Viscometer and method of using the same

Abstract

A viscometer includes a viscosity sensor having a liquid flow channel and at least two pressure sensors positioned along the liquid flow channel and configured to measure the pressure drop of the liquid flowing through the liquid flow channel; and a distribution mechanism configured to distribute the liquid from a syringe to the viscosity sensor at a known flow rate. The distribution mechanism and the viscosity sensor are configured to be connected to a syringe configured to contain the liquid. The viscometer further includes an electronic controller configured to control the operation of the distribution mechanism and to receive and process data from the viscosity sensor. The viscometer includes a sample loading interface included in the syringe, and the viscometer is configured to receive the liquid through the sample loading interface. The sample loading interface includes a selection valve connected to the viscosity sensor and the syringe and located between the two.

Description

[0001] The present application is a divisional application of a patent application with application number 201580030961.X, application date April 10, 2015, and title “VISCOMETER AND METHOD USING THE SAME”. Technical Field

[0002] The present application relates generally to viscometers including, but not limited to, viscometers that utilize flow-through type viscosity sensors to measure the viscosity of a liquid. Background Art

[0003] Viscosity is a measure of the resistance to flow of a liquid, and the viscosity value depends on the deformation rate for non-Newtonian liquids, as described in Dynamics of Polymeric Liquids, Vol. 1, 1987, by RB Bird, RC Armstrong and O. Hassager. The deformation rate is given by the shear rate in units of (time)-1. The viscosity measured at a known shear rate is the "real" viscosity. The dependence of the real viscosity on the shear rate is the viscosity curve, which characterizes the material and is an important factor in considering effective processing. However, in many cases, the viscosity is measured under unclear test conditions, making it impossible for the shear rate to be known or calculated. Under unclear conditions, the measured viscosity value is only "apparent". Since the real viscosity is measured at a known shear rate, the real viscosity is universal, while the apparent viscosity is not universal. On the contrary, the apparent viscosity depends on the measurement system. For example, as common knowledge, the torque of a mandrel immersed in a test liquid pool is measured when the mandrel rotates at a constant speed. In this case, the torque value only produces an apparent viscosity, because the test conditions are unclear and the shear rate is unknown. At most, the apparent viscosity can be measured as a function of the rotational speed of the mandrel. Only in the case of a known "constitutive equation" for the test liquid, the rotational speed of the mandrel can in fact be related to the shear rate. However, the "constitutive equation" is unknown for almost all non-Newtonian liquids. Therefore, for most non-Newtonian liquids, it is impossible to measure the true viscosity under unclear test conditions.

[0004] Viscosity measurement methods that only give the apparent viscosity have been studied and used for quality control in manufacturing and material characterization. Various online viscometers are designed for real-time viscosity measurement. U.S. Patents 5,317,908 (Fitzgerald et al.) and 4,878,378 (Harada) are related to systems for measuring apparent viscosity for process control. U.S. Patent 6,393,898 (Hajduk et al.) describes a system for measuring many test liquids simultaneously. These viscometers measure apparent viscosity. However, due to the non-universality of the apparent viscosity measurement, the correlation between the apparent viscosity and the true viscosity of a specific sample measured by a specific method must be found individually when necessary. Basic research on the formulation of materials requires true viscosity measurement. The design of processing equipment and accessories (e.g., molds, dies, extrusion screws, etc.) also requires the true viscosity of the material. However, the apparent viscosity measurement has been used for indication in rapid tests because it is easier and faster to measure and is generally more economical. The true viscosity is more difficult to obtain and can only be measured with the help of several types of instruments: rheometers and capillary viscometers. Rheometers obtain accurate and known shear rates for test specimens, thereby measuring true viscosity. Rheometers are varied and are usually equipped to measure other properties as well. Therefore, rheometers are usually expensive. In addition, a large number of samples need to be measured for viscosity by means of rheometers. Similarly, rheometers are not very suitable for online applications. Circular capillary viscometers can measure apparent viscosity and true viscosity, depending on whether appropriate compensation is taken into account. Capillary viscometers require pressure drop measurements along the capillary for viscosity. Since the capillary is of circular cross-section, only the pressure at the inlet and outlet can be measured. Due to this limitation, capillary viscometers only measure apparent viscosity, unless the inlet effect is corrected by using two different capillaries with different length-to-diameter ratios. However, using two capillaries makes the capillary viscometers bulky and / or time-consuming. Capillary viscometers are described in patents 6,575,019 (Larson), 4,920,787 (Dual et al.), 4,916,678 (Johnson et al.), and 4,793,174 (Yau). Microfluidic viscometers are disclosed in patent 6,681,616 (Michael Spaid et al.) and publication 2003 / 0182991 (Michael Spaid et al.). The residence time of a marker in a fluid channel is used to measure viscosity, which is true viscosity only if the test liquid is a Newtonian liquid. Only the apparent viscosity of non-Newtonian liquids is measured. The portable viscometer disclosed in patent 5,503,003 (Brookfield) uses a known torque measurement of a spindle rotating in a liquid pool for viscosity measurement. As shown and as known, this method only measures the apparent viscosity.

[0005] In a word, most viscosity measurement techniques obtain apparent measurements and require relatively large volumes of samples. Similarly, these instruments need to clean the parts (e.g., containers, spindles, etc.) in contact with the liquid before measuring the next sample. This cleaning is time-consuming, so that the viscosity measurement usually takes 30 minutes from setting to testing. Larger sample volume requirements under current technology also increase cleaning time and waste. Therefore, there is no real portable viscometer that measures the true viscosity of a small amount of sample and measures quickly. The slit viscometer disclosed in the applicant's patent 7,290,441 makes it possible to measure the true viscosity of a small sample. However, the slit viscometer requires a precision liquid dispensing system and related electronic devices to provide and control the liquid flow through the viscometer. A simple precision liquid dispensing system that is portable and can be used in conjunction with various samples is not disclosed in the prior art. Summary of the invention

[0006] According to some embodiments, a portable viscosity measuring instrument or viscometer includes: a micro viscosity measuring sensor; a portable precision liquid dispensing system for forcing a liquid sample through the micro viscosity measuring sensor; a controller for controlling the operation of the viscometer; and a display for displaying the measured viscosity of the liquid. The sensor design is described in the applicant's patents 6,892,583 and 7,290,441, which are incorporated herein by reference as if fully set forth herein. The portable system measures the true viscosity of the liquid and requires only a small volume of the liquid sample for measurement. The present invention also provides a quick and simple method of obtaining a liquid sample to be tested and placing the liquid sample in a viscometer for testing.

[0007] A portable precision liquid dispensing system according to some embodiments includes a positive displacement pump that operates in conjunction with a positive displacement sample container, hereinafter referred to as a positive displacement pipette, in which a liquid sample whose viscosity is to be measured is supplied. The pipette can be removed and replaced from the viscometer so that when the pipette is removed and separated from the viscometer, the liquid sample to be tested can be drawn into the pipette, and then the pipette with the liquid sample therein is inserted into the viscometer for measuring the viscosity of the liquid sample in the pipette. The pipette includes a plunger that slides in the pipette to draw the sample into the pipette (which can be done by hand) and forces the sample to leave the pipette when the pipette is in the viscometer. In one embodiment of the positive displacement pump, a precision motor drives a lead screw that moves a push-back portion to contact the pipette plunger when the pipette plunger is positioned in the viscometer. When the push-back moves the plunger in the pipette, liquid is dispensed from the pipette into the flow channel of the microviscosity measurement sensor. The control electronics control the operation of the precision motor to dispense the liquid to be tested from the pipette into the flow channel of the microviscosity measurement sensor at a known flow rate.

[0008] The micro-flow through viscosity measurement sensor includes a micron-scale flow channel, which is combined with a pressure sensor array, and the pressure sensor array measures the pressure drop of the fully developed flow of the liquid in the flow channel. In some embodiments, when the velocity field of the flow reaches a steady state (through the transition from the entrance of the flow channel), the flow is considered to be fully developed. In some embodiments, the fully developed flow of the liquid has the same velocity distribution along the length of the flow channel. For example, the speed of the fully developed flow of the liquid at the center of the flow channel near the first end of the flow channel is the same as the speed of the fully developed flow of the liquid at the center of the flow channel near the second end of the flow channel opposite to the first end. The pressure drop is proportional to the shear stress of the liquid flowing through the channel. The shear rate is proportional to the flow rate. The viscosity of the sample liquid is calculated by dividing the shear stress by the shear rate. The measurement result of the viscosity can be displayed in a display. A microcontroller or a microprocessor-based electronic device can form a controller electronic device (also referred to as an electronic controller herein) of a viscometer to control the motor of the pump and process data from the pressure sensor. The processed data can be displayed and can also be stored and / or sent to a remote device.

[0009] In some embodiments, if temperature control of the sample is desired, the sample in the viscometer, viscosity sensor, and / or pipette may be regulated to a set temperature via a Peltier-based temperature control device or other generally accepted temperature control device.

[0010] In some embodiments, the viscometer is configured to store a history of measured viscosity values ​​for various uses, and / or a database of known viscosity values ​​for various liquids (such as liquids that are expected to be measured frequently) can be stored. This allows a known viscosity of a known liquid to be quickly compared to a measured viscosity of a sample that is believed to be a known liquid. A difference between the known value and the measured value can indicate that the test liquid is not the liquid it is believed to be, or can indicate that there is a problem with the viscometer, allowing the viscometer to be checked.

[0011] According to some embodiments, the viscometer includes a viscosity sensor having a liquid flow channel and at least two pressure sensors positioned along the liquid flow channel and configured to measure the pressure drop of the liquid flowing through the liquid flow channel. The viscometer also includes a dispensing mechanism configured to cause the liquid to be dispensed from the syringe to the viscosity sensor at a known flow rate; and an electronic controller configured to control the operation of the dispensing mechanism and receive and process data from the viscosity sensor.

