Mobile device and method for analysing a fluid, in particular cerebrospinal fluid

Abstract

The invention relates to a device designed to measure and / or influence a property of a body fluid, in particular cerebrospinal fluid, provided in a fluidics module of the device. The device comprises the fluidic module, a reusable base part for receiving the fluidic module, a connecting tube or a tube coupling designed to connect the device to a body fluid source, in particular a patient, such that the body fluid can be guided through the connecting tube or the tube coupling into the fluidic module of the device, and a microfluidic chip arranged on or in the fluidic module and designed to influence the property of the body fluid.

Description

[0001]Möller Medical GmbH - 1 - March 25, 2025 möl-48WOP Mobile device and method for analyzing a fluid, in particular cerebrospinal fluid Description Field of the invention The present invention relates to a device and a method by means of which a property of a body fluid can be measured and / or influenced. Furthermore, the present invention also relates to a fluidics module for such a device and a microfluidic chip which is particularly suitable for the aforementioned device or method. Background and general description of the invention The starting point of the present technical development is the problem that certain analyses and diagnoses are still only accessible through laboratory medical examinations. Although point-of-care diagnostics, also called in-situ diagnostics, would be desirable, it has not yet been realized.Delays caused by laboratory transport of sample(s) can lead to serious complications. Delayed cerebral ischemia (DCI) occurs in up to one-third of patients with aneurysmal subarachnoid hemorrhage (aSAH). If left untreated, it can lead to secondary cerebral infarctions and is frequently associated with death or severe disability. Free hemoglobin (fHb) and its derivatives in the cerebrospinal fluid (CSF) are the main cause of DCI in patients with aneurysmal subarachnoid hemorrhage. Following the rupture of an aneurysm, red blood cells in the subarachnoid space lyse, releasing free hemoglobin (Hb), which plays a key role in the development of DCI. Patients with corresponding symptoms are usually admitted to intensive care.Furthermore, a ventricular or lumbar drain is typically placed, so that cerebrospinal fluid (CSF) is generally already available in the patient's environment for fHb quantification. aSAH occurs worldwide with an incidence of 8 per 100,000 person-years and is associated with an exceptionally high disease-specific burden in terms of mortality and long-term disability. aSAH is caused by the rupture of an aneurysm, leading to bleeding into the cerebrospinal fluid (CSF)-filled subarachnoid space. Brain damage in aSAH occurs in two phases. Early brain damage is caused by rising intracranial pressure, reduced cerebral blood flow, transient global ischemia, and the early toxic effects of the subarachnoid blood.Unique to aSAH, one-third of patients experience a delayed phase of brain injury due to delayed cerebral ischemia (DCI) 3 to 14 days after the initial hemorrhage. DCI leads to secondary infarctions and is the most important cause of long-term disability in patients who survive the initial hemorrhage, or can lead to death. Following erythrocytolysis in the subarachnoid CSF space, cell-free hemoglobin (CSF Hb) can be detected spectrophotometrically as oxygenated hemoglobin (oxyHb) and contributes significantly to the development of DCI. CSF Hb has previously been found to severely impair vascular nitric oxide signaling in isolated cerebral arteries. OxyHb infused into the CSF of sheep induces highly reproducible acute vasospasm. Acute hydrocephalus occurs in 20% of patients with aSAH and is treated in the acute phase with cerebrospinal fluid drainage (external ventricular drain or lumbar drain).The CSF is regularly drained, collected in measuring containers, and typically discarded. This offers the unique opportunity to perform regular CSF analyses in aSAH patients without additional invasive procedures, as the CSF is already present in measuring containers and is thus directly accessible for measurement, even without the patient possibly being directly connected. Continuous bedside measurement of free CSF Hb in aSAH may allow the determination of the patient-specific time profile of erythrocytolysis in the subarachnoid space and the monitoring of the risk of DCI at any time during the disease. Furthermore, these measurements may guide new therapeutic interventions to reduce CSF Hb toxicity in aSAH patients.However, repeated CSF spectrophotometry to monitor CSF hemoglobin levels in patients with aSAH is reserved for highly specialized centers, and there is no system for point-of-care diagnostic testing (POCT). Currently, CSF must be collected from external ventricular drains and analyzed in specialized laboratories using a manual two-step procedure, using a stationary laboratory centrifuge and appropriately trained personnel to exclude intact red blood cells. CSF hemoglobin (CSF hemoglobin) is traditionally analyzed using a two-step procedure consisting of centrifugation to exclude intact red blood cells, followed by spectrophotometric quantification.This approach suffers from the disadvantage of in vitro hemolysis if the sample is not processed immediately, if red blood cells release their hemoglobin prior to centrifugation, and if additional hemolysis occurs during centrifugation, leading to falsely high cell-free Hb readings. Such an effect can be mitigated by a POCT system, as samples can be processed without delay. This leads to several problems that are currently unsolved in practice. First, it limits the number of possible tests that can be performed. Second, the time difference between sample collection and measurement increases the variability of the results. Third, this process, which also requires sending the sample to the laboratory, reduces the accuracy of the measurement results. The invention proposed herein solves the aforementioned problems.It can be used