Devices, systems, and methods for conductivity measurement and the application of electric fields

Abstract

Disclosed herein are devices, systems, and methods that relate to conductance and / or conductivity measurement and / or the application of electric fields within the framework of spectroscopic or related measurements on a system consisting of a fluid containing chemical substances, with a focus, not limiting, on biological and synthetic macromolecules and colloids, and biologic drugs.

Description

[0001] Devices, Systems, and Methods for Conductivity Measurement and the Application of Electric Fields

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims benefit of priority of U.S. Provisional Application No. 63 / 545,339, filed October 23, 2023, and U.S. Provisional Application No. 63 / 639,426, filed April 26, 2024, each of which is hereby incorporated by reference in its entirety.

[0004] BACKGROUND

[0005] There remains a need for devices, systems, and methods for the analysis of fluid samples. The devices, systems, and methods described herein address these and other needs.

[0006] SUMMARY

[0007] Described herein are devices, systems, and methods that relate to conductance and / or conductivity measurement and / or the application of electric fields within the framework of spectroscopic or related measurements on a system consisting of a fluid containing chemical substances, with a focus, not limiting, on biological and synthetic macromolecules and colloids, and biologic medicine products.

[0008] For example, described herein are devices that can be inserted into a receptacle, and which are capable of (1) measuring the conductance and / or conductivity of the fluid in the cell containing chemical substances, which can also yield the concentration of electrolytes in the cell as they either change or stay steady in time; and / or (2) applying a substantially higher electric field to the fluid and its chemical contents, which can affect the properties and behavior of the fluid and its chemical contents. Furthermore, the receptacle can be insertable into a measuring instrument, such as a UV / visible spectrometer, fluorimeter, static light scattering, dynamic light scattering, circular dichroism, and other measuring instruments, which can monitor the effects of the electric field on the fluid containing the chemical substances as a function of time and / or as a function of other chemical substances.

[0009] The devices, systems, and methods are described in more detail in the specification and claims below. DESCRIPTION OF DRAWINGS

[0010] Figure 1 A shows the raw conductance (1 / Re) of the flat-electrode cuvette on the righthand axis and the conductivity of the solution, obtained by a Thermo Orion Star A215 conductivity instrument on the left-hand axis. The two sets of measurements are in excellent agreement.

[0011] Figure 1 B shows how the flat-electrode conductance data (in Siemens) is turned into absolute conductivity (in mS / cm) by multiplying the conductance by the calibration factor, CF=430.

[0012] Figure 1C shows the discrepancies between conductivities of NaCl solutions obtained from two authoritative sources; NIST and the CRC Handbook. The percentage deviation at each point is shown on the right-hand y-axis.

[0013] Figure 2 shows a photo of the flat platinum electrode device inside a 1 cm standard cuvette along with a dialysis cell with integrated stirring. The horizontal electrodes can be seen in the clear 5 mm gap towards the bottom of the cuvette.

[0014] Figure 3 A shows a block diagram of the operational setup of the electrode assembly (6) with a power supply (1), variable resistor (2) (which can also be a fixed resistor), ammeter (3), voltmeter (4) and a relay (5) for isolating the electrode assembly from the circuit. In some embodiments, the relay can be absent.

[0015] Figure 3B shows a block diagram of the operational setup of the electrode assembly (6) with a power supply (1), resistor (2), ammeter (3), voltmeter (4) and a relay (5) for isolating the power supply from the circuit. The relay can also be placed across the electrodes to intermittently short out the electrodes to keep the electrodes stable and free of any adsorption, polarization, and other effects. In some embodiments, the relay can be absent.

[0016] Figure 3C shows a block diagram of the operational setup of the electrode assembly (6) with a power supply (1) and resistor (2).

[0017] Figure 4 is a plot showing the effect of electric fields at 3.7 V / cm (Rv=667 ohms) and 2.1 V / cm on the protein immunoglobulin (IgG). IgG is degraded by the electric fields, with a higher degradation rate at the higher voltage.

[0018] Figure 5 is a plot showing current, I, and conductivity for the experiment of Figure 4 with Rv=667 Ohms. The current was essentially constant, and the conductivity was constant to within <1%. This indicates the interelectrode current is not measurably heating the liquid, as there would be a measurable increase in conductivity if the temperature increased.

[0019] Figure 6 is a plot showing how an applied 51 V / cm electric field induces aggregation of the protein chymotrypsinogen. Figure 7 is a plot showing the conductivity measured for solutions of varying |NaCl|, calibrated against the Thermo Orion Star A215 conductivity instrument.

[0020] Figure 8 shows an example design for a horizontal electrode assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, parallel plate electrodes are positioned horizontally adjacent to the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle. The higher the ratio of the electrode width to the interelectrode spacing, the more uniform the field between the electrodes.

[0021] Figure 9 shows an example design for an electrode assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, the parallel plate electrodes are vertically placed in the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle.

[0022] Figure 10 shows an example design for an electrode asssembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, the vertical electrodes include an aperture and are positioned parallel to the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle.

[0023] Figure 11 shows an example design for a cap assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, parallel plate electrodes are positioned horizontally adjacent to the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle.

[0024] Figure 12 shows an example design for a cap assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, parallel plate electrodes are positioned vertically adjacent to the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle.

[0025] Figure 13 shows an example design for a cap assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, parallel electrodes include an aperture and are positioned parallel to the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle. Figure 14 shows an example design for a cap assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, parallel electrodes are positioned horizontally adjacent to the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle. A sealed dialysis membrane can be secured to the dialysis membrane mounting post.

[0026] Figure 15 shows an example design for a cap assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, the parallel plate electrodes are positioned vertically in the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle. A sealed dialysis membrane can be secured to the dialysis membrane mounting post.

[0027] Figure 16 shows an example design for a cap assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, parallel verticalelectrodes include an aperture and are positioned parallel to the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle.

[0028] Figure 17A shows a circuit diagram for the device, including an a.c. or d.c. power supply Vo, a variable resistor Rv(which can also be replaced by a fixed resistor), a voltmeter across the electrodes E, reading the voltage across the electrodes Ve, an ammeter in series with the loop circuit that measures the total current flowing through the loop circuit A, the capacitance of the electrodes in a given electrolyte solution Ce, the variable capacitance across the electrodes that can build up in time due to electrical double layers Ce.v(t), electrode polarization, electrochemical reactions, and other effects, the resistance of the electrolyte solution Rs, which is the desired quantity to measure, and the variable electrode resistance Re.v(t), in series with Rs, due to the electrodes themselves and associated connections, and the change in resistance across the electrodes due to the buildup of adsorbed chemical layers on the electrodes, electrical double layers, electrode polarization, electrochemical reactions, and other effects. The total resistance across the electrodes, Rc, total is the sum of Rcand Rc,v(t).

[0029] Figure 17B has all the elements of Figure 17 A, but adds a relay across the electrodes, which can be on for a certain period and off for a certain period. When the relay is on, the electrodes are shorted out, allowing dissipation of any double layers, polarization, electrochemical adsorption and other effects which can cause the net resistance of the electrodes to drift in time. Figure 17C has all the elements of Figure 17A, but adds a relay into the loop circuit, which can be on for a certain period and off for a certain period. When the relay is on, the loop circuit is activated and current flows, when the relay is off the loop circuit is open and no current flows. When the device is used in usage #2 (as described in the Examples), A, Ve, and S are not necessary and may be absent.

[0030] Figure 18 shows an example electrode assembly that can be used to apply an electric field within a receptacle described herein (e.g., within fluids present within a receptacle described herein). The electrode assembly can be dimensioned such that a receptacle described herein (e.g., a cuvette) can be inserted within the electrode assembly, such that the electrodes are external to the receptacle, and hence not in contact with the liquid within the receptacle. The electrodes are independent from the cap assembly, in which they were integrally unified with the cap assembly in Figures 8-16. The electrode assembly can include one or more apertures within the electrodes to permit spectroscopic investigation of fluid(s) present within the receptacle.

[0031] Advantages of external electrodes (as compared to electrodes positioned in electrochemical contact with a fluid present in the receptacle) can include one or more of: i) nonfouling of the electrodes by components of sample present in the receptacle, and subsequent reusability, ii) avoiding any electrochemical reactions with components of sample present in the receptacle, iii) less expensive electrode materials can be used; e.g. copper, aluminum, or silver, instead of gold or platinum.

[0032] Figure 19 shows an example design for a cap assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, the parallel plate electrodes are positioned horizontally in the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle. A sealed dialysismembrane, or other type of membrane can be secured to the dialysis membrane mounting post. A stirring shaft with an impeller allows stirring of the first fluid through the use of a stepper motor located above the apparatus which is attached to the stirring shaft.

[0033] Figure 20 shows an example design for a cap assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, the parallel plate electrodes are positioned vertically in the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle. A sealed dialysis membrane, or other type of membrane, can be secured to the dialysis membrane mounting post. A stirring shaft with an impeller allows stirring of the first fluid through the use of a stepper motor located above the apparatus which is attached to the stirring shaft.

[0034] Figure 21 shows an example design for a cap assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, the parallel plate electrodes that include an aperture are positioned vertically in the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle. A sealed dialysis membrane can be secured to the dialysis membrane mounting post. A stirring shaft with an impeller allows stirring of the first fluid through the use of a stepper motor located above the apparatus which is attached to the stirring shaft.

[0035] Figure 22 shows an example design for a cap assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, the parallel plate electrodes are positioned horizontally in the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle. A stirring shaft with an impeller allows stirring of the first fluid through the use of a stepper motor located above the apparatus which is attached to the stirring shaft.

[0036] Figure 23 shows an example design for a cap assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, the parallel plate electrodes are positioned vertically in the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle. A stirring shaft with an impeller allows stirring of the first fluid through the use of a stepper motor located above the apparatus which is attached to the stirring shaft.

[0037] Figure 24 shows an example design for a cap assembly that includes electrodes to facilitate conductivity measurements of a fluid present in the receptacle. In this embodiment, the parallel plate electrodes including an aperture are positioned vertically in the optical path of the irradiation source from the principal monitoring instrument, allowing for the rapid and accurate conductivity measurements of a fluid present in the receptacle. A stirring shaft with an impeller allows stirring of the first fluid through the use of a stepper motor located above the apparatus which is attached to the stirring shaft.

[0038] Figure 25A shows the drift in voltage across the electrodes and current through them, with the resistance (V / I) in the inset. The conditions are 6.3 V a.c., 60 Hz, a load resistor of 48 ohms, 500mM KNO3 solution, Ag electrodes. Figure 25B shows data under the same conditions as in Figure 25 A, except that the electrodes are shorted out by a relay for 24s and opened 6s to permit current to flow. This gives a 30s cycle time. The relay is a programmable Phidgets REL2103 solid state relay. This has the effect of eliminating the drift of I and V, and hence also R, by allowing the electrodes to be brought to equal electric potential during the shorting process. This can interrupt electrode polarization, double layers, adsorption, and some of the other effects mentioned.

[0039] Figure 26A shows data obtained with a dialysis membrane separating fluid 1 and fluid 2. The Conductance (Ithrough circuit / Vacross electrodes, in 1 / Ohms) in Fluid 1 on the right-hand y-axis is when it initially contains pure water and Fluid 2 contains aqueous 5M [NaCl], where fluid 1 and 2 are separated by a Sigma-Aldrich D9277, cellulose, molecular weight cutoff -14 kDalton dialysis membrane. The left-hand y-axis is the absolute value of the conductivity in Fluid 2 minus the initial value of 235.2, where the conductivity was measured by a Thermo Scientific Orion Star A212 commercial conductivity meter. The conductivity in Fluid 2 diminishes in time, but is shown inverted so as to compare directly with the measured fluid 1 conductance.

[0040] Figure 26B shows the calibration curve for the electrode device, using a series of NaCl concentrations in water. The curve plots the know value of [NaCl] versus the measured conductance, C. It was found that an empirical double exponential fit captured all the data, with the equation

[0041] [NaCl](mM) = 42.259e76 733C+ 1.454%l(T15e697-6C

[0042] Figure 26C shows the concentration of NaCl in Fluid 1 during the dialysis, obtained from the conductance data of Figure 26 A and the above transformation equation from Figure 26B.

[0043] Figure 27A shows raw data for Mw / Mo and fluid 1 conductivity versus time for dialysis of DNA against NaCl. The DNA is ultrapure Herring Sperm DNA with 2,000 base pairs, from Invitrogen. The DNA was at concentration 5xl0’4g / cm3in pure water with a pH of 5.3. The device used flat platinum electrodes of dimensions 4mm x 8mm, with a spacing of 6.5mm between them. Voltage across the electrodes Veand current through the loop circuit A, were measured at 10 second intervals.

