device

Abstract

The present application relates to a sample collection device comprising: • - an inlet configured to be placed in fluid communication with a sample source; • - an outlet in fluid communication with a sequestration portion, • - a sequestration portion in fluid communication with the outlet, • - a sampling portion in fluid communication with the sequestration portion; The sample collection device comprises furthermore: at least one conduit for allowing fluid to enter the sequestration portion, -a filter barrier positioned between the sequestration portion and the sampling portion, and at least one valve for applying a negative pressure; and wherein the sequestration portion and the valve are sized and configured such that an aliquot of a sample may be drawn into the inlet to flow into the sequestration portion.

Description

[0001] Device

[0002] Field of the Invention

[0003] The present invention pertains to a multifunctional filtration device for use in the laboratory for collection of chemical and biological samples, including safe transfer, and optional separation intro filtrate and retentate, and transfer and collection utilizing reduced pressure.

[0004] Background of the invention

[0005] The vast majority of laboratory processes such as reactions, crystallisation and blending require physical samples to be taken from process vessel for analysis. This is one of the most hazardous steps for an experimentalist due to the raised likelihood of getting into contact with the chemicals in the vessel. Also, often such reactions often require maintaining an inert atmosphere by ensuring low oxygen concentrations. Examples of such process include for cooling, distillation, and anti-solvent based crystallisations, heterogeneous and homogenous catalysis and encapsulations.

[0006] Standard practices for sampling from a vessel involve using a pipette to remove a sample. This requires opening the vessel for experimenter to withdraw a sample. The pipettes are prone to dripping during movingto a sample vial.

[0007] Furthermore often in vessels with slurry or solid / liquid mixtures, sampling directly from such vessels may yield variations in the taken samples, for example due to crash cooling, and largely depends on the experimentalists skills. This is undesirable since reliably and repeatedly obtained representative samples are required to attain reliable accurate scientific data.

[0008] Also, when removing a slurry sample, there is a secondary operation, i.e. a filtration to separate the solids and liquids, commonly via a Buchner funnel. This requires a significantly large samples of at least 10 ml of volume to be taken, while only a small portion is later used for analysis. The filtered liquid then has to be pipetted again into a vial after filtration. This process is slow, prone to spillages and for crystallisation gives time for the sample to change making results unrepresentative. While autosamplers exist, those currently in use are not able to handle slurries and are too bulky, expensive and inadequate to use for every experiment.

[0009] Accordingly, there remains a need to allow for a reliable and reproducible manner to take samples avoiding the direct contact with any of the components.

[0010] Summary of the Invention

[0011] Accordingly, in a first aspect, the present invention relates to a sample collection device comprising:

[0012] - an inlet configured to be placed in fluid communication with a sample source;

[0013] - an outlet in fluid communication with a sequestration portion ,

[0014] - a sequestration portion in fluid communication with the outlet,

[0015] - a sampling portion in fluid communication with the sequestration portion;

[0016] -at least one conduit for allowing fluid to enter the sequestration portion,

[0017] -a filter barrier positioned between the sequestration portion and the sampling portion, and at least one valve for applying a negative pressure; and wherein the sequestration portion and the valve are sized and configured such that an aliquot of a sample may be drawn into the inlet to flow into the sequestration portion.

[0018] In a further aspect, the present invention provides a method for removing a sample aliquot from a sample source using a device according to the invention, comprising submerging a portion of the inlet into the sample source, and applying a pressure differential over the sample and / or sequestration portion.

[0019] In a further aspect, the present invention provides for the use of a device according to the present disclosure for the removal and / or separation of samples from a process vessel.

[0020] In yet further aspect of the present invention, there is provided a sample collection system comprising:

[0021] -a plurality of sample collection devices, each sample collection device comprising: an inlet configured to be placed in fluid communication with a sample source; an outlet in fluid communication with a sequestration portion, a sequestration portion in fluid communication with the outlet, a sampling portion in fluid communication with the sequestration portion; at least one conduit for allowing fluid to enter the sequestration portion, a filter barrier positioned between the sequestration portion and the sampling portion; and a plurality of valves, a negative pressure manifold in fluid communication with the plurality of valves, -a control system configured to control the operation of the plurality of valves.

[0022] In an embodiment, the control system sample collection system comprises at least one control unit and at least one processing unit, wherein the processing unit is configured to set parameters fortime and duration for activation of each valve and wherein the control unit is configured to control the actuation time and duration of a plurality of valves and wherein the control unit is in communication with the processing unit. Each valve in the sample collection system is independent in fluid communication with a corresponding sample collection device independently, and each valve is configured to generate negative pressure to a corresponding sampling collection device independently.

[0023] The sample collection system according to the present invention can be configured to collect either a single sample or multiple samples simultaneously, or at different timings, and different durations.

[0024] Brief Description of the Drawings

[0025] Fig. 1 shows an embodiment of the sampling unit.

[0026] Fig. 2A is a schematic illustration of a device according to an embodiment. It shows a diagram of sampler set up for sampling fluid samples. The system allows sampling where filtration is not required by directly attaching a vial to the top adaptor along with a syringe. Samples can be drawn into the vial using the syringe which can then be reversed to clear the sample line.

[0027] Fig. 2B is an actual photograph taken from a device according to a preferred embodiment. It shows a sampler set up for sampling solid liquid mixtures, such as slurries.

[0028] Fig. 3 is a schematic illustration of a device according to an embodiment, and shows method for its operation. Herein, to sample a slurry vacuum is applied to the sampler drawing air in via the filter and open port in the top adaptor. When ready to sample the open port is closed e.g. by covering it with a thumb, or by closing an attached valve. This causes liquid to be drawn from the vessel through the filter. Sampling can be controlled by allowing air to flow again causing any remaining liquid in the sample line to syphon back into the vessel. However, sampling will stop automatically when a small filter cake has built up due to the increased pressure drop across the filter.

[0029] Fig. 4 illustrates a sample collection device and its components according to an embodiment of the present invention of each sample collection device.