as a point-of-care device, essentially at the patient's bedside to monitor fHb in the cerebrospinal fluid (CSF). Alternatively, it can be used in the vicinity of the patient or in a diagnostic environment in the hospital. It is capable of measuring the concentration of fHb and its derivatives and / or blood cells and blood serum proteins in a provided amount of CSF. This enables monitoring of the patient's risk of DCI and allows earlier and reliable detection and treatment of DCI in the intensive care unit. In another aspect in which the present invention enables improvements over the prior art, the present invention can be used as a complement to existing procedures. For example, lumbar puncture (LP) is initially used to diagnose subarachnoid hemorrhage when imaging procedures such as computed tomography are inconclusive and / or unavailable.As in the previously described case, a CSF sample obtained can – until now – be sent to a specialized laboratory for analysis of the concentration of fHb and its derivatives. In this case, the laboratory also performs a two-step manual analysis. This, in turn, entails the previously mentioned problems of the time difference between sample collection and measurement (second) and reduced measurement accuracy (third). In this case, the significant time difference between sample collection and diagnosis can arise under unfavorable, but not uncommon, circumstances: the opening and reception hours of the laboratory, which are generally closed on weekends, the required processing time, and the time required for sample shipment – ​​especially in rural areas. All of these factors prolong the time to diagnosis and treatment, which in the meantime increases the risk for the patient.The device described in the present description, which can be used as a point-of-care device, can be used in particular to measure the concentration of fHb and its derivatives and / or blood cells and / or blood serum proteins in cerebrospinal fluid samples. It solves the aforementioned problems by replacing the laboratory process with an automated, standardized (i.e., repeatable), and rapid measurement. This facilitates the diagnosis of subarachnoid hemorrhage as a life-threatening emergency in the acute stage. Furthermore, the device enables the detection and quantification of leukocytes in the cerebrospinal fluid sample. This can be important, for example, for the diagnosis of infections and inflammations of the central nervous system, such as meningitis. The number and type of leukocytes can provide valuable diagnostic information and contribute to a more comprehensive assessment of the patient's condition.Currently, the aforementioned problems cannot be addressed because there is currently no point-of-care diagnostic testing system that could enable continuous and standardized testing. Current procedures involve collecting cerebrospinal fluid (CSF) from the external ventricular or lumbar drain and sending it to a specialized laboratory for fHb concentration measurement. In the laboratory, the sample is first centrifuged to exclude intact red blood cells, and then the fHb level in the supernatant is determined spectrophotometrically. This procedure is time-consuming, provides only discontinuous, snapshot-like measurements, and has multiple sources of variability. If the sample is not processed immediately, in vitro hemolysis can occur. The red blood cells release their hemoglobin before and possibly during centrifugation, resulting in falsely elevated fHb measurements.Manual processing and varying processing times lead to additional uncertainties. In remote areas or outside of working hours (weekends), laboratory analysis may not be possible at all. These problems are mitigated by the described point-of-care system with standardized and immediate sample processing. Furthermore, the diagnostic value of the measurement results obtained with the device can be greatly increased by adaptable and, if necessary, shorter measurement intervals. The monitoring system described in this description can enable virtually continuous and non-invasive quantification of fHb, derivatives, blood cells, and / or blood serum proteins in the CSF. It can be ensured that the CSF drainage system can remain permanently connected if necessary. Furthermore, the device described here eliminates the need for conventional centrifugation of the sample.Compared to the previously standard daily CSF collection process, which required manual handling of the CSF sample and its analysis in a specialized laboratory, the system offers improved user-friendliness, significantly simplified handling, and thus reduced susceptibility to errors and reproducibility. The direct display on the device allows for immediate detection of whether the sample collection was or is in progress correctly, allowing prompt intervention should any difficulties arise during the sample collection. Previously, a failed sample collection (or sample deterioration during transport or centrifugation, see above) could only be detected after the laboratory results were received. Finally, the direct display of the primary DCI biomarker enables physicians to detect and treat DCI early, as well as to facilitate the primary diagnosis of subarachnoid hemorrhage.In other words, the device presented here enables the doctor, when using the device, to make a corresponding diagnosis independently and, in particular, promptly, without having to rely on results from a specialist laboratory. The object of the present invention is therefore to provide a device and a method which eliminates or improves the aforementioned disadvantages. This object is achieved by the subject matter of the independent patent claims. Dependent claims form developments of the invention. The present description explains a device which is designed to measure and / or influence a property of a body fluid provided in a fluidic module of the device. The body fluid is, in particular, cerebrospinal fluid. The property is, for example, the presence of foreign bodies or foreign substances in the body fluid. In the case of cerebrospinal fluid as