaction gas. Operating heat applicator 240 may elevate temperature of the liquid reaction volume to an extent sufficient to cause, accelerate, and / or maintain a chemical reaction in the reaction mixture that produces reaction gas. In another example, reaction conditions may be established by removing gas (such as gas that separates the liquid reactant volumes) from the mixture in channel 202 sufficient to initiate a chemical reaction between reactants in vessel 150. In yet another example, applying heat, removing heat, and / or applying a reaction initiator, such as electromagnetic radiation to one or more components in vessel 150 may be utilized to establish or promote reaction conditions. In the embodiment illustrated in FIG. 2A, reaction zone 400 includes retentate side 222 of degassing chamber 210.

[0052] It is to be understood, however, that reaction zone 400 may be present without application of heat. In some embodiments, chemical reactions among the liquid reactant volumes may be promoted by agitation applied to the liquid reactant volumes that is driven by displacement gas pressure created by the pumping system 130. In some embodiments, agitation may include distal and proximal movement of the liquid reaction volumes along the channel defined by vessel 150. The distal and proximal movement may be repeated with a constant or non-constant frequency. Agitation of the liquid reaction volumes may be performed simultaneously or sequentially with the application of heat at reaction zone 400, or may be performed in the absence of applied heat. In some embodiments, the agitation of the liquid reaction volumes may be performed in the presence of a reaction promoter other than temperature, such as electromagnetic radiation or a chemical reaction promoter. In some embodiments, reaction zone 400 may further include temperature modulation of the liquid reaction volume. Temperature modulation may include one or more periods of applied thermal energy to the liquid reaction volume, one or more periods of withdrawal of thermal energy (cooling) from the liquid reaction volume, or both.

[0053] FIG. 5 illustrates degasser 360 for reaction system 300, according to some embodiments. Like degasser 160, degasser 360 may include a degassing chamber 210 and a separation membrane 220. The separation membrane 220 may define a retentate side 222 and permeate side 224. Degasser 160 may further include evacuation pump 230. Evacuation pump 230 may include one or more of evacuation conduit 232, vacuum sensor 234, and vacuum controller 236. In contrast to degasser 160 shown in FIGS. 1 and 2, degasser 360 may notinclude a heat applicator, such as heat applicator 240. Therefore, heat applicator 240 may be upstream of degasser 360, or absent altogether. Similar to degasser 160, degasser 360 can remove gas produced from a chemical reaction in vessel 150, or simply outgassed from over saturation. With the production of gas byproducts, the solution containing a target molecule may not be well distributed and may be randomly segmented within the total liquid reaction volume. Without the degassers of the present disclosure, it would be difficult to reliably obtain complete reactions among the liquid reactants. By providing the capability to degas the liquid reactant sample, and to therefore de-segment the liquid reactant volume, the reactants may consistently react to completion.

[0054] FIG. 6 illustrates parent controller system 250 for reaction systems 100, 300, and / or 375, according to some embodiments. Parent controller system 250 may be communicatively connected to one or more components in reaction systems 100, 300, and / or 375. As shown in FIG. 6, controller system 250 may be communicatively connected to one or more of pumping system 130, valve 140, vacuum controller 236, and heat applicator controller 242. Accordingly, parent controller system 250 may operably control the position of the liquid reaction mixture within vessel 150 sufficient to react the liquid reaction mixture. Parent controller system 250 may operably control the position of the produced reaction products and outgas sufficient to motivate the produced reaction products and outgas to move to degasser 360.

[0055] FIG. 7A illustrates fluid position 700 in reaction system 100, according to some embodiments. Fluid position 700 illustrates vessel 150, degassing chamber 210, displacement gas 702, liquid reaction mixture 710, and atmospheric gas 722. As shown in FIG. 7 A, pumping system 130 has transferred the liquid reaction mixture 710 through vessel 150 using displacement gas 702. Once liquid reaction mixture 710 has reached the reaction zone, such as reaction zone 400, the gas displacement from pumping system 130 may be stopped and the reaction may begin (such as by applying heat to liquid reaction mixture 710). The reaction may be initiated by establishing reaction conditions. For example, a gas separating two or more reactant volumes may be removed from vessel 150 by degassing sufficient to initiate a chemical reaction. Reaction conditions may be established or promoted by, for example, applying heat, removing heat, applying electromagnetic radiation, or agitating to the liquid reaction mixture 710, or combinations thereof. In one example, the air volume (displacement gas 702) used to position the fluids remains in contact with the leading edge of the liquid volume regardless of the amount of outgassing which segments the reaction product and / or reactant volumes duringreactions and / or heating. In another example, displacement gas 702 maintains an accurate volume by not being allowed to enter degassing chamber 210. In some embodiments, degassing of displacement gas 702 may be prevented by positioning the volume of displacement gas at a section of vessel 150 that is gas-impermeable. In this example, only the liquid reaction mixture 710 may be susceptible to diffusion through the membrane defining vessel 150 at degassing chamber 210.