[0044] Figure 27B shows Mw / Moversus [NaCl] for the data from Figure 27A, where a calibration curve for the Pt electrodes was established, which allowed turning conductance a, (1 / ohm) to [NaCl] by the empirical fit

[0045] [NaCl](mM) = 11.3e351c7

[0046] Figure 28 is a plot showing [HC1] versus conductivity. Using the devices and systems described herein, the conductance of the HC1 solution can be measured for a series of fixed

[0047] [HC1], and [HC1] is directly converted to pH by the relation pH=-logio([H+), where [H+]=[HC1]. This allows the devices and systems used herein to measure the pH of a solution in the receptacle.

[0048] Figures 29A-29C illustrate an embodiment of a device comprising a cap assembly dimensioned to be received within a receptacle. The body portion can be detachably connectable to (e.g., slidably engageable with) a first electrode and a second electrode (e.g., via an electrode support) in contact with a fluid present within the receptacle when the cap assembly is disposed within the receptacle. In the embodiments shown in Figures 29A-29C, the cap assembly further includes a stirrer, driven by a stepper motor at the top of the cap assembly. Figure 29A illustrates the body portion detached from the electrode support. Figure 29B illustrates the body portion connected to the electrode support. Figure 29C illustrates the cap assembly disposed within a receptacle (e.g., a cuvette).

[0049] Figures 30A-30C illustrate an embodiment of a device comprising a cap assembly dimensioned to be received within a receptacle. The body portion can be detachably connectable to (e.g., slidably engageable with) a first electrode and a second electrode (e.g., via an electrode support) in contact with a fluid present within the receptacle when the cap assembly is disposed within the receptacle. In the embodiments shown in Figures 30A-30C, the cap assembly further includes a mounting post, fluid inlet, and fluid outlet to allow for attachment of a membrane to the body portion, and a stirrer. Figure 30A illustrates the body portion detached from the electrode support. Figure 30B illustrates the body portion connected to the electrode support. Figure 30C illustrates the cap assembly disposed within a receptacle (e.g., a cuvette).

[0050] Figure 31 schematically illustrates the electrostatic situation present when an electric field is applied within a receptacle positioned within the device illustrated in Figure 18.

[0051] DETAILED DESCRIPTION

[0052] Definitions

[0053] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Methods and materials are described herein for use in the present invention; other, suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. The term “receptacle,” as used herein, refers to a fluid containment vessel, such as a cuvette or other container in which a fluid can be disposed for analysis. In some embodiments, the receptacle can be dimensioned so as to be reversibly insertable within a principal monitoring instrument. In some embodiments, the receptacle can be a square cuvette made of glass, quartz, or a transparent polymer. In other embodiments, its shape can be circular, polygonal, elliptical, or irregular.

[0054] The term “electrode” as used herein refers to any of a pair of conductors which can be placed in a fluid in the receptacle and which can receive voltage or current from a.c. or d.c. voltage or current sources. a.c. voltage is preferably used, as it reduces or eliminates electrode polarization, electrolytic reactions, build-up or plating on the electrodes. The current is transmitted between the electrodes by ions or other charged particles between the electrodes. The voltage or current source may be gated on and off intermittently, via a programmable switch or relay. The elecrodes may also be shorted out intermittently via a programmable switch or relay. The conductors can be made from any conducting material, such as, but not limited to metals, graphite, graphene, glassy carbon, carbon nanotubes, certain ceramics (e.g. zirconia), conductive polymers (e.g. polyanaline and polypyrrole), doped silicon, and metal oxides (e.g. indium tin oxide, titanium dioxide, etc.). The electrodes can take forms such as sheets or plates, wire meshes, wires, cylinders, or other specialized forms. The electrodes can be connected to the voltage or current source by wires or other conductors (e.g. metallic strips) affixed to the electrodes which lead out of the receptacle.

[0055] The term “electrode assembly” as used herein refers to the means in which the electrodes are disposed within the receptacle. The electrodes may be mounted on a cage-like or box-like device which inserts into the receptacle. The electrodes may also be mounted on a device containing a means of providing convection for the fluid, such as stirring. The electrodes may also be mounted on a device that allows separation of Fluid 1 from Fluid 2 by a membrane. The electrodes may also be mounted on a device that allows for both convection of the fluid, such as stirring, and separation of Fluid 1 from Fluid 2 by a membrane. The electrodes may also be freestanding within the receptacle, not attached to any other device in the receptacle. The electrodes may also fit into custom recesses in the walls of the receptacle. The electrodes may also be manufactured integrally with the receptacles. In the case where the electrodes are free standing, are affixed to the receptacle walls, or are integrated into the receptacle in the manufacturing process the term ‘electrode assembly’ is intended to include this. This latter case may also be termed ‘means of disposition of the electrodes within the receptacle’. The phrase “electrode support” refers to a structure on which one or more electrodes are disposed or attached. The electrode support can be fabricated from any suitable material. In some cases, the electrode support is fabricated from a conductive material, such as a metal. If desired, the electrode support is fabricated from the same material(s) as the one or more electrodes disposed or attached to the electrode support. In other embodiments, the electrode support can be fabricated from a polymer.

[0056] The phrase ‘cap assembly’ refers to a cap which can fit onto the receptacle in which the electrodes create an electric field. The cap assembly may be a simple cap that fits onto the receptacle. In some examples, the cap assembly may be a body portion with apertures to allow conductors attached to the electrodes, such as wires, to pass from the electrodes and through the body portion for external electrical connections. In other examples examples, the cap assembly may be a cap with apertures to allow the electrodes or the electrode support to extend from the receptacle through the cap for external electrical connections. In these embodiments, the body portion can be detachably connected to the electrode support, such that the electrode support can be slidably engageable with the body portion. Alternatively, the cap assembly may include a body portion integrally formed with the electrode support / electrode assembly that fits into the receptacle. The cap assembly may include a stirrer for stirring the contents of the receptacle, whether the electrode assembly is integral with the rest of the cap assembly, or resides inside the receptacle independently of the cap assembly. The cap assembly may include a means of affixing a membrane that divides the solution within the receptacle into a first fluid and a second fluid. This latter aspect may contain and combine any of the previously mentioned features.

[0057] The term “fluid,” as used herein, refers to a liquid, which may be pure, or have dissolved or suspended components. For example, a fluid may be a pure solvent such as, but not limiting, water, dimethylsulfoxide (DMSO), toluene, tetrahydrofuran, acetone, methanol, ethanol, carbon disulfide, and many other pure solvents. The pure fluid may be a mixture of two or more solvents. The pure fluid may have dissolved components such as, but not limiting, ions, small neutral molecules, surfactants, dyes, fluorescence markers, chelation agents, buffers, oligomers, and polymers of biological or synthetic origin. Suspended materials in the fluid include, for example, whole cells, clusters of cells, organelles from cells, micelles, liposomes, vesicles, nanoemulsions, microemulsions, emulsions, surfactant stabilized structures, quantum dots, metal sols, and combinations thereof.

[0058] The term “fluid 1” as used herein, refers to the fluid containing chemicals or agents of interest in the situation where the liquid in the receptacle is separated by a membrane into two fluid portions. The volume of Fluid 1 is typically in the range of 0.1 -5ml. The term “fluid 2” as used herein, refers to the fluid not containing chemicals or agents of interest in the situation where the liquid in the receptacle is separated by a membrane into two fluid portions. While the volume of Fluid 2 within the receptacle is typically 0.01-2mL, this is typically connected via fluid carrying tubes to a much larger reservoir volume in the range of 25mL to 4,000mL. The portion of Fluid 2 in the receptacle plus the fluid in the reservoir and circulation lines comprises the entirety of Fluid 2.

[0059] The terms “device” and “current device”, as used herein refer to the receptacle and any apparatus used to dispose the electrodes within a receptacle. The device can further include the voltage or current power supply (a.c. or d.c.), resistive and other circuit elements in the circuit containing the elecctrodes, wiring and terminals, as well as current and voltage measuring devices, and programmable relays that periodically interrupt the circuit. The device can further include a means of providing convection within the receptacle, such as by stirring the fluid contents, The device can further include the receptacle and the apparatus used to separate the fluid contents of the receptacle into two fluids separated by a membrane. The device can contain the electrode separate from the cap assembly, or as an integral part of the cap assembly. Other components of the device can provide for circulation or recirculation of the first and / or second fluids, such as a pump and external reservoir(s). The device may include the principal monitoring instrument into which the current device is placed, and any external monitoring instrument(s) used to monitor circulating or recirculating first and / or second fluid.

[0060] The term ‘loop circuit’ , as used herein refers to the components in the complete electrode circuit. The loop circuit comprises at least the electrodes and a power supply. It can additionally include such elements as an ammeter, voltmeter, and one or more resistors or capacitors, and a relay.

[0061] The term ‘calibration curve’ , as used herein refers to a procedure for converting the electrical readings from the voltmeter and ammeter in the electrode loop circuit into the conductivity of the fluid in the receptacle and / or into electrolyte concentrations in the receptacle. The preferred method for doing this is to put the voltmeter across the electrodes and to put the ammeter in the loop circuit. The value of current (A) divided by voltage (V) is then the conductance (1 / ohms, or S, Siemens) of the fluid. To convert the conductance into concentration of electrolyte a series of conductance measurements can be made at a series of electrolyte concentrations. This calibration curve then allows converting conductances from experiments using the device into electrolyte concentrations in the fluid in the receptacle. This conversion to electrolyte concentration is of utmost importance when using the device during dialysis of macromolecules or colloids against dialysates containing electrolytes. In some cases, the conductances for a given electrolyte concentration, or series of concentrations, can be matched to conductivity data obtained by a separate conductivity meter or from a source, such as NIST or the CRC Handbook, in order to obtain a calibration constant for the elelectrode device. The calibration constant converts the conductance reading into the conductivity of the fluid in the receptacle.

[0062] The term “relay” refers to any type of on / off switching mechanism. The relay may be controllable manually or through a computer interface. The relay is set to be ‘on’, which closes the switch for a desired period of time, and is set to be ‘off’, which opens the circuit, for a desired period of time.

[0063] The term “usage #1” refers to the device being used for measuring the conductance of fluid 1. This includes a voltmeter across the electrodes and an ammeter in the loop circuit to measure the current flowing through the loop circuit.

[0064] The term “usage #2” refers to the device being used to impart an electric field to a macromolecular or colloidal sample in fluid 1. In this case it is not necessary to have a voltmeter or ammeter, but they can be optionally used.

[0065] The term “membrane” refers to any type of membrane, whether open or closed, through which matter can pass, including, but not limited to, fluids, small molecules, ions, gases, polymers, colloids, and specific types of fluids, such as various polar and non-polar fluids. Examples, not limiting, include membranes made of polyvinylidene difluoride (PVDF), polyimide, polyamides (e.g., nylons and aramids), carboxymethylcellulose, hybrid membranes such as hyaluronic acid / carboxymethylcellulose, polyethersulphone, cellulose acetate, cellulose nitrate, sintered metals, gels, polycarbonate, polysulfone polytetrafluoroethylene (PTFE, sometimes called by one of its commercial names ‘Teflon’). Examples of membranes used in medical dialysis include Theranova 400, Theralite 2100, Revaclear 400, Polyflux 17L. The Membrane may also comprise a biological tissue, such as, but not limited to, skin, muscle, fat, neurons, and bone.

[0066] It will be understood that a membrane need not be a flat 2D membrane. The term “membrane” can also encompass 3D membranes, such as hollow filter ultrafiltration membranes, membranes used in lithium-ion batteries, and in hydrogen production. Makers of example membranes include Membrane System Specialists, Inc., Pall Corporation, MilliporeSigma, Dow Chemical Company, Sigma- Aldrich, Lab Filtration Papers, Koch Membrane Systems, SPX Flow, Alfa Laval, Merck Group, Siemens Corporation, GEA Goup Aktiengesellschaft, Toray Industries, International Polymer Solutions, J.G. Rinneran, and others. The term “open membrane,” as used herein, refers to a single lamina or single surface of membrane used to separate the first and second fluids.

[0067] The term “closed membrane,” as used herein, refers to a membrane existing in 3 dimensions, which can be filled by a fluid, such as in cylindrical form, not limiting, which may also allow flow of liquid into and out of said membrane. In the case where the membrane is initially open on both ends, e.g., a length of dialysis tubing, the membrane can be formed into a closed membrane by sealing one end. In such circumstances, sealing may be accomplished using an adhesive, such as, but not limited to, Gorilla Super Glue Gel XL, and / or a mechanical fastener, such as a clip. Alternatively, the membrane may be manufactured to have one sealed end. The portion of the cap assembly that holds the membrane can also have grooves and a solid base, such that an open membrane can be sealed around said portion without need of sealing one end of the open membrane.

[0068] The term “monitoring instrument,” as used herein, refers to a device that can perform continuous or rapid periodic measurements of a liquid sample. Examples of monitoring instruments include both optical instruments, such as, but not limited to, static and dynamic light scattering instrucments, turbidity probes, UV / visible spectrometers, fluorimeters, polarimeters, refractometers, circular dichroism or birefringence instruments, as well as non-optical instruments, such as conductimeters, pH meters, viscometers, dissolved gas sensors, ion-specific probes, and other molecular specific probes. Other suitable monitoring instruments include chromatographic separation systems that allow periodic injection of small aliquots of the first fluid and / or second fluid (e.g., present in a fluid circulation path) for chromatographic analysis. In these embodiments, the circulation path can contain a manual or automatic injection valve, which can periodically inject a small portion of fluid circulating within a fluid circulation path into a chromatographic separation system for analysis.