the body fluid, foreign bodies orForeign substances are components that should not be present in the cerebrospinal fluid or should only be present in very small quantities. This particularly applies to blood cells such as leukocytes, erythrocytes and / or hemoglobin. The device is particularly advantageously configured so that it can be used directly on the patient to enable a POCT analysis or in-situ analysis of the body fluid. This means that the sample does not have to be transported to a laboratory center, but the analysis can be carried out directly on the patient, directly in the POCT environment or directly in the hospital. In particular, the device is designed so that it can determine an analysis result independently or almost independently, so that the condition of the body fluid can be assessed in the hospital. It has a structure consisting of at least two parts.At least the fluidics module and a base part for holding the fluidics module on or in the device are provided. Components that can be regularly and permanently reused, such as control and electronic components, can be housed in the base part. Sensors, a pump, the power supply, and data interfaces such as a radio module can be housed in the base part. In other words, it might be tempting to arrange those components that do not come into contact with the fluid to be measured or modified – and thus are not contaminated – in the base part. For example, all components that come into contact with the fluid are arranged in the fluidics module. In the case of a reusable fluidics module, only the fluidics module needs to be cleaned, not the base part. If the fluidics module is designed as a disposable module, it can be disposed of.In both cases, the base part can be ready to accommodate a fresh, i.e., cleaned or new, fluidics module. The particularly expensive components in the base part can always be reused. The fluidics module can be designed as a disposable module. A disposable module means that the fluidics module can no longer be used in the POCT area or the clinical environment after its use, but must be disposed of or reprocessed. The disposable module is then also configured to house those components that come into contact with the body fluid or could otherwise be contaminated. The fluidics module is disposed of after a single use, so that complex cleaning and reprocessing of the fluidics module is not necessary in this case.Since this is a relatively cost-intensive process in a clinical environment, a higher base price can be justified by simply using the fluidics module as a disposable module, as any measuring components would then also be disposed of after only one use. On the other hand, the fluidics module can be designed so that certain components to be arranged there are easily accessible, in particular those components that are to be arranged in the fluidics module, for example, for metrological reasons, but which do not actually come into contact with the body fluid. In this case, the fluidics module can be designed so that these components can be removed from the fluidics module after use, for example, and sent for reprocessing (for example, for a functional test).Finally, it may also prove advantageous if the fluidic module is placed in a designated container after use, but the fluidic module(s) can then be reprocessed after thorough testing and cleaning. Complete reuse, for example, should be evaluated according to economic criteria, so that if further developments occur in this area (or material costs should increase significantly relative to labor costs), it cannot be ruled out that a disposable module can also be reused after reprocessing.In this case, it can still be described as a disposable module because it cannot be reused after use – in contrast to the base module, which can be used again immediately for the next measurement or series of measurements after the fluidics module has been replaced. Depending on the application, the fluidics module can therefore either be disposed of after a single or multiple use, or reused after appropriate cleaning and processing. During reuse, suitable sterilization processes can be used to ensure that no cross-contamination occurs between different patients. The device can be configured to include an interface such as a connecting tube and / or a tube coupling, designed to connect the device to a body fluid source. In one example, the body fluid source is the patient to be treated or diagnosed.In this case, the connection to the body fluid source is advantageously established with a connecting tube. In another case, the body fluid source can be an external reservoir into which the body fluid has previously been introduced. The external reservoir can be docked to the device. For example, the analysis module can have a reservoir receptacle; furthermore, for example, a recess or the like can be formed in the analysis module housing into which the external reservoir can be inserted. If the interface is arranged in the reservoir receptacle, the fluidic connection between the external reservoir and the fluidic module can be established at the same time as inserting the external reservoir into the reservoir receptacle. As a result, the body fluid can be guided into the fluidic module of the device, in particular through the connecting tube or the tube coupling. In other words, the device can be used in various ways.The device can be directly connected to a patient and, upon request from the device (needing a next measurement), or, for example, upon detection of cerebral hypertension in the cerebrospinal fluid (provided this is measured simultaneously), a subsequent sample can be taken and submitted for measurement in the fluidics module. Alternatively, the device can also be used completely separate from the patient and used for diagnostics of a sample already taken. The device can be used purely for the analysis of the sample introduced into the fluidics module, i.e., even in a non-therapeutic environment.However, the device can also be particularly advantageously designed to analyze the sample (by means of corresponding