[0030] Fig. 5 illustrates a sample collection system 500 comprising a plurality of sample collection devices. Fig. 6 illustrates an aspect of the subject matter in accordance with one embodiment, specifically the control system with the processing unit 640, and control unit 650, a plurality of valves 630 and a pressure negative manifold 620 of the sample collection system.

[0031] Detailed Description of the Invention

[0032] Embodiments of the present disclosure are described in detail with reference to the drawing figures wherein like reference numerals identify similar or identical elements. It is to be understood that the disclosed embodiments are merely examples of the disclosure, which may be embodied in various forms. Well-known functions or constructions are not described in detail to avoid obscuring the present disclosure in unnecessary detail. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present disclosure in virtually any appropriately detailed structure.

[0033] The present invention relates to a sample collection device that is a sampling unit allowing samples to be taken from a vessel directly into a vial without the use of a pipette either using a syringe or vacuum on the actual process vessel. For solid-liquid mixtures, such as for slurries, the device also allows for a simultaneous separation of solids and liquids. It further reduces potential experimentalist contacts with the sample chemicals, and reduces the risk of spillage, thereby improving safety. It also, especially for slurry sampling, reduces the number of steps in the sampling process and due to the rapid and reproducible separation of solids from liquids increases the representativeness of the samples. The laboratory vessel sampler furthermore advantageously allows a sample to be taken directly into a vial, without the need to open the vessel, or the use of a pipette. It also removes the need for a separate filtration and additional pipetting or decantation step, as this can be carried out in the same process. The sampling may furthermore advantageously be executed rapidly, and takes on controllable volumes from the process vessel as required. For dispersions or slurries, the system may also self-limit the sample volume to prevent over-sampling, by forming a filter cake, whereby the pressure drop balances out the pressure differential, and stops, or at least slows down the sampling to a very slow pace.

[0034] The present invention advantageously allows samples to be taken from a vessel safely without using a pipette or opening the vessel. It may use a reduced pressure, by applying a vacuum line ora syringe that is drawing vacuum to draw samples directly into the sample vial portion. For example, vacuum may be applied through a valve while a fluid opening is closed, for example, manually or by other means, to regulate the pressure differential and facilitate the flow of the sample into the sample portion. Alternatively, vacuum can be applied through a controlled mechanism, such as an automated vacuum line, to draw samples directly into the sample vial portion (sampling portion), eliminating the need for manual operation.

[0035] In an embodiment, filtration may also conveniently be performed in the same step, for example by using a filter barrier comprising a filter medium. The filter barrier may also include additional components, such as filter support means, and / or fastening means. The filter medium could be selected from filter paper, fabric, membranes, or woven meshes and is configured to perform the actualfiltration. Preferably, the device and method for slurry filtration is self-limitingto prevent over- sampling.

[0036] The invention more particularly pertains to a device for the automated transfer and separation of liquid, components and filterable substances by the utilization of a filter medium as a means for capturing a filterable substance while utilising a first manifold to transfer and remove the transferred fluids in a separation chamber, and utilising a second manifold to remove liquids and filter the filterable substances on the filter medium which forms the filter barrier.

[0037] The invention is applicable to all types of laboratory and biological testing and filtering applications including the use of standard biological processes which typically include sample volumes from 0.5 ml to 10 ml, from vessels 10 ml to 20L in scale, separation of the liquid components from the transferred fluids and subsequently filtering of the sample through either a filter or another suitable filter medium by layered housing to provide for the separation of the liquid, and particulate materials utilizingthe combination of a first manifold, second manifold and separation chamber.

[0038] Advantageously, the present invention is applicable to all types of filter media such as ceramic or glass frits, nitrocellulose, paper, nylon non-woven or woven materials and other suitable filter media. The invention allows automation to be used in test procedures which heretofore could not accommodate the drawing of air into filterable media due to the introduction of inaccurate results. Also, the device allows for the reproducible removal of predetermined sample volumes, and hence increases the accuracy of the attained samples.

[0039] The apparatus according to the invention furthermore may be configured to handle any type of filter media as well as air sensitive substrates captured in the filter; advantageously providing an automated filtering technique, to replace the heretofore tedious manual operations including pipetting, filtration in open filters, and / or decantation.

[0040] In addition, the vessel may advantageously be operated under a protective gas atmosphere. Also, advantageously gaseous components or materials of the sample may be removed from the sample.

[0041] The invention also in particular pertains to a device for the transfer and separation of liquid components and filterable substances by the utilization of a filter barrier as a means for capturing the filterable substances while utilizing a manifold to transfer liquid components from a separation chamber into a sample vessel, whereby filterable substances are removed on a filter barrier. The apparatus according to the invention is applicable to all types of laboratory and biological testing and filtering applications involving separation of solid, liquid and gas components from transferred samples, by using a layered housing to provide for the separation of the liquid, particulate and gaseous materials utilizing the combination of a first manifold, filter barrier, and a separation chamber. The filter barrier may be removable or replaceable ensure consistent filtration over multiple uses. The filter barrier may comprise a filter medium. The filter barrier may optionally comprise additional components, such as structural support(s), and / or fastening means. In an embodiment, first a sample line is fed into the vessel and routed into the sampler by a fluid conduit, also referred to as tubing or tube, comprising a 180°bend.The sample tube is then attached to the sampler top via a compression fitting. The sampler top adapter may have a small glass Buchner top screwed into it, with threads corresponding to those of a sample vial, and has an additional port to allow air flow via a suitably sized fluid tube. The Buchner top may then be clipped to a Buchner base with filter paper in between, acting as filter barrier. The Buchner base may advantageously comprise a glass or porcelain frit to support the filter paper. The Buchner base is pushed through the sample bottom adaptor which can have a vial screwed into it and a vacuum line attached.

[0042] Advantageously, using the apparatus, i.e. the sample collection device, according to this embodiment, in order to sample an aliquot of a slurry, a pressure differential may be applied to a valve , also referred to as a second valve, drawing the gaseous content of the sequestration vessel via the filter barrier and open port into the top adaptor. When ready to sample the open port is closed, causing an aliquot of the liquid to be drawn from the process vessel through the fluid conduit and through the filter barrier.

