WO2025185816A1

WO2025185816A1 - A medical device for processing a sample

Info

Publication number: WO2025185816A1
Application number: PCT/EP2024/055757
Authority: WO
Inventors: Dominik DAUME; Tim HEUMÜLLER
Original assignee: Moeller Medical GmbH
Current assignee: Moeller Medical GmbH
Priority date: 2024-03-05
Filing date: 2024-03-05
Publication date: 2025-09-12
Anticipated expiration: 2026-09-05
Also published as: WO2025186353A1; WO2025185816A8; WO2025186353A8

Abstract

A medical device and method for processing a sample, which may be a cell or tissue sample, in particular of a human lipoaspirate, optimizing a processing of such sample based on inline measurements during the processing. Accordingly, a medical device (10) for processing a sample is suggested, comprising a holder (12) for accommodating a receptacle (14) comprising the sample, at least a first reservoir (16) for a first solution and connectable to an inlet of the receptacle (14), a pump (18), coupled at least to the first reservoir (16) and configured to convey a portion of the respective solution to the inlet of the receptacle (14) in the connected and accommodated state of the receptacle (14) so as to form a fluid stream to an outlet of the receptacle (14), at least one sensor (24), being couplable to an outlet side of the receptacle (14) and configured to measure a particle level within the fluid stream downstream of the inlet, and a control unit (26), communicatively coupled with the at least one sensor (24) and the pump (18) and configured to actuate the pump (18) based on the measurement value of the at least one sensor (24).

Description

A medical device for processing a sample

Technical field

The invention relates to a medical device and method for processing a sample, preferably a cell or tissue sample, in particular lipoaspirate of a mammalian or human. In particular, the invention relates to optimizing a processing of such sample based on inline measurements during its processing.

Technological Background

Patients suffering from a variety of diseases may under certain circumstances benefit from the selective administration of particular autologous tissue and/or cell material. Such grafting typically requires that tissue and/or cells are extracted from a patient and may e.g. be injected or reapplied to the patient after appropriate processing. For example, a lipoaspirate may be extracted from a patient during surgery and may be processed for isolation of particular cells and/or enrichment of the tissue sample, after which the processed sample may be injected back into the patient. In particular, this enables isolated adipose tissue to be e.g. selectively administered into one or more joints of the patients, which has been shown to be advantageous in the treatment of various degrees of arthritis. Furthermore, a selective application of isolated adipose tissue has also been shown to be advantageous in the field of aesthetic and/or plastic surgery.

To process the extracted sample, the sample may be transferred into a device, such as a container, tube, or other receptacle. In case of a lipoaspirate, the processing of the extracted sample and hence the preparation of graft material may e.g. be performed using additional enzymes like collagenase and/or by addition of other ingredients. The mixture containing lipoaspirate will then typically be further processed using e.g. a buffer solution for rinsing and washing, wherein the waste material is discharged. The processed adipose tissue may then subsequently be taken from the receptacle for reapplication to the patient, wherein the processed adipose tissue may be optionally enriched with platelet rich plasma or hyaluronic acid. An enrichment of the extracted sample, e.g. of adipose tissue, may be obtained by incubation with an enzyme containing solution or washing solution, preferably after performing one or more washing steps. The mixture may optionally be mixed and the sample is subsequently centrifuged after incubation for a predefined time at a predefined speed. Thereby, density gradient layers may be obtained, wherein either a particular layer comprising the cells of interest may be aspirated or the waste material may be removed or aspirated, e.g. in case pellet material is to be reapplied to the patient. Such washing or other processing steps and subsequent centrifugation may be repeated according to protocol for a predefined number of times.

Summary of the invention

Starting from the known prior art there is a need to further facilitate the preparation of extracted samples, more specifically tissue samples, in particular a mammalian or a human adipose tissue in a reliable and efficient manner. Preferably, the sample to be processed contains a target cell fraction which may be used, once purified, for therapeutic purposes. Purification requires its isolation from other cell fractions and other non-cellular components. In case of adipose tissue, that tissue comprises debris or other non-cellular components as well as endothelial cells, blood cells, fibroblasts, pericytes, preadipocytes, macrophages, and several types of immune cells (commonly referred to as the adipose tissue stromal vascular fraction (SVF)) and a smaller fraction of stem cells. Typically, adipocytes as well as the adipose-derived stromal cells (ADSC) and/or mesenchymal stem cells are the target cells to be isolated, in particular from the SVF.

According to the invention it has been recognized that standard protocols for preparation of extracted tissue, in particular of human adipose tissue, are cumbersome, as they frequently require multiple manual processing steps, including aspiration and transferring of the sample to enable centrifugation. Furthermore, being subjected to manual handling, any such approach reduces reproducibility of the preparation of the extracted tissue sample, thereby potentially affecting the quality of the purification and/or enrichment of the target cells. To improve the level of purification, typically, a predefined number of washing steps and centrifugation steps are defined in the corresponding protocol.

While, on the one hand, centrifuges may not be readily available, the centrifugation steps, on the other hand, are typically detrimental for the target cells to be purified. Moreover, the total number of washing steps and total centrifugation time as prescribed in the respective protocol may not be appropriate for an individual extracted tissue sample. For example, treatment of the extracted tissue sample with one or more enzymes might require deviations from the standard protocol defining a given number of e.g. washing steps. In case of a lower degree potential contaminants or impurities, strict application of a protocol defining the number of washing steps might not be required either. By the same token, the predefined number of washing and centrifugation steps may be insufficient, e.g. in case a higher level of impurities is present or in case of a larger volume of the extracted tissue or cell sample. Thus, the prior art does not address the individual characteristics of a given sample.

Accordingly, a clinician is not provided with a reliable measure to assess the efficacy of any washing or other processing steps to be performed. The processing time is furthermore defined by a corresponding protocol and is not adapted to the individual extracted tissue sample and the required level of purification for the respective medical application.

It is hence an object of the present invention to provide an improved processing of a tissue or cell sample, in particular by providing a processing that is gentle to the cells and/or which ensures an improved reproducibility and processing efficiency.

The above object is solved by means of a medical device for processing a sample, preferably a cell or tissue sample, in particular a mammalian or human tissue or cell sample, comprising the features of claim 1. Further preferred embodiments are presented in the dependent claims, the description and the Figures.