evaluation electronics typically arranged in the base part) and to output an analysis result, so that this analysis result can also be used to subsequently initiate treatment of a patient. The device can therefore be used in advance of a later treatment of a patient. However, the device itself never carries out one or more therapeutic steps. In the usual form of use, a patient is not directly influenced by the device and no therapeutic step is carried out overall, which is why the device as a whole is not a therapeutic device and no therapeutic method is carried out with the device.The device described here further comprises a microfluidic chip arranged on or in the fluidics module, which is configured to influence the property of the body fluid. The microfluidic chip can be used, in particular, to separate a component of the body fluid in order to enable, improve, or simplify subsequent measurement of the remaining body fluid. The device is advantageously a mobile device. For example, the device can be configured or suitable as a point-of-care diagnostic device. The device can thus be used directly at the body fluid source and perform the relevant analysis there. The property of the body fluid is, for example, the presence of particles, suspended particles, or cells such as blood cells and / or blood serum proteins in the body fluid.Blood cells are understood to mean the cellular components of the blood, in particular erythrocytes, leukocytes, and / or thrombocytes. Blood serum proteins include, for example, methemoglobin (MetHb), oxyhemoglobin (HbO2), albumin, heme albumin, and / or bilirubin. It has been shown that a potentially relevant property of the body fluid for the present description is the bilirubin level. The property of the body fluid can further be described as the presence of hemoglobin or a derivative thereof in the body fluid. Hemoglobin is a chromoprotein consisting of two - and -globin chains, each of which has a heme bound as a prosthetic group. For the purposes of the present invention, "hemoglobin or a derivative thereof" refers to molecules containing - and / or -globin chains.This includes all human hemoglobin types and their derivatives, such as conformations or oxidation forms, such as oxygenated hemoglobin (oxyhemoglobin, oxyHb) or deoxygenated hemoglobin (deoxyhemoglobin, HHb), as well as methemoglobin (MetHb) or carboxyhemoglobin (COHb). Hemoglobin derivatives preferably consist of two - and two -globin chains. Derivatives also include hemoglobin molecules whose primary structure has been altered by substitution, deletion, or addition of amino acids. Products of hemoglobin degradation, such as bilirubin, are also included. Within the context of the above list, some components fall under the term blood serum proteins as well as under the term hemoglobin or a derivative thereof. Although hemoglobin is also a protein, it is typically found within red blood cells (erythrocytes) and not in blood serum.The components mentioned in the preceding paragraphs are also to be understood as examples only; they represent the important components that need to be identified for a targeted main application, namely cerebrospinal fluid analysis. Generally speaking, influencing the properties of the body fluid can comprise the separation or isolation of particles, suspended particles, or cells from the body fluid. The device can further comprise a measuring device arranged in or on the fluidics module for determining the properties of the body fluid. The measuring device is preferably designed to detect or quantify hemoglobin or a derivative thereof in the body fluid. The measuring device can further comprise an optical sensor arranged in or on the fluidics module, in particular a spectrophotometer.To further simplify handling of the device, it can further comprise a body fluid reservoir arranged in or on the fluidics module. It is advantageous if the body fluid reservoir is arranged upstream of the microfluidic chip. The terms upstream or upstream on the one hand, and downstream or downstream on the other hand, refer in this description to the flow path through the fluidics module. The furthest upstream point in the fluidics module is where the liquid enters the fluidics module. The furthest downstream point in the fluidics module is where the liquid flow ends – this is preferably in a residue receiving volume arranged in or on the fluidics module. If the residue receiving volume is arranged downstream of the fluidics module in the flow direction, the residue receiving volume can be designed to be even easier to empty or replace.For example, the waste collection volume can be docked to the fluidics module with a quick-release coupling, allowing it to be removed in a single action. This is also advantageous if the fluidics module is designed for multiple use and is rinsed for reuse. This results in a larger amount of fluid, which can be removed from the fluidics module in the waste collection volume and disposed of. The body fluid reservoir can include a fill level sensor or a fill level indicator. With the possible evaluation of the fill level of the body fluid reservoir, it is possible to regulate the flow of body fluid through or within the fluidics module based on this fill level. As long as the fill level of the body fluid reservoir is too low, the body fluid (cerebrospinal fluid) is sucked in until the reservoir is sufficiently filled.The body fluid can then be conveyed further in the fluidics module, for example to one of the downstream components. This further conveyance in the fluidics module can, for example, be pressure-controlled or valve-controlled (or both). At least one switchable valve, in particular a solenoid valve, can be arranged in the fluidics module. This switchable valve is preferably arranged downstream of the body fluid reservoir. Thus, in particular, the fluid path on the outlet side of the body fluid reservoir can be made switchable. In this case, it is particularly irrelevant if a controllable valve, with which the flow rate can be regulated, is used instead of a switchable valve. Due to the present