[0012] In some embodiments, the dispensing mechanism is configured to be coupled to a syringe, and the syringe is coupled to the viscosity sensor and is configured to contain a liquid.

[0013] In some embodiments, the viscometer includes a sample loading interface through which the viscometer is configured to receive liquid. In some embodiments, the syringe includes the sample loading interface. In some embodiments, the sample loading interface includes a selector valve or switch valve (when used herein, the term "selector valve" is used throughout to represent a wide range of valves) coupled to the viscosity sensor and the syringe and located between the viscosity sensor and the syringe.

[0014] In some embodiments, the viscometer includes a delivery device configured to couple with the syringe and the dispensing mechanism. The delivery device is configured to move the syringe between a first position for drawing the test liquid into the syringe and a second position for coupling the syringe to the viscosity sensor, wherein the second position is different from the first position and the delivery device is configured to move the syringe between the first position and the second position independently of user intervention.

[0015] In some embodiments, the viscometer is configured to draw the test liquid into the syringe independent of user intervention.

[0016] In some embodiments, the viscometer includes a viscosity sensor module including a plurality of viscosity sensors.

[0017] In some embodiments, a plurality of liquid flow channels are defined in the viscosity sensor, and at least two pressure sensors are positioned along each of two or more of the plurality of liquid flow channels.

[0018] In some embodiments, the viscometer includes a temperature control device. In some embodiments, the temperature control device is coupled to an electronic controller, and the electronic controller is configured to control the temperature control device. In some embodiments, the viscosity sensor is temperature controlled. In some embodiments, the injection tube is temperature controlled.

[0019] In some embodiments, the electronic controller is configured to determine viscosity values ​​of a liquid at a plurality of temperatures, the liquid comprising a first type of protein; and determine a melting temperature of the first type of protein from the viscosity values ​​of the liquid at the plurality of temperatures.

[0020] In some embodiments, the electronic controller is configured to: determine viscosity values ​​of a second liquid at multiple temperatures, the second liquid including a second type of protein; and determine a melting temperature of the second type of protein from the viscosity values ​​of the second liquid at the multiple temperatures.

[0021] In some embodiments, the viscometer includes a mixer that is coupled to an electronic controller and configured to mix a liquid with a solvent to obtain a mixed solution. The concentration of the solute in the mixed solution is different from the concentration of the solute in the liquid. The electronic controller is configured to: measure the viscosity of the mixed solution; and initiate repeated mixing and measuring to obtain viscosity values ​​of the mixed solution at multiple solute concentrations.

[0022] In some embodiments, the viscometer includes a sample syringe. The sample syringe is configured to distribute a continuous stream of liquid to the viscosity sensor. The continuous stream of liquid includes two or more batches of test liquid. Any two adjacent batches of test liquid of the two or more batches of test liquid are separated by at least one inert liquid that is immiscible with the two adjacent batches of test liquid.

[0023] In some embodiments, the viscometer includes a pump configured to dispense the cleaning solution through the liquid flow channel of the viscosity sensor.

[0024] In some embodiments, the viscometer is configured to couple to a gas source and provide the gas through the liquid flow channel.

[0025] In some embodiments, the viscometer is configured to self-calibrate by using a pre-selected reference liquid.

[0026] In some embodiments, the viscometer includes one or more of the following: a pH meter, a density meter, and a conductivity meter.

[0027] In some embodiments, the liquid flow channel comprises a rectangular liquid flow channel.

[0028] In some embodiments, the viscosity sensor has an inlet and an outlet, the inlet being configured to couple with the syringe, and the viscometer further includes a positive pressure source coupled to the outlet of the viscosity sensor.

[0029] According to some embodiments, a method for performing viscosity measurement includes: at a viscometer including a viscosity sensor having a liquid flow channel, receiving liquid entering the liquid flow channel from a syringe at a known flow rate. The viscometer further includes a distribution mechanism and an electronic controller. At least two pressure sensors are positioned along the liquid flow channel and are configured to measure the pressure drop of the liquid flowing through the liquid flow channel. The electronic controller is configured to control the operation of the distribution mechanism and to receive and process data. The distribution mechanism is configured to be coupled to the syringe and cause the distribution of the liquid in the syringe to the viscosity sensor at a known flow rate. The method also includes measuring the viscosity of the liquid. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Additional features and advantages of the present invention will be apparent from the following detailed description taken in conjunction with the accompanying drawings. Figure 1The features of the exemplary embodiments have been described above by way of example.

[0031] Figure 1 is a schematic diagram of a portable viscometer according to some embodiments.

[0032] Figure 2A is a schematic diagram of a flow through a viscosity sensor according to some embodiments.

[0033] Figure 2B is a schematic cross-sectional diagram of a flow through a viscosity sensor according to some embodiments.

[0034] Figure 2C is a schematic cross-sectional diagram of a flow through a viscosity sensor according to some embodiments.

[0035] Figure 3 is a cross-sectional view of a pipette that may be used in the system, showing the pipette plunger in an intermediate position of the pipette, according to some embodiments.

[0036] Figure 4 According to some embodiments Figure 3 , showing the pipette plunger in a position before a liquid sample has been aspirated into the pipette or after a liquid sample has been dispensed from the pipette.

[0037] Figure 5 is a schematic diagram of a portable viscometer according to some embodiments.

[0038] Fig. 6A is a schematic diagram of a viscometer according to some embodiments.

[0039] Figure 6B is a schematic diagram of a viscometer according to some embodiments.

[0040] Figure 6C is a schematic diagram of a viscometer according to some embodiments.

[0041] Fig.6D is a schematic diagram of a viscometer according to some embodiments.

[0042] Fig. 6E is a schematic diagram of a viscometer according to some embodiments.

[0043] Figure 7 is a graph illustrating a method of determining a dissolution temperature according to some embodiments.

[0044] Fig. 8A - Figure 8C is a flow chart illustrating a method of measuring the viscosity of a liquid according to some embodiments.

[0045] Reference will now be made to the exemplary embodiments described, and specific language will be used herein to describe the same. It will however be understood that no limitation of the scope of the invention is thereby intended. DETAILED DESCRIPTION

[0046] According to some embodiments, an improved viscometer is described that is portable, easier to use, more accurate, and has a faster method of measuring the viscosity of a liquid sample than prior art viscometers. Figure 1 , the viscometer 22 includes: a precision pump, generally indicated by reference numeral 20; a liquid container 14 for supplying a liquid sample for which viscosity measurement is desired; a flow-through viscosity sensor 15; a controller 18; and a display 19.

[0047] The pump 20 is used in conjunction with the sample container shown, which is called a pipette 14, and the pipette 14 has a pipette barrel or body 13 and a plunger 12, which is slidably positioned in the pipette barrel 13, and the plunger end 24 extends from the end of the barrel 13. The pipette 14 can be removably positioned and maintained in the viscometer by means of a mounting mechanism 28, so that the pipette can be removed, filled with a liquid sample to be tested and then placed back into the mounting mechanism of the viscometer, or can be removed and replaced with another similar pipette that accommodates the liquid sample to be tested. The pipette can be made disposable so that for each liquid sample, a new clean pipette is used. The pump comprises: a precision motor 23; a lead screw 10 rotatable by the motor 23 through a drive mechanism 26 (such as a gear drive or a belt drive); and a push back 11 mounted on the lead screw 10, which contacts the tip 25 of the pipette plunger end 24 when the pipette 14 is positioned on the viscometer. The push back 11 moves laterally along the lead screw 10 in response to the rotation of the lead screw 10 caused by the motor 23.

[0048] exist Figure 3 and Figure 4 An example of a pipette construction is shown in FIG. A pipette plunger 41 has a plunger head 42 which is received in a sealed and slidable manner in a pipette barrel 40, with an end 45 extending from one end of the pipette barrel 40. Both the pipette barrel and the pipette plunger can be made of plastic by injection molding. The plunger can slide back and forth inside the barrel 40. To minimize air entrainment when filling the pipette with sample liquid, the end of the plunger head 42 is shaped to fit snugly into the end 43 of the liquid flow barrel, as shown in FIG. Figure 4 As shown, to minimize any air gap 44 between them. Figure 4In the illustrated case, the liquid flow end 43 of the pipette can be inserted into the liquid whose viscosity is to be determined. The user can grasp the end 45 of the plunger 41 extending from the pipette barrel 40 and pull the plunger back from the end 43 of the pipette barrel to draw the sample into the pipette barrel through the opening in the barrel end 43. Figure 3 The plunger 41 is shown pulled back from the barrel end to form a space 46 in the pipette barrel, which will contain the liquid sample drawn into the pipette. As the pipette plunger 41 continues to be pulled back in the pipette barrel 40, the sample will continue to be drawn into the increased space 46. When the desired amount of sample is drawn into the pipette barrel, the user stops pulling back the plunger 41. If the plunger 41 is pushed toward the liquid flow end 43 of the barrel 40, the fluid in the space 46 is discharged from the barrel 40 through the opening in the barrel end 43.

[0049] The flow-through viscosity sensor 15 includes a liquid inlet connector 16 and a liquid outlet connector 21. Figure 1 As shown, the liquid discharged from the end of the pipette barrel 13 is connected to the liquid inlet of the viscosity sensor 15 through the liquid inlet connector 16. The liquid discharge tube 17 is connected through the liquid outlet connector 21 to guide the liquid away from the liquid outlet of the viscosity sensor 15.

[0050] Figure 2A A perspective view of a flow-through viscosity sensor 15 is shown, according to some embodiments. Figure 2A Also shown are planes AA and BB, which are drawn to facilitate understanding. Figure 2B and Figure 2C .

[0051] Figure 2B is according to some embodiments along plane AA ( Figure 2A ) is a cross-sectional view of a flow through a viscosity sensor 15.