Accordingly, in one aspect, a medical device for processing a sample is suggested, comprising a holder for accommodating a receptacle comprising the sample, at least a first reservoir for a first solution and connectable to an inlet of the receptacle, a pump, coupled at least to the first reservoir and configured to convey a portion of the respective solution to the inlet of the receptacle in the connected and accommodated state of the receptacle so as to form a fluid stream to an outlet of the receptacle. The "portion" of the solution is understood to be a volume fraction of the total volume of the solution. The medical device furthermore comprises at least one sensor, being couplable to an outlet side of the receptacle and configured to measure a particle level within the fluid stream downstream of the inlet, and a control unit, communicatively coupled with the at least one sensor and the pump and configured to actuate the pump based on the measurement value of the at least one sensor. The "particle level" is understood to represent the total amount components being dissolved, dispersed, or emulsified in a fluid, including cells and other components. The amount of particles is determined by e.g. optical methods, ultrasonic methods, and/or inductive methods to determine the properties of the measured fluid.

By means of the at least one reservoir and the coupled pump, a solution may be conveyed to the inlet of an accommodated and fluidical ly coupled receptacle. Thereby, it is enabled that several processing steps requiring e.g. the addition of an enzyme solution or washing solution may be administered essentially automatically, hence avoiding any manual handling. The actuation of the pump, e.g. by means of a control signal output by the control unit, avoids any inaccuracies when administering the respective solution, which may otherwise potentially occur during manual handling. Furthermore, the sensor that is arranged at the outlet end of an accommodated receptacle provides a closed feedback loop mechanism by providing measurements to the control unit regarding the particle level being present at the outlet of the receptacle or downstream thereof. Said particle level may be considered as a measure for an achieved purity of the sample being processed or as a measure for an efficacy of the sample preparation.

For example, the sample, in particular a cell or tissue sample may be a human lipoaspirate, hence forming a liquid or semi-solid and/or at least partially colloidal sample comprising a variety of cells, e.g. aside from adipocytes and/or adipose derived stem cells (ADSC), which may be the target cells to be obtained with the processing, also hematopoietic cells, smooth muscle cells, endothelial cells, etc. Accordingly, the types of cells and their relative proportion may vary for each sample. By means of the application of the at least one solution, a (corresponding) portion of the fluid or semi-solid sample may be discharged from the receptacle via its corresponding outlet. A portion, e.g. a partial volume or a volume fraction, of the sample is, however, retained within the receptacle, e.g. due to the presence of one or more filters present in the receptacle and based on a pore size. The pore size may be appropriately chosen in view of the size of the target cells to be retained in the receptacle or subsequently collected.

The portion of the sample being conveyed towards and/or exiting the outlet may e.g. comprise blood cells, debris, and/or other cells or tissue not being of interest, which may hence be washed out of the sample by the application of the at least one solution. The sample may e.g. be treated with a solution comprising an enzyme or lysis agent; thereby, lysed or digested particle, e.g. cells or other components, may e.g. penetrate through correspondingly sized pores of a filter or membrane used in the receptacle and exit the receptacle via its outlet. By means of the (subsequent or simultaneous) application of e.g. a washing solution, a purification of the portion of the sample being retained within the receptacle is enabled, while impurities may be discarded. Thereby, centrifugation steps may be effectively avoided.

In this regard, the measurement of the downstream particle level may hence indicate that impurities are (still) being washed out of the receptacle. In such case, the control unit may actuate the pump of at least the first solution e.g. to continue or repeat a corresponding washing step until a desired level of purity is achieved.

The inventors of the present application have found that the inline processing according to the invention hence provides an advantageous ex vivo closed fluidic system; thereby an accommodated receptacle is f I u idical ly coupled to the at least one solution at its inlet. Preferably, the receptacle is fluidically coupled to a waste reservoir or waste bag at its outlet, which may optionally be present in the medical device. Thereby, the solution(s) required for the processing are hence integrated in the device and automatically administered. Waste may optionally be automatically collected. Manual handling or manual processing steps may be largely avoided, such that the reproducibility is improved and the risk of error may be significantly reduced.

Furthermore, the provision of the closed loop feedback system, which is based on the at least one sensor and the control unit to actuate the pump of the fluidic system, enables that the processing steps may be adapted to the actual sample in the receptacle. That approach may also establish a desired purity level of the retained sample in a time-efficient manner that may process the delicate cells more gently. The provision of a retaining structure within the receptacle, e.g. one or more filters and/or membranes, furthermore renders centrifugation steps obsolete.

In other words, the medical device according to the invention enables to automatically control the process time and efficacy of a method for preparation of a sample, in particular a tissue or cell sample, such as human adipose tissue sample. In this regard, the sensor and the control unit, which together form a closed loop control system, ensure that the shortest possible washing procedure, which is also gentler to the adipose tissue without causing any damage to the cells, may be implemented.

Preferably, the at least one (first) solution may e.g. be a washing solution or buffer solution, preferably an aqueous solution, more preferably a buffered aqueous solution, such as Ringer's solution or saline. It may, additionally or alternatively, also comprise one or more particular enzymes or lysis agents, as required for the respective sample and medical application. For example, a lysis buffer and/or solution comprising one or more enzymes may be added to the sample prior to accommodating the receptacle into the holder or may be added to the sample accommodated in the holder e.g. as an initial solution and/or in intermediate steps. A washing solution may subsequently be added to the sample to wash out any lysed cells, particles, and/or debris from the sample via the outlet of the receptacle.

The medical device may comprise more than one sensor, which may be arranged in a spacedapart or adjacent manner along a flow direction. The provision of multiple sensors may provide a level of redundancy and/or may enable the measurement of different or more specific characteristics. The medical device may also comprise a single sensor, which may provide an improved cost efficiency and may reduce computational effort. Furthermore, the use of a single sensor may reduce the cognitive efforts required for operation of the medical device and may provide a more intuitive and/or simplified operation mode.

The at least one sensor preferably allows for multiple measurements during the processing of the sample. Such measurements may be provided continuously or periodically. A series of measurements may be preferably performed at least during the actuation of the pump and the application of the first solution to the sample comprised within the receptacle. Preferably, the at least one sensor is configured for optical measurements or acoustic measurements. In particular, the at least one sensor may be configured as a turbidimeter, a nephelometer, a spectrometer, a light gate, a camera system, or an ultrasound device.

The at least one sensor is preferably configured as a turbidimeter or spectrometer so as to provide a measure for the intensity of scattering or transmission, which may be directly related to the amount of particles or components being present at the downstream or outlet end of the receptacle. However, other optical systems may be implemented, such as an infrared sensor, a machine vision system or a multispectral machine vision system. Likewise, acoustic sensors may be implemented, enabling the measurement of an ultrasonic distance or time of flight of the particles or components being present. The type of sensor may be chosen in accordance with the level of accuracy and specificity required and/or may be dependent on the available or desired arrangement of the sensor, i.e. whether the sensor may be arranged at an angle, e.g. to avoid incident light from an illumination source.