[0043] The valve may be in fluid communication with a negative pressure source, or alternatively a negative pressure manifold.

[0044] Advantageously, sampling volumes and speed can be controlled by allowing the pressure differential to reduce, e.g. by allowing air to flow again causing any remaining liquid in the sample line to syphon back into the process vessel. Furthermore, sampling will also be slowed down or fully stopped when a filter cake has built up due to the increased pressure drop across the filter (medium). The arrangement of the manifold together with a fluid separation chamber for the separation of transferred fluids into solid and liquid components, advantageously, together with a valve for activating the manifold to provide for the separate treatment and filtration of discrete samples allows for the ease of transfer of large and small quantities of filtrable materials to a filter medium and the separate filtering of each of the discrete samples without cross-contamination.

[0045] The valve may advantageously comprise a conduit in fluid connection with the exterior of the sampling unit, which can be closed off by an actuator. The latter may simply be provided by the operator by covering the valve orifice with a digit, such as a finger or a thumb, or it can be mechanically actuated valve unit.

[0046] In an embodiment, the sample collection system of the present invention may be fully automated without requiring any manual intervention. In an embodiment, the sample collection device comprises at least one valve configured to apply negative pressure differential, wherein further this valve can be an electrically actuated valve. Further, the at least one valve can be controlled

[0047] In this manner the invention also provides for one or more filter media which advantageously are impervious to solid filtrates, to provide for rapid transfer, filtering and handling of filtrable components from fluids while allowing subsequent washings and reagent additions or reactions to not interfere with the filter medium. The arrangement is also useful in collecting noxious materials from the first manifold without the necessity of using a hood or other laboratory equipment as well as the collection of hazardous fluids.

[0048] The separation chamber preferably has a total volume greater than the total volume of the sample to be transferred and filtered. The device of the invention can be advantageously constructed to accommodate samples and quantities of liquid from 0.5 ml to 1 ,000 ml or more. However, in each case the total volume of the separation chamber should be about 5% to 100% greater and preferably 30-50% greater than the volume of fluid transferred, to provide for the simultaneous transfer and separation of liquids and filterable substances, and any gaseous components that may be present in the sample.

[0049] As used herein, "sample " can include any sample from a chemical and / or biological process, which comprises a fluid portion, and optionally, a solid portion dispersed, suspended or simply present in the fluid portion.

[0050] As used herein, the words "proximal" and "distal" refer to the direction closer to and away from, respectively, a user who would place the device into contact with a process vessel. Thus, for example, the end of a device connecting to the process vessel would be the distal end, while the opposite end of the device (e.g., the end of the device being manipulated by the user) would be the proximal end of the device. Preferably, the sequestration portion and the sampling portion form a unipart sampling chamber, creating a single unified structure, or a separate portions in fluid communication with each other via a junction, the junction being configured to facilitate the transfer of fluid between the sequestration and the sampling portions while maintaining their operational integrity.

[0051] Preferably, the sequestration portion comprises a chamber comprising a lumen, the lumen being defined by an outer chamber wall that at least partially circumscribes a base, and a base abutting the lumen. The base of the sequestration portion may comprise the filter barrier, which is preferably the filter barrier is a solid retentate filter barrier. The filter barrier can be mechanically attached to the base of the sequestration portion using support elements and fastening means, such that the filter barrier is positioned between the sequestration portion and the sampling portion.

[0052] Preferably, the base of the sequestration portion comprises a solid retentate filter barrier. Preferably, the inlet comprises a fluid conduit comprising a bend in order to position the conduit above the outlet.

[0053] The sample collection device of the present invention may comprise a junction between the sequestration portion and the sampling connection. The junction may connect the sequestration portion (with the filter barrier) to the sampling portion.

[0054] The sequestration portion and the sampling portion of the sample collection device may be aligned along a common vertical axis, with the filter barrier positioned between them in a stacked arrangement, where the filter column is positioned above the sampling portion. In this configuration, the sequestration portion is positioned above the filter barrier, while the sampling portion is positioned below the filter barrier, along a common vertical axis. This allows for more compact and space efficient design, which minimizes leaks and allows faster sampling.

[0055] Preferably, the sequestration portion may comprise a junction having a proximal end connected with distal end of the filter barrier, the junction comprising a seal for a sampling portion positioned sealably below the junction, and further comprising a fluid channel guide entering the lumen of the sampling portion, and a valve, also referred to as fluid outlet valve, or second valve, positioned above the distal end of the channel guide, wherein the (second) valve is configured to apply a negative pressure differential over the sample portion, such that a sample aliquot may be drawn into the sequestration portion, and a filtrate through the filter barrier into the sample portion, thereby displacing at least part of the gaseous content of both portions.

[0056] Preferably, a retentate or filtrate aliquot is sequestered on the filter barrier, and wherein a liquid filtrate portion of the sample aliquot is drawn into the sampling portion thought the outlet port when a pressure differential is applied between the inlet, the first sequestration portion and the sampling portion.

[0057] Preferably, the sequestration portion includes an inner surface that faces the filter barrier, and wherein inner surface of the junction comprises a seal, allowing to separate the sequestration portion into the filter barrier and the outer wall portion, in order to remove the solid retentate and / or to insert and remove a filter medium.

[0058] Preferably, the device according to the present disclosure comprises (a) an inlet portion; a cap lid portion comprising a first manifold, the manifold comprising a fluid guide, a seal for the sequestration portion, and a valve; wherein the sequestration portion is configured as an open ended chamber; and (b) a second portion comprising a filter barrier or filter support, means for detachably joining the first portion to said second portion, and (c) a second manifold comprising a fluid conduit, a valve having a vacuum inlet; and a sampling vessel attached to the second manifold.

[0059] Preferably, the first and / or second valve are configured to permit entry of a cannula for removal of a sample aliquot, preferably, through a septum. Preferably, at least one seal, preferably both seals are executed as one-way seal(s). Preferably, the sequestration and / or sample portion may be furnished with a protective inert gas flow.