field of application and the very low fluid quantities, a switchable valve is considered advantageous. However, a controllable valve could also be used; this is simply typically more complex.The fluidics module further preferably comprises a residue receiving volume arranged in or on the fluidics module. The residue receiving volume further preferably comprises a reservoir, i.e., a vessel in which the residue receiving volume is arranged. The residue receiving volume is further preferably connected to the microfluidic chip, such that residues separated or separated from the body fluid by the microfluidic chip can be discharged directly into the residue receiving volume. The term "residuals" is used generically for components that are separated from the body fluid. Alternatively or additionally, the residue receiving volume is connected to the measuring device, such that volumes of the body fluid measured by the measuring device can be discharged into the residue receiving volume.The waste collection volume can include a fill level sensor or a fill level indicator to display the fill level of the waste collection volume, so that information can be output, particularly when a maximum fill level is reached, or the fluidics module can be replaced with a new fluidics module. This is particularly helpful when the device is used continuously, i.e., when measurements are performed regularly or at regular intervals, thus continuously increasing the amount of accumulated waste in the fluidics module. A flushing device can also be arranged in or on the fluidics module.The arrangement of a flushing device in the fluidics module makes it possible to flush the fluidics module, for example, during waiting periods between measurements, so that any body fluid still present in it does not block the lines, for example by clumping or sticking. A check valve can be arranged on the inlet side of the fluidics module, in particular upstream of the body fluid reservoir. Alternatively or cumulatively, a check valve can also be arranged upstream of the reservoir. The arrangement of a check valve can be helpful, for example, in the previously described case when a flushing device is used in the fluidics module. If a flushing agent escapes or is expelled from the flushing device, an upstream check valve prevents the flushing agent from entering the connecting hose or the body fluid source.The microfluidic chip used in the fluidics module preferably has an inlet channel and / or a bifurcation. The body fluid can enter the microfluidic chip via the inlet channel. For example, the body fluid can be pumped into the microfluidic chip. The inlet channel is preferably elongated. Alternatively or additionally, the microfluidic chip has a separation device for separating particles, particles, or cells from the body fluid. The separation device can comprise at least one piezoelectric component, in particular a piezoelectric transducer. The separation device can, for example, be arranged at the inlet channel or act on all or part of the inlet channel, so that the body fluid is separated in the inlet channel.By correctly adjusting the separation device, the component to be separated can be separated from the body fluid in the microfluidic chip. For example, it can be designed so that the separation device acts on the body fluid in the input channel, pushing the component to be separated into the center of the input channel, thereby forcing the remaining body fluid to escape to the edge of the input channel. With appropriate design of the flow guidance through the microfluidic chip, it is thus possible to easily achieve a splitting of the two fluid streams. The separation device can, for example, be configured to generate sound pressure, in particular for acoustophoresis. This creates an acoustic torque on the fluid in the input channel.A gas bubble detection and / or separation device for identifying and / or separating gaseous components can be arranged upstream of the microfluidic chip. In other words, this can be used, for example, to separate bubbles or gas inclusions from the body fluid. While no gaseous components should be present in the body fluid if the supply line and all connections are sealed, it would be expected that measuring a body fluid containing gas bubbles would produce an erroneous result. Thus, incorporating a device for detecting or separating gas bubbles can further improve the results obtainable with the device. The connecting tube is, for example, designed for connection to an external ventricular drainage system. Alternatively or additionally, the connecting tube is designed for direct connection to the fluidics module.Alternatively or additionally, the fluidics module can be configured for connection to the connecting tube. Finally, alternatively or additionally, the fluidics module can comprise a tube coupling for connection to the connecting tube. In other words, the device preferably comprises an interface for direct connection to a body fluid source, in particular a patient or an external ventricular drainage. This enables in-situ analysis of the body fluid without prior transport to the laboratory. A fluid detector can be arranged on or in the fluidics module in the device, which makes it possible to determine the presence of body fluid in the fluidics module. By incorporating a fluid detector into the fluidics module, it can be ensured that it can be determined whether the body fluid is passing from the body fluid source into the fluidics module.This makes it possible to initiate corrective measures, such as checking the passage, in particular the hose passage. On the other hand, it can also be used to isolate or rule out blockages in the flow path outside or inside the fluidics module. The device preferably comprises a pump for providing overpressure and / or underpressure. Atmospheric air (filtered if necessary) can preferably be used to provide overpressure or underpressure in the fluidics module. Depending on the application, a gas can also be used, which may already be provided at overpressure (compressed gas cylinder). Thus, in any case, no