[0056] FIG. 7B illustrates fluid position 725 in any reaction system of the present disclosure, according to some embodiments. Fluid position 725 illustrates vessel 150, degassing chamber 210, displacement gas 702, reaction product 728, and outgas volumes 720. FIG. 7B illustrates the fluid(s) within vessel 150 after the production of or outgassing of gas within the liquid volume. In some embodiments, this production of or outgassing of gas may be the result of applying heat to the liquid reaction mixture sufficient to start a chemical reaction. In other embodiments, gas volumes 720 may be deliberately introduced into vessel 150 to separate reactants until displaced into degassing chamber 210. As shown, outgas volumes 720 segment reaction product 728. FIG. 7C illustrates fluid position 750 in any reaction system of the present disclosure, according to some embodiments. Fluid position 750 illustrates vessel 150, degassing chamber 210, displacement gas 702, reaction product 728, and atmospheric gas 722. As shown in FIGS. 7A-7C, the interface between displacement gas 702 and liquid (such as liquid reaction mixture 710 and reaction product 728) does not move during the reaction. After the chemical reaction, evacuation pump 230 may drive degassing through a membrane as described above to remove outgas volumes 720 in degassing chamber 210 and / or vessel 150. The original fluid slug volume is restored by removing outgas from vessel 150.

[0057] Figures 7D-7F illustrate an embodiment in which an initial reaction volume is provided at a reaction zone of vessel 150, wherein the initial reaction volume includes two or more liquid reactant volumes 780, 782 separated by a gas volume 784. Reaction conditions may be established or promoted by removing the gas volume 784 from the initial reaction volume by degassing the initial reaction volume. Once gas volume 784 has been degassed from the initial reaction volume, the reactant volumes are contactable with one another for reaction, as shown in Figure 7E. In some embodiments, a reaction promoter may be applied to the contactable reactant volumes, as described above. The reaction product 728 is illustrated in Figure 7F.

[0058] Reaction systems 100, 300, and 375 may be used to prepare a sample for various downstream processes. In one example, reaction systems 100, 300, and 375 can preparesamples for analytical equipment. For example, analytical equipment may include high performance liquid chromatography, matrix assisted laser desorption ionization, mass spectrometry, and ion mobility. Often, samples for analytical technology are manually manufactured. Manual manufacturing typically includes pipetting samples and utilizing a centrifuge. In contrast, reaction systems 100, 300, and 375 can accurately and efficiently prepare samples for downstream equipment in an in-line reaction system. By using controllers and precise liquid volumes, reaction systems 100, 300, and 375 provide highly accurate samples for analytical equipment. In-line systems are advantageous as the sample is not exposed to the atmosphere and contaminants.

[0059] Referring to FIG. 8, method 800 for conditioning fluid in a reaction system is illustrated, according to some embodiments. The reaction system may include a vessel defining a lumen, a heat applicator for applying heat to a reaction zone of the lumen, and a degasser having a degassing chamber and a separation membrane disposed in the degassing chamber to define a retentate side in fluid communication with the lumen, and a permeate side in fluid communication with an evacuation pump. Method 800 includes one or more of the following steps:

[0060] STEP 810, FORM A GAS-BOUNDED LIQUID REACTION VOLUME IN THECHANNEL, WHEREIN THE LIQUID REACTION VOLUME IS BOUNDED ON AT LEAST ONE AXIAL END BY A GAS VOLUME WITHIN THE CHANNEL, includes forming a gas-bounded liquid reaction volume in the channel, such as channel 202, wherein the liquid reaction volume is bounded on at least one axial end by a gas volume, such as air, within the channel. In one example, the liquid reaction volume may be bounded on two axial ends by first and second discrete gas volumes within the channel. In another example, the liquid reaction volume is bounded radially by a vessel wall defining the channel. The gas-bounded liquid reaction volume may include one or more of solvents, reactants, samples, proteins, and enzymes. The gas-bounded liquid reaction volume may include samples, reagents, reactants, and / or solvents. Examples of solvents include methanol, acetone, ethanol, benzene, hexane, water, acetonitrile, and isopropanol. The gas-bounded liquid reaction volume may include a mixture of reactants from a first reactant source and reactants from a second reactant source. The reactants from the first reactant source and the reactants from the second reactant source may be mixed with one or more fluid pumps.