[0060] Preferably, the method for removing a sample aliquot from a sample source using a device according to the present disclosure comprises submerging a portion of the inlet into the sample source, and applying a pressure differential over the sample and / or sequestration portion. Preferably, the method comprises using a device according to the disclosure to obtain a fluid sample and / or a solid sample, the method comprising: (i) coupling the device to an inlet of the device, the coupling of the device to the inlet configured to produce a negative pressure differential within at least a portion of a sample source; (ii) establishing a fluid communication between the sequestration portion and the sample portion (ii) applying a negative pressure differential to the valve (second valve); and (iii) applying a pressure differential over the sequestration and sample portions, to allow an initial aliquot of a fluid sample to flow from an inlet though the outlet into the sequestration portion in response to the negative pressure differential; and

[0061] (iv) maintaining the pressure differential to allow a filtrate aliquot of a fluid sample to flow through the filter barrier and into the sampling portion, and maintaining the pressure differential until either the filter barrier is blocking further flow, or until a desired sample volume is achieved.

[0062] Preferably, the method comprises removing at least part of the sample aliquot from the sequestration and / or sample portion, preferably by using a syringe and cannula.

[0063] The components of the sample collection device may be manufactured using various techniques, including3D printing, injection moulding, orother suitable methods. Preferably, the components are 3D printed.

[0064] The sample collection device is configured to remove and / or collect a sample aliquot. Further the sample collection device may be configured to separate the sample aliquot’s components, such as retentate and filtrate, through the filter barrier.

[0065] In an embodiment, the sample collection device comprises a sequestration portion, a sampling portion, at least one conduit, an adapter positioned on top of the sampling portion, a filter barrier, a sample receiver, a junction.

[0066] Furthermore, the sample collection device is operatively connected to at least one valve. The junction comprising support elements and optionally fastening means such as screws. The conduit includes an inlet at its proximal end to receive a sample aliquot and an outlet at its distal end to deliver the sample into the sequestration portion. The sequestration portion and the sampling portion may be positioned along a common vertical axis. The sample collection device includes a filter barrier positioned between the sequestration portion and the sampling portion along a common vertical axis, the filter barrier configured to separate components of a mixture or dispersion. Preferably, the sequestration portion, the filter barrier and the sampler portion can be in a stacked arrangement along a common vertical axis.

[0067] In this configuration, the filter barrier can be integrated with the base of the sequestration portion. Beneath the filter barrier, a sample receiver can be positioned, which serves as a conduit to channel liquid filtrate into the sampling portion. The filter barrier retains solid particles or retentate from the sample, while allowing the liquid component (filtrate) to pass through. The sample receiver, located beneath the filter barrier, facilitates the transfer of liquid between portions.

[0068] The sample collection device further includes at least one valve configured to create a negative pressure or vacuum to assist in the movement of liquid. Preferably, a retentate or filtrate aliquot is retained on the filter barrier, forming a filter cake, while a liquid filtrate portion of the sample aliquot is drawn into the sampling portion through an outlet port. In this case, the valve is used to draw air out of the system, thereby reducing the pressure within the sequestration and sampling portions, thereby creating a negative pressure differential.

[0069] The sample collection device may comprise a sample receiver, wherein the sample receiver is positioned within the sampling portion such that a lower section of the sample receiver extends into the sampling portion, while an upper portion of the sample receiver is in fluid communication with the filter barrier. This allows a sample aliquot to be taken from the sample source and filtered, with the filtrate being collected directly into a sampling portion, while the retentate is retained by the filter barrier. For example, the sample receiver can be a funnel, preferably a Buchner funnel.

[0070] Further, the sample collection device may include an air inlet. This air inlet may be configured to create a siphoning effect, allowing the filtrate to flow back into the sample source when necessary.

[0071] The sample collection device may comprise at least one outlet port located on the adapter or another suitable location and can be connected to a valve. This configuration enables the creation of a negative pressure differential, facilitating the movement of the sample.

[0072] The sample collection device may comprise at least one valve. The valve can be proximal to the sampling portion, positioned beneath the sequestration portion, and configured to apply a negative pressure differential between the sampling portion and the sample source. This may create negative pressure in the sampling portion, drawing the sample aliquot through the filter barrier into the sequestration portion. The valve can be proximal to the negative pressure source and in communication with the sample collection device.

[0073] Various valves can be used in the sample collection device, for example the valve can be an electrically controlled valve, such as solenoid valve. Pneumatic or vacuum-controlled valves can also be used. Alternatively, the valve can be a manually operated valve.

[0074] In a preferred embodiment, the valve of the sample collection device is an electrically controlled solenoid valve. The valve is configured to be actuated at predefined times, enabling a sample aliquot from the sample source to be drawn into the sample collection device.

[0075] The present invention also relates to a sample collection system comprising at least one sample collection device according to any embodiment of the present invention, a plurality of valves, and a negative pressure manifold in fluid communication with the plurality of valves, and a control system configured control the operation of the valves, and / or to actuate the plurality of valves, and each of the sample collection devices in the system.

[0076] The plurality of valves in the system may correspond to the valves of the plurality of sample collection devices accordingto the present invention, such that each sample collection device includes one of the plurality of valves, and further each valve may be independently in fluid communication with a corresponding sample collection device and is configured to generate negative pressure to its corresponding sample collection device independently.

[0077] The control system of the sample collection system according to the present invention refers to a component or combination of components responsible for generating, regulating, and managingthe negative pressure in the sampling system.

[0078] This system ensures precise control of sample collection / separation by managing the operation of the negative pressure manifold and plurality of valves. This control system may comprise elements like a processing unit, control unit, communication interface. The sample collection system may comprise an enclosure that houses the control system, negative pressure manifold, and valves within a single, integrated structure,

[0079] The control of the sampling process in the sample collection system may be performed using a control platform configured to enable automated operation of the system.

[0080] The sample collection system comprises a negative pressure manifold, that is preferably a vacuum manifold. The negative pressure manifold may be in fluid communication with a negative pressure source, preferably a vacuum source. The negative pressure manifold includes a plurality of valves. The negative pressure manifold together with the valves can be housed within a control box enclosure. Each valve functions to control the flow of negative pressure (vacuum) to an individual sample collection device.