[0052] refer to Figure 2B, the flow through viscosity sensor 15 includes a liquid flow channel 31, wherein the flow channel inlet 35 and the flow channel outlet 36 are formed in the channel substrate 39. The flow channel 31 has a rectangular cross-section, wherein the channel substrate 39 provides three sides of the flow channel 31, leaving one open side. An integral sensor plate 38 formed by a pressure sensor membrane 37 and a pressure sensor substrate 30 is combined with the channel substrate 39 to close the open side of the flow channel 31. The integral sensor plate 38 provides a plurality of independent pressure sensors, and is positioned relative to the channel substrate 39 to position at least two independent pressure sensors spaced apart along the flow channel 31 far enough from the channel inlet 35 and the channel outlet 36, whereby the pressure drop of the fully developed flow of the liquid through the flow channel 31 can be measured by the pressure sensor. As explained above, the pressure drop is proportional to the shear stress of the liquid flowing through the channel. The shear rate is proportional to the flow rate. The viscosity of the sample liquid is calculated as the shear stress divided by the shear rate.

[0053] exist Figure 2B In the embodiment shown, three independent pressure sensors are provided by an integral sensor plate 38 along the flow channel 31. Each independent pressure sensor is formed by a cavity 33 in a pressure sensor membrane 37. When pressure is applied to a portion 34 of the pressure sensor membrane extending over a respective cavity 33, the portion 34 of the pressure sensor membrane 37 extending over a respective cavity 33 will deflect into the respective cavity 33. The amount of deflection into the respective cavity is proportional to the pressure applied to the pressure sensor membrane over the respective cavity by the liquid flowing in the flow channel 31.

[0054] A detector is provided in each cavity for detecting the displacement of the film into the corresponding cavity, the displacement of the film providing a measure of the pressure applied to the film above the cavity. Various detectors can be used, such as a capacitive detector, in which one capacitor electrode is located on the pressure sensor film above the cavity and the other capacitor electrode is located on the sensor substrate 30 covering the cavity. The displacement of the film moves the capacitor electrodes closer to each other and changes the capacitance providing a measure of the pressure. It will be noted that the surface of the pressure sensor film 37 along the liquid channel 31 is a substantially smooth and continuous surface, without a separate pressure sensor being inserted into the surface to form irregularities or discontinuities. This smooth channel surface is important for obtaining accurate pressure measurements. A more detailed description of the pressure sensor and variations and different embodiments of the pressure sensor construction and flow-through viscosity sensor are provided in U.S. Patent Nos. 6,892,583 and 7,290,441, which are incorporated herein by reference in their entirety. A liquid inlet connector 16 attached to the channel substrate 39 around the liquid channel inlet 35 provides a connection to a source of pressurized sample liquid (here, liquid discharged from the pipette 14), and a liquid outlet connector 21 attached to the channel substrate 39 around the liquid channel outlet 36 provides a connection to a sample liquid discharge outlet or reservoir.

[0055] Figure 2C is according to some embodiments along plane BB ( Figure 2A ) is a cross-sectional view of a flow through the viscosity sensor 15. Figure 2C As shown, in some embodiments, a plurality of liquid flow channels are defined in the viscosity sensor. In some embodiments, at least two pressure sensors are positioned along each of two or more liquid flow channels of the plurality of liquid flow channels. In some other embodiments, only a single liquid flow channel is defined in the viscosity sensor.

[0056] In some embodiments, a plurality of viscosity sensors are formed on a single substrate, and the single substrate defines a plurality of channels for the plurality of viscosity sensors. In some embodiments, each viscosity sensor of the plurality of viscosity sensors is formed on a respective substrate.

[0057] Return to reference Figure 1, the controller 18 controls one or more microcontrollers or microprocessors and other electrical and electronic components for controlling the operation of the viscometer and peripheral components, for performing calculations, for controlling a display 19 capable of displaying measured viscosity and other information (such as the status of the viscometer), and for communicating with other devices such as other computers and transmitting data. Communications can be made through ports such as RS232 or USB ports, or can be made by wireless or other communication means. The controller 18 will generally include an interface device, such as a keyboard, a touch button pad or keypad, an external computer, or other data input devices such as buttons, a mouse, or a touch screen in the display 19, whereby a user can input control and other instructions and information into the controller.

[0058] In order to measure the viscosity of a sample of liquid, a sample of the liquid whose viscosity is to be determined is obtained in a liquid sample holding pipette. The sample of liquid in the pipette can be drawn back into the pipette from a liquid source by the user of the viscometer, or can be supplied to the user of the viscometer in other ways and into the pipette. Figure 1 As shown, the pipette 14 is mounted in the viscometer 22 and is held in place in the viscometer by the mounting mechanism 28. The controller is then activated to control the viscometer to obtain a viscosity measurement. The controller will operate the motor 23 to advance the push-back portion 11 to a position such as Figure 1 The position shown rests against the tip 25 of the pipette plunger. Alternatively, the push-back 11 may be positioned by the user, such as manually, when the pipette is installed in the viscometer before activating the controller.

[0059] In the case where the push back portion 11 is positioned against the end 25 of the pipette plunger, the controller controls the motor 23 so that the lead screw 10 is rotated, so that the push back portion 11 and the pipette plunger 12 are advanced at a desired speed or multiple speeds to discharge the liquid from the pipette at a known desired flow rate or multiple flow rates. When the plunger moves, the liquid is forced to enter the viscosity sensor 15 from the pipette and flow through the flow channel 31, in which the pressure sensor of the integral pressure sensor 38 measures the pressure drop of the fully developed flow of the liquid. The pressure is measured as the local pressure above the corresponding membrane portion of the pressure sensor that deflects the sensor membrane portion 34 to the corresponding cavity 33 along the flow channel 31. The pressure drop measured along the flow channel 31 (the pressure difference measured between the successive pressure sensors along the flow channel) is proportional to the viscosity of the liquid at a specific flow rate. If the sample viscosity changes with the flow rate, then the control device can be instructed to sequentially dispense liquids with different flow rates when the flow stops or the flow does not stop. When the pressure value is acquired and the viscosity value is calculated as a function of the flow rate, the relationship of non-Newtonian viscosity is corrected in a known manner. The measured viscosity can be displayed on the display 19, can be stored in the controller memory or auxiliary memory, and / or transmitted to a remote memory or computer.

[0060] When liquid is injected into the liquid flow channel 31 of the viscosity sensor 15 at the initially set flow rate (or shear rate), the viscometer senses the pressure inside the liquid flow channel 31. The controller can be programmed to determine whether the pressure level is optimal for the highest accuracy or ensuring accuracy of the viscosity measurement. If the pressure level is too low, the controller determines and sets the next flow rate value and ramps up the flow rate to the new set value. The controller continues to iterate to reach the optimal flow rate for this specific viscosity measurement. In this way, the viscosity of an unknown liquid can be accurately and automatically measured.

[0061] When the viscosity measurement or multiple measurements of the sample for the liquid have been obtained, the push-back portion 11 is operated to move it back to the following position: this position allows the used pipette to be removed and a new pipette with a new liquid sample for testing is inserted into the viscometer. The pipette with the new liquid sample to be tested can be a new disposable pipette or a used pipette of reloading. For the new viscosity measurement, the controller operates the viscometer as described above to determine the viscosity of the new liquid sample. In this test, the liquid from the new sample replaces the liquid from the old sample in the viscosity sensor 15. In this way, it is not necessary to clean the viscosity sensor. If the two successive liquids to be tested are incompatible or miscible, then before the new liquid is distributed in the viscosity sensor 15, it is necessary to clean the viscosity sensor 15 with a cleaning liquid that is compatible with both liquids. This cleaning can be carried out between the two liquids tested as follows: the pipette containing the cleaning liquid is loaded into the viscometer, and the viscometer is operated to force the cleaning liquid to pass through the viscosity sensor 15.

[0062] The viscometer 22 may be powered by batteries, such as rechargeable batteries, making the viscometer truly portable, or by connecting the viscometer to a power source as the viscometer 22 is moved between locations.

[0063] In some cases, it may be desirable to control the temperature of the liquid whose viscosity is being measured. If temperature control is desired, the viscometer 22, viscosity sensor 15, and / or the sample in the pipette 14 may be regulated at a set temperature using a Peltier-based temperature control device or other generally accepted temperature control device. For example, Figure 5 As shown, the figure is Figure 1Similarly, the temperature control device 50 can be arranged in the pipette mounting mechanism 28 or in contact with the pipette mounting mechanism 28, so that when the pipette is installed in the mounting mechanism 28, the liquid sample holding pipette 14 and the liquid sample contained therein are heated or cooled. Depending on how the temperature control device 50 is installed in the pipette mounting mechanism 28, the pipette mounting mechanism can also be heated or cooled to a set temperature. It may take some time for the sample in the pipette to reach the set temperature. Similarly, the temperature control device 52 can be arranged in the viscosity sensor 15 or in contact with the viscosity sensor 15, so as to heat or cool the material forming flow channel 31 of the viscosity sensor 15 and maintain the temperature of the material forming flow channel 31 at a set temperature. This will tend to maintain the material flowing through the flow channel 31 at a substantially set temperature. As shown, the temperature control device can be a Peltier device or other known temperature control devices. In addition, the temperature sensor can be positioned to measure the temperature of the sample liquid at various positions of the viscometer. For example, a temperature sensor can be included at one or more locations of the sensor membrane 37 along the flow channel 31, as shown in the applicant's previously cited patent documents. Rather than individually controlling the temperature of individual components of the viscometer 22 as described above, the viscometer 22 or the portion thereof to be temperature controlled can be mounted in a housing, wherein the temperature within the housing and therefore the temperature of the entire viscometer or the portion thereof within the housing is temperature controlled together.