[0061] STEP 820, APPLY A POSITIVE OR NEGATIVE PRESSURE TO THE GAS VOLUME TO MOTIVATE THE LIQUID REACTION VOLUME TO THE REACTIONZONE, includes applying a positive or negative pressure to the gas volume, such as air, to motivate the liquid reaction volume to the reaction zone. In one example, the gas volume does not enter the reaction zone. In another example, only a portion of the gas volume enters the reaction zone. In yet another example, the gas volume may completely enter the reaction zone. The reaction system may include a fluid pump for applying the pressure to the gas volume. The fluid pump (such as those included in pumping system 130) may include one or more syringe pumps and may apply a positive or negative pressure to the gas volume. The gas volume may be maintained at about atmospheric pressure. For example, atmospheric pressure may range from about 0.9 bar to about 1.1 bar. In one example, atmospheric pressure may range from about 0.95 bar to about 1.05 bar. In another example, atmospheric pressure may range from about 1 bar to about 1.02 bar. The reaction zone may be disposed fluidically along the channel between the fluid pump and the degassing chamber. The reaction zone may be a region of the vessel at which the liquid reactant volume is mixed, agitated, heated, cooled, irradiated, catalyzed, and / or otherwise induced or promoted to react.

[0062] STEP 830, OPTIONALLY OPERATE THE HEAT APPLICATOR TO ELEVATE THE TEMPERATURE OF THE LIQUID REACTION VOLUME TO AN EXTENT SUFFICIENT TO CAUSE OUTGASSING OF A REACTION GAS FROM THE LIQUID REACTION VOLUME, includes operating the heat applicator, such as heat applicator 240, to elevate the temperature of the liquid reaction volume to an extent sufficient to cause outgassing of a reaction gas from the liquid reaction volume, such as at / to above 30 °C. In one example, the heat applicator may elevate a temperature of the liquid reaction volume to at least 30 °C. In another example, the heat applicator may elevate a temperature of the liquid reaction volume to at least 40 °C. In yet another example, the heat applicator may elevate a temperature of the liquid reaction volume to at least 50 °C. Operating the heat applicator may include elevating the temperature of the liquid reaction volume to an extent sufficient to cause a chemical or enzymatic reaction in the reaction volume that produces the reaction gas. In one example, subsequent to elevating temperature of the liquid reaction volume, pressure may be applied to motivate the liquid reaction volume through the channel to the retentate side of the degassing chamber.

[0063] STEP 840, OPERATE THE EVACUATION PUMP TO ESTABLISH A PRESSURE GRADIENT ACROSS THE SEPARATION MEMBRANE THAT IS SUFFICIENT TO PROMOTE PERMEATION OF THE REACTION GAS THROUGH THE SEPARATION MEMBRANE TO THE PERMEATE SIDE OF THE CHAMBER, includesoperating the evacuation pump, such as evacuation pump 230, to establish a pressure gradient across the separation membrane that is sufficient to promote permeation of the reaction gas through the separation membrane to the permeate side of the chamber. STEP 840 may be performed simultaneously or subsequently to STEP 830. In one example, the separation membrane may be the walls of the vessel, such as vessel 150. The vessel may include a gas permeable separation membrane. In this example, the retentate side may be within vessel 150 and the permeate side may be outside of vessel 150. Reaction gas may permeate through the separation membrane sufficient for reaction gas to be removed from the vessel. The evacuation pump may be controlled based on a vacuum sensor in fluidic communication with one or more of the permeate side of the chamber and the evacuation pump.

[0064] Method 800 may be completed using reaction systems 100, 300, or 375 and the steps may be completed in any order. Method 800 may further include using a pumping system to motivate reaction products to a system outlet. In one example, method 800 is completed under atmospheric pressure conditions. In another example, method 800 produces a reaction product suitable for use in downstream analytical equipment. In yet another example, method 800 may motivate the reaction products sufficient to transfer the reaction products to downstream analytical equipment.