[0081] In an embodiment, the negative pressure manifold comprises solenoid valves for controlling the application of negative pressure. Each solenoid valve is controlled separately, meaning negative pressure (vacuum) can be applied only where needed, without affecting other sample collection devices in the system.

[0082] These valves of the negative pressure manifold can be connected to the sample collection devices via conduits, such that each of the plurality of valves is in fluid communication with a corresponding sample collection device independently, and each valve is configured to generate negative pressure to a corresponding sampling collection device. Each valve of the negative pressure manifold may be in communication with a control unit and / or processing unit.

[0083] The control system may comprise a processing unit and a control unit, wherein the control unit is communication with the valves. The processing unit is configured to run a software that calculates predefined parameters, such as the time and duration (length of sampling ) for each valve's actuation, based on real-time process conditions or experimental data. Thus, the processing unit is configured to manage timing of valves operation, sampling sequence and volume control, and realtime monitoring of pressure and flow.

[0084] The processing unit can be for example a microcontroller, single-board computers (SBCs), programmable logic controllers (PLCs), or other microcontroller-based development boards. The control unit, is configured to regulate the activation of each of the plurality of valves independently based on the signals from the processing unit, thereby enabling selective application of negative pressure to individual sample collection devices without affecting them all at the same time.

[0085] The control unit can be selected from a relay board, MOSFET switch module, solenoid driver board. The control system may further comprise s a control unit. The control unit is configured to receive the calculated parameters from the processing unit and to generate and regulate the negative pressure applied to the valves via the negative pressure manifold. By actuating the valves based on the predefined parameters, the control unit ensures that the correct level of negative pressure, preferably vacuum, is maintained to collect samples at the appropriate times and conditions from the sample source. After collecting a sample, the valve closes, and the system self-resets. Further, the sample collection system is preferably configured to operate automatically without the presence of an operator, However, manual input can also be accommodated when necessary.

[0086] The control system of the sample collection system may comprise sensors or sensor interface configured to receive pressure data from at least one pressure sensor. The control system may further comprise wired or wireless communication. The control system may comprise an actuator interface operatively connected to at least one valve actuator for controlling negative pressure (vacuum) regulation; The control system may comprise a memory configured to store predefined sampling parameters, including negative pressure thresholds, actuation times, and valve open durations. The control system may comprise a clock module or timing circuit configured to track sampling intervals and valve actuation duration; The control system may have a power supply.

[0087] The control system may comprise an electrical control box housing all component of the control system. For example, the electrical control box may enclose the processing unit, sensor interface, actuator interface, optionally power supply, and wiring. The electrical control box is configured to provide protection and organization of the control system components. The control system may comprise a power supply.

[0088] Further, the negative pressure or vacuum manifold being configured to distribute negative pressure to multiple sample collection devices via the valves, may be positioned beneath the electrical control box; Further the control system may comprise a common cover enclosing the electrical control box, negative pressure manifold, and the plurality valves together, forming this way an integrated unit. This integrated unit can be in communication with the sample collection devices.

[0089] The sample collection system collects a sample aliquot, which is then filtered to separate its components.

[0090] The sample collection system is configured for automated sampling at predefined times and durations, achieved by a control unit programmed to actuate the valves in the vacuum manifold.

[0091] The sample collection system according to the present invention comprises :a plurality of sample collection devices, each device includinga sequestration portion, a sampling portion, a filter barrier, and at least one conduit; a vacuum manifold operatively connected to the plurality of sample collection devices, a control unit configured to control the operation of the valves, and also to actuate the valves to create a negative pressure differential for drawing samples from a sample source into the sample collection devices,

[0092] Preferably, the sample collection system comprising a plurality of sample collection devices. Each sample collection device in the system comprises a sequestration portion, a sampling portion, and at least one conduit ((also referred to as tubing) with a proximal inlet and a distal outlet. The sequestration portion and the sampling portion may be arranged along a common vertical axis, with the filter barrier positioned between the sequestration portion and the sampling portion.

[0093] In an embodiment, the sample collection system comprises a plurality of sample collection devices, a plurality of valves, a negative pressure manifold in fluid communication with the plurality of valves, a control system configured to actuate the plurality of valves, wherein each sample collection device comprises an inlet configured to be placed in fluid communication with a sample source, an outlet in fluid communication with a sequestration portion, a sequestration portion in fluid communication with the outlet, a sampling portion in fluid communication with the sequestration portion; at least one conduit for allowing fluid to enter the sequestration portion, a filter barrier positioned between the sequestration portion and the sampling portion, and at least one valve for applying a negative pressure.

[0094] An adapter with an outlet maybe positioned on top of the sampling portion of each sample collection device, and a filter barrier is located between the sequestration portion and the sampling portion. Each sample collection device may also include a sample receiver situated beneath the filter barrier. Further the filter barrier in each sample collection device enables separation and retention of both liquid and solid phases of the sample.

[0095] Additionally, the sample collection device may feature a junction that comprises at least one support element, preferably two support elements, and may optionally include fastening means, such as screws. Each sample collection device of the system further includes or is in communication with at least one valve.

[0096] The junction is configured to hold together the sequestration portion, the sampling portion, the filter barrier, and the optionally sample receiver. The sample receiver may have an upper section and a lower section, wherein the sample receiver is positioned within the sampling portion such that a lower section of the sample receiver extends into the sampling portion, while an upper section of the sample receiver is in fluid communication with the filter barrier. Y1

[0097] These sample collection devices of the system can be positioned on support structure, such as a rack. The sample collection system may further include a negative pressure manifold (vacuum manifold) for creating a negative pressure differential across the sample collection devices.

[0098] The negative pressure manifold may include a plurality of valves, each connected to a vacuum source. These valves can be for example, solenoid valves that are electrically actuated. In an embodiment, the vacuum manifold of the system describe above comprises a plurality of solenoid valves.

[0099] Further, the number of valves in the system may correspond to the number of sample collection devices. Forexample, if the system includes more than two, three, four, five, six, or more than seven sample collection devices, the vacuum manifold may include an equal number of valves to provide independent control of the vacuum supply to each sample collector device in the system. In an embodiment, the sample collection system described above includes a configuration where the number of sample collection devices is greater than two. Forexample, the sample collection system may include more than 3, more than 5, more than 7, more than 10, more than 15, more than 20, sample collection devices, depending on the specific application requirements.