The at least one sensor is preferably configured for optical measurements at one or more wavelengths or one or more wavelength ranges. For example, a broadband spectrometer may be implemented as a sensor, such that the measurement may e.g. be adapted to a particular wavelength or wavelength range. It may also be provided that only specific wavelengths are detected, wherein one or more wavelength ranges are not within the detection range, e.g. to increase the specificity of the measurement. That approach may e.g. be advantageous if a larger number of non-target cells are present in the sample. Excitation or illumination of said cells at a particular wavelength may cause distorted measurements at other wavelengths.

Furthermore, the control unit may determine the particle level also based on two or more wavelengths that preferably provide no spectral overlap. Thereby, not only a level of redundancy may be provided, but also the accuracy and reliability of the measurement may be improved. For example, the absence of a measurement signal at a given wavelength may indicate an erroneous operation of the sensor, while unexpected high measurement values may e.g. indicate an erroneous calibration or clogging. To further improve the accuracy of the measurement, the measurement values observed at the two or more wavelengths or wavelength ranges may be averaged, whenever said measurement values are within an expected and predefined measurement range.

The different wavelengths may also be used to indicate an unexpected number or concentration of cells being present at the downstream end that should e.g. be retained within the receptacle. For example, a larger measurement value at a wavelength being associated with adipose tissue may indicate that e.g. one or more filters or membranes at the outlet end of the receptacle are malfunctioning or leaking. Accordingly, the control unit is preferably configured to output a warning signal, if the measurement value at a particular wavelength or wavelength range exceeds a predefined threshold.

The sensor measurement is carried out at a downstream end, i.e. at the outlet side of the receptacle. Thereby, the effect of the addition of a portion of the at least one solution may be detected; thereby, it may be determined whether e.g. a washing step of the sample actually results in a discharge of waste particles, such as cells, or components or debris. Accordingly, at least one of the at least one sensor may be couplable to a tube fluidically coupled with and downstream of the outlet and/or may be arranged to be adjacent to said outlet in the accommodated state of the receptacle.

For example, a tube or tube set may be fluidically coupled to the outlet of the receptacle, wherein the sensor may be coupled to said downstream tube. Such an arrangement has the advantage that the sensor may e.g. be pre-installed prior to accommodating a receptacle into the holder. The provision of a downstream tube may also facilitate the coupling of the sensor due to the simple and continuous shape/geometry of the tube and the possibility to provide an extended tube length. An operator may accordingly mount the sensor (and optionally the tube) at a predefined position that may be easily accessed. To further facilitate the coupling of the sensor to the tube, one or more brackets or clips may be provided or integrated with the sensor to ensure a predefined position of the sensor relative to the tube and inner lumen thereof. For example, the sensor may comprise a corresponding recess for a predefined tube diameter and/or may comprise one or more retention elements so as to at least partially enclose the tube in the coupled state. Accordingly, the tube or tube set may be e.g. clipped into the sensor, for example, by interference fit or positive locking.

In order to establish a more compact integrated design, the sensor may also be configured to be adjacent to the outlet, in particular by at least partially surrounding a portion of the outlet portion of the receptacle. The sensor may hence be arranged directly downstream of the sensor and/or may extend, at least partially, along the outlet. Thereby, a more direct measurement within the receptacle or directly downstream of the receptacle may be ensured. The total inner lumen volume of a downstream tube or tube set may be reduced as well. Accordingly, the amount of solution being added to the sample within the receptacle may also be reduced and a more direct adjustment of the pump actuation may be provided.

Preferably, the medical device comprises a flow cuvette that is arranged to be in fluid communication with the outlet in the accommodated state of the receptacle, wherein one of the at least one sensors is arranged to measure the particle level within the flow cuvette. The flow cuvette may be arranged downstream of the outlet and may e.g. be fluidically coupled to the outlet via a connecting tube. Thereby, more flexibility may be provided with regard to the position and arrangement of the cuvette and installment of the cuvette may be facilitated. The provision of a flow cuvette has the advantage that the measurement quality or resolution may be improved, in particular in case of optical measurements. Furthermore, the (in particular optical) coupling of the at least one sensor may be facilitated.

The control unit is preferably configured to actuate the pump to convey a predefined volume of the respective solution, to convey the volume of the respective solution for a predefined time, and/or to convey the volume of the respective solution at a predefined flow rate based on the measurement value of the at least one sensor. The control unit may hence accordingly adjust a pump duration and/or pump pressure to apply the solution as required based on the measurement.

For example, a washing step initiated by actuation of the pump for the corresponding solution may be performed with a predefined volume of said solution and/or may be performed for a predefined washing time. Thereby, it may be ensured that any undesired particles are removed from the sample, i.e. are washed out of the receptacle. Still, the target cells are retained within the receptacle, e.g. due to the presence of one or more corresponding filters or membranes. Such washing step may also be performed at a predefined flow rate, which may be advantageous to control e.g. the level of mixing of the sample, wherein the flow rate may also be dependent on the density of the retained sample.

Accordingly, the flow rate, volume, and duration of the addition of the one or more solutions may be adapted depending on the efficacy of the particle/component removal and the corresponding measurement of the particle level at the downstream end or outlet end of the receptacle. For example, an initially measured high turbidity may cause the pump to be actuated for a longer time and/or at a higher pump pressure than a successive fine tuning, when the turbidity is reduced and a corresponding measured intensity level is improved.

The control unit may be configured to actuate the pump to convey the portion of the respective solution continuously or to convey successive portions of the respective solution based on the measurement value of the at least one sensor.

The continuous addition of the solution may be advantageous to continuously determine the effect on the particle level and to detect or avoid any potential measurement fluctuations. The application of successive portions or solution volumes enables that the incubation time of the sample with the respective solution, e.g. a solution comprising one or more enzymes or lysis agents, may be controlled and potentially adjusted. Such incubation steps or other intermediate processing steps may e.g. be alternated with washing steps. Thereby, an iterative purification of the sample may be provided, wherein preferably the flow rate, duration, and/or volume of the solution to be added may be adjusted based on the current measurement value provided by the sensor. In order to avoid an application of excessive solution and/or to ensure that a desired or predefined purity of a retained sample is obtained, the control unit may be configured to actuate the pump based on a comparison of an actual measurement value with a predefined threshold value. The threshold value is preferably a predefined percentage of a measurement value obtained for a reference value.