[0065] Referring to FIG. 9, method 900 for conditioning fluid in a reaction system is illustrated, according to some embodiments. The reaction system may include a vessel defining a channel and a degasser having a degassing chamber and a separation membrane disposed in the degassing chamber to define a retentate side in fluid communication with the channel, and a permeate side in fluid communication with an evacuation pump. Method 900 includes one or more of the following steps:

[0066] STEP 910, FORM A GAS-BOUNDED LIQUID REACTION VOLUME IN THE CHANNEL, WHEREIN THE LIQUID REACTION VOLUME INCLUDES A FIRST LIQUID REACTANT AND A SECOND REACTANT, THE LIQUID REACTION VOLUME BEING MOTIVATABLE THROUGH THE CHANNEL UNDER A FORCE APPLIED THROUGH A GAS VOLUME BOUNDING AT LEAST ONE AXIAL END OF THE LIQUID REACTION VOLUME, includes forming the gas-bounded liquid reaction volume in the channel, such as channel 202, wherein the liquid reaction volume includes the first liquid reactant and the second reactant.

[0067] In one example, the liquid reaction volume may be bounded on two axial ends by first and second discrete gas volumes within the channel. In another example, the liquidreaction volume is bounded radially by a vessel wall defining the channel. The liquid reaction volume may be motivatable through the channel by applying force using one or more fluid pumps. The channel may be fluidically connectable to a first source of the first liquid reactant and a second source of the second liquid reactant through a multiple-port valve. This multipleport valve may be a shear valve.

[0068] STEP 920, ESTABLISH THE REACTION CONDITIONS AT THE LIQUID REACTION VOLUME, includes establishing reaction conditions, such as temperature conditions, at the liquid reaction volume. Establishing reaction conditions may include using a heat applicator to increase the liquid reaction volume temperature. In one example, the heat applicator may elevate a temperature of the liquid reaction volume to at least 30 °C. In another example, the heat applicator may elevate a temperature of the liquid reaction volume to at least 40 °C. In yet another example, the heat applicator may elevate a temperature of the liquid reaction volume to at least 50 °C. Establishing reaction conditions may be sufficient to initiate a chemical or enzymatic reaction in the reaction zone and / or outgassing from the liquid reaction volume. The reaction zone may include the retentate side of the degassing chamber. In another example, reaction conditions may be established by removing gas (such as gas separating reactants) from vessel 150 sufficient to initiate a chemical or enzymatic reaction between reactants in vessel 150. The gas may separate the first liquid reactant and the second liquid reactant. In this example, the degasser may be utilized to remove gas from vessel 150 sufficient to initiate a chemical reaction. In yet another example, applying heat, removing heat, and / or applying light radiation (such as UV light) to one or more components in vessel 150 may be utilized to establish reaction conditions. Further, the retentate side of the degassing chamber may be a portion of the lumen.

[0069] STEP 930, APPLY A FIRST PRESSURE TO THE GAS VOLUME TO MOTIVATE THE LIQUID REACTION VOLUME AXIALLY ALONG THE CHANNEL TO THE RETENTATE SIDE OF THE DEGASSING CHAMBER, includes applying a first pressure to the gas volume, such as from a fluid pump, to motivate the liquid reaction volume axially along the channel to the retentate side of the degassing chamber, such as degassing chamber 210. In one example, a fluid pump may provide pressure to the gas volume to move the liquid reaction volume axially along the channel. In another example, a syringe pump may provide pressure to the gas volume to move the liquid reaction volume axially along the channel. In yet another example, a syringe pump may provide the gas volume to the channelsufficient to motivate the liquid reaction volume axially along the channel. A syringe pump may apply a positive or negative pressure to the gas volume.