[0100] The vacuum manifold in the sample collection system of the present invention may comprise a plurality of valves and is preferably connected to a control unit, the control unit including electrical components configured to regulate and control the operation of the valves.

[0101] The valves can be actuated independently and managed by a control unit in conjunction with software, enabling automated regulation of the sampling process, without an interference of an operator.

[0102] The sample collection system comprises a control system for controlling the valves in the negative pressure manifold that regulate the negative pressure distribution, preferably vacuum distribution.

[0103] This control unit is configured to execute commands and ensures that each valve that is in communication with each sample collection device operates independently.

[0104] The sample collection system may further include a control unit configured to enable sampling at specific process steps. The control unit assigns specific timings to each sampling device in the system through an input configuration, determining the start time and duration forvalve actuation. Based on this configuration, the control unit sends signals to actuate the valves, allowing vacuum to be applied to the sampling devices at the appropriate times. This process creates the necessary negative pressure differential to facilitate the sampling operation. Thus, the control unit is configured to actuate the plurality of valves at predetermined timings and for predefined durations, and wherein the control unit is in communication with the processing unit.

[0105] The sample collection system provides automated control for sampling at precise times and under specific conditions, eliminatingthe need for manual intervention by the operator.

[0106] Thus, the control unit regulates the negative pressure, enabling the precise drawing of samples into the sample collection devices in accordance with the set parameters.

[0107] Further, each sample collection device may optionally comprise an air opening located at the sequestration portion, which facilitates the drainage of the sample back into the sample source by promoting a siphoning effect, wherein the sample collection device is positioned at a level suitable for enabling siphoning effect. For example, the sample collection device whether alone or in the sample collection system can be positioned at the same level or higher with the samples source. The air opening may allow air to enter the sequestration portion, equalizing pressure and preventing the formation of negative pressure (vacuum) , thereby facilitating the drainage of the sample back into the sample source.

[0108] The method for removing or collecting a sample from a sample source using the sample collection system of the present invention involves arranging the sample collection devices on the support structure, for example a rack, and connecting each sample collection device to the sample source via a conduit. The sample collection system operates by creating a negative pressure differential through the activation of valves, such as solenoid valves, within a vacuum manifold, controlled by a programmable control unit. This negative pressure draws a sample aliquot from the sample source into the sequestration portion of each sample collection device, where a filter barrier separates the liquid and solid phases of the sample, enabling efficient collection and retention of both phases.

[0109] As used herein, the terms "sampling tubing”, “tubing” and "conduit" are used interchangeably.

[0110] In an embodiment there is provided a method for removing / collecting a sample aliquot from a sample source, comprising: providinga pluralityof sample collection devices operatively connected to a vacuum manifold; using a control unit to actuate valves within the vacuum manifold; applying a negative pressure differential through the vacuum manifold to drawa sample aliquot into the sample collection devices at predefined times and durations; and separating liquid and solid phases of the sample using a filter barrier within the sample collection devices. Figure 1 shows an embodiment of a sampling unit (100) composed of standard units. Herein a PFAsampling tubing (102) supported by a 180° bend (101) enters the sample vessel lumen through a lid portion convenientlyformed as cap (103) and ferrule (104). The lid portion above the lumen (106) is also provided with an actuation port to start sample taking (105). The lid further comprises an adaptor (118) to connect the sample vessel to the lid, preferably configured to screw the vessel to the lid (threads not shown), the actuation port and the vessel body (107) to ensure a leakage-free connection. Also, there is provided a tubing (115) to the vacuum supply.

[0111] The term "PFA sampling tubing" refers to tubing / conduit made from PFA (perfluoroalkoxy alkane), a copolymer of hexafluoropropylene and perfluoroethers.

[0112] Figure 2A shows a preferred embodiment of the apparatus, i.e. sample collection device, configured to separate solid components and liquid components from a sample taken from a vessel (217), which is the sample source. Herein, a 180° tube turner (201) is attached to a PFA sampling tubing (205), which enters a lid portion formed by a cap (203) and ferrule (204). An actuation port to start sample taking is provided (206). The lid portion comprises an adaptor (218) to connect the sample tube-to-sample vessel adapter, which is configured to screw to the lid (204), the actuation port and the sample vessel body (208) to ensure a leakage-free and gas-tight connection. A clip (210) holds the sample vial manifold (213) and lower flange of the first vessel (207) in place; the manifold being provided a filter medium (211) positioned on a frit (212). The manifold (213) extends through a second cap (214) holding the sample vessel (216), and into the sample vessel to a point below the vacuum line (215) provided in the second cap. There is provided a tubing (215) to the vacuum supply. The sample vessel (216), being part of the sampling portion, is positioned directly beneath the sequestration portion (207), with the filter barrier (211) positioned in between. Together with all connecting components, they form a single integrated unit.

[0113] Figure 2B is a photograph taken from an actual testing unit in line with a preferred embodiment of the present invention, of the apparatus configured to separate solid components and liquid components from a sample taken from a vessel (217). Herein, a 180° tube turner (201) is attached to a PFA sampling tubing (205), which enters a lid portion formed by a cap (203) and ferrule (204). An actuation port to start sample taking is provided (206). The lid portion comprises an adaptor (207) to connect the sample tube-to-sample vessel adapter, which is configured to screw to the lid, the actuation port and the sample vessel body (208) to ensure a leakage-free and gas-tight connection. A clip (210) holds the sample vial manifold (213) and lower flange of the first vessel (207) in place; the manifold being provided a filter medium (211) positioned on a frit (212)The frit (212) serves as a supporting component for the filter medium. The manifold (213) extends through a second cap (214) holding the sample vessel (216), and into the sample vessel to a point below the vacuum line (215) provided in the second cap. There is provided a tubing (215) to the vacuum supply.