[0069] The term “optical instrument,” as used herein, refers to an instrument which has a source of electromagnetic radiation, whose radiation can be directed to impinge on a fluid sample for purposes of analyzing one or more characteristics of the fluid sample. Examples include, but are not limited to static light scattering (SLS) instruments (also termed ‘total intensity light scattering instruments), dynamic light scattering (DLS) instruments, electrophoretic light scattering instruments, Mie scattering instruments, turbidity measuring instruments, laser diffraction scattering instruments, ultraviolet absorption instruments, visible light absorption instruments, infra-red absorption instruments, microwave absorption instruments, spectrofluorimeters, polarimeters, circular dichroism instruments, and circular birefringence instruments. The term “principal monitoring instrument,” as used herein, refers to a monitoring instrument positioned and configured to receive a receptable and interrogate a fluid sample present within the receptacle. In the case of an optical instrument, the principal monitoring instrument can include an optical measuring path, and the receptacle can be placed within the optical measuring path, such that electromagnetic radiation from the optical instrument can impinge on a fluid sample present within the receptacle. This can allow the optical instrument to analyze one or more characteristics of the fluid sample within the receptacle. The principal monitoring instrument can also be a non-optical instrument, such as a head space gas chromatograph for monitoring the emission of gas from a fluid in the receptacle.

[0070] The term “external monitoring instrument,” as used herein, refers to any monitoring instrument that is physically separated from the receptacle such that it does not house or enclose the receptacle. In some embodiments, the external monitoring instrument can be configured to interrogate a circulating fluid present within a flow path. For example, one or more external monitoring instruments can be fluidly connected to circulation tubing forming a circulation path through which the first fluid and / or the second fluid is circulated. Examples of such instruments include, but are not limited to, flow-cell equipped light scattering, UV / visible absorbance, fluorescence, turbidity, polarimeter, and circular dichroism and birefringence instruments. In other examples, the external monitoring instrument (or a portion thereof) can be submerged in a reservoir forming part of the circulation of the first fluid and / or second fluid. Examples of such instruments include pH, conductivity, specific ion sensitive, and dissolved gas probes. An external monitoring instrument can also interrogate a fluid present within a receptable located within the principal monitoring instrument, provided its active measuring component does not make direct measurements on the receptacle and its contents.

[0071] The phrase “flow-cell equipped instrument,” as used herein, refers to any instrument equipped with a flow-cell that can make measurements on the fluid passing through the flowcell. Examples of flow-cell equipped instruments include, but are not limited to, refractometers, differential refractometers, UV / visible spectrophotometers, static light scattering instruments, dynamic light scattering instruments, fluorescence detectors, turbidity, pH, and conductivity detectors, polarimeters, NMR, Infra-red detectors, near infra-red detectors, and circular dichroism and birefringence detectors.

[0072] The phrase “instrument components,” as used herein, refers to any and all components used in any embodiment of the Device. These include, but are not limited to, Principal and External Monitoring Instruments, tubing used in circulation flow paths, pumps or other means of causing circulation through circulation flow paths, reservoirs in the circulating flow paths, any computer used for data gathering, analysis, and interpretation from the Device.

[0073] The phrase “first fluid,” as used herein in the context of the fluid contents of the receptacle being separated by a membrane, refers to the fluid sample in the receptacle which is characterized via the principal monitoring instrument, for example, by passing electromagnetic radiation from the principal monitoring instrument through the fluid sample or by measurements made directly on the receptacle contents, such as the evolution of gas in a chemical or biological process.

[0074] The phrase “second fluid,” as used herein in the context of the fluid contents of the receptacle being separated by a membrane,, refers to the fluid sample in the receptacle which is not measured by the principal monitoring instrument in which the receptacle is located, whether this fluid be contained inside a closed membrane, or separated from the first fluid by a sealed membrane sheet.

[0075] The phrase “membrane-mediated process,” as used herein, refers to the flow or exchange of material between the first fluid and second fluid, across the membrane that separates them, including, but not limited to the fluids themselves, small molecules, ions, oligomers, polymers and colloids. Membrane-mediated processes may also be referred to as membrane exchange processes.

[0076] The phrase “heterogeneous time-dependent static light scattering (HTDSLS),” as used herein, refers to the instrumentation and methods whereby diffusive or convective motion of colloids in solution is used to produce countable light scattering spikes which can be counted and characterized to determine number density of the colloids. In certain cases, information on the colloidal size distribution can also be obtained. Such instrumentation and methods are described in R. Schimanowski, R. Strelitzki, D.A. Mullin, W. F. Reed "Heterogeneous Time Dependent Static Light Scattering", Macromolecules, 1999, 32: 7055-7063.

[0077] The phrase “continuous monitoring,” as used herein, refers to measurements made at time intervals sufficiently short that no time-dependent information is lost between successive measurements. Such monitoring measurements can also be termed “substantially continuous.” Typically, continuous measurements imply that at least twenty, but preferably more, measurements are made during the complete time-course of the process.

[0078] The phrase “discrete monitoring,” as used herein, refers to measurements made at intervals not considered continuous, such as measurements whose time between measurements is limited by the instrument. Examples of discrete monitoring include, but are not limited to, measurements made using chromatographic systems such as gel permeation chromatography, size exclusion chromatography, interaction chromatography, two-dimensional chromatography, high pressure liquid chromatography, and field flow fractionation.

[0079] The terms “macromolecule” and “polymer” are used interchangeably and also include small polymers and oligomers. These terms refer to any polymer or oligomer of synthetic or biological origin, including proteins, polysaccharides, RNA, DNA and related polynucleic acids, combinations of these, monoclonal antibodies and other protein drugs.

[0080] The term “colloid,” as used herein, refers to any entity, on the nanometer, micrometer, or millimeter scale which is suspended in a fluid but not dissolved in the chemical sense. Examples include biological cells, clusters of cells, cell organelles, virus particles, lipid nanoparticles, viral capsids, metal, semi-conductor, and dielectric particles, micelles, liposomes, vesicles, and other self-organizing structures.

[0081] The phrase “biological cells,” as used herein, refers to, but not limited to, bacteria, yeast and other fungi, blood cells, neurons, and other specialized cells, and other microbes, such as, but not limited to any species of archaea, protozoa, algae, and lichens.

[0082] The phrase “electromagnetic radiation,” as used herein, includes any wavelength or frequency of the electromagnetic radiation spectrum, including, but not limited to, ultra-violet and visible light, and infrared, x-ray, and microwave radiation.

[0083] The phrase “acceptably complete,” as used herein, refers to a process that is carried out so that some specification of an acceptable final state is reached. Examples include, but are not limited to, a minimum or maximum final concentration of one or more components in the first fluid and / or the second fluid, such as the concentration of ions, small molecules, and polymers.

[0084] The term “circulation,” as used herein, can refer both to open loop and closed-loop circulation of the first fluid and / or second fluid. For example, a circulating second fluid may be diverted to a measuring instrument or waste container, without being re-circulated into the receptacle.

[0085] The term “recirculation,” as used herein, refers to a closed-loop circulation of the first fluid or second fluid with any type of pumping device, such as, but not limited to, a peristaltic pump, piston pump, slot pump, diaphragm pump, gear pump, reciprocating syringe pump. The closed circulation loop may contain a reservoir of fluid content the same as the first fluid or second fluid itself. The circulating fluid may pass through a measuring device, such as, but not limited to, an optical instrument, a conductivity meter, a pH meter, or a dissolved gas probe.

[0086] The phrase “first fluid circulation path” is used to refer to a circulation path through which the first fluid is circulated. The phrase “second fluid circulation path” is used to refer to a circulation path through which the second fluid is circulated. The phrase “control of a membrane-mediated process,” as used herein, refers to any action taken by a human, machine, or automaton that interrupts or changes the conditions of the membrane exchange process. Examples include, but are not limited to; stopping the membrane exchange process when it is acceptably complete, changing the rate of circulation or recirculation of the first fluid and / or second fluid, and changing the nature or composition of the first fluid and / or second fluid.

[0087] The term “reversibility,” as used herein, refers to a process in which a polymer or colloid, having an initial state under initial solution conditions, changes its characteristics due to a change in solution conditions (for example, but not limiting, ionic strength, pH, electrolytes, temperature, mechanical agitation, presence of denaturant, chelating agent), and then reverses to its initial state when the solution conditions are brought back to the initial solution conditions. For example, ionic strength, pH, electrolytes, denaturants and chelating agents can be removed using dialysis, wherein the state of the polymer or colloid is monitored.

[0088] The phrase “means of circulation or recirculation,” as used herein, refers to any device, such as a pump, such can direct fluid along a fluid flow path. Examples include, but are not limited to peristaltic pumps, piston pumps, slot pumps, syringe pumps, reciprocating syringe pumps, gear pumps, diaphragm pumps, and pressurized lines.

[0089] The phrase “small molecule,” as used herein, refers to molecules having a molecular weight of less than 1000 Da (e.g., less than 800 Da, or less than 500 Da), including gases, dyes, fluorophores, surfactants, oligomers, emulsifiers, chelating agents, buffer components, biocides, toxins, and simple electrolytes, which can include salts, and their respective ions, such as, but not limited to, NaCl, KBr, MgCh, CaSO4, and borax, as well as acids and bases, such as HC1, NaOH, H2O4, and organic acids, but not limited to, formic, acetic, butyric, ascorbic, and oxalic acids. Other soluble small molecules include, but are not limited to, chaotropic agents which can interrupt non-covalent bonds, such as hydrogen bonds, leading to, for example, unfolding or denaturation of polynucleic acids (e.g., RNA and DNA) and proteins. Chaotropic agents include, but are not limited to, urea, guanidine hydrochloride, and norbomene salts. Other small, soluble molecules include anti-chaotropic agents (also termed ‘kosmotropic’), which contribute to the stability of structure stabilized by hydrogen bonds and other non-covalent bonds and effects. Small Molecules also include small molecule active agents (drugs), such as, but not limited to salicylic acid, losartan, naproxen, fexofenadine, carvedilol, trazondone, lamictal, and valproic acid.

[0090] The phrase “osmotic virial coefficient,” as used herein, refers to coefficients used to express non-ideality in solutions that contain two or more components. For example, a solvent, such as water might contain a polymer at a certain concentration, and one or more virial coefficients can be used to express light scattering, osmotic pressure, chemical potential, or other quantities to characterize the non-ideality. One set of virial coefficients for this, not limiting, are those expressed in mass terms, such as the second virial coefficient A2 (cm3-mole / g2), third virial coefficient A3 (cm6-mole / g3), etc. Other, related definitions and terminology are also found, such as B2 (cm3) instead of A2, B3 instead of A3, and other forms.

[0091] The phrase “supramolecular assembly,” as used herein, refers to a structure composed of molecules, polymers, and / or colloids that are held together by non-covalent forces and effects. These include, but are not limited to micelles, block copolymer assemblies, liquid crystals, natural and artificial membranes, and emulsions, including nano- and microemulsions. The assembly may be driven by electrostatics, hydrogen bonding, dipolar forces, hydrophobic effects, depletion effects, entropic effects, and osmotic pressure.

[0092] The phrase ‘biologic drug’ includes any therapeutic agent, whether in discovery, formulation, or commercial production, derived from natural biological sources or synthesized to resemble or be equivalent to biological products. Biologic drugs include, but are not limited to, proteins of any sort, including monoclonal antibodies, polyclonal antibodies, polysaccharides, protein-polys accharide complexes, oligopeptides, vaccines, lipid nanoparticles, viral capsids, nucleic acids, oligonucleotides, and polynucleic acids such as RNA and DNA. Also included are agents, not necessarily biological, which are used to enhance, functionalize, encapsulate, or deliver a biological agent, such as, but not limited to, encapsulation / delivery synthetic polymers, dendrimers, liposomes, vesicles, and micelles. The phrase ‘biologic medicine product’ is an alternate phrase for ‘biologic drug’.

[0093] The phrase ‘contact stir’ refers to any means of stirring the liquid in the receptacle such that the agent that causes the stirring motion is in contact with the receptacle itself. An example, not limiting, is where the agent that causes the stirring motion is a magnetically driven stir bar that resides and spins on the bottom inside surface of the receptacle.

[0094] The phrase ‘non-contact stir’ refers to a means of causing convection in the fluid in the receptacle where the agent that causes the convective motion makes no contact with any surface of the receptacle. An example, not limiting, is a shaft with an impeller connected to one of its ends and inserted into the fluid contained in the receptacle, without the impeller making contact with the walls or any other part of the receptacle, the impeller being driven by a motor to provide the convective motion, or, in the case of a suspended magnetic stir bar impeller making no contact with the receptacle, the magnetic stir bar impeller can be driven by a rotating magnet external to the receptacle. The phrase ‘stir’ can mean the reciprocal motion of an impeller within the fluid contained in the cuvette, in addition to a rotational stir motion.