[0070] STEP 940, OPERATE THE EVACUATION PUMP TO ESTABLISH A PRESSURE GRADIENT ACROSS THE SEPARATION MEMBRANE THAT IS SUFFICIENT TO PROMOTE PERMEATION OF THE REACTION GAS THROUGH THE SEPARATION MEMBRANE TO THE PERMEATE SIDE OF THE CHAMBER, includes operating the evacuation pump, such as evacuation pump 230, to establish a pressure gradient across the separation membrane. The pressure gradient may be sufficient to promote permeation of the reaction gas through the separation membrane, such as the walls of vessel 150, or a barrier applied to the vessel to at least partially enclose the channel, to the permeate side of the chamber, such as degassing chamber 210. The separation membrane may be a gas permeable membrane and a liquid impermeable membrane. The evacuation pump may be controlled based on a vacuum sensor in fluidic communication with one or more of the permeate side of the chamber and the evacuation pump. Method 900 may further include applying a second pressure (such as a negative pressure) to the reaction products sufficient to transfer the reaction products through a valve, wherein the valve is upstream of the chamber. This second pressure may motivate the liquid reaction volume out from the retentate side of the degassing chamber. This second pressure may act to motivate the liquid reaction volume axially along the channel.

[0071] FIG. 10 illustrates an isometric schematic view of degasser system 1000, according to some embodiments. Degasser system 1000 may be used in any reaction system of the present disclosure. Degasser system 1000 includes enclosure 1010, degassing chamber 1020, and evacuation pump connection 1030. Degasser system 1000 may further include a heat applicator within enclosure 1010 or degassing chamber 1020. Vessel 150 may enter degassing chamber 1020 and may include a coiled conduit within degassing chamber 1020. Coiled conduit may allow for a greater volume of reactant gases to interact with degassing chamber 1020 and may include two or more loops. In one example, coiled conduit increases the surface area of the separation membrane exposed to the degassing environment. Accordingly, coiled conduit may decrease the time necessary to complete the degassing process.

[0072] Vessel 150 may exit the degassing chamber and may extend to a vent. The vent may maintain fluids in vessel 150 at about atmospheric pressure. Degasser system 1000 may further include an evacuation pump in fluidic connection with evacuation pump connection 1030. Evacuation pump connection 1030 is sufficient to allow reaction gases to pass throughand exit degassing chamber 1020. FIG. 11 illustrates a side view of degasser system 1000, according to some embodiments. Degasser system 1000 includes enclosure 1010, degassing chamber 1020, and structure 1040. Degasser system 1000 may include seal 1050 for sealing enclosure 1010 to degassing chamber 1020. Degasser system 1000 may further include a heat applicator within enclosure 1010, degassing chamber 1020, and structure 1040. The heat applicator may be optionally mounted near degasser system 1000.

[0073] FIG. 12 illustrates an isometric view of degasser system 1200, according to some embodiments. Degasser system 1200 may be used in any reaction system of the present disclosure. Degasser system 1200 includes enclosure 1210, degassing chamber 1220, and evacuation pump connection 1230. Degasser system 1200 may further include an optional heat applicator within enclosure 1210 or degassing chamber 1220. FIG. 13 illustrates a side view of degasser system 1200, according to some embodiments. Degasser system 1200 includes enclosure 1210 and degassing chamber 1220. Degasser system 1200 may include seal 1250 for sealing enclosure 1210 to degassing chamber 1220. Degasser system 1200 may further include a heat applicator within enclosure 1210 or degassing chamber 1220. The heat applicator may be optionally mounted near degasser system 1200. The degassers of the present disclosure may be used to adjust the position of liquid reaction volumes within an air segmented tubular vessel. The degassers may be used to concentrate reagents and samples by causing pervaporation through a separation membrane. Heated concentration of liquid samples or reagents can be caused by adjusting the level of vacuum to an absolute pressure lower than the vapor pressure of the mixture at the temperature of the reaction zone.

[0074] Importantly, the reaction systems of the present disclosure may automatically prepare samples for analysis without exposing the sample to the atmosphere. Exposing the sample to atmosphere may result in evaporation and contamination issues. The pumping system of the present disclosure provides reproducibility and in-vessel mixing. This pumping system may accurately position the reactants and products in the vessel. The degassers of the present disclosure may also be utilized under certain conditions where outgassing of reaction products occurs without elevated temperatures. By removing outgas from the vessel, the liquid reactants and / or products may be properly distributed within the vessel with correct positional accuracy.

[0075] While the disclosure has been described with reference to an exemplary embodiment s), it will be understood by those skilled in the art that various changes may be made, and equivalents may be substituted for elements thereof without departing from the scope of the embodiment s). In addition, many modifications may be made to adapt a particularsituation or material to the teachings of the embodiment(s) without departing from the essential scope thereof. Therefore, it is intended that the disclosure is not limited to the disclosed embodiment s), but that the disclosure will include all embodiments falling within the scope of the appended claims. Various examples have been described. These and other examples are within the scope of the following claims.