[0114] Figure 3 illustrates the operation of the preferred apparatus of Figures 2A and 2B. In Fig, 3. the arrow 311 shows the flow of air or a protective gas, or of the sample through the apparatus. Initially (301), air is drawn through the sampling device by applying vacuum at the sample vessel vacuum outlet (312) but letting air enter at the actuation port valve acting as an air inlet (311); then (302) the actuation port valve is closed, e.g. by covering with a thumb to start sampling from the sampling line and the process vessel, passing the sample drawn from the process vessel through the filter unit (filter barrier); until (303) a filter cake comprising a solid filtrate (314) is formed on the filter unit, and a liquid mother liquor (315) is separated off. The increased pressure drops due to the saturation of the filter medium by the separated off solids (314) may advantageously cause the sampler to selflimit a sample at a desired volume, wherein the mother liquor fluid (315) is collected in the sample vessel below. The sample vessel can advantageously be separated off and / or replaced with minimal operation, and without havingto manipulate the two components.

[0115] While several embodiments of the disclosure have been shown in the drawings, it is not intended that the disclosure be limited thereto, as it is intended that the disclosure be as broad in scope as the art will allow and that the specification be read likewise.

[0116] Fig. 4 illustrates a sample collection device according to an embodiment of the present invention. With reference to Fig. 4, the sample collection device comprises a sequestration portion 410, a sampling portion 420 (vial), a conduit (not shown), an adapter 430 with an outlet 490, a filter barrier 480, such as filter paper, a sample receiver 405, support elements (440, 445) and fastening means 460, such as screws.

[0117] The outlet 490 is in fluid communication with at least one valve (not shown). This valve controls the application of negative pressure, enabling sample extraction. The sample receiver 405 is a Buchner funnel having an elongated section 406 also referred to as a lower section, and a funnel section 407 also referred to as un upper section. The elongated section 406 i.e. narrow cylindrical stem that extends downward of the funnel section, is located within the sampling portion 420. The funnel section 407 i.e., a wide, open-top section, is in communication with the filter barrier 480 and the sequestration portion 410. The sample aliquot enters through the sequestration portion 410 and then passes through the filter barrier 480 into the sample receiver 405. The sample receiver 405 allows the filtered liquid (filtrate) to pass through and exit into the sampling portion 420, The conduit has an inlet and an outlet, wherein the inlet is located at a proximal end of the conduit for receiving an aliquot of sample, while the outlet is located at a distal end to deliver the aliquot of sample into the sequestration portion. Further the sample collection device of Fig. 4 includes a filter barrier 480 having a filter medium, such as filter paper, configured for separating mixtures or dispersions.

[0118] The support elements, forming the junction, include an upper clamp 440 and a lower clamp 445.

[0119] The upper clamp is associated with the base of the sequestration portion 410 and a lower clamp connected to the adapter 430. These clamps (440, 445) join the sequestration portion 410 to the sampling portion 420 by holding the filter barrier 480 i.e. a filter paper in place between them and fastening together using screws 460, thereby connecting the base 425 of the sequestration portion 410 to the adapter 430 and subsequently to the sampling portion 420.

[0120] Fig. 5 illustrates an embodiment of the present invention, showing a sample collection system 500 comprising a plurality of sample collection devices connected to a negative pressure manifold (shown in Fig. 6). Each sample collection device includes an inlet 515, inlet conduit 585, a sequestration portion 510, a sampling portion 520, a junction 550, a sample receiver (not shown) a filter barrier 580, an outlet 590 and at least one outlet conduit 555. Further the junction 550 comprises an upper clamp 540 and a lower clamp 545 and fastening means (screws) 560. This prevents leaks and maintains the negative pressure.

[0121] The sample collection device of Fig. 5 includes an adapter 530 having an outlet 590 in communication with conduit 555. The conduits (tubes) 555 are guided and secured by conduit guides and are operatively connected to the valves (as shown in Fig. 6). Each conduit 555 is individually connected to a dedicated valve in the negative pressure manifold, allowing for independent control. When the valve in the negative pressure manifold opens, suction is applied to the connected sample collection device through outlet conduit 555, and the resulting pressure differential draws the sample into the sample collection system. As the sample moves forward, it encounters the filter barrier 580, which is positioned between the sequestration portion 510 and the sampling portion 520, where an initial separation or retention of the sample occurs. The liquid filtrate is collected in the sampling portion 520, after passing through the filter barrier 580.

[0122] The sample collection system 500 includes a support means, such as a rack 570, configured to support or hold each of the sample collection devices. Each of sample collection devices is removably positioned in the rack 570, allowing each sample collection device to be easily removed and disassembled for sample retrieval.

[0123] Fig. 6 illustrates an exemplary embodiment of the sample collection system including the control system, a negative pressure manifold 620 connected to a vacuum source, and a plurality of valves 630 in communication with the negative pressure manifold and the control system 610. The control system 610 comprises an enclosure 600, such as electrical control box (enclosure). While the control system 610 is depicted aswall-mounted, this is merely an example, and other configurations are possible. Further, the control system comprises a control unit 650 and a processing unit 640.

[0124] With reference to Fig. 6, the control unit 650 is an 8-channel relay board that receives signals from the processing unit 640 and controls the activation and deactivation solenoid valves 630 accordingly. The processing unit 640 is configured to execute software instructions and is further configured to set parameters for the time and duration of vacuum application to each sampling device.

[0125] The valves 630 are configured to control the application of negative pressure (vacuum) to each sample collection device (not shown). Each valve 630 in the sample collection system is dedicated to a separate sample collection device and applies negative pressure independently of the other valves. With refence to Fig. 6, the valves 630 are solenoid valves. Each solenoid valve 630 is connected to the vacuum manifold 620 and is also electrically connected via wiring to the control unit 650. Each valve 630 in the negative pressure manifold is actuated independently, at set times causing a sample to be drawn from the sample source to into the sample collection device.

[0126] The sample collection system comprising a plurality of sample collection devices illustrated in Fig. 5 can be connected to the plurality of valves shown in Fig. 6, allowing for controlled sample collection and distribution. Therefore, the above description should not be construed as limiting, but merely as exemplifications of particular embodiments. Those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto. The invention is defined by the claims.