[0095] Aspects of the devices, systems, and methods described can be further understood in view of International Application Number PCT / US2024 / 026575, filed April 26, 2024, which is hereby incorporated herein by reference in its entirety.

[0096] Devices and Systems

[0097] The devices, systems and methods are targeted for use in fluids containing chemicals. Two main capabilities are contemplated: Usage #1, directly monitoring the electrical conductance of the fluid containing chemicals, frequently with the goal of determining electrolylte concentrations in fluid 1, and usage #2, monitoring behaviors and properties of the chemicals that can be influenced by an electric field.

[0098] Furthermore, the device can be placed in a measuring instrument to monitor the effect of the electric field on one or more properties of the chemicals in the fluid, while the device simultaneously monitors solution conductance. Instruments which can monitor such changes in the chemicals include, but are not limited to, static and dynamic light scattering, fluorimetry, UV / visible absorption, circular dichroism, and dielectric spectroscopy. The device fits into a receptacle, such as, but not limited to, spectroscopic cuvettes, such as are made of plastic, glass, quartz, and other materials.

[0099] The devices and systems described herein can include some or all of the following components:

[0100] (1) a source of a constant voltage or current, such as a power supply, which can be either alternating current (a.c.) or direct current (d.c.). The voltages of the source can range from less than a millivolt to tens of thousands of volts. The amplitude of the source voltage is designated as Vo, and is the d.c. value, or the root mean square voltage in the case of a.c. The current can range from less than nanoamperes to tens of amperes.

[0101] If the voltage or current is a.c. the frequency can be varied from less than one Hertz to over a Gigahertz. The wave shape of a.c. can be sinusoidal, square, triangular, or any other periodic form. Specifically configured bursts of voltage, with Fourier Transform definable shapes can also be used instead of periodic waveforms.

[0102] (2) a first electrode and a second electrode that reside inside the fluid in the receptacle and which form that part of the assembly that resides inside the receptacle. The electrodes can simply be wires, or planes of different shapes, such as flat planes, flat grids or meshes, including planes which may have apertures to let incident spectroscopic electromagnetic radiation into and out of the receptacle. The material for the electrodes will be a conductor, such as any metal, or conductive material such as, but not limited to, graphite, graphene, glassy carbon, carbon nanotubes, certain ceramics (e.g. zirconia), conductive polymers (e.g. polyanaline and polypyrrole), and doped silicon, or other semiconductor, metal oxides (e.g. indium tin oxide, titanium dioxide, etc.)

[0103] The first and second electrodes can be contained in an assembly that fits into the receptacle, independent of a cap or any cap assembly, in which case the electrodes are in contact with a fluid in the receptacle. Alternately, the electrodes can be incorporated into a unified cap assembly which fits into the receptacle. In both the case of an independent electrode assembly and a cap assembly with an integral electrode assembly, the electrodes will have terminals / points of electrical connections.

[0104] Yet another means is to affix the electrodes to the inside walls of the cuvette via a bonding material, by an integral cuvette fabrication process containing the electrodes, by recesses in the internal walls of the cuvette. Alternatively, the electrodes can be free-standing but placed against the inner cuvette walls. In any of these latter cases, there is no need for a special assembly to hold the electrodes and introduce them into the cuvette.

[0105] In some embodiments, the first and second electrodes are configured to generate an approximately uniform electric field within a region of the receptacle / cuvette (e.g., in a region interrogated by the principal monitoring instrument). In some embodiments, the first and second electrode each have a width that is greater than the separation between the first electrode and the second electrode. The greater the ratio of the electrode width to interelectrode separation the more uniform the electric field between the plates. In certain embodiments, the first and second electrode each have a width that is at least 1.25 times, at least 1.5 times, at least 1.75 times, or at least 2 times greater than the separation between the first electrode and the second electrode. In other embodiments, the first and second electrode each have a width that is from 0.5 to 1.25 times greater (or from 0.5 to 1.0 times greater) than the separation between the first electrode and the second electrode.

[0106] (3) A current loop comprising:

[0107] A resistor. The resistor can be chosen so that the power dissipation when the resistor alone is connected across the power supply is less than the supply’s maximum power output Pmax, in which case the following expression is satisfied V02 / Rv<Pmax, where Vois the amplitude of the voltage of of the power supply, and Rvis the resistance of the resistor, which can be either a variable resistor or a fixed resistance. In some cases, the resistor can comprise two resistors (an optional safety resistor, Rsafety, and a variable resistor, Rv). The safety resistor, Rsafety, can be chosen so that the power dissipation when it alone is connected across the source Vo is such that Vo2 / RSafety<Pmax, where Pmax is the maximum power dissipations permissible for the power source and associated circuit components. E.g. if Vo=15V, and the Pmax=5W then, Rsafety>45 Ohms. If the power source is rated in terms of a maximum current Imax, then Vo / Rsafety<Imax. e.g. if Imax=2A, and Vo=15V then Rsafety>7.5 Ohms. The variable resistor Rv, which is optional, can run from 0 ohms up to several megohms, and allows the voltage across the electrodes in the fluid containing receptacle, Vs, to be modulated as desired. Increasing Vsincreases the electric field E between the electrodes, and vice versa. A fixed resistor can be used in place of a variable resistor.

[0108] The electrodes immersed in the fluid contained in the receptacle, whose two terminals can be connected to the other elements of the current loop. This constitutes a current loop circuit element with a resistance Rsand a capacitance Cs.

[0109] 4) A voltage measuring device (voltmeter) placed across the terminals of the electrodes, such that the voltage across the electrodes, ve, is measured.

[0110] 5) A current measuring device (ammeter) in series with the current loop. This measures the current in the current loop which passes through the voltage (or current) source, Rsafety (if used), Rv, and the electrodes.

[0111] 6) A relay, acting as a switch and programmable to cycle through an open circuit for a certain time interval and closed circuit for a certain time interval. The switch can be used to either i) short out the electrodes periodically, which can reduce or eliminate a number of possible effects, such as electrode polarization, electrical double-layer formation at the electrode surfaces, electrochemical reactions, etc., or, interrupt the voltage or current source, minimizing polarization, double layer and other effects.

[0112] A basic circuit diagram, shown in Figures 17A-C, and method of calibration, along with determination of the calibration factor are described below.

[0113] Usage #1. When low currents («100mA) are used then the device can be used to produce low electric fields between the electrodes which will not significantly affect the chemicals in the fluid, while measurements of conductance are made. (2) When higher voltages are used the electric fields may affect the properties and behavior of the chemicals in the solution, which is the goal when it is desired to monitor the effect of electric fields on chemicals, such as biologic drugs, macromolecules, and colloids.

[0114] By way of example, referring now to Figures 8-10, in some examples, provided herein are devices (100) that comprise an electrode assembly (102) dimensioned to be received within a receptacle. The electrode assembly can comprise an electrode support (104) insertable within an opening of a receptacle; and a first electrode (106) and a second electrode (106) disposed on the electrode support. The first electrode and the second electrode are each electrically connected to an electrical lead (e.g., via a terminal 110) extending outside of the receptacle when the electrode assembly is positioned within the receptacle.

[0115] The electrode assembly can be dimensioned (e.g., can have a size and shape) such that when the electrode assembly is disposed within the receptacle, the electrodes are positioned in electrochemical contact with a fluid present within the receptacle. In some examples, the electrode support, the first electrode, and the second electrode are dimensioned to allow for right angle (90°) detection when the electrode assembly is seated in a receptacle and positioned within a principal monitoring instrument. If desired, the design can further allow for measurement at angles other than 90 degrees without any modification. Namely the angular range above and below 90 degrees, 9, is given by tan 0 = L / w, where L is the separation between the electrodes and w the width of the electrodes. For example, in the case of an example device with L = 8mm and w = 6mm, 0 = 53 degrees, so such a device would exhibit an angular range of from 37 degrees to 143 degrees.

[0116] In some examples, the electrode support, the first electrode, and the second electrode are dimensioned to allow for zero angle to low angle detection (0° to 30°) when the electrode assembly is seated in a receptacle and positioned within a principal monitoring instrument. In some examples, the electrode support, the first electrode, and the second electrode are dimensioned to allow for transmission of incident electromagnetic radiation and backscatter detection (at angled of from 150° to 180°) when the electrode assembly is seated in a receptacle and positioned within a principal monitoring instrument.

[0117] In some examples, the first electrode and the second electrode comprise parallel plate electrodes. In other examples, the first electrode and the second electrode comprise parallel wire mesh electrodes.

[0118] In some examples, the first electrode and the second electrode are sized and positioned to generate an electric field between them, through which the incident electromagnetic radiation emitted by a principal monitoring instrument passes when the electrode assembly is seated in a receptacle and positioned within the principal monitoring instrument. In some examples, the first electrode and the second electrode are separated by a distance of 10 mm or less, such as a distance of from 2 mm to 5 mm. In some examples, the electrode assembly is sized to be received within a 1 cm pathlength cuvette cell.

[0119] Also provided are systems that comprise a receptacle (e.g., a cuvette) housing a fluid; a device described above; a power supply; and a current loop operatively coupled to the first electrode, the second electrode, and the power supply.

[0120] In some examples, the current loop comprises: a resistor; and an ammeter configured to measure a current in the current loop which passes through the power supply, the resistor, the first electrode, and the second electrode. In some examples, the current loop comprises a volmeter configured to measure a voltage across the first electrode and the second electrode. In some examples, the current loop comprises a relay that can be used to interrupt the current loop circuit. For example, the relay can intermittently short out the first electrode and the second electrode. Alternatively, the relay can intermittently opens the loop circuit, interrupting current flow through the loop circuit.

[0121] In some embodiments, the resistor is chosen so that the power dissipation when the resistor alone is connected across the power supply, the following expression is satisfied Vo2 / R<Pmax, where Vois the amplitude of the voltage of of the power supply, R is the reisistance of the resistor, and Pmaxis the minimum value of the maximum power dissipations permissible for the power source and associated circuit components.

[0122] Also by way of example, referring now to Figure 18, in some examples, provided herein are devices (200) that comprise an electrode assembly (202) dimensioned (e.g., sized and shaped) to receive a receptacle therewithin. For example, in some embodiments, the electrode assembly can include an internal cavity (201) dimensioned (e.g., sized and shaped) to receive a receptacle, such as a cuvette, therewithin. The electrode assembly can comprise an electrode support (204) dimensioned to house the receptacle therewithin; and a first electrode (206) and a second electrode (208) disposed on the electrode support. The first electrode and the second electrode are each electrically connected to an electrical lead or terminal 210.

[0123] In some examples, the electrode support, the first electrode, and the second electrode are dimensioned to allow for right angle (90°) detection when a receptacle is seated within the electrode assembly and positioned within a principal monitoring instrument. In some examples, the electrode support, the first electrode, and the second electrode are dimensioned to allow for zero angle to low angle detection (0° to 30°) when a receptacle is seated within the electrode assembly and positioned within a principal monitoring instrument. In some examples, the electrode support, the first electrode, and the second electrode are dimensioned to allow for transmission of incident electromagnetic radiation and backscatter detection (at angled of from 150° to 180°) when a receptacle is seated within the electrode assembly and positioned within a principal monitoring instrument.

[0124] In some examples, the first electrode and the second electrode comprise parallel plate electrodes. In other examples, the first electrode and the second electrode comprise parallel wire mesh electrodes.

[0125] In some examples, the first electrode and the second electrode are sized and positioned to generate an electric field between them, through which the incident electromagnetic radiation emitted by a principal monitoring instrument passes when the receptacle is seated in the electrode assembly and the electrode assembly is positioned within a principal monitoring instrument. In some examples, the first electrode and the second electrode are separated by a distance of 1.5 cm or less, such as a distance of from 1 cm to 1.5 cm. In some examples, the electrode assembly is sized to receive therewithin a 1 cm pathlength cuvette cell.

[0126] Also provided are systems that comprise a receptacle (e.g., a cuvette) housing a fluid; a device described above; a power supply; and a current loop operatively coupled to the first electrode, the second electrode, and the power supply.

[0127] In some examples, the current loop comprises: a resistor; and an ammeter configured to measure a current in the current loop which passes through the power supply, the resistor, the first electrode, and the second electrode. In some examples, the current loop comprises a volmeter configured to measure a voltage across the first electrode and the second electrode. In some examples, the current loop comprises a relay that can be used to interrupt the current loop circuit. For example, the relay can intermittently short out the first electrode and the second electrode. Alternatively, the relay can intermittently opens the loop circuit, interrupting current flow through the loop circuit.

[0128] In some embodiments, the resistor is chosen so that the power dissipation when the resistor alone is connected across the power supply, the following expression is satisfied

[0129] V 02 / R<P max , where Vois the amplitude of the voltage of of the power supply, R is the reisistance of the resistor, and Pmaxis the minimum value of the maximum power dissipations permissible for the power source and associated circuit components.