[0064] As shown in the previously cited patent documents of the applicant, the flow-through viscosity sensor is very small and is usually constructed of semiconductor materials or other materials used in micro-fabrication processes. For example, the pressure sensor membrane can be a part of a silicon wafer, and the pressure sensor substrate and the channel substrate can be parts of a silicate glass wafer. The flow channel can typically be as small as a width of about ten microns and a depth of about one micron, and a length as short as about one hundred microns. Therefore, the flow channel viscosity sensor is very small, and a small sample size can be used to determine viscosity. This small size of the flow-through viscosity sensor and the small amount of sample required for viscosity testing means that other viscometer components such as pipettes and pumps can also be made relatively small, so that the viscometer can be easily manufactured as a relatively small portable unit.

[0065] Rather than making a portable viscometer, the same viscometer construction can be used to provide a static viscometer where samples of the liquid to be tested can be collected from different locations with different pipettes and then transferred to the viscometer and tested at the location of the viscometer.

[0066] If necessary, a database of known or otherwise known viscosity values ​​for liquids that are often measured or may be measured can be stored in the memory of the viscometer controller. Where such a database is available, the user can easily display known viscosity values ​​from the database for selected liquids, and compare it with the viscosity values ​​measured for the sample liquid that is considered to be a known liquid. The difference between the public value and the measured value can indicate that the test liquid is not the liquid that it is considered to be or can indicate that there is a problem with the viscometer, so that the viscometer can be checked. In addition, for various reasons, it may be advantageous for the user to occasionally access the known viscosity values ​​of a specific liquid other than the liquid being tested at this time. In addition, the viscometer can utilize appropriate identification to store the history of the measured viscosity values, which history may be used for various purposes by the user of the viscometer equally. For example, utilizing the history of such measured viscosity values, the user can compare the viscosity of the liquid component used for manufacturing process at different times, to ensure that the liquid component is within the required specification of the liquid component, or the viscosity value of the component can be determined and associated with the specific desired attribute of the formed product.

[0067] Although illustrative embodiments of a pump are shown and in some embodiments described as including a motor, a leadscrew, and a push-back portion for moving a plunger in a pipette, various other devices for moving a plunger in a pipette may be used or various other devices for providing precise discharge of sample liquid from a sample container may be used.

[0068] Fig. 6A is a schematic diagram of a viscometer according to some embodiments.

[0069] Fig. 6A The viscometer is shown to include a viscosity sensor module 610. In some embodiments, the viscosity sensor module 610 includes a single viscosity sensor. In some embodiments, the viscosity sensor module 610 includes a plurality of viscosity sensors. In some embodiments, the viscosity sensor has a liquid flow channel and at least two pressure sensors. The at least two pressure sensors are positioned along the liquid flow channel (e.g., a first pressure sensor is located at an upstream position in the liquid flow channel, and a second pressure sensor is located at a downstream position in the liquid flow channel), and are configured to measure a pressure drop of a liquid flowing through the flow channel.

[0070] like Fig. 6A As shown, the viscometer also includes a dispensing mechanism 630 (e.g., a precision pump 20, Figure 1). In some embodiments, the dispensing mechanism 630 is configured to be coupled to a syringe 620 (e.g., a pipette). In some embodiments, the dispensing mechanism 630 is configured to be removably coupled to the syringe 620. The dispensing mechanism 630 is configured to cause the dispensing of liquid from the syringe 620 to the viscosity sensor at a known flow rate. In some embodiments, the syringe 620 is coupled to the viscosity sensor. In some embodiments, the syringe 620 is removably coupled to the viscosity sensor.

[0071] Fig. 6A Also shown, the viscometer includes an electronic controller 660 configured to control the operation of the dispensing mechanism 630 and to receive and process data from the viscosity sensor module 610 (or one or more viscosity sensors in the viscosity sensor module 610).

[0072] In some embodiments, the dispensing mechanism 630 includes an autosampler. In some embodiments, the autosampler is configured to collect liquid samples from multiple containers (e.g., tubes, vials, or wells in a plate) and then dispense the collected liquid samples (e.g., dispense a first liquid sample from a first container, then dispense a second liquid from a second container, etc.).

[0073] In some embodiments, the viscometer includes a selector valve 650. In some embodiments, the selector valve 650 is coupled to an inlet of the viscosity sensor module 610 (or a viscosity sensor in the viscosity sensor module 610) at one end and to the injection tube 620 at the other end. Typically, the selector valve 650 is located between the viscosity sensor module 610 and the injection tube 620. In some embodiments, the selector valve 650 is configured to receive one or more of a gas and a liquid from one or more sources outside of the injection tube 620. Figure 6C and Fig. 6E In some embodiments, the electronic controller 660 is configured to control the operation of the selector valve 650 .

[0074] In some embodiments, the electronic controller 660 is configured to store a predetermined viscosity value for a preselected liquid (e.g., in a non-volatile memory of the electronic controller 660, or in a separate storage device located in or remote from the viscometer). In some embodiments, the predetermined viscosity value for the preselected liquid is used to identify the liquid whose viscosity is measured by the viscometer.

[0075] In some embodiments, the viscometer further includes an outlet module 670. The outlet module 670 is coupled to an outlet of the viscosity sensor module 610 (or an outlet of a viscosity sensor in the viscosity sensor module 610). In some embodiments, the outlet module 670 is coupled to one or more outlets of a viscosity sensor in the viscosity sensor module 610.

[0076] Figure 6B is a schematic diagram of a viscometer according to some embodiments. Figure 6B The viscometer shown includes the above Fig. 6A The viscosity sensor module 610, the dispensing mechanism 630, and the electronic controller 660 described above are described in some embodiments. Fig. 6A Certain features as described apply to Figure 6B For the sake of brevity, these features are not repeated in this paper.

[0077] Figure 6B As shown, in some embodiments, the viscosity sensor module 610 includes a viscosity sensor 612 . Figure 6B Also shown is that in some embodiments, the viscosity sensor module 610 includes a sample pre-conditioner 614 .

[0078] In some embodiments, the sample preconditioner 614 includes a temperature control device (e.g., a thermoelectric device, in particular, a solid-state thermoelectric device such as a Peltier device, which is configured for cooling, heating, or both). In some embodiments, the sample preconditioner 614 is configured to control the temperature of the sample liquid using the temperature control device. In some embodiments, the sample preconditioner 614 includes a temperature sensor to measure the temperature of the sample liquid.

[0079] In some embodiments, the viscosity sensor 612 in the viscosity sensor module 610 is coupled to a temperature control device. The temperature control device coupled to the viscosity sensor 612 is configured to control the temperature of the viscosity sensor 612. In some embodiments, the viscosity sensor 612 is coupled to a temperature sensor. In some embodiments, the viscosity sensor module 610 is coupled to a temperature control device. The temperature control device coupled to the viscosity sensor module 610 is configured to control the temperature of the viscosity sensor module 610. In some embodiments, the viscosity sensor module 610 is coupled to a temperature sensor. In some embodiments, the injection tube 620 is coupled to a temperature control device. The temperature control device coupled to the injection tube 620 is configured to control the temperature of the injection tube 620. In some embodiments, the injection tube 620 is coupled to a temperature sensor.

[0080] In some embodiments, the electronic controller 660 is configured to cause the operation of the one or more temperature control devices (eg, heating operation or cooling operation). In some embodiments, the electronic controller 660 is configured to receive temperature information from the one or more temperature sensors.

[0081] In some embodiments, the syringe 620 includes one or more of a barrel 622 and a plunger 624 (also referred to as a piston). For example, in some embodiments, the syringe 620 includes both the barrel 622 and the plunger 624 to dispense liquid to the viscosity sensor. In some embodiments, the syringe 620 includes the barrel 622 but does not include the plunger 624, through which the liquid is dispensed to the viscometer.

[0082] In some embodiments, the dispensing mechanism 630 includes one or more of an adapter 632, a motor 634, and a lead screw 636. In some embodiments, the lead screw 636 is coupled to the motor 634 and the adapter 632. For example, in some embodiments, the rotation of the motor 634 causes the rotation of the lead screw 636, which in turn causes the linear movement of the adapter 632 along the longitudinal direction of the lead screw 636. In some embodiments, the adapter 632 is configured to cooperate with the plunger 624 of the syringe 620. In some embodiments, the adapter 632 is configured to detachably cooperate with the plunger 624 of the syringe 620. For example, in some embodiments, the rotation of the motor 634 causes the linear movement of the plunger 624.

[0083] Figure 6B It is also shown that, in some embodiments, the viscometer includes a sample loading interface 626. In some embodiments, the syringe 620 is connected to the sample loading interface 626. In some embodiments, the syringe 620 includes the sample loading interface 626. In some other embodiments, the selection valve 650 includes the sample loading interface 626. In some embodiments, the selection valve 650 is connected to the sample loading interface 626. In some embodiments, the distribution mechanism 630 includes the sample loading interface 626. In some embodiments, the distribution mechanism 630 is configured to be connected to the sample loading interface 626. For example, in some embodiments, the distribution mechanism 630 includes a peristaltic pump, which causes the liquid received by the sample loading interface 626 to be distributed to the viscometer (e.g., through the syringe 620). In such an embodiment, the viscometer does not require a plunger (therefore, in some embodiments, the syringe 620 does not include a plunger).

[0084] In some embodiments, the outlet module 670 includes one or more of the following: a positive pressure source 672, a pH meter 674, a conductivity meter 676, and a density meter 678. The pH meter 674 is configured to measure the pH of the liquid. When used herein, pH represents a measure of the acidity or alkalinity of the liquid. The density meter 678 is configured to measure the density of the liquid. The conductivity meter 676 is configured to measure the conductivity of the liquid. In some embodiments, the pH meter 674 is configured to measure the pH of the liquid while measuring the viscosity of the liquid (e.g., by a viscometer). In some embodiments, the density meter 678 is configured to measure the density of the liquid while measuring the viscosity of the liquid (e.g., by a viscometer). In some embodiments, the conductivity meter 676 is configured to measure the conductivity of the liquid while measuring the viscosity of the liquid (e.g., by a viscometer).