Claims

WHAT IS CLAIMED IS:

1. A fluid reaction system, comprising: a first reactant source containing a first liquid reactant; a multiple-port fluid valve having a first port fluidically connected to the first reactant source; a channel; a pumping system for pumping a first volume of the first liquid reactant through the valve into the channel, the pumping system further being adapted to pump a gas volume into contact with the first volume in the channel, such that the first volume of the first liquid reactant is motivatable through the channel by the gas volume as directed by the pumping system; a degasser having a degassing chamber and a separation membrane disposed in the degassing chamber to define a retentate side fluidically connected with the channel, and a permeate side, the separation membrane being permeable to gas but impermeable to liquid, the degasser further including an evacuation pump for evacuating the permeate side of the degassing chamber; and a heat applicator for elevating a temperature of the first volume to at least 40 °C in one or more of the channel and the retentate side of the chamber.

2. The fluid reaction system as in Claim 1, including a second reactant source containing a second liquid reactant, and wherein the pumping system is adapted to pump a second volume of the second liquid reactant through the valve into the channel into contact with the first volume to form a liquid reactant mixture.

3. The fluid reaction system as in Claim 2 wherein the pumping system is adapted to pump the gas volume into contact with the liquid reactant mixture such that the liquid reactant mixture is motivatable through the channel by the gas volume as directed by the pumping system.

4. The fluid reaction system as in Claim 3 wherein the multiple-port fluid valve includes a second port fluidically connected to the second reactant source.

5. The fluid reaction system as in Claim 2 wherein the pumping system includes one or more fluid pumps.

6. The fluid reaction system as in Claim 2 wherein the heat applicator applies heat to the liquid reactant mixture while in the degassing chamber.

7. The fluid reaction system as in Claim 2 wherein the heat applicator applies heat to the liquid reactant mixture while not in the degassing chamber.

8. The fluid reaction system as in Claim 1 wherein the separation membrane is non- porous.

9. The fluid reaction system as in Claim 1 wherein the evacuation pump is fluidically connected to the permeate side of the degassing chamber through a port.

10. The fluid reaction system as in Claim 1 further including a vent, wherein the vent is sufficient to maintain one or more fluids within the channel at about atmospheric pressure.

11. The fluid reaction system as in Claim 1 wherein the channel includes a coiled conduit within the degasser.

12. A method for conditioning fluid in a reaction system having a channel, a heat applicator for applying heat to a reaction zone of the channel, and a degasser having a degassing chamber and a separation membrane disposed in the degassing chamber to define a retentate side in fluid communication with the channel, and a permeate side in fluid communication with an evacuation pump, the method comprising:(a) forming a gas-bounded liquid reaction volume in the channel, wherein the liquid reaction volume is bounded on at least one axial end by a gas volume within the channel;(b) applying a positive or negative pressure to the gas volume to motivate the liquid reaction volume to the reaction zone;(c) operating the heat applicator to elevate the temperature of the liquid reaction volume to an extent sufficient to cause at least one of outgassing and formation of a reaction gas from the liquid reaction volume; and(d) operating the evacuation pump to establish a pressure gradient across the separation membrane that is sufficient to promote permeation of the reaction gas through the separation membrane to the permeate side of the chamber.

13. The method as in Claim 12, including, subsequent to elevating temperature of the liquid reaction volume, applying pressure to motivate the liquid reaction volume through the channel to the retentate side of the degassing chamber.

14. The method as in Claim 12, including operating the heat applicator to elevate temperature of the liquid reaction volume to an extent sufficient to cause a chemical or enzymatic reaction in the reaction volume that produces the reaction gas.

15. The method as in Claim 12 wherein the liquid reaction volume is bounded on two axial ends by first and second discrete gas volumes within the channel.

16. The method as in Claim 15 wherein the liquid reaction volume is bounded radially by a vessel wall defining the channel.

17. The method as in Claim 12 wherein the reaction system includes a fluid pump for applying the pressure to the gas volume, and wherein the reaction zone is disposed fluidically along the channel between the fluid pump and the degassing chamber.

18. The method as in Claim 17 wherein the pressure is selected from positive and negative.

19. The method as in Claim 12, including operating the heat applicator to elevate temperature of the liquid reaction volume to at least 40 °C.