[0130] Also by way of example, referring now to Figures 11-16, 19-24, 29A-29C, and 30A-30C, described herein are devices that comprise a cap assembly (300) dimensioned to be received within a receptacle. The cap assembly can comprise a body portion (302) insertable within an opening of the receptacle; and a first electrode (306) and a second electrode (308) in contact with a fluid present within the receptacle when the cap assembly is disposed within the receptacle. The first electrode and the second electrode can be electrically connected to a terminal or terminals (310) present outside of the receptacle when the cap assembly is disposed within the receptacle.

[0131] In some embodiments, the first electrode and the second electrode are disposed on an electrode support (304) extending from a bottom of the body portion of the cap assembly. In some embodiments, the electrode support is dimensioned such that when the cap assembly is disposed within the receptacle, the electrode support extends into the receptacle such that the electrodes are in contact with a fluid present within the receptacle.

[0132] In some embodiments, the terminal or terminals disposed on the body portion of the cap assembly.

[0133] In some embodiments, the first electrode, the second electrode, and the electrode support (when present) are dimensioned to allow for right angle (90°) detection when the cap assembly is seated in a receptacle and positioned within a principal monitoring instrument. In some embodiments, the first electrode, the second electrode, and the electrode support (when present) are dimensioned to allow for zero angle to low angle detection (0° to 30°) when the cap assembly is seated in a receptacle and positioned within a principal monitoring instrument. In some embodiments, the first electrode, the second electrode, and the electrode support (when present) are dimensioned to allow for transmission of incident electromagnetic radiation and backscatter detection (at angled of from 150° to 180°) when the cap assembly is seated in a receptacle and positioned within a principal monitoring instrument.

[0134] In some embodiments, the first electrode and the second electrode comprise parallel plate electrodes. In other embodiments, the first electrode and the second electrode comprise parallel wire mesh electrodes.

[0135] In some embodiments, the first electrode and the second electrode are sized and positioned to generate an electric field between them, through which the incident electromagnetic radiation emitted by a principal monitoring instrument passes when the cap assembly is seated in a receptacle and positioned within the principal monitoring instrument. In some embodiments, the first electrode and the second electrode are separated by a distance of 10 mm or less, such as a distance of from 2 mm to 5 mm. In some embodiments, the cap assembly is sized to be received within a 1 cm pathlength cuvette cell.

[0136] In some embodiments, the cap assembly (300) further comprises: a post (316) extending from a bottom of the body portion (302), wherein the post is configured for attachment of a membrane; and a first fluid inlet (318) and a first fluid outlet (320) fluidly disposed on the body portion and fluidly extending to the post so as to fluidly connect to a fluid sample present within a membrane affixed to the post. In some embodiments, the cap assembly further comprises a second fluid inlet and a second fluid outlet fluidly disposed on the body portion and fluidly extending to the bottom of the body portion as to fluidly connect to a fluid sample present within the receptacle when the cap assembly is disposed within an opening of the receptable.

[0137] In some embodiments, the cap assembly (300) further comprises a stirrer (322) extending from the bottom of the body portion of the cap assembly.

[0138] Also provided herein are systems that comprise a cap assembly described above, a receptacle housing a fluid; a power supply; and a current loop operatively coupled to the first electrode, the second electrode, and the power supply.

[0139] In some examples, the current loop comprises: a resistor; and an ammeter configured to measure a current in the current loop which passes through the power supply, the resistor, the first electrode, and the second electrode. In some examples, the current loop comprises a volmeter configured to measure a voltage across the first electrode and the second electrode. In some examples, the current loop comprises a relay that can be used to interrupt the current loop circuit. For example, the relay can intermittently short out the first electrode and the second electrode. Alternatively, the relay can intermittently opens the loop circuit, interrupting current flow through the loop circuit.

[0140] In some embodiments, the resistor is chosen so that the power dissipation when the resistor alone is connected across the power supply, the following expression is satisfied Vo2 / R<Pmax, where Vois the amplitude of the voltage of of the power supply, R is the resistance of the resistor, and Pmaxis the minimum value of the maximum power dissipations permissible for the power source and associated circuit components.

[0141] In some embodiments of the systems described above, the system can further comprise a principal monitoring instrument configured to repeatedly interrogate the fluid, wherein the receptacle is reversibly insertable within the principal monitoring instrument. In certain embodiments, the receptacle is reversibly insertable within a sample holder disposed within the principal monitoring instrument.

[0142] In some embodiments, the principal monitoring instrument is chosen from a static light scattering detector, a dynamic light scattering detector, combined static and dynamic light scattering detector, a fluorimeter, an absorption spectrometer, a refractometer, a differential refractometer, a turbidity monitor, an NMR, a polarimeter, or a circular birefringence or dichroism detector. In some embodiments, the principal monitoring instrument can measure more than one property of the fluid. In some embodiments, the more than one property comprises static light scattering, dynamic light scattering, fluorescence, ultraviolet absorption, visible absorption, turbidity, circular dichroism, circular birefringence and infrared absorption.

[0143] In some embodiments, the principal monitoring instrument is configured to continuously interrogate the fluid. In some embodiments, the principal monitoring instrument is configured to interrogate the fluid at discrete intervals.

[0144] In some embodiments, the system is configured to apply an electric field that straddles path length of incident electromagnetic radiation emitted by a principal monitoring instrument.

[0145] In some embodiments, the receptacle has a perimeter is defined by a geometric shape chosen from square, rectangular, polygonal, hemi-polygonal, and circular. In certain embodiments, the receptacle comprises a 1 cm pathlength cuvette cell sized to be received within a sample holder of a spectrometer. In some embodiments, the receptacle is fabricated from a transparent material, such as quartz, glass, or a plastic.

[0146] In some embodiments, the fluid comprises a mixture of components.

[0147] In some embodiments, the fluid comprises a small molecule, a polymer, a colloid, or a combination thereof.

[0148] Methods of Use

[0149] Some example applications and methods of using the devices and systems described herein are included below.

[0150] 1) The device may be used in usage #1, directly measuring the conductance of the fluid between the electrodes using very low electric fields that do not affect the chemicals in the fluid contained in the receptacle. The measured conductance can also be used to determine the concentration of ions or charged particles in the fluid at any given instant, via a calibration curve of measured conductance versus ion or charged particle concentration. An example is given in Figure 26B.

[0151] 2) A further application of usage #1, involves the low E-field application of the device to measure conductance and / or conductivity of fluid 1 in a cell configured to evaluate membrane- mediated processes, which conductance can then be used to determine the concentration of electrolytes via a calibration curve. This avoids the need to infer the conductivity of the first fluid via recirculation of a much larger volume of a second fluid through an external conductivity meter. Furthermore, when the second fluid has high conductivity and the first fluid low conductivity, there is little decrease in conductivity of large volume the second fluid compared to a large change in conductivity of small volume first fluid, and hence gives very poor inference of first fluid conductivity. An example of the superior results obtained for conductance in fluid 1 measured directly byt the device, as compared to conductivity of fluid 2, is shown in Figure 26A.

[0152] 3) Proteins may denature and aggregate under applied electric fields, an example of which is seen in Figure 6. The device, in usage #2, provides a means of directly monitoring the sensitivity of protein denaturation, or other effects, to electric fields while (optionally) monitoring the conductivity. Voltage pulses are currently being used for preserving food instead of using chemicals or ionizing radiation. The device may aid in developing this technology, and may lead to routinely used devices.

[0153] 4) In terms of electric-field induced protein aggregation, some features of the robustness of therapeutic proteins may be determined by their response to electric field denaturation in usage #2. This could be of use in the biopharma / biotechnology sector, and might lead to Food and Drug Administration (FDA) criteria in drug approval. For example, membrane bound proteins can be subjected to large electric fields inside of membranes with imbalances of electrolytes on either side.

[0154] 5) Proteins may also degrade into fragments under applied electric fields in usage #2. This behavior is in sharp contrast to aggregation; i.e. in the case of fragmentation the molar mass measured by light scattering decreases, whereas molar mass increases when aggregation occurs. An example of degradation is shown in Figure 4.

[0155] 6) The behavior of DNA, RNA, vaccines, lipid nanoparticles, viruses, gene delivery vehicles under electric fields can be investigated in usage #2, along with any other synthetic or biological small molecules, macromolecules or colloids, including cell organelles and whole cells.

[0156] 7) Phenomena such as ionization under fields and dielectric breakdown of polymeric and colloidal materials can be investigated. Abrupt changes in I and veshould occur when these phenomena occur, and corresponding change in their structures will be monitored by the spectroscopic (and / or other) measuring instruments.

[0157] The devices, systems, and methods described herein can also be used to guide the formulation of biologic active agents (e.g., biologic drugs) to find concentration regimes of specific formulation components over which the biologic drug formulation is stable. For example, not limiting, the stability of a biologic drug, such as a monoclonal antibody, over a range of concentrations of formulation components can be determined, including pH ranges. These formulation components can include, but are not limited to, electrolytes of different valences and symmetries -e.g. NaCl (monovalent, symmetric), MgCF (asymmetric with divalent cation), MgSC (symmetric divalent)- surfactants, and any other additives, excipients, and stabilizers.

[0158] In some embodiments, the devices and systems described herein can be used to measure the conductance of the fluid. In certain embodiments, the concentration of one or more electrolytes in the fluid is determined from the measured conductance of the fluid, for example, via a calibration curve or table.

[0159] In some embodiments, the devices and systems described herein can be used to measure a concentration of an electrolyte in the fluid. In certain embodiments, the devices and systems described herein can be used to to measure a pH of the fluid.

[0160] In some embodiments, the devices and systems described herein can be used to to apply an electric field within a fluid. Optionally, the fluid (and components within the fluid) can be interrogated with a principle monitoring instrument before, during, and / or after application of the electric field within a fluid present in the receptacle.

[0161] In the cases of devices and systems described above where electrodes are positioned external to the receptacle, such devices and systems can only be used for usage #2, i.e., to produce an electric field inside of the receptacle but with no ionic or current flow. In these embodiments, operation of devices and systems change from a situation with a circuit with current flowing to a purely electrostatic situation, with no charge flow, which makes it quite different from usage #1 where there is a complete circuit and ionic and electron current flow.

[0162] External electrodes cannot be used for usage #1, but can be for usage #2. In the case of external electrodes there will be an electric field in the two walls of the receptacle, Er, (ignoring fringe E- fields on the parallel sides of the receptacle), and in the solution Escontained within the receptacle.

[0163] The electrostatic situation can be represented as shown in Figure 31 where Vo= voltage of the source; rms voltage for a.c. source; Er= E-field in the receptacle wall; Es= E-field in the solution, the E-field that affects the sample being monitored; ec= permeability of cuvette wall; es= permeability of solution; L=total length of receptacle; and d / 2= thickness of receptacle wall.

[0164] Es, the field inside the sample solution within the receptacle is the principal quantity of interest, as this affects the sample being monitored. The effect of the wall of the receptacle on Esis straightforward to find (ignoring fringe fields).

[0165] Fo= ES(E - d) + Erd

[0166] The continuity of the displacement field, D, at the interface requires

[0167] E)r= Ds= srEr= ESESwhich yields where Ksand Krare the dielectric constants of the solution and receptacle, respectively.

[0168] By way of example, in a typical case, ks~80 (water) and kr~4 (Typical glass, quartz, and transparent plastic). For this situation, — Kr~20.

[0169] Furthermore, for a typical cuvette receptacle, L~ 1.2cm, d~0.2cm, and typical voltage

[0170] Vo=lOV. Then, 1 + 20 . 0.2

[0171] In this case Esis smaller than it would be without the receptacle walls Es,nOreceptacie=8.3 V / cm. So for a typical 1cm (i.d.) cuvette made of glass, quartz, or plastic, Esis reduced by approximately a factor of four, compared to when there are no such walls and the fluid has length L.