[0085] In some embodiments, the positive pressure source 672 includes a pump. In some embodiments, the pump is configured to provide a predefined pressure to an outlet of the viscosity sensor module 610 (or the viscosity sensor 612 in the viscosity module 610). In some embodiments, the positive pressure source 672 includes a pressurized gas source (e.g., a pressurized gas tank, such as a nitrogen tank, or a pump that provides pressurized air). In some embodiments, the pressure provided to the outlet of the viscosity sensor module 610 by the positive pressure source 672 causes the liquid in the viscosity sensor module 610 (or the viscosity sensor 612 in the viscosity module 610) to move toward the syringe 620. In some cases, applying a negative pressure from the syringe 620 (e.g., by pulling the plunger 624) to move the liquid in the viscosity sensor 612 to the syringe 620 damages the pressure sensor in the viscosity sensor 612 (e.g., in some cases, the vacuum created by the absorption from the syringe 620 damages the pressure sensor in the viscosity sensor 612). Therefore, applying a positive pressure to the outlet of the viscosity sensor 612 can achieve, without applying a negative pressure to the viscosity sensor 612, moving the liquid in the viscosity sensor 612 to the syringe 620, thereby avoiding damage to the pressure sensor in the viscosity sensor 612. In some embodiments, both the positive pressure applied to the outlet of the viscosity sensor 612 and the negative pressure applied to the inlet of the viscosity sensor 612 are used to move the liquid in the viscosity sensor 612 to the syringe 620. In such an embodiment, without applying a positive pressure to the outlet of the viscosity sensor 612, the negative pressure applied to the inlet of the viscosity sensor 612 is less than the negative pressure required to move the liquid in the viscosity sensor 612 to the syringe 620, thereby reducing damage to the pressure sensor in the viscosity sensor 612.

[0086] In some embodiments, the pressure provided by the positive pressure source 672 is controlled by the electronic controller 660. For example, when the positive pressure source 672 includes a pump, the electronic controller 660 is configured to control the operation of the pump (e.g., starting and stopping). In another embodiment, when the positive pressure source 672 includes a pressurized gas source with a control valve, the electronic controller 660 is configured to control the operation of the control valve (e.g., opening and closing). In some embodiments, the positive pressure source 672 includes a waste container.

[0087] Liquid can be provided to the viscometer in a variety of ways.

[0088] In some embodiments, before the liquid is distributed to the viscosity module 610, the liquid is first provided to the syringe. In some embodiments, the barrel 622 includes a side port through which the barrel 622 is connected to the sample loading interface 626. In some embodiments, the plunger 624 is moved to an end position, thereby allowing the sample to be loaded into the barrel 622 through the sample loading interface 626. The liquid is then injected into the barrel 622. In some cases, the injected liquid fills the syringe 620 (or the barrel 622 of the syringe 620). By moving the adapter 632 of the dispensing mechanism 630, the plunger 624 is moved to start injecting the liquid into the viscosity sensor module 610. By controlling the speed of the adapter 632 (and therefore the speed of the plunger 624), the flow rate and shear rate of the liquid in the viscosity sensor 612 are controlled.

[0089] In some embodiments, the injected liquid is drawn back to the syringe 620. This is often necessary if the volume of the liquid is limited or the liquid is to be reused. In this case, the plunger 624 is pulled by the movement of the adapter 632. In some embodiments, the positive pressure source 672 (or the positive pressure applied by the positive pressure source 672) is used to facilitate the withdrawal of the injected liquid. In particular, the positive pressure source 672 (or the positive pressure applied by the positive pressure source 672) greatly increases the withdrawal speed of the injected liquid. Therefore, in some embodiments, the injected liquid is drawn back to the syringe 620 mainly by the pressure applied by the positive pressure source 672. In some embodiments, the injected liquid is drawn back to the syringe 620 only by the pressure applied by the positive pressure source 672.

[0090] In certain embodiments, an automatic sampler is used to provide liquid to the viscometer. The automatic sampler is configured to accommodate a series of vials or holes (e.g., holes in 96-well plates). The series of vials or holes include corresponding liquids for viscosity measurement. The automatic sampler is configured to draw the liquid in the vial or hole into the syringe (which is different from the syringe 620 in some embodiments) of the syringe, and then move the syringe's syringe to the sample loading interface 626 to load the liquid into the syringe 620. In certain embodiments, the viscometer is connected to a liquid handling device, which is used to test many samples unattended. In certain embodiments, the liquid handling device is configured to withdraw the sample solution from the vial in a tray or orifice plate (e.g., 96-well plates or 384-well plates).

[0091] In certain embodiments, syringe 620 and allocation mechanism 630 are integral parts of automatic sampler. Automatic sampler is configured to position syringe 620 for liquid aspirated into syringe 620, and is configured to use allocation mechanism 630 to start loading liquid into syringe 620. Automatic sampler is configured to, after liquid is loaded into syringe 620, move and position syringe 620 for liquid distribution into the inlet of viscosity sensor module 610, and uses allocation mechanism 630 to start distributing liquid for viscosity measurement under controlled flow rate. In certain embodiments, all these operations are controlled by electronic controller. In certain embodiments, one or more viscosity values ​​measured are displayed. In certain embodiments, these operations are fully automatic and are repeatedly used for multiple liquids, which increases the throughput of viscosity measurement.

[0092] In some embodiments, liquid is loaded through a selection valve 650 located between the viscosity sensor module 610 and the injection tube 620. In some embodiments, the selection valve 650 has more than two ports. For example, in some embodiments, a two-position three-port valve is used. The first port is connected to the viscosity sensor module 610, the second port is connected to the injection tube 620, and the third port is used to receive liquid. When the valve is in the first position, the third port and the second port are fluidly connected (for example, the liquid provided to the third port flows into the injection tube 620 through the second port), while the first port is fluidly disconnected (for example, the liquid provided to the third port or the liquid in the injection tube 620 connected to the second port does not flow into the viscosity sensor module 610). When the valve is in the second position, the first port and the second port are fluidly connected (for example, the liquid in the injection tube 620 connected to the second port flows into the viscosity sensor module 610 connected to the first port), while the third port is fluidly disconnected (for example, the liquid provided to the third port does not flow into the viscosity sensor module 610 connected to the first port or the injection tube 620 connected to the second port). While the valve is in the first position, the plunger 624 is pulled to draw liquid from the third port to the syringe 620. In some embodiments, when an air gap is formed adjacent to the end of the plunger 624, additional liquid can be provided through the sample loading interface 626 to remove the air gap. After the liquid is loaded into the syringe 620, the valve is switched to the second position, thereby fluidly connecting the syringe 620 and the viscosity sensor module 610. The dispensing mechanism 630 then dispenses the liquid into the viscosity sensor module 610 at a controlled speed or shear rate for viscosity measurement.

[0093] In certain embodiments, syringe 620 comprises the combination of injection valve.In certain embodiments, syringe 620 comprises the combination of injection valve without plunger 624 or barrel.The combination of injection valve promotes the semi-continuous test of liquid.In certain embodiments, liquid (also referred to as sample liquid in this article) is provided to the sample loop of injection valve, and then liquid is injected into liquid stream.In certain embodiments, liquid is loaded into sample loop and liquid is injected into liquid stream repeatedly.This repetition can realize semi-continuous viscosity measurement.

[0094] In some embodiments, the sample liquid is surrounded by a mobile eluent. In some embodiments, the mobile eluent is miscible with the sample liquid. In some embodiments, the mobile eluent is immiscible with the sample liquid. For example, fluorocarbons are excellent eluents. In some embodiments, the mobile eluent is provided by an immiscible liquid source 682, as described below. Figure 6C Describe it.

[0095] In some embodiments, liquid is loaded directly into the syringe 620 without using the sample loading interface 626. For example, in some embodiments, the syringe 620 is separated from the viscosity sensor module 610, and one end of the syringe 620 (the end opposite to the plunger 624 of the syringe 620) is inserted into the sample liquid. The sample liquid is loaded into the syringe 620 by withdrawing the plunger 624. The syringe 620 is then moved to connect with the inlet of the viscosity sensor module 610. After the syringe 620 is connected with the inlet of the viscosity sensor module 610, the sample liquid is injected for viscosity measurement. In some embodiments, it is available to use a conveying device (e.g., a robotic arm in an automatic sampler) to position and move a positive syringe up and down.

[0096] The viscometers described herein are capable of operating in high pressure environments (e.g., if the pressure sensor in the viscosity sensor 612 is configured to detect only above the sensor membrane 33 ( Figure 2B ) and the pressure difference below the sensor membrane 33, the pressure can be as high as 30,000 psi. This can be achieved by forming a vent line 31 ( Figure 2B ) is achieved. The ventilation line allows the top of the membrane (37, Figure 2B ) and the pressure below (33) is balanced. When the liquid flows through the flow channel (34, 35, 36, Figure 2B ), the viscosity of the liquid increases the pressure above the membrane (37). This pressure increase is controlled by the chip (39, Figure 2B ) to measure accurately.

[0097] In some embodiments, the liquid in the syringe 620 is maintained at a preselected pressure. In some embodiments, the dispensing mechanism 630 is maintained at a preselected pressure. This is important because, in the case of some liquids, the viscosity of the liquid varies depending on the pressure of the liquid. In the case of such a liquid, the liquid in the syringe needs to be maintained under the desired pressure conditions for accurate viscosity measurement. For example, during the extraction process (e.g., from a deep well), the viscosity of the oil is very useful for oil operations. During the extraction process, the oil in the deep well is typically maintained at a high pressure (e.g., the field pressure in the deep well is typically at a pressure higher than atmospheric pressure). However, measuring the viscosity of the oil under low pressure (e.g., atmospheric pressure) is inaccurate because the volatiles in the oil dissolved in the oil under high pressure evaporate under low pressure and change the viscosity of the oil. After the volatiles have evaporated, the process cannot be simply reversed by re-pressurizing the oil to high pressure. Therefore, in such applications, the liquid in the syringe needs to be maintained at a preselected pressure for accurate viscosity measurement.