pump may be required to provide overpressure.Typically, however, the use of a pump will be simpler and more practical than providing a compressed gas cylinder, which empties with use and thus requires monitoring its fill level. Möller Medical GmbH - 7 - March 25, 2025 möl-48WOP The pump can advantageously be connected to the fluidics module, so that the overpressure and / or negative pressure can be provided in the fluidics module. Alternatively or additionally, the pump can be connected to the fluidics module via at least one pressure connection coupling. Möller Medical GmbH - 8 - March 25, 2025 möl-48WOP body fluid, so that the portion of the body fluid can be supplied to the first outlet opening and a purified body fluid can be supplied to the second outlet opening. In the microfluidic chip, the separation device can be configured to guide the portion of the body fluid, in particular by means of acoustophoresis, into a central part of the inlet channel. The purified body fluid can then escape into a side region of the inlet channel, so that in the region of the bifurcation and with the application of a fluid flow, the portion of the body fluid is guided to the first outlet opening and the purified body fluid is guided to the second outlet opening of the microfluidic chip. The separation device can further comprise a piezoelectric transducer. The microfluidic chip can comprise a glass wafer and / or a silicon wafer; if appropriate, the glass wafer is bonded to the silicon wafer.Also within the scope of the present description is a method for diagnosing a body fluid, in particular cerebrospinal fluid, in particular using the device and / or the fluidic module or microfluidic chip described above. The method comprises the following steps: introducing the body fluid into a fluidic module, conveying the body fluid to a microfluidic chip arranged in or on the fluidic module for influencing a property of the body fluid, in particular for separating erythrocytes and / or leukocytes from the body fluid, by means of or in the microfluidic chip, conveying the body fluid to a measuring device arranged in or on the fluidic module for determining the same or another property of the body fluid, conveying the body fluid from the measuring device and into a residual material receiving volume arranged in the fluidic module.The method can further be equipped with the step of starting the pumping of the body fluid in the fluidics module as soon as a body fluid reservoir arranged in the fluidics module is sufficiently supplied with the body fluid. The steps of pumping the body fluid can be carried out, for example, by means of a pump arranged in the device, in particular in a base module of the device. The device can further be designed as a mobile device. The method can be designed as a point-of-care diagnostic method. The device proposed here can be designed to automatically carry out a concentration measurement of fHb and its derivatives in cerebrospinal fluid samples. These can either be repeated measurements in which cerebrospinal fluid is taken, for example, over several days from the tube system of a ventricular or lumbar drainage.Or it can be a single measurement, with the CSF sample obtained through a LP. The following schematic describes the device design again in other words: The system consists of the reusable medical device (MD), which contains all electronic components, and a disposable unit that comes into contact with the patient's CSF and can be disposed of and replaced between uses on different patients. The reusable MD can include an embedded system that controls a pump, multiple valves, a cell sorting mechanism, several different sensors such as flow, pressure, and temperature, and an optical acquisition unit. Measurement results and user inputs are provided via the human-machine interface (HMI), e.g., a touchscreen or similar.The fluid flow can be controlled, particularly using valves, but these are advantageously not part of the disposable product. The pump can selectively draw and push fluid depending on the automatically controlled valve setting. To perform a measurement, the CSF sample is drawn into the reservoir until a specific volume is reached, which is detected by a level detector. The sample is then pushed into the cell sorting mechanism, which separates the red blood cells and / or leukocytes from the sample. Cell sorting is achieved by acoustophoresis. A fluid channel is ultrasonically excited by a piezoelectric element to concentrate the red blood cells and / or leukocytes in a specific area of ​​the channel and separate them from purified CSF.Feedback control of the separation parameter setpoints is used to stabilize the cell focusing process based on a sensor measurement of the separation efficiency. The spectrophotometric detection unit then measures the photon absorption in the cell-poor CSF. Based on the absorption at specific wavelengths or in specific spectral ranges, the concentration of fHb and derivatives can be calculated in the integrated processor and displayed to the user on the HMI. Finally, the CSF and cellular material are collected in the waste bag (waste collection volume). An additional fluid path can enable flushing of the disposable system with a cleaning solution. The system with the disposable device can be designed, for example, for repeated automated measurements over a period of up to 10 days on a single patient. Möller Medical GmbH - 9 - 25.03.2025 möl-48WOP Essential components of this description are the cell-fluid separation unit (microfluidic chip), the pump and valve configuration for conveying cerebrospinal fluid or rinsing agent through the flow paths, and the measurement unit or photometric detection unit. The architecture and interconnection of the blocks into a single system for cerebrospinal fluid analysis enable a completely novel system that offers a multitude of innovations and thus defines a new class of device that is also POC-capable (can be used at the point of care). On the other hand, the design of the system as a compact, mobile device, particularly with a reusable base