[0172] Generally, the ratio of Esto the E-field with no walls, d=0, Es,no wails

[0173] From this, Eshas the following regimes

[0174] While — K > 1 when the solution is aqueous and the receptacle made of typical glass, r quartz, or plastic, the four-fold reduction is generally not a serious issue, as Vocan simply be replaced by a higher voltage. Strategies for making Es> Es no waiis include using liquids of lower K (e.g. k=24.3, 7.6, 2.4 for ethanol, tetrahydrofuran, and toluene, respectively), or decreasing the receptacle wall thickness d. Another strategy is to make the length of the fluid in the receptacle L-d shorter, e.g. by having thicker walls of the receptacle, or at least thicker where the electrodes reside. Another means would be with the receptacle having its wall portions abutting the electrode to be made of windows of high dielectric material. For example, K is approximately 100, 300, and 5000 for TiCh , SrTiCh, BaTiCh, respectively. The limit of increase £ of -5- for high wall thickness and / or high K is L / (L-d). s,no walls

[0175] In some examples, provided herein are methods for monitoring the effect of an applied electric field on a chemical component present in a fluid. These methods can comprise introducing the fluid comprising the chemical component into a receptacle; positioning a cap assembly within the receptacle, wherein the cap assembly comprises: a body portion insertable within an opening of the receptacle; an electrode support extending from a bottom of the body portion; and a first electrode and a second electrode disposed on the electrode support; wherein the first electrode and the second electrode are each electrically connected to a terminal disposed on the body portion; and wherein the electrode support is dimensioned such that when the cap assembly is disposed within the receptacle, the electrode support extends into the receptacle such that the electrodes are in contact with the fluid present within the receptacle; operatively coupling the cap assembly to a power supply and a current loop, wherein the current loop comprises: a resistor; a voltmeter configured to measure a voltage across the first electrode and the second electrode; and an ammeter configured to measure a current in the current loop which passes through the power supply, the resistor, the first electrode, and the second electrode; inserting the receptacle into a principal monitoring instrument; and repeatedly interrogating the fluid with the principal monitoring instrument while applying an electric field that straddles path length of incident electromagnetic radiation emitted by the principal monitoring instrument.

[0176] In some examples, the method comprises monitoring a change in one or more properties of the fluid using the principal monitoring instrument while varying a characteristic of the applied electric field. In certain examples, the principal monitoring instrument is chosen from a static light scattering detector, a dynamic light scattering detector, combined static and dynamic light scattering detector, a fluorimeter, an absorption spectrometer, a refractometer, a differential refractometer, a turbidity monitor, an NMR, a polarimeter, or a circular birefringence or dichroism detector.

[0177] In some examples, provided herein are methods for monitoring the conductance of a fluid. These methods can comprise introducing the fluid comprising the chemical component into a receptacle; positioning a cap assembly within the receptacle, wherein the cap assembly comprises: a body portion insertable within an opening of the receptacle; an electrode support extending from a bottom of the body portion; and a first electrode and a second electrode disposed on the electrode support; wherein the first electrode and the second electrode are each electrically connected to a terminal disposed on the body portion; and wherein the electrode support is dimensioned such that when the cap assembly is disposed within the receptacle, the electrode support extends into the receptacle such that the electrodes are in contact with the fluid present within the receptacle; operatively coupling the cap assembly to a power supply and a current loop, wherein the current loop comprises: a resistor; a voltmeter configured to measure a voltage across the first electrode and the second electrode; and an ammeter configured to measure a current in the current loop which passes through the power supply, the resistor, the first electrode, and the second electrode; inserting the receptacle into a principal monitoring instrument; and interrogating the fluid with the principal monitoring instrument; and measuring a conductance of the fluid.

[0178] In these methods, the voltmeter can be used to measure voltage across the electrodes while the ammeter is used to measure current in the loop circuit. This allows for determination of the circuit resistance, and its reciprocal, the conductance. If desired, the conductance can be used to calculate the concentration of electrolyte(s) present in a fluid in the receptacle, for example, via a calibration curve or lookup table. If desired, the conductance measured can be converted to the conductivity of the solution in the receptacle using a calibration curve from conductivity data obtained from a commercial conductivity meter, or from conductivity data from sources such as National Institute of Science and Technology, the CRC Handbook, or other sources.

[0179] Examples of biologic active agents include, but are not limited to, Adalimumab (sold under the trade name Humira), Rituximab (sold under the trade name Rituxan), Etanercept (sold under the trade name Enbrel), Trastuzumab (sold under the trade name Herceptin), Bevacizumab (sold under the trade name Avastin), Infliximab (sold under the trade name Remicade), Insulin glargine injection (sold under the trade name Lantus), Pegfilgrastim (sold under the trade name Neulasta), Interferon beta-la (sold under the trade name Avonex), Ranibizumab (sold under the trade name Lucentis), insulin, glucagon, interferons, interleukins, hormones, blood factors, recombinant proteins (e.g. erythropoietin), fusion proteins (alefacept), lipid nanoparticles, viral capsids and other gene therapy delivery agents, classical viral vaccines, polysaccharide conjugate vaccines, and mRNA / lipid nanoparticle vaccines.

[0180] EXAMPLES

[0181] The devices, systems, and methods will be described in greater detail by way of certain specific examples described below. The following examples are offered for illustrative purposes, and are not intended to limit the invention in any manner. Those of skill in the art will readily recognize a variety of non-critical parameters which can be changed or modified to yield essentially the same results.

[0182] In order to obtain an essentially spatially uniform electric field, a device was fabricated that held two flat electrode plates. Both silver and platinum were used in prorotyping, as well as a variety of dimensions and plate separation. For example, silver electrode sheets 5mm x 5mm were fabricated and separated by 3mm. These dimensions are not limiting, rather, they were just selected for one of the many prototypes designed and tested. The 3mm separation was sufficient to let through the probe beam for the various spectroscopic devices which can accommodate the cuvette device. Additionally, the electrode sheets are configured such that light passing through the sample solution between them can be detected at 90 degrees, at 0 degrees (i.e., directly intercepting the incident beam path), and at low angles up to 30 degrees, and angles less than 180 degrees (backscatter) down to 150 degrees. The electrodes can exist horizontally, vertically, or at a specified angle within the receptacle. When the electrodes are vertical on or more apertures can be made in one electrode to allow detecting light at 90° and other angles.

[0183] The device and associated methods are targeted for use in fluids containing chemicals and has two main capabilities:

[0184] 1) Usage #1 : Directly monitoring the electrical conductivity of the fluid containing chemicals, usually with the goal of converting the conductivity into an ion concentration, via a calibration curve, and

[0185] 2) Usage #2: Monitoring behaviors and properties of the chemicals that can be influenced by an electric field. The conductivity can be measured i) when the electric field is high enough to influence chemical properties and ii) at very low electric field, in order to measure conductivity where there is no electric field influence on any chemicals present.

[0186] Flat-electrode cuvette devices, with either silver or platinum electrodes, were fabricated from a polymer using a 3D printer and calibrated to yield absolute conductivity, by measuring the resistance of the device (in Ohms) when filled with aqueous solutions with varying concentrations of NaCl, then taking the reciprocal of this resistance to find the conductance (in Siemens), and then comparing this conductance with the conductivity of the solutions (in mS / cm), obtained by a calibrated, commercial conductivity instrument, to find the calibration factor, CF, between the conductance of the flat electrode cuvette and the absolute conductivity provided by the commercial instrument. The resistance was obtained by measuring the current flowing through the circuit, I, with an ammeter, under a constant a.c. voltage source of 6.3 V, 12.6 V (RMS value), or less than 0.1 V. Frequencies for the latter ranged from 60Hz to lOOKHz. The voltage across the electrodes, Vc, was also measured and the resistance of the electrode assembly, including the solution between the electrodes, RC=VC / I was computed. Residual resistance from wires and electrodes when the electrodes were shorted was subtracted from this resistance to obtain the resistance Re, due to the saline solution between the electrodes.

[0187] Figure 1 A shows the raw conductance (1 / Re) of the flat-electrode cuvette on the righthand axis and the conductivity of the solution, obtained by a Thermo Orion Star A215 conductivity instrument on the right-hand axis.

[0188] Figure IB shows how the flat-electrode conductance data (in Siemens) is turned into absolute conductivity (in mS / cm) by multiplying the conductance by CF=430. Conductivity from each instrument is plotted on the same scale on the left-hand axis of Figure IB.

[0189] While flat, parallel electrodes are optimal for creating spatially uniform electric fields, in some instances non- flat electrodes for other field patterns may be used. As an example, if cylindrical electrodes are used (e.g., wires or cylinders rather than flat metal sheets) the electric field will be concentrated around the electrodes and weaken and become non-uniform between them.

[0190] The frequency of the a.c. voltage or current sources may vary, as well as the shape. The effect of varying frequency and shape on the response of macromolecules may be a research dimension in itself. In other cases, D.C. voltage or current sources may be useful, especially where electrophoretic motion may be important.

[0191] Figure 2 shows a photo of the flat silver electrode device inside a 1 cm standard cuvette. The electrodes can be seen in the clear 3 mm space towards the bottom of the cuvette. Each electrode is attached to a platinum wire which rise through holes in the grey body and are attached to copper plates for connection into the complete circuit.

[0192] Figure 3 shows the electrode assembly in the cuvette attached in series in the circuit containing the 48 Ohm safety resistor Rsafety, the 12.6V a.c. power supply and connections to the ammeter and voltmeter (neither seen in the photo)

[0193] Calibration considerations

[0194] There are several means of calibrating the device. One, illustrated in Figures 1A and IB, calibrates measured conductance against conductivity of an electrolyte, such as NaCl, obtained by a commercial conductivity meter. Literature values of conductivity of electrolytes in solution at STP could also be used for calibration. There is, however, considerable discrepancy in conductivity values for electrolytes in solution at STP. Figure 1C shows data for NaCl conductivity in aqueous solution from two authoritative sources; CRC Handbook and the National Institute of Science and Technology (NIST). Also shown in the graph is the percentage deviation of the values between the two sources. The deviations from each other run from -5% to nearly 25%.

[0195] In fact, the invention here does not require knowledge of absolute conductivity for one of the main applications in usage #1 ; i.e. for determining concentration of electrolytes in fluid 1. The measured conductance in this application is a means to determine electrolyte concentration, via a calibration curve. In light of this, as well as the above mentioned discrepancies between conductivity measurements from authoritative sources, self-calibration of the electrodes is an attractive approach. For any given electrode device its response is calibrated against the concentration of an electrolyte. For example, not limiting, an electrode device is calibrated by measuring the resistance (and the conductance by taking its reciprocal) across the electrodes of a series of a given electrolyte at different concentrations (This involves measuring the voltage across the electrodes and current through the loop circuit). Using these data, or finding an empirical equation (e.g. single or double exponential) relating measured conductance to electrolyte concentration, establishes a calibration curve for when the device is used to measure concentration of that electrolyte when monitoring processes, such as, but not limited to, dialysis. An example of such a calibration curve is shown in Figure 26B, which allowed converting the conductance of fluid 1 into the concentration of NaCl in fluid 1, as NaCl entered fluid 1 from fluid 2 via dialysis.

[0196] In the case of usage #2, where the device is used to apply electric fields to molecules in solution to monitor the effects of the fields, knowledge of the electrolyte concentration or solution conductivity are not chief concerns. Rather, it is the electric field strength that is the physical characteristic of interest, and this is well approximated by the voltage across the electrode divided by the distance between the electrodes. Furthermore, most experiments that are run for monitoring electric field effects will have known, fixed solution conditions, such as pH, buffer type (if any), and electrolyte and other concentrations.

[0197] Usage #1: Use of the Device at for Measuring Conductivity at Very Low Currents

[0198] Frequently, the conductivity of the cell contents will need to be known, but without the electric field between the electrodes measurably influencing the behavior of chemicals in solution. For this, Rvcan be set very high, so that only milliamps, or less, of current flow through the cell. In Figure 7, Rv=l 14,230 Ohms. Figure 7 shows the conductivity measured for solutions of varying [NaCl], calibrated against the Thermo Orion Star A215 conductivity instrument. Figure 7B shows the essentially steady current of 120 micoamps during the calibration procedure at a single [NaCl] concentration. Usage #1: Use of the Device for Measuring Conductance and Electrolyte Concentration During Dialysis

[0199] An important application of the device is to measure conductance and electrolyte concentration in Fluid 1 during dialysis. Figure 26A shows the Conductance (Ithrough circuit / Vacross electrodes, in 1 / Ohms) in Fluid 1 on the right-hand y-axis when it initially contains pure water and Fluid 2 contains aqueous 5M [NaCl], where Fluid 1 and 2 are separated by a Sigma- Aldrich D9277, cellulose, molecular weight cutoff ~14kDalton dialysis membrane. The left-hand y-axis is the absolute value of the conductivity in Fluid 2 minus the initial value of 235.2, where the conductivity was measured by a Thermo Scientific Orion Star A212 commercial conductivity meter. This representation is shown, rather than the dropping value of the conductivity in Fluid 2 (NaCl is passing from Fluid 2 to Fluid 1 through the membrane, reducing conductivity in Fluid 2), in order to directly compare the performance of the electrode device in Fluid 1 with the conductivity in Fluid 2. The agreement is quite good up until about 2,000s, after which the commercial meter hits the limit of its resolution, and its data become unreliable. The data from the electrode device is clearly smoother and less noisy than the data from the commercial device. This is expected since the volume in fluid 1 is much smaller than in fluid 2, so the change in conductance in fluid 1 is much greater than in fluid 2. At this time there is no commercially available conductivity measuring device which fits into fluid 1. The electrical conditions for the dialysis test were: 6.3V a.c., 48 ohm load resistor, voltmeter across the electrodes, current meter in the single loop circuit, current ranged from -30- 100mA during the dialysis, and a Phidgets REL2103 solid state relay with Phidgets HUB0007_0 1-port VINT hub relay controller was used to short the electrodes for a period of 50s and unshort the electrodes for 10s to obtain the current and voltage readings. This ensured drift-free operation of the electrode device. Fluid 1 was stirred by a non-contact stirring device integral to the cuvette device cap and driven by a Motor- Phidgets 3316 unipolar stepper motor, controlled by a Phidgets 1067_OB Bipolar HC. The relay and motor controllers were operated with custom written programs in Python.