[0098] Figure 6C is a schematic diagram of a viscometer according to some embodiments. Figure 6C The viscometer shown in the above reference includes Fig. 6A and Figure 6B The viscosity sensor module 610, the dispensing mechanism 630, and the electronic controller 660 are described. In some embodiments, the above reference Fig. 6A and Figure 6B Some of the features described apply to Figure 6C For the sake of brevity, these features are not repeated in this paper.

[0099] Figure 6C The viscometer also includes the above reference Figure 6B A selector valve 650 is described.

[0100] In some embodiments, the selector valve 650 is coupled to the second syringe 680. In some embodiments, the viscometer includes the second syringe 680. In some embodiments, the syringe 620 is configured to provide a first liquid, and the second syringe 680 is configured to provide a second liquid. In some embodiments, the first liquid includes a first type of protein, and the second liquid includes a second type of protein.

[0101] In some embodiments, the second syringe 680 is coupled to a second dispensing mechanism 690. In some embodiments, the second syringe 680 is coupled to a dispensing mechanism 630, which is also coupled to the syringe 620.

[0102] In some cases, it is necessary to measure the viscosity of a liquid mixture. In some embodiments, the liquid is first mixed offline before measuring the viscosity of the mixture. In some embodiments, the viscometer includes a mixer configured to mix multiple liquids online. In some embodiments, the viscometer measures the viscosity of the mixture as a function of concentration by adjusting the mixing ratio (e.g., the ratio of the flow rate of the liquid). In some embodiments, if an external pump is used to distribute the liquid, the mixing ratio of the liquid is changed by changing the pumping rate of one or more liquids. For example, the first liquid is a solvent, and the second liquid is a solution of a polymer dissolved in the solvent at a high concentration. By changing the mixing ratio, the viscosity of the mixture can be measured as a function of polymer concentration. In some embodiments, the mixture is directly injected into the inlet of the viscosity sensor module 610. In some other embodiments, the mixture is first injected into the injection tube 620. In some embodiments, the selection valve 650 is used to mix the liquid. For example, in some embodiments, the selection valve 650 includes a multi-port variable flow rate valve configured to adjust the flow rate ratio of multiple liquids.

[0103] In some embodiments, the selector valve 650 is connected to an immiscible liquid source 682. In some embodiments, the immiscible liquid source 682 includes a pump and a reservoir configured to store immiscible liquids. The immiscible liquid source 682 is configured to provide a liquid that is immiscible with the liquid in the syringe 620 and the second syringe 680. For example, when the syringe 620 and the second syringe 680 include polar liquids (e.g., water), the immiscible liquid source 682 is configured to provide a non-polar liquid. In some embodiments, the electronic controller 660 is configured to control the operation of the immiscible liquid source 682. In some embodiments, the electronic controller 660 is configured to start providing an immiscible liquid between two liquid samples entering the viscosity sensor module 610. Providing an immiscible liquid between the two liquid samples prevents mixing between the two liquid samples.

[0104] Fig.6D is a schematic diagram of a viscometer according to some embodiments. Fig.6D The viscometer shown includes the above reference Fig. 6A and Figure 6B A viscosity sensor module 610 , a dispensing mechanism 630 , and an electronic controller 660 are depicted. Fig.6D Also shown above reference Fig. 6A and Figure 6B In some embodiments, the viscometer includes the above reference Fig. 6A - Figure 6C The selector valve 650 described above. In some embodiments, the Fig. 6A - Figure 6C Some of the features described apply to Fig.6D For example, in some embodiments, Fig.6D The viscometer shown includes one or more of the following: a second injection tube 680 ( Figure 6C ) and the second distribution mechanism 690 ( Figure 6C ). For the sake of brevity, these features are not repeated in this article.

[0105] exist Fig.6D In some embodiments, the viscometer further includes a delivery device 692 configured to be coupled to the syringe 620 and the dispensing mechanism 660. In some embodiments, the delivery device 692 is configured to move the syringe 620 between a first position and a second position, the first position being used to draw the test liquid into the syringe 620 (e.g., Fig.6D The second position is used to connect the syringe 620 to the viscosity sensor module 610 (or the viscosity sensor in the viscosity sensor module 610) (for example, Figure 6B The position of the injection tube 620 is shown). Figure 6B and Fig.6DAs shown, the second position (for connecting the injection tube 620 to the viscosity sensor module 610, Figure 6B ) and a first position (for drawing the test liquid into the syringe 620, Fig.6D In some embodiments, the delivery device 692 is configured to move the syringe 620 between the first position and the second position independently of user intervention (e.g., without manual input from the user). In some embodiments, the electronic controller 660 is configured to control the operation of the delivery device 692.

[0106] In some embodiments, when in the first position, the syringe 620 is in contact with a test liquid in a test liquid container 696 (e.g., a vial, tube, bottle, etc.). In some embodiments, the dispensing mechanism 630 is activated to begin drawing the test liquid into the syringe 620 (e.g., by pulling back a plunger of the syringe 620).

[0107] In some embodiments, the delivery device 692 includes a robotic arm. In some embodiments, the delivery device 692 includes one or more rotary joints. In some embodiments, the delivery device 692 includes one or more tracks 694. In some embodiments, the delivery device 692 includes a belt and pulley mechanism for moving the syringe 620 between the first position and the second position. In some embodiments, the electronic controller 660 is configured to control the delivery device 692.

[0108] Fig. 6E is a schematic diagram of a viscometer according to some embodiments. Fig. 6E The viscometer shown includes the above reference Fig. 6A and Figure 6B A viscosity sensor module 610 , a dispensing mechanism 630 , and an electronic controller 660 are depicted. Fig.6D Also shown above reference Fig. 6A and Figure 6B In some embodiments, the viscometer includes the above reference Fig. 6A - Figure 6C The selector valve 650 described above. In some embodiments, the Fig. 6A - Fig.6D Some of the features described apply to Fig. 6E For example, in some embodiments, Fig. 6E The viscometer shown includes a delivery device 692 ( Fig.6D ). In another example, in some embodiments, Fig. 6E The viscometer shown includes a second injection tube 680 ( Figure 6C ) and the second distribution mechanism 690 ( Figure 6C ). For the sake of brevity, these features are not repeated in this article.

[0109] In some embodiments, the selector valve 650 couples one or more of the following: a cleaning solution source 697, a gas source 698, and a reference liquid source 699. In some embodiments, at least one of the cleaning solution source 697, the gas source 698, and the reference liquid source 699 comprises a pump and a reservoir configured to store the corresponding gas or liquid.

[0110] In some embodiments, the cleaning solution source 697 is configured to provide a cleaning solution. For example, in some embodiments, the cleaning solution source 697 provides a cleaning solution to the selection valve 650 to clean the selection valve 650. In some embodiments, the cleaning solution source 697 provides a cleaning solution to clean the viscosity sensor module 610 (or the viscosity sensor in the viscosity sensor module 610, and in particular, the liquid flow channel of the viscosity sensor). In some embodiments, the cleaning solution source 697 provides a cleaning solution to clean the injection tube 620. In some embodiments, a miscible and volatile solution is used as the cleaning solution, thereby enabling faster evaporation of the cleaning solution.

[0111] In some embodiments, the gas source 698 is configured to provide gas. In some embodiments, the gas provided by the gas source 698 is a dry gas (e.g., dry nitrogen and clean dry air, air injected with a dew point of -100°F). In some embodiments, the gas source 698 provides gas to the selector valve 650 to dry the selector valve 650. For example, the gas is used to dry any remaining liquid (e.g., cleaning solution). In some embodiments, the gas source 698 provides gas to dry the viscosity sensor module 610 (or the viscosity sensor in the viscosity sensor module 610). In some embodiments, the gas source 698 provides gas to dry the injection tube 620.

[0112] In some embodiments, the reference liquid source 699 is configured to provide a reference liquid. In some embodiments, the reference liquid is a liquid of known viscosity (e.g., under one or more measurement conditions, such as under one or more temperatures). In some embodiments, the reference liquid source 699 provides the reference liquid to the viscosity sensor module 610 (or a viscosity sensor in the viscosity sensor module 610). In some embodiments, the viscosity sensor module 610 measures the viscosity of the reference liquid under one or more measurement conditions for calibration.

[0113] In some embodiments, the electronic controller 660 is configured to control the operation of the cleaning solution source 697. In some embodiments, the electronic controller 660 is configured to control the operation of the gas source 698. In some embodiments, the electronic controller 660 is configured to control the operation of the reference liquid source 699. In some embodiments, the electronic controller 660 is configured to start providing the cleaning solution in response to the completion of the viscosity measurement. In some embodiments, the electronic controller 660 is configured to start providing the gas in response to the completion of providing the cleaning solution. In some embodiments, the electronic controller 660 is configured to provide a reference liquid between two liquid samples. In some embodiments, the electronic controller 660 is configured to start providing one or more of the cleaning solution and the gas in response to the completion of providing the reference liquid.

[0114] Viscometers can be used in a variety of applications. In some embodiments, the viscometer is used to determine the molecular size (or molecular weight) of a macromolecule. The intrinsic viscosity is related to the size of the molecule. The intrinsic viscosity [η] is calculated by the following equation:

[0115]

[0116] Among them, η s is the viscosity of the solvent, c is the concentration of the solute (e.g., polymer), and η is the viscosity of the solution, which includes the solvent and the solute. To measure the intrinsic viscosity, the viscosity values ​​of solutions with different solute concentrations are measured. In some embodiments, the intrinsic viscosity is determined by inferring the measured viscosity value by approaching the zero concentration of the solute.