For example, the actual measurement value may be compared with a corresponding threshold or threshold range indicative of a predefined turbidity level. An actual measurement value or intensity may hence be indicative of the particle level being discharged or washed out of the receptacle and may be an indirect measure of an achieved purity of the portion of the sample being retained within the receptacle. The threshold value in this regard may e.g. define a tolerable or target measurement value, e.g. an intensity. The pump may hence be automatically actuated, if the measurement value exceeds said threshold, e.g. a measured intensity is larger than said threshold, wherein the larger intensity indicates a low particle level.

To accommodate for potential measurement inconsistencies, the threshold value is preferably a predefined percentage of a measurement value obtained for a reference value. For example, prior to the addition of one or more solutions to the receptacle comprising the sample, the sensor may be calibrated by rinsing a reference solution through a downstream tube or flow cuvette coupled to the sensor. Accordingly, the sensor measurement of said reference solution, e.g. saline, may provide a base line, without any particles or components being present. The predefined percentage may e.g. be between 70 percent and 100 percent, preferably between 80 percent and 95 percent of the measurement value obtained with the initial reference solution. Thereby, a sufficient efficacy of any rinsing, washing, and/or enrichment steps performed during the processing may be ensured.

The particle level in this regard hence preferably does not provide an absolute particle amount or concentration and/or preferably is not particle-specific or cell-specific. Instead, it preferably indicates a relative level to the reference solution. Thereby, performing the sensor measurement may be facilitated and the control of the pump may be significantly simplified.

For example, when conveying one or more solutions to the inlet of the receptacle, a measurement intensity of the sensor may decrease compared with the measurement intensity obtained with the initial reference solution. This is because due to addition of the solution, particles or components are being washed out of the receptacle via its outlet and the particle level at the outlet end, e.g. within a downstream tube or flow cuvette, is increased. Accordingly, the turbidity of the downstream flow is increased, such that e.g. the level of transmitted light is reduced or the level of scattered light is increased in case of an optical measurement. The control unit hence automatically actuates the pump, e.g., to initiate a further washing step and reduce the downstream particle level while improve the rinsing of particles or components from the portion or volume of the sample being retained in the receptacle.

Once a measurement value is obtained that does not exceed the threshold value, the actuation of the pump may be omitted as a sufficient purity of the retained sample is achieved.

The control unit may also be configured to determine a rate of change for obtained measurement values and to actuate the pump based on said rate of change.

For example, in case a small rate of change is determined at a measurement value indicating the presence of a large particle level, a corresponding larger volume of a washing solution or a corresponding increase in the flow rate of the solution, i.e. an increased pump duration or increased pump pressure, may be indicated. The rate of change may also be compared with a corresponding threshold value, which may furthermore optionally be dependent e.g. on the number of washing steps that have been performed and/or the volume of the sample within the receptacle.

Such threshold value for the rate of change may also be dependent on an initial measurement value, e.g. obtained when a solution is conveyed to the inlet of the receptacle for the first time. Accordingly, an initially determined high particle level may require a corresponding larger rate of change, such that the threshold value for the rate of change may be accordingly larger in comparison with a threshold value for an initial low particle level. Thereby, it may be provided that a sufficient rate of change is achieved in accordance with the initial downstream particle level.

The control unit may also be configured to output a warning signal, whenever an insufficient rate of change is determined at a predefined particle level or relative percentage. For example, a warning signal may be output, if a high initial particle level and failure of a sufficient rate of change to reduce said particle level is detected. A warning signal may also be output if an adjustment of the pump variables does not result in a (sufficient) improvement of the rate of change. Thereby, an operator may monitor the sample and adequate operation of the medical device to ensure proper processing of the sample.

For an operator to monitor the processing of the sample, the control unit may also be coupled to a display, which may optionally be integrated in the medical device. The control unit outputs a signal related to measurement value to said display. Accordingly, an operator may e.g. monitor a current value and/or a course or progression of the processing, optionally also a rate of change, predefined threshold values, and/or baseline measurement values for a reference solution.

As described above, the cell or tissue sample may preferably comprise or essentially consist of a lipoaspirate. Such lipoaspirate may have been obtained during surgery, e.g. by liposuction, of a patient. A purified fraction of the lipoaspirate may be administered to the patient after processing or preparation of the sample. As a result of the automated processing enabled by the medical device of the present invention, the sample may be purified and/or enriched in an automated and time-efficient manner. Thereby, a specific cell fraction, e.g. stem cells, may be enriched and/or purified from the initial patient sample. The quality of the processed sample may allow for a be significantly enriched fraction of the target cell fraction, moreover typically in a reproducible manner. This is particularly advantageous for lipoaspirates. Fractions of the initial sample containing non-cellular components, e.g. debris and/or non-target cell types may be removed and, thereby, the target cell types, e.g. adipocytes or ADSCs, may be concentrated or purified or isolated. They may be advantageously used for the therapeutic applications. The automatic processing according to the present invention is hence particularly advantageous, as prior art inferior methods based on manual operations rarely allow to arrive at reproducible results. Moreover, such manual methods do typically not encompass any feedback loop allowing the monitoring of the quality of the purified target fraction. Thereby, the inventive method ensures an unprecedented upgrading of the initially surgically removed adipose tissue by enriching and purifying its target fraction.

The medical device may furthermore comprise a mechanical processing device couplable to the receptacle in the accommodated state of the receptacle. The control unit may preferably be configured to actuate the mechanical processing device based on the measurement value of the at least one sensor. The receptacle may e.g. be coupled with a stirring or mixing device, e.g. a magnetic stirrer that is either present in the receptacle or is coupled to its outer wall. Such mechanical processing may e.g. be foreseen in an intermediate step after and/or prior to a washing step, e.g. in an alternating manner. Alternatively, such mechanical processing may also be performed simultaneously with conveying of the one or more solutions towards the inlet of the receptacle, e.g. to enable a more efficient mixing.

The actuation of the mechanical processing device may be based on a determined rate of change of the measurement value and/or a relative measurement value, e.g. an achieved percentage of an intensity relative to an initial reference solution. By the same token, the duration of the actuation and/or speed or pressure of the mechanical processing may also be dependent on the actual status of the sample being processed according to the recorded measurement values.

Enrichment to the sample and/or to provide different processing steps, e.g. both washing and selective digestion, may be preferably achieved by the medical device according to the invention. It may comprise more than one reservoir for a respective solution, each reservoir being connectable to an inlet of the receptacle and being coupled to at least one pump of the medical device. The medical device preferably comprises a respective pump for each reservoir. For example, one reservoir, e.g. the first reservoir, may comprise a washing solution or saline while a second reservoir may comprise an enzyme solution and/or lysis agent. Thereby, processing steps may be based on the actuation of the pump to the individual reservoir, e.g. in an alternating manner. While a single pump may be coupled to multiple reservoirs, the medical device preferably comprises multiple pumps or a pumping system to convey the solution from the respective reservoirs. Alternatively, a single pump may also be provided. A pump head of a single pump embodiment may be displaced or moved so as to be coupled with one of the reservoirs based on the signal obtained from the control unit.