[0200] Figure 26B shows the calibration curve for the electrode device, using a series of NaCl concentrations in water. The curve plots the know value of [NaCl] versus the measured conductance. It was found that an empirical double exponential fit captured all the data, with the equation

[0201] [NaCl](mM~) = 42.259e76733C+ 1.454xl0“15e697'6CWhere C is the measured conductance.

[0202] Figure 26C shows the concentration of NaCl in Fluid 1 during the dialysis, obtained from the conductance data of Figure 26 A and the above transformation equation from Figure 26B. Source of electrode current and voltage drifts

[0203] Sometimes, even with high frequency a.c. voltages, the electrode properties can change in time, such that their resistance and capacitance drift over time. An example of drifing voltage across the electrodes and current in the circuit is shown in Figure 25A. Several factors can lead to such drifts, including; polarization of the electrodes, formation of electrical double layers around the electrodes, corrosion, oxidation, various electrochemical reactions, adsorption of ions onto electrode surfaces, electrochemical deposition, electrode fouling, and temperature drift.

[0204] Specifically, the resistance and capacitance of the electrodes can change over time due to these processes. As such, the electrode assembly is more complex than simply a resistor, whose resistance is determined by the concentration of electrolyte in solution The electrodes have an inherent capacitance, Ce, that of a parallel plate capacitor in a dielectric medium, given by

[0205] Ce= Ds0A / d where D is the dimensionless dielectric constant of the liquid medium, E0is the permittivity of free space (8.85xl012N-nr / C2), A is the area of each plate, and d their separation. There are additional effects due to shielding due to ionic strength. Consider an example pair of electrodes in water: D~80, A=36mm2=3.6xl0"5m2, d=3mm=0.003m. This gives

[0206] Ce~8.5%10-12F

[0207] This is an extremely small capacitance, and no measurable effects from it are expected. However, with the above mentioned factors the net capacitance C can change in time, C=C(t), which may lead to measurable effects. The capacitive reactance Xc (ohms) is where f is the a.c. source frequency in Hz.

[0208] The resistance is the sought after resistance of the solution Rs, which is used to find the conductivity of the solution, plus any resistance that accumulates in time, Re,v(t) due to processes at the electrodes (e.g. a double layer or an adsorbed layer) so that the net electrode resistance, Re.totai(t) is the sum

[0209] Re.total(t) = RS+ Re,v t)

[0210] So, the electrode circuit is a time-changing (variable) capacitor in parallel with a time-changing (variable) resistor. The net electrode resistance, Rnet,e(t) is that of this parallel combination: Hence, Re.net(t) can increase or decrease in time, and not necessarily monotonically. If Rs+ Re,v(O » 2?r / 'C(t), then Re,net(t) will increase in time. If the capacitive term is on the order of the resistive term the Rnet,e(t) may decrease in time. If C(t) and Re,v(t) both increase in time, then the effects on Re.net(t) are countervailing, with the resistive term increasing it and the capacitive term decreasing it.

[0211] An equivalent circuit is shown in Figures 25A-C, which show the possibly drifting capacitance and resistance of the electrodes as Ce,v(t) and Re,v(t).

[0212] Normally, the effects of the capacitive term and Re,v.(t) are small compared to Rs, the desired measurement, so that they can be ignored. However, the next section addresses a method for reducing or eliminating these effects, when present to a degree as to affect Rnet,e.

[0213] Eliminating electrode polarization effects

[0214] Some times, even with high frequency a.c. voltages, the electrode properties can drift in time, such that their resistance and capacitance drift over time. An example is shown in Figure 25 A, where the drift in voltage across the electrodes and current through them is shown, with the resistance (V / I) in the inset. The conditions are 6.3V a.c., 60 Hz, a load resistor of 48 ohms, 500mM KNO3 solution, Ag electrodes.

[0215] Figure 25B shows data under the same conditions except that the electrodes are shorted out by a relay for 24s and opened 6s to permit current to flow. This gives a 30s cycle time. The relay is a programmable Phidgets REL2103 solid state relay. This has the effect of eliminating the drift of I and V, and hence also R, by allowing the electrodes to be brought to equal electric potential during the shorting process. This can interrupt electrode polarization, double layers, adsorption, and some of the other effects mentioned.

[0216] The durations of on / off cycles using a relay are entirely flexible, and the particular intervals used in this latter example are in no way limiting.

[0217] Other means to reduce or eliminate electrode polarization and drift include, but are not limited to; use of coatings on electrodes, such as Titanium nitride (TiN) an oxide (TiO2), and other oxides, such as those of iridium, zinc, and ruthenium. Carbon-based electrodes, such as carbon nanotubes. Various polymer coatings. Also, the use of Pt and Au electrodes provides more inert surfaces. Surface roughening.

[0218] Experimental Demonstration of Device’s Ability to Simultaneously Measure the

[0219] Effect of the Electric Field on Macromolecules (usage #2) and Conductance of the Solution Containing the Macromolecules (usage #1)

[0220] The flat electrode cuvette device was tested using a 12.6 Volt, 60Hz A.C. power supply, and the effects of the corresponding electric field between the electrodes on two proteins, immunoglobulin (IgG) and chymotrypsynogen, were monitored using total intensity static light scattering in an Argen light scattering instrument (Fluence Analytics, New Orleans, Lousiana).

[0221] The effect of electric fields at 3.7 V / cm and 2.1 V / cm on the protein immunoglobulin (IgG) are shown in Figure 4. The electric field causes the IgG’s molar mass to degrade, indicating that the electric field is fragmenting the protein. Also shown in Figure 4 are single exponential fits of the degradation. The higher electric field causes faster degradation of the IgG.

[0222] Vnet.e and I were recorded simultaneously, using one Fluke 289 recording multimeter for Vnet,e and a second Fluke 289 recording multimeter for I. The conductivity of the IgG solution is found according to the above calibration procedure. Namely, the cell resistance Rnet,e=Ve / I is computed, and its reciprocal, the conductance is multiplied by the above-determined calibration factor of CF=430.

[0223] Figure 5 shows I and conductivity for the experiment with Rv=667 Ohms (held constant). The current is essentially constant, and the conductivity is constant to within <1%. This is an important demonstration that there is no significant Joule heating in the cell, as the conductivity would rise notably for any increase in temperature; i.e. the aggregation of the protein is being caused by the electric field due to the voltage, and not due to any heating. Similarly constant values of I and Vc, and hence conductivity, were found for the other experiments.

[0224] In these experiments the current flowing through the cell containing the electrodes is on the order of 10-20 milliamps. Below, data are shown for the device with non-perturbing electric fields, and microampere currents, used when the conductivity of the cell contents is to be measured, while not affecting the chemicals in solution.

[0225] The electric field, E, between the flat electrodes is essentially constant and given by

[0226] Ve

[0227] E= ~ a where d is the separation of the flat electrodes. Table 1 below summarizes electrical parameters of the two experiments.

[0228] Table 1. Electrical parameters for IgG degradation under applied a.c. voltage. [IgG]=0.002 g / cm3, lOOmM NaCl. Figure 6 demonstrates how a 51 V / cm electric field causes aggregation of the protein chymotrypsinogen. The aggregation of chymotrypsinogen under an electric field contrasts with the degradation under electric field of IgG, shown above. The behavior of different proteins under electric fields may be correlated to their secondary and tertiary structure, and their stability and behavior under other stressors, such as temperature, mechanical stress, and changes in solution conditions, such as pH, ionic strength, electrolyte valence, excipients, etc.

[0229] Also shown in Figure 6 is the demonstration that without an applied electric field the Chymotrysinogen remains stable.

[0230] Use of the electrode device to measure the pH of fluid 1

[0231] The electrode device, via conductance measurements of fluid 1 and a calibration curve, can determine the concentration of ions in a solution. A determination of pH can be obtained in fluid 1 by calibrating conductance of the cell against concentration of the acid or base, which in turn can be directly converted to pH. Acids or bases to be used include, but are not limited to, HC1, HNO3, H2SO4, HCLO4, NaOH, KOH, LiOH. Figure 28 shows the concentration of HC1, [HC1], which can be determined from measured conductance, and the calibration between conductance and [HC1], which is determined by measuring conductance of fluid 1. pH is then related to [HC1] via pH=-logio([H+).

[0232] The pH in fluid 1 can change due to many factors. For example, when the electrode device is used in conjunction with the dialysis cap assembly, acids or bases can be dialyzed into fluid 1 to monitor the behavior of macromolecules or colloids as pH changes. Buffer at a given pH in fluid 2 could also be dialyzed into fluid 1 at a given pH in the same or different pH. The electrodes can determine the pH via the conductance measurements so that data on the changes in the macromolecules or colloids, e.g. molar mass, polydispersity, size, can be represented versus pH, as well as versus time. In other cases, reactions can occur in fluid 1 which can change the pH.

[0233] The devices, systems, and methods of the appended claims are not limited in scope by the specific devices, systems, and methods described herein, which are intended as illustrations of a few aspects of the claims. Any devices, systems, and methods that are functionally equivalent are intended to fall within the scope of the claims. Various modifications of the devices, systems, and methods in addition to those shown and described herein are intended to fall within the scope of the appended claims. Further, while only certain representative compounds, components, compositions, and method steps disclosed herein are specifically described, other combinations of the compounds, components, compositions, and method steps also are intended to fall within the scope of the appended claims, even if not specifically recited. Thus, a combination of steps, elements, components, or constituents may be explicitly mentioned herein or less, however, other combinations of steps, elements, components, and constituents are included, even though not explicitly stated. The term “comprising” and variations thereof as used herein is used synonymously with the term “including” and variations thereof and are open, non-limiting terms. Although the terms “comprising” and “including” have been used herein to describe various embodiments, the terms “consisting essentially of’ and “consisting of’ can be used in place of “comprising” and “including” to provide for more specific embodiments of the invention and are also disclosed. Other than where noted, all numbers expressing geometries, dimensions, and so forth used in the specification and claims are to be understood at the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, to be construed in light of the number of significant digits and ordinary rounding approaches.

[0234] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of skill in the art to which the disclosed invention belongs. Publications cited herein and the materials for which they are cited are specifically incorporated by reference.

Claims

WHAT IS CLAIMED IS:

1. A device comprising an electrode assembly dimensioned to be received within a receptacle, wherein the electrode assembly comprises: an electrode support insertable within an opening of a receptacle; and a first electrode and a second electrode disposed on the electrode support; wherein the first electrode and the second electrode are each electrically connected to an electrical lead extending outside of the receptacle when the electrode assembly is positioned within the receptacle.

2. The device of claim 1 , wherein the electrode assembly is dimensioned such that when the electrode assembly is disposed within the receptacle, the electrodes are positioned in electrochemical contact with a fluid present within the receptacle.

3. The device of any of claims 1-2, wherein the electrode support, the first electrode, and the second electrode are dimensioned to allow for right angle (90°) detection when the electrode assembly is seated in a receptacle and positioned within a principal monitoring instrument.

4. The device of any of claims 1-2, wherein the electrode support, the first electrode, and the second electrode are dimensioned to allow for zero angle to low angle detection (0° to 30°) when the electrode assembly is seated in a receptacle and positioned within a principal monitoring instrument.

5. The device of any of claims 1-4, wherein the electrode support, the first electrode, and the second electrode are dimensioned to allow for transmission of incident electromagnetic radiation and backscatter detection (at angled of from 150° to 180°) when the electrode assembly is seated in a receptacle and positioned within a principal monitoring instrument.

6. The device of any of claims 1-5, wherein the first electrode and the second electrode comprise parallel plate electrodes.

7. The device of any of claims 1-5, wherein the first electrode and the second electrode comprise parallel wire mesh electrodes.

8. The device of any of claims 1-7, wherein the first electrode and the second electrode are sized and positioned to generate an electric field between them, through which the incident electromagnetic radiation emitted by a principal monitoring instrument passes when the electrode assembly is seated in a receptacle and positioned within the principal monitoring instrument.

9. The device of any of claims 1-8, wherein the first electrode and the second electrode are separated by a distance of 10 mm or less, such as a distance of from 2 mm to 5 mm.

10. The device of any of claims 1-9, wherein the electrode assembly is sized to be received within a 1 cm pathlength cuvette cell.

11. A system comprising a receptacle housing a fluid; a device defined by any one of claims 1-10; a power supply; and a current loop operatively coupled to the first electrode, the second electrode, and the power supply.

12. The system of claim 11, wherein the current loop comprises: a resistor; and an ammeter configured to measure a current in the current loop which passes through the power supply, the resistor, the first electrode, and the second electrode.

13. The system of any one of claims 11-12, wherein the current loop comprises a volmeter configured to measure a voltage across the first electrode and the second electrode.