[0117] In some embodiments, a group of solutions is prepared by mixing a macromolecular solute with a solvent at different concentrations of the macromolecular solute. In some embodiments, the group of solutions is prepared off-line (e.g., outside a viscometer). In some other embodiments, the group of solutions is prepared online. In some embodiments, the group of solutions is prepared using a mixer in a viscometer. For example, a first injection tube is loaded with a solution (also referred to herein as a stock solution) at a high solute concentration, and a second injection tube is loaded with a solution with a low solute concentration or a solution that does not include a solute (e.g., a solvent). By changing the flow rate, the solution in the first and second injection tubes is provided at the flow rate to obtain a mixture with different solute concentrations. In this way, the concentration can be changed continuously or in a discrete manner.

[0118] The intrinsic viscosity is related to the molecular weight of the polymer according to the Mark-Houwink-Sakurada equation:

[0119]

[0120] Wherein, M is the molecular weight, and K and a are parameters that depend only on the temperature of the solution. Thus, in some embodiments, the molecular weight of a macromolecule (e.g., a protein) is determined from the intrinsic viscosity of the solution and the values ​​of K and a for the temperature of the solution using the Mark-Houwink-Sakurada equation. In some embodiments, the viscometer stores predetermined values ​​of K and a for multiple temperatures.

[0121] In some embodiments, a viscometer is used to determine the dissolution temperature of a protein (e.g., a high molecular weight protein). The dissolution temperature of a protein is defined as the threshold temperature at which the protein becomes denatured. At the dissolution temperature, the protein typically loses its function (usually described as the loss of its efficacy). It is known that the dissolution temperature of a protein is related to the stability of the protein in the solution. Therefore, the dissolution temperature of a protein is of great importance in biological and chemical reactions. Circular dichroism and differential scanning calorimetry have been used to measure the dissolution temperature of a protein. However, these conventional methods have limitations. For example, in many practical applications, the protein concentration is low, which makes it challenging to accurately measure by these conventional methods. In addition, in determining the dissolution temperature of a protein, the residence time or duration of a solution subjected to a constant temperature is an important parameter. Using conventional methods, the temperature of the protein is ramped up or down at a constant scan rate, and the residence time cannot be changed independently, thereby making it challenging to accurately determine the dissolution temperature. In addition, it is still challenging to correlate the change in the viscosity of the solution with the dissolution temperature of the protein in the solution. In fact, the solution in a conventional rheometer remains exposed to air, and evaporation of the solvent in the solution and permanent denaturation of the protein result in inaccurate viscosity measurements. Other conventional methods, such as those based on circular dichroism, cannot measure the viscosity of solutions with high protein concentrations.

[0122] In a word, replace intrinsic viscosity, traditional viscometer measures apparent viscosity, and requires large liquid volume. Large liquid volume requirement in the case of traditional viscometer also increases the wasted volume of cleaning time and cleaning solution. Different from traditional viscometer, viscometer described in this article is configured to accurately measure the dissolution temperature of protein. In at least one aspect, solution is fully enclosed in viscometer described in this article, and the evaporation of solution (or solute in solution) is zero. Therefore, solute concentration is accurately retained for high-precision viscosity measurement.

[0123] In some embodiments, the viscosity of the polymer is measured as a function of temperature. Figure 7 is a graph illustrating a method of determining a dissolution temperature according to some embodiments. Figure 7 The viscosity of phosphate buffered saline (PBS) at various temperatures is shown (indicated by the circular markers). Figure 7As shown, the viscosity of phosphate buffer decreases monotonically with increasing temperature. Figure 7 It is also shown that within the temperature range of 62° C. and below, the viscosity of a bovine immunoglobulin solution (eg, a 3 mg / ml bovine immunoglobulin solution) decreases as the temperature increases (indicated by the square marks). Figure 7 It is further shown that the viscosity of the globulin solution stabilizes or increases at and above 64°C. The temperature at the point of stability or increase in viscosity is related to the dissolution temperature. Therefore, in this example, the dissolution temperature of the globulin is determined to be 64°C.

[0124] Fig. 8A - Figure 8C is a flow chart representing a method 800 of measuring viscosity of a liquid, according to some embodiments.

[0125] In some embodiments, each of the following operations is performed by the viscometer independent of (eg, without) user intervention.

[0126] In some embodiments, the method includes (802) coupling a syringe to a viscosity sensor (e.g., at Figure 6B In some embodiments, the syringe 620 is coupled to the viscosity sensor 612 in the viscosity sensor module 610. In some embodiments, the syringe is coupled to the viscosity sensor so that the syringe is configured to dispense liquid to the viscosity sensor (eg, a liquid flow channel in the viscosity sensor).

[0127] In some embodiments, the syringe includes a sample loading interface (e.g., Figure 6B In the embodiment, the injection tube 620 includes a sample loading interface 626).

[0128] In some embodiments, the method includes (804) moving the syringe between a first position for drawing the test liquid into the syringe and a second position for coupling the syringe to the viscosity sensor, independent of user intervention. The second position is different from the first position. For example, Figure 6B and Fig.6D As shown, the injection tube 620 is in a first position (eg Fig.6D ) and the second position (as shown Figure 6B shown).

[0129] In some embodiments, moving the syringe between the first position and the second position includes (806) moving the syringe between the first position and the second position using a delivery device. Fig.6D As shown, a transport device (e.g., a robotic arm) is used to move the syringe between a first position and a second position. Figure 6BThe delivery device 692 is not shown, but one of ordinary skill in the art will appreciate that the delivery device 692 is capable of transferring the syringe from Fig.6D The first position shown is moved to Figure 6B The second position is shown.

[0130] In some embodiments, the method includes (808) aspirating the test liquid into the syringe independent of user intervention. Fig.6D As shown, the dispensing mechanism 630 is used to draw the test liquid into the syringe 620 by pulling the plunger of the syringe 620. In some embodiments, the test liquid is stored in a pressurized container and is forced into the syringe 620 without the use of the dispensing mechanism 630.

[0131] The method includes (810) providing a viscosity sensor (eg, viscosity sensor 612, Figure 6B ) at a viscometer, receiving liquid from an injection tube into a liquid flow channel at a known flow rate. The viscometer includes a dispensing mechanism (e.g., a dispensing mechanism 630, Figure 6B ) and an electronic controller (e.g., electronic controller 660, Figure 6B At least two pressure sensors are positioned along the liquid flow channel and are configured to measure a pressure drop of the liquid passing through the liquid flow channel (e.g., Figure 2B ). An electronic controller (eg, electronic controller 660, Figure 6B ) is configured to control the operation of the dispensing mechanism and receive and process data. The dispensing mechanism is configured to be coupled to the syringe and cause the liquid in the syringe to be dispensed to the viscosity sensor at a known flow rate.

[0132] The method includes (812) measuring the viscosity of the liquid. In some embodiments, using the viscosity sensor module 610 (or the viscosity sensor 612 in the viscosity sensor module 610, Figure 6B ) measures the viscosity of a liquid. Figure 2B The measurement of viscosity of liquids is described and will not be repeated for the sake of brevity.

[0133] In some embodiments, the viscometer includes a sample loading interface (e.g., sample loading interface 626, Figure 6B ), the viscometer is configured to receive liquid through the sample loading interface.

[0134] In some embodiments, a plurality of liquid flow channels are defined in the viscosity sensor, and at least two pressure sensors are positioned along each of two or more of the plurality of liquid flow channels. Figure 2C The liquid flow path shown is defined within a single viscosity sensor.

[0135] In some embodiments, the viscometer includes a viscosity sensor module that includes a plurality of viscosity sensors. For example, in some embodiments, Figure 2C Each liquid flow channel 31 shown is used by a corresponding viscosity sensor. In some embodiments, a plurality of viscosity sensors are located in a single viscosity sensor module. In some embodiments, a plurality of viscosity sensors increase the dynamic range of shear rate that can be measured by a viscometer. In some embodiments, the dynamic range of shear rate is increased by including a plurality of viscosity sensor modules, a plurality of syringes, and a plurality of distribution modules. For example, a first combination of a first viscosity sensor module and a first syringe is configured to measure a first range of shear rates, and a second combination of a second viscosity sensor module and a second syringe is configured to measure a second shear rate range that is different from the first shear rate range. The combination of two shear rate ranges allows viscosity measurement in a wider shear rate range. This is desirable in certain applications. In some embodiments, a combination of a plurality of viscosity sensor modules, a plurality of syringes, and a plurality of distribution modules is used to increase the throughput of viscosity measurement.

[0136] In some embodiments, the liquid includes ( 814 ) a polymer (eg, a macromolecule), and the method further includes determining a molecular weight of the polymer.

[0137] In some embodiments, the liquid includes ( 816 ) a protein, and the method further includes determining a dissolution temperature of the protein.

[0138] In some embodiments, the method includes (818) determining viscosity values ​​of a liquid at a plurality of temperatures, the liquid including a first type of protein (e.g., a globulin); and determining a dissolution temperature of the first type of protein based on the viscosity values ​​of the liquid at the plurality of temperatures. In some embodiments, determining the dissolution temperature of the first type of protein includes identifying a temperature at which the viscosity of the first type of protein increases or levels off as the temperature increases. In some embodiments, determining the dissolution temperature of the first type of protein includes identifying an inflection point in a viscosity-temperature curve for the first type of protein.

[0139] In some embodiments, the method includes (820) determining viscosity values ​​of a second liquid at a plurality of temperatures. The second liquid includes a second type of protein (e.g., fibrin). The method also includes determining a dissolution temperature of the second type of protein based on the viscosity values ​​of the second liquid at the plurality of temperatures. Details of determining the dissolution temperature of the first type of protein are applicable to determining the dissolution temperature of the second type of protein and, therefore, are not repeated for the sake of brevity.