According to another aspect of the invention, a system is suggested, comprising a medical device according to the invention and a receptacle for receiving the sample. The receptacle comprises an inlet and an outlet, wherein the inlet is f I ui dical ly connected to at least the first reservoir and an outlet end of the receptacle is coupled to the at least one sensor.

The receptacle may be provided separately from the medical device and may e.g. be accommodated within the holder, once the sample has been introduced into the receptacle. The receptacle may e.g. be formed as a container, tube, reservoir, or syringe. Its shape may be dependent on the size or volume of the sample and the required handling and/or extraction method of the sample. The receptacle is preferably configured as a disposable. While the inlet is fluidical ly connected to the at least one reservoir comprising a respective solution, the outlet is preferably fluidically connected to a waste reservoir, waste bag, or downstream discharge line. Thereby, undesired non-target particles or components may be removed from the sample, e.g. by means of one or more washing steps.

An inner chamber of the receptacle retains at least a portion of the sample within the receptacle. A flow of an undesired portion of the sample out of the outlet is typically established, once a solution has been provided to the inlet of the receptacle. In order to retain the desired portion within the receptacle, the receptacle preferably comprises one or more filters and/or membranes with a predefined pore size and/or filter size. The features of the receptacle which may be adapted to the individual application and may hence be dependent on the type of sample to be processed and the type of cell(s) to be purified and obtained by said processing.

According to another aspect of the invention, a method for processing a sample, preferably a cell or tissue sample, is suggested, comprising the steps of: providing the sample, preferably comprising or essentially consisting of a lipoaspirate, in a receptacle; fluidically coupling an inlet of the receptacle with at least a first reservoir; and actuating a pump coupled at least to the first reservoir to convey a volume of a solution contained in the respective reservoir to the inlet of the receptacle to form a fluid stream to an outlet of the receptacle, wherein the actuation of the pump is based on a measurement value of at least one sensor coupled to an outlet side of the receptacle and configured to measure a particle level within the fluid stream downstream of the inlet.

The features and advantages discussed with respect to the medical device also apply to the method and vice versa. The advantages and potential embodiments described for the medical device according to the invention thus apply to the method according to the invention as well.

As described above, the addition of a portion of the solution, e.g. a predefined volume, causes a fluid stream downstream of the inlet. The fluid passes or runs through at least a portion of the sample before exiting the receptacle at the outlet. Thereby, non-target tissue components and/or debris, for example, may be effectively removed from the receptacle and the sample comprised therein. The particle level measured downstream of the inlet, i.e. at the outlet or downstream of the outlet and preferably not at the level of the sample itself, may hence be considered as a measure for the efficacy of the purification level of the sample. Upon decrease, e.g. gradual decrease, of the measured particle level, the amount of undesired non-target components or particles of the sample, e.g. non-target cells and/or debris, within the sample, the contamination of the target component, e.g. the target cell-type, by non-target components is been reduced.

The automated processing provided by the method according to the invention results in a portion of the sample being retained in the receptacle. The retained portion comprises an improved purity of the cells and/or tissue to be subsequently used for medical applications. The retention of the target portion of the sample within the receptacle may be ensured by one or more filters and/or membranes. Alternatively, or in addition, cam-based solutions may be provided, e.g. for retaining structural extracellular matrix proteins such as collagen. The filter size or pore size may be adapted to the particular application, in particular to a cell size of the cell type being of primary interest.

Actuation of the pump may be caused by the provision of a corresponding control signal. The control signal may be output by a control unit or, alternatively, directly from the sensor itself. The control unit is typically communicatively coupled with the at least one sensor and the pump. The provision of the sensor that is coupled, e.g. optically and/or mechanically, to the outlet side of the receptacle advantageously allows for an inline measurement is provided. Removal of the receptacle is hence not required. As a result, processing of the sample may be significantly expedited. Furthermore, direct feedback regarding the efficacy of the processing as established by the sensor measurement enables an automatic control of the processing by means of the pump control. Accordingly, the sample may be processed in a closed fluidic system. The feedback loop provided by the inline measurement enables an optimized and automated processing of the sample to achieve a predefined quality of the retained portion of the sample, advantageously in a time-efficient, reproducible and tissue or cell preserving manner.

The sensor measurement may preferably be based on the turbidity of the fluid stream. Such turbidity may e.g. be recorded by an optical sensor. The turbidity may e.g. be determined from a level of scattering or transmission. Accordingly, the measured data may e.g. be collected by means of a sensor configured as a turbidimeter, a nephelometer, a spectrometer, a light gate, a camera system, or, alternatively, an ultrasound device.

Preferably, the sensor measurement may be an optical measurement at one or more wavelengths or one or more wavelength ranges. For example, the measurement may be carried out by a spectrometer using a broadband spectrum or may be restricted to particular wavelength ranges. By means of a measurement at one or more wavelengths using a spectrometer, the measurement may be easily implemented and may potentially be performed more accurately or in a cell or tissue-specific manner. Preferably, the optical measurement may include two or more wavelengths, wherein e.g. a signal averaging may be performed to improve the quality, accuracy, and reliability of the measurement. For example, by measuring at two or more wavelengths, a level of redundancy may be implemented. Measurement fluctuations may be preferably flattened by averaging or other suitable approaches. Furthermore, measurement values that are recorded as lying outside of a predefined range at a particular wavelength may be identified and discarded as an artefact. Measurements at one or more wavelengths serving as a base line may be obtained to monitor proper sensor measurement. Positive and negative control measurements may serve to validate the measurement. Thereby, a positive control sample may be provided containing one or more one or more agents or (cellular) components providing a positive standard measurement result at one or more given wavelengths. Also, the wavelength(s) applied should typically not trigger significant intensity variations or fluctuations.

The measurement is preferably performed through a flow cuvette being in fluid communication with the outlet. As described above, the provision of a flow cuvette, preferably being coupled to a tube fluidically coupled with and arranged downstream of the outlet, enables an inline measurement with improved quality and reproducibility, in particular when using an optical sensor. Measurements may also be performed at a corresponding tube or discharge line, directly at the outlet of the receptacle itself, or to another downstream reservoir, yet upstream of a potential waste reservoir or waste bag.