14. The system of any one of claims 11-13, wherein the current loop comprises a relay that can be used to interrupt the current loop circuit.

15. The system of claim 14, wherein the relay intermittently shorts out the first electrode and the second electrode.

16. The system of claim 14, wherein the relay intermittently opens the loop circuit, interrupting current flow through the loop circuit.

17. A device comprising an electrode assembly dimensioned to receive a receptacle therewithin, wherein the electrode assembly comprises: an electrode support dimensioned to house the receptacle therewithin; and a first electrode and a second electrode disposed on the electrode support; wherein the first electrode and the second electrode are each electrically connected to an electrical lead or terminal.

18. The device of claim 17, wherein the electrode support, the first electrode, and the second electrode are dimensioned to allow for right angle (90°) detection when the receptacle is seated in the electrode assembly and the assembly is positioned within a principal monitoring instrument.

19. The device of any of claims 17-18, wherein the electrode support, the first electrode, and the second electrode are dimensioned to allow for zero angle to low angle detection (0° to 30°) when the receptacle is seated in the electrode assembly and the assembly is positioned within a principal monitoring instrument.

20. The device of any of claims 17-19, wherein the electrode support, the first electrode, and the second electrode are dimensioned to allow for transmission of incident electromagnetic radiation and backscatter detection (at angled of from 150° to 180°) when the receptacle is seated in the electrode assembly and the electrode assembly is positioned within a principal monitoring instrument.

21. The device of any of claims 17-20, wherein the first electrode and the second electrode comprise parallel plate electrodes.

22. The device of any of claims 17-20, wherein the first electrode and the second electrode comprise parallel wire mesh electrodes.

23. The device of any of claims 17-22, wherein the first electrode and the second electrode are sized and positioned to generate an electric field between them, through which the incident electromagnetic radiation emitted by a principal monitoring instrument passes when the receptacle is seated in the electrode assembly and the electrode assembly is positioned within a principal monitoring instrument.

24. The device of any of claims 17-23, wherein the first electrode and the second electrode are separated by a distance of 1.5 cm or less, such as a distance of from 1 cm to 1.5 cm.

25. The device of any of claims 17-24, wherein the electrode assembly is sized to receive there within a 1 cm pathlength cuvette cell.

26. A system comprising a receptacle housing a fluid; a device defined by any one of claims 17-25; a power supply; and a current loop operatively coupled to the first electrode, the second electrode, and the power supply.

27. The system of claim 26, wherein the current loop comprises: a resistor; and an ammeter configured to measure a current in the current loop which passes through the power supply, the resistor, the first electrode, and the second electrode.

28. The system of any one of claims 26-27, wherein the current loop comprises a volmeter configured to measure a voltage across the first electrode and the second electrode.

29. The system of any one of claims 26-28, wherein the current loop comprises a relay that can be used to interrupt the current loop circuit.

30. The system of claim 29, wherein the relay intermittently shorts out first electrode and the second electrode.

31. The system of claim 29, wherein the relay intermittently opens the loop circuit, interrupting current flow through the loop circuit.

32. A device comprising a cap assembly dimensioned to be received within a receptacle, wherein the cap assembly comprises: a body portion insertable within an opening of the receptacle; and a first electrode and a second electrode in contact with a fluid present within the receptacle when the cap assembly is disposed within the receptacle; wherein the first electrode and the second electrode are electrically connected to a terminal or terminals present outside of the receptacle when the cap assembly is disposed within the receptacle.

33. The device of claim 32, wherein the first electrode and the second electrode are disposed on an electrode support extending from a bottom of the body portion of the cap assembly.

34. The device of claim 33, wherein the electrode support is dimensioned such that when the cap assembly is disposed within the receptacle, the electrode support extends into the receptacle such that the electrodes are in contact with a fluid present within the receptacle.

35. The device of any one of claims 32-34, wherein the terminal or terminals disposed on the body portion of the cap assembly.

36. The device of any of claims 32-35, wherein the first electrode, the second electrode, and the electrode support (when present) are dimensioned to allow for right angle (90°) detection when the cap assembly is seated in a receptacle and positioned within a principal monitoring instrument.

37. The device of any of claims 32-35, wherein the first electrode, the second electrode, and the electrode support (when present) are dimensioned to allow for zero angle to low angle detection (0° to 30°) when the cap assembly is seated in a receptacle and positioned within a principal monitoring instrument.

38. The device of any of claims 32-37, wherein the first electrode, the second electrode, and the electrode support (when present) are dimensioned to allow for transmission of incident electromagnetic radiation and backscatter detection (at angled of from 150° to 180°) when the cap assembly is seated in a receptacle and positioned within a principal monitoring instrument.

39. The device of any of claims 32-38, wherein the first electrode and the second electrode comprise parallel plate electrodes.

40. The device of any of claims 32-38, wherein the first electrode and the second electrode comprise parallel wire mesh electrodes.

41. The device of any of claims 32-40, wherein the first electrode and the second electrode are sized and positioned to generate an electric field between them, through which the incident electromagnetic radiation emitted by a principal monitoring instrument passes when the cap assembly is seated in a receptacle and positioned within the principal monitoring instrument.

42. The device of any of claims 32-41, wherein the first electrode and the second electrode are separated by a distance of 10 mm or less, such as a distance of from 2 mm to 5 mm.

43. The device of any of claims 32-42, wherein the cap assembly is sized to be received within a 1 cm pathlength cuvette.

44. The device of any of claims 32-43, wherein the cap assembly further comprises: a post extending from a bottom of the body portion, wherein the post is configured for attachment of a membrane; and a first fluid inlet and a first fluid outlet fluidly disposed on the body portion and fluidly extending to the post so as to fluidly connect to a fluid sample present within a membrane affixed to the post.

45. The device of claim 44, wherein the cap assembly further comprises a second fluid inlet and a second fluid outlet fluidly disposed on the body portion and fluidly extending to the bottom of the body portion as to fluidly connect to a fluid sample present within the receptacle when the cap assembly is disposed within an opening of the receptacle.

46. The device of any of claims 32-45, further comprising a stirrer extending from the bottom of the body portion of the cap assembly.

47. A system comprising a receptacle housing a fluid; a cap assembly dimensioned to be received within the receptacle, wherein the cap assembly comprises: a body portion insertable within an opening of the receptacle; and a first electrode and a second electrode in contact with the fluid present within the receptacle when the cap assembly is disposed within the receptacle; wherein the first electrode and the second electrode are electrically connected to a terminal or terminals present outside of the receptacle when the cap assembly is disposed within the receptacle a power supply; and a current loop operatively coupled to the first electrode, the second electrode, and the power supply.

48. The system of claim 47, wherein the current loop comprises: a resistor; and an ammeter configured to measure a current in the current loop which passes through the power supply, the resistor, the first electrode, and the second electrode.

49. The system of any one of claims 47-48, wherein the current loop comprises a volmeter configured to measure a voltage across the first electrode and the second electrode.

50. The system of any one of claims 47-49, wherein the current loop comprises a relay that can be used to interrupt the current loop circuit.

51. The system of claim 50, wherein the relay intermittently shorts out first electrode and the second electrode.

52. The system of claim 50, wherein the relay intermittently opens the loop circuit, interrupting current flow through the loop circuit.

53. The system of claim 48-52, wherein the resistor is chosen so that the power dissipation when the resistor alone is connected across the power supply, the following expression is satisfiedVo2 / R<Pmax, where Vois the amplitude of the voltage of of the power supply, R is the reisistance of the resistor, and Pmax is the minimum value of the maximum power dissipations permissible for the power source and associated circuit components.

54. The system of any of claims 47-53, wherein the first electrode, the second electrode, and the electrode support (when present) are dimensioned to allow for right angle (90°) detection when the assembly is seated in the receptacle and positioned within a principal monitoring instrument.

55. The system of any of claims 47-53, wherein the first electrode, the second electrode, and the electrode support (when present) are dimensioned to allow for zero angle to low angle detection (0° to 30°) when the cap assembly is seated in the receptacle and positioned within a principal monitoring instrument.

56. The system of any of claims 47-55, wherein the first electrode, the second electrode, and the electrode support (when present) are dimensioned to allow for transmission of incident electromagnetic radiation and backscatter detection (at angled of from 150° to 180°) when the cap assembly is seated in the receptacle and positioned within a principal monitoring instrument.

57. The system of any of claims 47-56, wherein the first electrode and the second electrode comprise parallel plate electrodes.

58. The system of any of claims 47-56, wherein the first electrode and the second electrode comprise parallel wire mesh electrodes.

59. The system of any of claims 47-58, wherein the first electrode and the second electrode are sized and positioned to generate an electric field between them, through which the incident electromagnetic radiation emitted by a principal monitoring instrument passes when the cap assembly is seated in a receptacle and positioned within the principal monitoring instrument.

60. The system of any of claims 47-59, wherein the first electrode and the second electrode are separated by a distance of 10 mm or less, such as a distance of from 2 mm to 5 mm.

61. The system of any of claims 47-60, wherein the cap assembly further comprises: a post extending from a bottom of the body portion, wherein the post is configured for attachment of a membrane; and a first fluid inlet and a first fluid outlet fluidly disposed on the body portion and fluidly extending to the post so as to fluidly connect to a fluid sample present within a membrane affixed to the post.

62. The system of claim 61, wherein the cap assembly further comprises a second fluid inlet and a second fluid outlet fluidly disposed on the body portion and fluidly extending to the bottom of the body portion as to fluidly connect to a fluid sample present within the receptacle when the cap assembly is disposed within an opening of the receptable.

63. The system of any of claims 47-62, further comprising a stirrer extending from the bottom of the body portion of the cap assembly.

64. The system of any of claims 11-16, 26-31, or 47-63, further comprising a principal monitoring instrument configured to repeatedly interrogate the fluid, wherein the receptacle is reversibly insertable within the principal monitoring instrument.

65. The system of claim 64, wherein the receptacle is reversibly insertable within a sample holder disposed within the principal monitoring instrument.

66. The system of any of claims 11-16, 26-31, or 47-65, wherein the fluid comprises a mixture of components.

67. The system of any of claims 11-16, 26-31, or 47-66, wherein the fluid comprises a small molecule, a polymer, a colloid, or a combination thereof.

68. The system of any of claims 11-16, 26-31, or 47-67, wherein the receptacle has a perimeter is defined by a geometric shape chosen from square, rectangular, polygonal, hemi- polygonal, and circular.

69. The system of any of claims 11 -16, 26-31 , or 47-68, wherein the receptacle comprises a 1 cm pathlength cuvette cell sized to be received within a sample holder of a spectrometer.

70. The system of any of claims 11-16, 26-31, or 47-69, wherein the receptacle is fabricated from a transparent material, such as quartz, glass, or a plastic.

71. The system of any of claims 11-16, 26-31, or 47-70, wherein the principal monitoring instrument is chosen from a static light scattering detector, a dynamic light scattering detector, combined static and dynamic light scattering detector, a fluorimeter, an absorption spectrometer, a refractometer, a differential refractometer, a turbidity monitor, an NMR, a polarimeter, or a circular birefringence or dichroism detector.

72. The system of any of claims 11-16, 26-31 , or 47-71 , wherein the principal monitoring instrument can measure more than one property of the fluid.

73. The system of claim 72, wherein the more than one property comprises static light scattering, dynamic light scattering, fluorescence, ultraviolet absorption, visible absorption, turbidity, circular dichroism, circular birefringence and infrared absorption.

74. The system of any of claims 11-16, 26-31, or 47-73, wherein the principal monitoring instrument is configured to continuously interrogate the fluid.

75. The system of any of claims 11-16, 26-31, or 47-74, wherein the principal monitoring instrument is configured to interrogate the fluid at discrete intervals.

76. The system of any of claims 11-16, 26-31, or 47-75, wherein the system is configured to apply an electric field through which incident electromagnetic radiation emitted by a principal monitoring instrument passes.

77. The system of any of claims 11-16 or 47-76, wherein the system is configured to measure the conductance of the fluid.

78. The system of claim 77, wherein a concentration of an electrolyte in the fluid is determined from the measured conductance of the fluid, via a calibration curve or table.

79. The system of any of claims 11-16 or 47-77, wherein the system is configured to measure a concentration of an electrolyte in the fluid.

80. The system of any of claims 11-16 or 47-77, wherein the system is configured to measure a pH of the fluid.

81. The use of the device of any one of claims 1-10 or 32-46 or the system of any of claims 11-16 or 47-78 for the measurement of the conductance of a fluid.

82. The use of the device of any one of claims 1-10 or 32-46 or the system of any of claims 11-16 or 47-78 for the measurement of a concentration of an electrolyte in a fluid.

83. The use of the device of any one of claims 1-10 or 32-46 or the system of any of claims 11-16 or 47-78 for the measurement of a pH of a fluid.

84. The use of the device of any one of claims 1-10, 17-25, or 32-46 or the system of any of claims 11-16, 26-31, or 47-78 to apply an electric field within a fluid.

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