20. The method as in Claim 12, including maintaining one or more fluids in the channel located in the reaction zone at about atmospheric pressure.

21. A method for conditioning fluid in a reaction system having a channel and a degasser having a degassing chamber and a separation membrane disposed in the degassing chamber to define a retentate side in fluid communication with the channel, and a permeate side in fluid communication with an evacuation pump, the method comprising:(a) forming a gas-bounded liquid reaction volume in the channel, wherein the liquid reaction volume includes a first liquid reactant and a second reactant that together produce a reaction gas when mixed at reaction conditions, the liquid reaction volume being motivatable through the channel under a force applied through a gas volume bounding at least one axial end of the liquid reaction volume;(b) establishing the reaction conditions at the liquid reaction volume;(c) applying a first pressure to the gas volume to motivate the liquid reaction volume along the channel to the retentate side of the degassing chamber; and(d) operating the evacuation pump to establish a pressure gradient across the separation membrane that is sufficient to promote permeation of the reaction gas through the separation membrane to the permeate side of the chamber.

22. The method as in Claim 21 wherein step (c) is performed subsequent to step (b).

23. The method as in Claim 21, including alternately applying a positive pressure and a negative pressure to the liquid reaction volume to promote the establishment of the reaction conditions.

24. The method as in Claim 21 wherein the lumen is fluidically connectable to a first source of the first liquid reactant and a second source of the second reactant through a multipleport valve.

25. The method as in Claim 24 wherein the multiple-port valve is a shear valve.

26. The method as in Claim 21, including applying a second pressure to the gas volume to motivate the liquid reaction volume out from the retentate side of the degassing chamber.

27. The method as in Claim 26 wherein the second pressure acts to motivate the liquid reaction volume axially along the lumen.

28. The method as in Claim 21, including establishing the reaction conditions at the liquid reaction volume while the liquid reaction volume is in a reaction zone.

29. The method as in Claim 28, including applying heat to the liquid reaction volume in the reaction zone to elevate temperature of the liquid reaction volume to an extent sufficient to cause outgassing of the reaction gas from the liquid reaction volume.

30. The method as in Claim 29, including operating the heat applicator to elevate temperature of the liquid reaction volume to an extent sufficient to cause a chemical reaction in the reaction volume that produces the reaction gas.

31. The method as in Claim 30, including operating the heat applicator to elevate temperature of the liquid reaction volume to at least 40 °C.

32. The method as in Claim 29 wherein the reaction zone includes the retentate side of the degassing chamber.

33. The method as in Claim 32 wherein the retentate side of the degassing chamber is a portion of the channel.

34. The method as in Claim 33 wherein the liquid reaction volume is bounded radially by a vessel wall defining the channel.

35. The method as in Claim 32 wherein the separation membrane is a portion of the vessel wall.

36. The method as in Claim 21, wherein step (b) is performed subsequent to step (c).

37. The method as in Claim 21, wherein establishing the reaction conditions at the liquid reaction volume includes applying radiation to the liquid reaction volume.

38. A method for conditioning fluid in a reaction system having a channel and a degasser having a degassing chamber and a separation membrane disposed in the degassing chamber to define a retentate side in fluid communication with the channel, and a permeate side in fluid communication with an evacuation pump, the method comprising:(a) forming a gas-bounded liquid reaction volume in the channel, wherein the liquid reaction volume includes a first liquid reactant separated from a second liquid reactant by a separating gas volume, wherein the first and second liquid reactants are reactable with one another at reaction conditions, the liquid reaction volume being motivatable through the channel under a force applied through a terminal gas volume bounding at least one axial end of the liquid reaction volume;(b) applying a first pressure to the terminal gas volume to motivate the liquid reaction volume along the channel to the retentate side of the degassing chamber; and(c) operating the evacuation pump to establish a pressure gradient across the separation membrane that is sufficient to promote permeation of gas in the separating gas volume through the separation membrane to the permeate side of the chamber.

39. The method as in Claim 38, including establishing the reaction conditions by operating the evacuation pump sufficient to remove the separating gas volume through the separation membrane.

40. The method as in Claim 39 wherein establishing the reaction conditions further includes alternately applying a positive pressure and a negative pressure to the liquid reaction volume sufficient to mix the first and second liquid reactants.

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