The pump may be actuated based on a comparison of an actual measurement value and a predefined threshold value, the threshold value being a predefined percentage of a measurement value observed and recorded for a reference sample. Thereby, rather than establishing recordation of absolute values, a relative value may be recorded. The reference value, observed by a measurement with e.g. saline, may provide a base line without any particles or components of the sample being present. Performing the sensor measurement may be facilitated and the control of the pump may be significantly simplified. The predefined percentage may e.g. be between 70 percent and 100 percent, preferably between 80 percent and 95 percent of the measured value observed and recorded for the initial reference solution. Thereby, efficacy of any rinsing, washing, and/or enrichment steps performed during the processing may be determined or ensured.

As described above, the pump may be actuated to convey a predefined portion or volume of the respective solution, to convey the volume of the respective solution for a predefined time, and/or to convey the volume of the respective solution at a predefined flow rate based on the measurement value of the at least one sensor. Likewise, the pump may be actuated to convey the volume of the respective solution continuously or to convey successive volumes of the respective solution based on the measurement value of the at least one sensor.

Preferably, the method furthermore comprises the step of determining a rate of change for observed measurement values. The pump may be actuated based on said rate of change.

Thereby, a suitably adjusted, in particular a larger volume of e.g. a washing solution or an increase in the flow rate of the solution, i.e. an increased pump duration or increased pump pressure, may be implemented, whenever the rate of change falls below a predefined value or below a predefined threshold value.

In addition to e.g. any washing, rinsing, selective digestion, selective lysis, and/or incubation of the sample, the method may furthermore comprise the step of actuating a mechanical processing device coupled to the receptacle based on the measurement value of the at least one sensor. A mixing the sample and/or disintegrating the content, e.g. tissue, of the sample may be enabled, for example, to facilitate the removal of undesired non-target particles or components from the sample. For example, a magnetic stirrer may be provided in the receptacle, which may be activated by a corresponding signal of the control unit. The speed and duration of the stirrer may be based on the observed measured value, the determined particle level, or the determined rate of change of the measured value.

The provision of such mechanical processing inline with the automated fluidic system, i.e. the pump-driven at least one reservoir with a respective solution, the receptacle, and an optional downstream waste reservoir, enables the processing of the sample to be performed in a fully automated or semi-automated manner. In addition to e.g. one or more washing steps, the sample may also be mechanically mixed to expedite the processing and removal of undesired particles or components. By means of the closed feedback based on the sensor measurement, such washing and mixing may be automatically adjusted depending on the actual particle or component level in the fluid flow being discharged via the outlet of the receptacle.

Brief of the

The present disclosure will be more readily appreciated by reference to the following detailed description when being considered in connection with the accompanying drawings in which:

Figure 1 shows a schematic depiction of a medical device according to the invention;

Figure 2 shows a schematic depiction of method steps for an automated processing of a sample according to the invention;

Figure 3 shows a schematic depiction of measurement values observed by a sensor for a reference solution and a processing of a lipoaspirate sample;

Figure 4 schematically shows the effect of particles or components on a transmission intensity at different wavelengths of an optical sensor; and

Figure 5 schematically shows alternative embodiments and arrangements of an optical sensor for measuring a particle or component level at an outlet end of a receptacle.

Detailed description of preferred embodiments

In the following, the invention will be described in more detail with reference to the accompanying figures. In the Figures, like elements are denoted by identical reference numerals and repeated description thereof may be omitted in order to avoid redundancies.

In Figure 1 a schematic depiction of a medical device 10 is shown, which may be used for automated processing of a tissue sample, in particular for a lipoaspirate comprising adipose tissue, e.g. for the purification of adipose derived stem cells. The medical device 10 comprises a holder 12 which is configured to accommodate a receptacle 14. Within the receptacle 14 a tissue sample may be provided prior to accommodating the receptacle 14 into the holder 12. The holder 12 may e.g. be configured to provide an interference fit or positive locking with the receptacle in order to secure the receptacle 14 in place. For example, the receptacle 14 may have a container shape, wherein the holder 12 comprises a corresponding recess to receive the container and/or may comprise one or more clamps or springs to bias the container into a predefined position relative to the holder 12.

The receptacle 14 is fluidically connected to a reservoir 16, which comprises a solution, e.g. a washing solution or buffer compatible with the tissue sample, such as saline. The fluid connection is achieved by means of an inlet of the receptacle 14 and an outlet of the reservoir 16, wherein a valve or other selective fluid restriction means may be present at the outlet of the reservoir 16. In order to apply or administer a portion of the solution, e.g. a predefined volume of the solution contained in the reservoir 16, a pump 18 is coupled to the reservoir 16, which is shown having a piston for displacing the solution and to convey the solution towards the inlet of the receptacle 14. However, it will be understood that the pump 18 may have different configurations enabling an alternative coupling with the respective reservoir 16.

When the pump 18 is actuated, a fluid flow is established within the receptacle 14 upon addition of the volume of the solution. While undesired (non-target) particles or components may be washed out of the receptacle 14, the desired tissue or cells are retained within the receptacle 14 due to the presence of a downstream filter 20. Accordingly, a filter size or pore size of the filter 20 may be chosen, such that the cells to be retained are prevented from passing through the filter 20 in the downstream direction. Debris, lysed cells and other components or types of cells that have a smaller diameter than the pore size, however, may pass through the filter 20 and may hence be discharged via a downstream tube at the outlet side towards a waste bag 22 for disposal.

In order to determine the efficacy of e.g. a washing step enabled by the pump 18 and the reservoir 16, a sensor 24 is arranged at the outlet side of the receptacle 14. In the present, exemplary embodiment, said sensor 24 is arranged along a downstream tube and is preferably configured as an optical sensor, such as a turbidimeter or spectrometer. Once the downstream fluid flow is established upon actuation of the pump 18, the sensor 24 measures a particle or component level, e.g. based on a detected turbidity or reduction in light transmission at one or more wavelengths.

The observed measurement value of the sensor 24 is then forwarded to a control unit 26, wherein it is determined whether the measurement value of the sensor 24 corresponds to a measurement value of a reference solution, e.g. saline, which may have been provided to the sensor 24 prior to accommodating the receptacle 14 into the holder 12. Accordingly, it may be determined whether the current measurement value approaches the measurement value indicating no or no significant number of particles or amount of components as being present in the downstream fluid flow. It is thus determined that the washing step has been effective and terminated. If the particle level is still high and the observed measurement value with the sample does not match with a predefined percentage of the measurement value of the reference solution, the control unit 26 may actuate the pump 18. Thereby, the administration of the respective solution is continued, either continuously or periodically with a predefined volume of the solution, such that e.g. a washing step may be prolonged or repeated as required.