[0140] In some embodiments, the method includes (822) controlling a temperature of the viscosity sensor. In some embodiments, controlling the temperature includes (824) operating one or more temperature control devices (eg, one or more thermoelectric heating or cooling devices).

[0141] In some embodiments, the method includes (826) maintaining the temperature of the viscosity sensor at a first temperature and maintaining the temperature of the injection tube at a second temperature, the second temperature being different from the first temperature. In some embodiments, the method includes maintaining the temperature of the viscosity sensor and the temperature of the injection tube at the same temperature.

[0142] In some embodiments, the method includes (828) controlling a temperature of the injection tube. In some embodiments, controlling the temperature includes operating one or more temperature control devices (eg, one or more thermoelectric heating or cooling devices).

[0143] In some embodiments, the method includes (830) mixing a liquid with a solvent at a viscometer to obtain a mixed solution. The concentration of the solute in the mixed solution is different from the concentration of the solute in the liquid. The method also includes measuring the viscosity of the mixed solution. The method further includes repeating the mixing and measuring to obtain viscosity values ​​of the mixed solution at multiple solute concentrations. In some embodiments, the method includes determining an intrinsic viscosity of the liquid from the viscosity value of the mixed solution. In some embodiments, determining the intrinsic viscosity of the liquid includes inferring the viscosity value of the mixed solution to obtain a possible viscosity value for a solution that does not include the solute.

[0144] In some embodiments, the method includes (832) moving at least a portion of the liquid in the liquid flow channel back to the injection tube. This can enable multiple viscosity measurements using a limited volume of liquid. For example, in some embodiments, the viscosity of the liquid at multiple temperatures is measured using the liquid moved from the liquid flow channel back to the injection tube.

[0145] In some embodiments, the method includes (834), prior to measuring the viscosity of the liquid, identifying a flow rate that satisfies pressure criteria for at least two pressure sensors. For example, in some embodiments, prior to measuring the viscosity of the liquid, the viscometer determines whether a fully expanded flow of the liquid exists in a liquid flow channel of the viscosity sensor.

[0146] In some embodiments, the method includes (836) dispensing a continuous stream of liquid to the viscosity sensor. The continuous stream of liquid includes two or more batches of test liquid. Any two adjacent batches of the two or more batches of test liquid are separated by at least one inert liquid that is immiscible with the two adjacent batches of test liquid. The two adjacent batches are adjacent to each other in the continuous stream of liquid in the order of the batches. However, in some embodiments, the two adjacent batches do not contact each other because the two adjacent batches are separated by the immiscible liquid.

[0147] In some embodiments, the method includes (838) dispensing a cleaning solution through a liquid flow channel of the viscosity sensor. In some embodiments, dispensing a cleaning solution through a liquid flow channel of the viscosity sensor includes cleaning the liquid flow channel of the viscosity sensor. In some embodiments, the method includes dispensing the cleaning solution to a selector valve. In some embodiments, dispensing the cleaning solution to the selector valve includes cleaning the selector valve. In some embodiments, the method includes dispensing the cleaning solution to a syringe. In some embodiments, dispensing the cleaning solution to the syringe includes cleaning the syringe.

[0148] In some embodiments, the method includes (840) flowing a gas through a liquid flow channel. In some embodiments, flowing a gas through a liquid flow channel includes drying the liquid flow channel. In some embodiments, the method includes providing a gas to a selector valve. In some embodiments, providing a gas to a selector valve includes drying the selector valve. In some embodiments, the method includes providing a gas to an injection tube. In some embodiments, providing a gas to an injection tube includes drying the injection tube. In some embodiments, the gas includes clean dry air. In some embodiments, the gas includes dry nitrogen.

[0149] In some embodiments, the method includes (842) calibrating the viscometer using a preselected reference liquid independent of user input. For example, in some embodiments, the viscosity of the preselected reference liquid is measured, and the measured viscosity is compared to the viscosity of the preselected reference liquid stored prior to the measurement (also referred to herein as the previously known viscosity of the preselected reference liquid). In some embodiments, subsequent viscosity measurements are adjusted based on the difference between the measured viscosity and the previously known viscosity of the preselected reference liquid. In some embodiments, the viscosity of the preselected reference liquid is measured at multiple temperatures, and the viscosity values ​​measured at the multiple temperatures are used to calibrate the viscometer. In some embodiments, multiple preselected reference liquids are used to calibrate the viscometer.

[0150] In some embodiments, the method includes (844) measuring one or more of: pH, density, and conductivity of the liquid. In some embodiments, the pH and conductivity of the liquid are measured simultaneously. In some embodiments, the pH and viscosity of the liquid are measured simultaneously. In some embodiments, the conductivity and viscosity of the liquid are measured simultaneously. In some embodiments, the density and viscosity of the liquid are measured simultaneously. In some embodiments, the density and pH of the liquid are measured simultaneously. In some embodiments, the density and conductivity of the liquid are measured simultaneously.

[0151] For the purpose of explanation, the foregoing description has been described with reference to specific embodiments. However, the above illustrative discussion is not intended to be exhaustive or to limit the invention to the disclosed precise form. In view of the above teachings, many modifications and variations are possible. These embodiments are selected and described to best explain the principles of the invention and its practical application, so that other persons skilled in the art can best utilize the present invention and various embodiments with various modifications suitable for the specific purpose expected.

Claims

1. A viscometer comprising: a viscosity sensor having a liquid flow channel and at least two pressure sensors positioned along the liquid flow channel and configured to measure a pressure drop of a liquid flowing through the liquid flow channel, wherein the viscosity sensor has an inlet and an outlet, the inlet being configured to couple with a syringe; a dispensing mechanism configured to cause dispensing of liquid from the syringe to the viscosity sensor at a known flow rate, wherein the dispensing mechanism is configured to couple with the syringe and the syringe is coupled with the viscosity sensor; an electronic controller configured to control operation of the dispensing mechanism and to receive and process data from the viscosity sensor; and A positive pressure source is coupled to the outlet of the viscosity sensor to facilitate drawing liquid in the liquid flow channel into the syringe.

2. The viscometer according to claim 1, wherein The positive pressure source includes a pump.

3. The viscometer according to claim 1, wherein The positive pressure source includes a pressurized gas source.

4. The viscometer according to claim 3, wherein: The viscometer further includes a control valve coupled to the pressurized gas source.

5. The viscometer according to claim 1, wherein The electronic controller is coupled to the positive pressure source to control operation of the positive pressure source.

6. The viscometer according to claim 1, wherein The viscometer further comprises a temperature control device.

7. The viscometer according to claim 6, wherein: The temperature control device is coupled to the electronic controller, and the electronic controller is configured to control the temperature control device.

8. The viscometer according to claim 7, wherein: The electronic controller is configured to: determining viscosity values ​​of the liquid at a plurality of temperatures, the liquid comprising a first type of protein; as well as The dissolution temperature of the first type of protein is determined by the viscosity values ​​of the liquid at the plurality of temperatures.

9. The viscometer according to claim 8, wherein: The electronic controller is configured to: determining viscosity values ​​of a second liquid at a plurality of temperatures, the second liquid comprising a second type of protein; as well as The dissolution temperature of the second type of protein is determined by the viscosity values ​​of the second liquid at the plurality of temperatures.

10. The viscometer according to claim 6, wherein: The viscosity sensor is temperature controlled.

11. The viscometer according to claim 6, wherein: The injection tube is temperature controlled.

12. The viscometer according to claim 1, wherein The viscometer further comprises a mixer coupled to the electronic controller and configured to mix the liquid with a solvent to obtain a mixed solution, wherein the concentration of the solute in the mixed solution is different from the concentration of the solute in the liquid, wherein the electronic controller is configured to: measuring the viscosity of the mixed solution; and The mixing and measuring are repeated to obtain viscosity values ​​of the mixed solution at multiple solute concentrations.

13. A method for performing viscosity measurements, the method comprising: dispensing liquid from a syringe at a known flow rate to an inlet of a viscosity sensor having a liquid flow channel and at least two pressure sensors positioned along the liquid flow channel and configured to measure a pressure drop of liquid flowing through the liquid flow channel; as well as Positive pressure is applied to the outlet of the viscosity sensor to cause the liquid in the viscosity sensor to move to the syringe.

14. The method according to claim 13, wherein: The liquid is moved to the syringe without applying negative pressure to the viscosity sensor.

15. The method according to claim 13, wherein: Positive pressure applied to the outlet of the viscosity sensor and negative pressure applied to the inlet of the viscosity sensor both cause the liquid in the viscosity sensor to move to the syringe.

16. The method according to claim 13, wherein: The method further includes reusing the liquid drawn back into the syringe for viscosity measurement.

17. The method according to claim 13, wherein: The liquid includes a polymer, and the method further includes determining a molecular weight of the polymer.

18. The method according to claim 13, wherein: The liquid includes a protein, and the method further includes determining a dissolution temperature of the protein.

19. The method according to claim 13, wherein: The method comprises: determining viscosity values ​​of the liquid at a plurality of temperatures, the liquid comprising a first type of protein; and The dissolution temperature of the first type of protein is determined by the viscosity values ​​of the liquid at the plurality of temperatures.

20. The method according to claim 19, wherein: The method further comprises: determining viscosity values ​​of a second liquid at a plurality of temperatures, the second liquid comprising a second type of protein; and The dissolution temperature of the second type of protein is determined by the viscosity values ​​of the second liquid at the plurality of temperatures.

21. The method according to claim 13, wherein: The method further comprises: mixing the liquid with a solvent to obtain a mixed solution, wherein the concentration of the solute in the mixed solution is different from the concentration of the solute in the liquid; measuring the viscosity of the mixed solution; and The mixing and the measuring are repeated to obtain viscosity values ​​of the mixed solution at a plurality of solute concentrations.

Images