Claims

Claims1 . A sample collection device comprising:- an inlet configured to be placed in fluid communication with a sample source;- an outlet in fluid communication with a sequestration portion ,- a sequestration portion in fluid communication with the outlet,- a sampling portion in fluid communication with the sequestration portion; at least one conduit for allowing fluid to enter the sequestration portion,-a filter barrier positioned between the sequestration portion and the sampling portion, and at least one valve for applying a negative pressure; and wherein the sequestration portion and the valve are sized and configured such that an aliquot of a sample may be drawn into the inlet to flow into the sequestration portion.

2. The device according to claim 1 , wherein the sequestration portion and the sampling portion form a unipart sampling chamber, or a separate portions in fluid communication with each other via a junction.

3. The device according to claim 1 or claim 2, wherein the sequestration portion comprises a chamber comprising a lumen, the lumen being defined by an outer chamber wall that at least partially circumscribes a base, and a base abutting the lumen.

4. The device according to any one of claims 1 to 3, wherein the inlet comprises a fluid conduit comprising a bend in order to position the conduit above the outlet.

5. The device according to claims 2 to 4, wherein the junction comprises at least one support element, preferably two support elements.

6. The device according to any one of the preceding claims, further comprising a sample receiver, wherein the sample receiver is positioned within the sampling portion such that a lower section of the sample receiver extends into the sampling portion, while an upper section of the sample receiver is in fluid communication with the filter barrier.

7. The device according to any one of claims 5 or 6, wherein the junction is configured to hold together the sequestration portion, the sampling portion, the filter barrier, and the sample receiver.8 The device accordingto anyone of claims 1 to 7, wherein the filter barrier is located between the base of the sequestration portion and a top side of the sampling portion, wherein wherein the filter barrier is a solid retentate filter barrier.9 The device according to claim 8, wherein the sequestration portion further comprises a junction having a proximal end connected with distal end of the filter barrier, the junction comprising a seal for a sampling portion positioned sealably below the junction, and further comprising a fluid channel guide entering the lumen of the sampling portion, and the at least one valve positioned above the distal end of the channel guide, wherein the valve is configured to apply a negative pressure differential over the sample portion, such that a sample aliquot may be drawn into the sequestration portion, and a filtrate through the filter barrier into the sample portion, thereby displacing at least part of the gaseous content of both portions.10 The device according to any one of claims 8 or 9, wherein a retentate is sequestered on the filter barrier, and wherein a filtrate portion of the sample aliquot is drawn into the sampling portion thought the outlet port when a pressure differential is applied between the inlet, the first sequestration portion and the sampling portion.

11. The device in accordance with any one of claims 8-10, wherein the sequestration portion includes an inner surface that faces the filter barrier, and wherein inner surface of the junction comprises a seal, allowing to separate the sequestration portion into the filter barrier and the outer wall portion, in order to remove the solid retentate and / or to insert and remove a filter medium.

12. The device according to any one of claims 1 to 11 , comprising(a) an inlet portion; a lid portion comprising a first manifold, the first manifold comprising a fluid guide, a seal for the sequestration portion, and a valve; wherein the sequestration portion is configured as an open-ended chamber; and(b) a second portion comprising a filter barrier or filter support, means for detachablyjoining the first portion to said second portion, and(c) a second manifold comprising a fluid conduit, a valve having a vacuum inlet; and a sampling vessel attached to the second manifold.

13. A device according to any one of claims 1 to 12, wherein at least one seal, preferably both seals are executed as one-way seal(s).

14. A method for removing a sample aliquot from a sample source using a device according to any one of claims 1 to 13, comprising submerging a portion of the inlet into the sample source, and applying a pressure differential over the sample and / or sequestration portion, and preferably, wherein the sequestration and / or sample portion may be furnished with a protective inert gas flow.

15. The method of using a device according to any one of claims 1 to 13 to obtain a fluid sample and / or a solid sample, the method comprising:(i) coupling the device (160) to an inlet of the device, the coupling of the device to the inlet configured to produce a negative pressure differential within at least a portion of a sample source;(ii) establishing a fluid communication between the sequestration portion and the sample portion (ii) applying a negative pressure differential to a valve; and(iii) applying a pressure differential over the sequestration and sample portions, to allow an initial aliquot of a fluid sample to flow from an inlet though the outlet into the sequestration portion in response to the negative pressure differential; and(iv) maintaining the pressure differential to allow a filtrate aliquot of a fluid sample to flow through the filter barrier and into the sampling portion, and maintaining the pressure differential until either the filter barrier is blocking further flow, or until a desired sample volume is achieved.

16. A method according to any one of claims 14 or 15, further comprising removing at least part of the sample aliquot from the sequestration and / or sample portion, preferably by using a syringe and cannula.

17. Use of a device according to any one of claims 1 to 13 for the removal and / or separation of samples from a process vessel.

18. A sample collection system comprising: a plurality of sample collection devices according to any one of claims 1 to 13,a plurality of valves, and a negative pressure manifold in fluid communication with the plurality of valves, a control system configured to control the operation of the plurality of valves.

19. The sample collection system according to claim 18, wherein the control system comprises at least one control unit and at least one processing unit.

20. The sample collection system according to any one of claims 18 to 19, wherein the processing unit is configured to set parameters for time and duration for activation of each valve.21 . The sample collection system according to any one of claims 18 to 20, wherein the control unit is configured to actuate the plurality of valves at predetermined timings and for predefined durations, and wherein the control unit is in communication with the processing unit.

22. The sample collection system according to any one of claims 18 to 21 , wherein each of the plurality of valves is independently in fluid communication with a corresponding sample collection device, and each valve is configured to generate negative pressure to a corresponding sampling collection device independently.

23. The sample collection system according to any one of the claims 18 to 22, further comprising an enclosure configured to house the control system, negative pressure manifold, and valves within a single, integrated structure.

24. The sample collection system according to any one of the claims 18 to 23, further comprising at least one sensor.

25. The sample collection system according to any one of the claims 18 to 24, is configured to collect either a single sample or multiple samples simultaneously, or at different timings.

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