If the particle level obtained from the measurement value is confirmed to lie within a predefined percentage of the reference solution, e.g. between 85 percent and 95 percent of the measurement value observed for the reference solution, the processing of the sample may be considered to have been terminated. No further actuation of the pump 18 is required. Thereby, an automated processing is achieved in a time-efficient manner, while avoiding the use of excess solution.

In Figure 2, a schematic depiction of corresponding method steps for an automated processing of a sample is shown. Accordingly, in step S100, a sample comprising a lipoaspirate is introduced into a receptacle, wherein the receptacle is configured to be brought into fluid communication with a reservoir at an inlet side. It is preferably connected to a discharge line or downstream tube for efficient waste collection and disposal. Once the receptacle has received the sample and has been fluidically coupled, a pump may convey a solution to the receptacle inlet in step S110, such that a fluid flow or stream towards an outlet side of the receptacle is established.

A sensor measurement is then performed in step S120. The sensor measurement may be performed continuously. The sensor is preferably an optical sensor and is configured to measure a particle level within the fluid stream downstream of the inlet, such that e.g. the efficacy of a washing step may be determined. If the washing step has been sufficiently applied and has been terminated, the measurement value corresponds to a reference value in step S130. As described above, the reference value corresponds to a measurement value observed for a reference solution, such as saline, for which the particle level may be considered "zero" or at least insignificant.

If the measurement value or particle level comes close to the measurement value observed for the reference solution, e.g. if it corresponds to about 90 percent or more, step S150 enables determination that a sufficient number of particles have been washed out of the sample being retained in the receptacle. The washing step(s) is/are hence terminated. Accordingly, the receptacle may be removed and the retained, purified sample may be used for subsequent applications, e.g. for medical purposes.

However, if the measurement value or particle level downstream of the sample is not within such percentage range, step S140, an undesirable number of particles may still reside within the sample contained in the receptacle. In such case, the actuation of the pump may be continued or repeated in step S110 so as to improve the purity level of the sample retained in the receptacle.

An example of intensities observed by an optical sensor, e.g. a turbidimeter, for a reference solution and after a washing step of a sample is depicted schematically in Figure 3. Accordingly, the signal amplitude measured by the sensor is initially at a maximum intensity l_max at a time point To for a reference solution, as indicated with reference numeral 28. Said maximum intensity lmax may hence establish a base level for subsequent measurements as a result of the processing of e.g. a lipoaspirate sample.

At time point , the washing step indicated with reference numeral 30, the intensity significantly decreases due to the high particle level and corresponding e.g. to the turbidity occurring in the fluid stream being measured. At this point, the larger decrease of the signal intensity is due to debris like collagen in the washing fluid pumped into the waste reservoir (time span T1-T2).

As a result of the purification of the adipose tissue, the amount of debris in the waste fluid gets less, such that the sensor signal level rises again, as shown for the time span T₂-T₃. At time point T₃,the sensor reaches the level of the initial state or its measurement is at least within a predefined percentage, e.g. between 90 percent and 100 percent (indicated at time point T₄), of the reference solution. Such a purity may be considered as sufficient for further usage of the purified sample.

Figure 4 schematically shows an experimental setting, wherein the effect of particles on a transmission intensity at different wavelengths of an optical sensor is assessed. Accordingly, a time dependent intensity of the isolated wavelengths is identified in Figure 4. The scale is presented based on a logarithmic scale for better visualisation. It is shown that at each wavelength the light transmission intensity or percentage decreases, when particles or components from a tissue sample, such as adipose tissue obtained from a lipoaspirate, pass along the sensor. Hence, a broad wavelength spectrum may be chosen, as either of said wavelengths is suitable for a potential optical sensor, such as a light gate. Although not shown in Figure 4, the observed measurement signals are verified for not representing illumination dependent artefacts.

Figure 5 schematically shows alternative embodiments and arrangements of an optical sensor 24 for measuring a particle level at an outlet end of a receptacle. As shown in panel A, the sensor 24 may be coupled to a tube 32 arranged downstream of an outlet of the receptacle, as indicated by the arrowhead, wherein the sensor 24 surrounds the tube 32 in an adjacent manner. In this example, the sensor 24 is an optical sensor, which may be configured as a light gate, as indicated by the dashed line crossing the lumen of the tube 32. Such configuration enables a simple implementation of a sensor 24 and ensures a higher level of flexibility for the arrangement and coupling of the sensor 24 relative to the tube 32.

An alternative configuration of the sensor 24 is depicted in panel B, wherein the sensor 24 is arranged at a distance from the tube 32. Here, the sensor 24 is configured as a camera, depicted on the left, and an illumination source, depicted on the right. The camera and the illumination source are arranged at a 90 degree angle to the corresponding tube section so as to enable a measurement based on transmission. Such an arrangement also enables a machine vision system; such a system may act at least partially for evaluation of the observed measurement values and/or may acts as a control unit. Thereby e.g. a direct feedback coupling to a pump to be actuated may be established.

In panel C, a configuration of a sensor 24 as a machine vision system is depicted in another arrangement. The camera and the illumination source are arranged on the same side of the tube 32. In contrast to the configuration depicted in panel B, reflective properties of the fluid comprising particles or components may be measured by that configuration. As shown by the straight lines, the light emitted from the illumination source does not provide any incident light to the camera, i.e. is not detected by the camera in a direct manner, but only via reflection or scattering of the particles or components within the fluid being discharged.

The use of a spectrometer as a sensor 24 is schematically shown in panel D. Here, the sensor 24 is arranged similar to the arrangement in panel B, but instead of a camera, a broadband spectrometer and corresponding illumination source is implemented. Thereby, a large selectivity of the wavelength to be measured may be ensured, such that the measurement provided by the sensor 24 may e.g. be specific for one or more cell types or types of tissue. To further improve the optical resolution, a flow cuvette 34 is used to perform the measurement. An inlet of the flow cuvette 34 is fluidical ly coupled to a tube arranged downstream of the outlet of the receptacle and an outlet of the flow cuvette 34 may be fluidical ly coupled to a discharge line or waste bag.

In addition to improved optical resolution, the flow cuvette 34 may also facilitate the optical coupling, since it may optionally be provided with holding brackets 36; thereby, the flow cuvette may be secured in place and be arranged at a predefined position relative to the sensor arrangement. It will be understood, that such holding brackets 36 may also be applicable to a tube 32 or corresponding tube section in other configurations, e.g. those depicted, but not limited to panels A, B and C.