module and an easily replaceable analysis unit with fluidic connection to the cerebrospinal fluid outlet, can contribute to its use as a point-of-care diagnostic device.Alternative solutions are possible for the technical implementation of the individual functional subsystems; such alternative solutions are explicitly considered to be covered by this description. Cell sorting can be achieved using any type of separation process, possibly with different control. Examples include surface wave acoustophoresis. The optical detection unit is either a broadband spectrometer covering the spectral absorption range of the analyte or an array of light sources with specific, narrowband spectra tailored to the absorption peaks of the analyte. The photometric measurement can be performed in a separate cuvette in which the analyte is collected or, alternatively, in the flow on the microfluidic chip. Finally, the pump does not have to be of a specific type; it simply needs to meet the fluidic requirements of the system.The invention will be explained in more detail below using exemplary embodiments and with reference to the figures. Similar or identical elements have the same reference numerals, and the features of the various exemplary embodiments can be combined with one another. Fig.1 shows the schematic structure of a first embodiment of the device, Fig.2 shows the schematic structure of a further embodiment of the device, Fig.3 shows the schematic structure of a further embodiment of the device, Fig.4 shows the schematic structure of a further embodiment of the device, Fig.5 shows the schematic structure of a further embodiment of the device, Fig.6 shows the schematic structure of a further embodiment of the device, Fig.7 shows the schematic structure of a further embodiment of the device, Fig.8 shows the schematic structure of a further embodiment of the device, Fig.8 shows the schematic structure of a microfluidic chip, Fig.9 shows a microscopic representation of a prototypically used microfluidic chip with the splitting of the body fluid shown, Fig.10 shows a flow diagram of the method. Möller Medical GmbH - 10 - 03 / 25 / 2025 möl-48WOP was. In this case, the device 1 is completely independent of any patient to be treated and is not connected to them. The device 1 is then purely a device for analyzing a measurement sample 2 provided in an external body fluid source 2, which is at least partially fed to the fluidic module 40. For example, the connecting line 5 can be provided with strain relief in the area of ​​the housing passage 49 of the fluidic module housing 48 or can be pressed into the housing 48 or thickened there, but the connecting line 5 can otherwise form a continuous line with the supply line 41. Body fluid 95 can be introduced into the fluidic module 40 via the connecting line 5. If necessary,The hydrostatic force distribution between the measurement sample 2 and the fluidic module 40 can be adjusted such that the body fluid 95 automatically flows into the storage container 55 until a measured fill level is reached. For example, the measured fill level in the storage container 55 can be above the height of the inlet opening of the connecting line 5 on the storage container 55, so that the liquid level 56 in the storage container 55 covers the inlet opening and thus stops the flow of further body fluid 95. Typically, however, it is preferred to be able to control or regulate the fluid flow into and within the fluidic module 40. In this case, or if the body fluid 95 does not automatically flow into the device 1, the inflow and distribution in the fluidic module 40 can be regulated by means of the pump 20 arranged in the base part 10. In this embodiment, the pump 20 is connected to the fluidic module 40 via the pressure connection 32.More precisely, the connection in the fluidics module 40 leads via the pressure connection 82, the connecting line 84 to the bodily fluid storage container 55. In this way, the storage container 55 can advantageously act to a certain extent as a pressure equalization volume, so that when a negative pressure is applied to the storage container 55, a gentle suction is created on the connecting line 5 and thus on the bodily fluid source 2. The storage volume 55 is filled until a measuring fill level 56 is set in the volume 55. For example, this can be checked by a fill level sensor 57. The pump 20 can then be switched over to generate an overpressure, which can then be applied to the volume 55. If necessary, it can be set hydrostatically in such a way that no pressure is exerted on the connecting line 5, or a check valve, switching valve or other option is used, e.g.The shut-off is provided in or on the connecting line 5 so that no excess pressure reacts on the body fluid source. A line 42 is connected to the body fluid reservoir 55, which connects a microfluidic chip 60. This allows the body fluid 95 to flow from the reservoir 55 to the microfluidic chip 60. It is preferred if the fluid 95 is conveyed further with slight pressure, so that a standing column of fluid rests against the microfluidic chip 60 and thus the fluid arrives uninterrupted, which could potentially disrupt the function of the microfluidic chip 60 or the downstream measuring device 70. The microfluidic chip 60 has two outlets 62, 63 (see Figs. 8, 9), which on the one hand connect the measuring device 70 to the inlet line 43 and on the other hand connect a residual material receiving volume 75 to the inlet line 45.Separated components of the body fluid 95 can be removed via line 45, whereas the remaining body fluid 95 without these components is fed to the measuring device 70 via line 43. The presence of this fluid component is the property of the body fluid 95, and the separation of the fluid component influences or changes the property of the body fluid 95. Using the measuring device 70, this or another property of the body fluid 95 can be determined, for example, the presence of this or another fluid component. If the fluid 95 is cerebrospinal fluid and the fluid component is blood cells, the microfluidic chip 60 separates blood cells from