It will be obvious for a person skilled in the art that these embodiments and items only depict examples of a plurality of possibilities. Hence, the embodiments shown here should not be understood to form a limitation of these features and configurations. Any possible combination and configuration of the described features can be chosen according to the scope of the invention.

List of reference numerals

10 Medical device

12 Holder

14 Receptacle

16 Reservoir

18 Pump

20 Filter

22 Waste bag

24 Sensor

26 Control unit

28 Reference solution

30 Sample washing step

32 Tube

34 Flow cuvette

36 Bracket

S100 Provide sample in receptacle

S1 10 Convey solution to receptacle inlet

S120 Perform sensor measurement

S130 Determine if measurement value corresponds to reference value

S140 No

S150 Yes

Claims

1 . A medical device (10) for processing a sample, comprising a holder (12) for accommodating a receptacle (14) comprising the sample, at least a first reservoir (16) for a first solution and connectable to an inlet of the receptacle (14), a pump (18), coupled at least to the first reservoir (16) and configured to convey a volume of the respective solution to the inlet of the receptacle (14) in the connected and accommodated state of the receptacle (14) so as to form a fluid stream to an outlet of the receptacle (14), at least one sensor (24), being couplable to an outlet side of the receptacle (14) and configured to measure a particle level within the fluid stream downstream of the inlet, and a control unit (26), communicatively coupled with the at least one sensor (24) and the pump (18) and configured to actuate the pump (18) based on the measurement value of the at least one sensor (24).

2. The medical device (10) according to claim 1 , wherein the at least one sensor (24) is configured for optical measurements or acoustic measurements.

3. The medical device (10) according to claim 2, wherein the at least one sensor (24) is configured as a turbidimeter, a nephelometer, a spectrometer, a light gate, a camera system, or an ultrasound device.

4. The medical device (10) according to claim 2 or 3, wherein the at least one sensor (24) is configured for optical measurements at one or more wavelengths or one or more wavelength ranges.

5. The medical device (10) according to claim 4, wherein the control unit (26) is configured to output a warning signal, if the measurement value for a particular wavelength or wavelength range exceeds a predefined threshold.

6. The medical device (10) according to any of the preceding claims, wherein at least one of the at least one sensor (24) is couplable to a tube (32) fluidical ly coupled with and downstream of the outlet and/or is arranged to be adjacent to said outlet in the accommodated state of the receptacle (14).

7. The medical device (10) according to claim 6, comprising a flow cuvette (34) arranged to be in fluid communication with the outlet in the accommodated state of the receptacle (14), wherein one of the at least one sensors (24) is arranged to measure the particle level within the flow cuvette (34).

8. The medical device (10) according to any of the preceding claims, wherein the control unit (26) is configured to actuate the pump (18) to convey a predefined volume of the respective solution, to convey the volume of the respective solution for a predefined time, and/or to convey the volume of the respective solution at a predefined flow rate based on the measurement value of the at least one sensor (24).

9. The medical device (10) according to any of the preceding claims, wherein the control unit (26) is configured to actuate the pump (18) to convey the volume of the respective solution continuously or to convey successive volumes of the respective solution based on the measurement value of the at least one sensor (24).

10. The medical device (10) according to any of the preceding claims, wherein the control unit (26) is configured to actuate the pump (18) based on a comparison of an actual measurement value with a predefined threshold value.

1 1. The medical device (10) according to claim 10, wherein the threshold value is a predefined percentage of a measurement value observed for a reference value.

12. The medical device (10) according to any of the preceding claims, wherein the control unit (26) is configured to determine a rate of change for observed measurement values and to actuate the pump (18) based on said rate of change.

13. The medical device (10) according to any of the preceding claims, wherein the sample is a cell or tissue sample, preferably comprising or essentially consisting of a lipoaspirate.

14. The medical device (10) according to any of the preceding claims, comprising a mechanical processing device couplable to the receptacle (14) in the accommodated state of the receptacle (14), wherein the control unit (26) is configured to actuate the mechanical processing device based on the measurement value of the at least one sensor (24).

15. The medical device (10) according to any of the preceding claims, comprising more than one reservoir (16) for a respective solution, each reservoir (16) being connectable to an inlet of the receptacle (14) and being coupled to at least one pump (18) of the medical device (10), wherein the medical device (10) preferably comprises a respective pump (18) for each reservoir (16).

16. A system comprising a medical device (10) according to any of the preceding claims and a receptacle (1 ) for receiving the sample, the receptacle (14) comprising an inlet and an outlet, wherein the inlet is fluidically connected to at least the first reservoir (16) and wherein an outlet end of the receptacle (14) is coupled to the at least one sensor (24).

17. Method for processing a sample, comprising the steps of: providing the sample (S100), preferably comprising or essentially consisting of a lipoaspirate, in a receptacle; fluidically coupling an inlet of the receptacle with at least a first reservoir; and actuating a pump coupled at least to the first reservoir to convey a volume of a solution (S110) contained in the respective reservoir to the inlet of the receptacle to form a fluid stream to an outlet of the receptacle, wherein the actuation of the pump is based on a measurement value of at least one sensor (S120) coupled to an outlet side of the receptacle and configured to measure a particle level within the fluid stream downstream of the inlet.

18. The method according to claim 17, wherein the sensor measurement (SI 20) is a measure for the turbidity of the fluid stream.

19. The method according to claim 17 or 18, wherein the sensor measurement (S120) is an optica] measurement at one or more wavelengths or one or more wavelength ranges.

20. The method according to any of claims 17 to 19, wherein the sensor measurement (S120) is performed through a flow cuvette being in fluid communication with the outlet.

21 . The method according to any of claims 17 to 20, wherein the pump is actuated based on a comparison of an actual measurement value with a predefined threshold value, the threshold value being a predefined percentage of a measurement value observed for a reference value (S130).

22. The method according to any of claims 17 to 21 , wherein the pump is actuated to convey a predefined volume of the respective solution, to convey the volume of the respective solution for a predefined time, and/or to convey the volume of the respective solution at a predefined flow rate based on the measurement value of the at least one sensor (S120).

23. The method according to any of claims 17 to 22, wherein the pump is actuated to convey the volume of the respective solution continuously or to convey successive volumes of the respective solution based on the measurement value of the at least one sensor (S120).

24. The method according to any of claims 17 to 22, further comprising the step of determining a rate of change for observed measurement values, wherein the pump is actuated based on said rate of change.

25. The method according to any of claims 17 to 24, further comprising the step of actuating a mechanical processing device coupled to the receptacle based on the measurement value of the at least one sensor.