the cerebrospinal fluid. Using the measuring device 70, hemoglobin in the cerebrospinal fluid can then be determined, for example.Alternatively or additionally, it may be advantageous to arrange a measuring device between the microfluidic chip 60 and the waste collection volume 75 to detect or quantify the presence of blood cells. After the measurement with the measuring device 70, the body fluid 95 is also fed to the waste collection volume 75. The waste collection volume 75 then serves as a "waste collector" in the fluidics module 40 to collect the waste, so that the fluidics module 40 requires no further connections and, in particular, remains clinically clean. Once the waste collection volume 75 is full, the fluidics module can be replaced to continue the measurements. Depending on the circumstances, the fluidics module can be disposed of or recycled, or reused after appropriate cleaning.Such recycling, if desired, advantageously takes place outside the clinical environment but can be performed at a suitably equipped facility. This can involve the complete reprocessing of the fluidics module 40 or simply the removal of valuable and reusable parts. If necessary, the fluidics module 40 can also be configured so that certain components are removable and can be removed by the clinic before the fluidics module 40 is disposed of. These can be corresponding sensors, which can be activated, for example, via push buttons or other mechanical means. Möller Medical GmbH - 11 - 25.03.2025 möl-48WOP. Möller Medical GmbH - 12 - 03 / 25 / 2025 möl-48WOP The microfluidic chip 60 shown in Fig. 3, like Fig. 1, has two outputs, so that the output lines 43 and 45 are connected to them. Furthermore, a further switching valve 73 (solenoid valve) is arranged between the measuring device 70 and the residue receiving volume 75, so that the body fluid 95 can be drained from the measuring volume 72 in a controlled manner. This also allows a certain degree of control over the fluid column from the body fluid reservoir 55 via the microfluidic chip 60 to the valve 73, so that the fluid flow through the fluidic module 40 can be influenced by controlling the valves 58, 73. The embodiment shown in Fig. 3 has a dead volume reduced to a minimum, so that the requirement for body fluid (95), such as cerebrospinal fluid, is further reduced.Furthermore, a sieve can be used, for example, in the area of ​​the hose coupling 51, with the check valve 52, or at least upstream of the microfluidic chip 60, for example with or in the check valve 59, for example to filter coagulated blood in the cerebrospinal fluid. Overall, the entire fluidic module 40 could also be used as a sieve to separate coagulated blood from the cerebrospinal fluid if the body fluid 95 purified in the microfluidic chip 60 were reused instead of depositing the cerebrospinal fluid in the waste collection volume 75. Möller Medical GmbH - 13 - 03 / 25 / 2025 möl-48WOP Figure 6 shows yet another embodiment of the device 1, wherein the fluid control in this case is carried out via pneumatically controlled valves 58, 73, 79, 92. For this purpose, a plurality of switching outputs 30 are provided on the base part 10 for applying switching pressures to the fluidic module 40 for individually switching the respective pneumatic valves 58, 73, 79, 92. The arrangement of two separate pumps 20, 21 in the base part 10 enables a secure separation of the switching unit and the associated compressed air lines from the body fluid 95, since it is ensured there that no body fluid 95 enters the lines. This allows these components to be implemented more cost-effectively or with fewer requirements. According to the embodiment of Fig.6, the switching pump 21 is supplied with ambient air (or a gas) via the air inlet 22 and the inlet filter 23.A reservoir pressure can be stored in a pressure accumulator 25, which can be filled up to a reservoir pressure using the pressure sensor 24. If necessary, this can provide a different pressure range than for the fluid feed pump 20. For example, the switching of the valves 58, 73, 79, 92 can require a minimum pressure that should not be passed on to the fluid side. By using two pumps 20, 21, it is also ensured that the lines carrying body fluid are not subjected to excessive overpressure. Finally, a very finely dosed fluid pump 20 can be used for the comparatively very low negative and positive pressures used for fluid feed, and a (cheaper) coarser control pump 21 can be used for the larger control pressures for controlling the valves. The individual control lines can be pressurized or depressurized via the control valves 31.from the pressure accumulator 25. Each pressure valve 58, 73, 79, 92 typically has a "standard state", for example "normally closed" or "normally open", so that without pressurization the respective valve assumes a fail-safe state. For example, the valve 92 of the flushing device 90 is used in the fail-safe "normally closed" state, so that the flushing agent can only enter the fluid-carrying lines when the associated valve 92 is pressurized and thus changes the opening state from closed to open. Finally, with reference to Fig. 7, the embodiment of Fig. 6 is shown, wherein the electrical connecting lines 34 and the control module 33 are additionally included in the schematic representation. In the embodiment shown, an evaluation module 93 for evaluating the measurement data generated by the measuring device 70 is also arranged in the control module 33.With the evaluation module 93, the measurement can also be evaluated simultaneously with the device 1 and, if necessary, output to a display device. This can be shown on the practical large-format screen, similar to the example of the compact LiquoGuard device from the applicant, and, if necessary, further information such as other measured values ​​can be obtained or the measurement can be influenced by inputs via buttons or a touch-sensitive screen, for example, the optical frequencies used for the measurement with the sensor 74 can be changed. Furthermore, a memory module 94 is provided, by means of which the measurement data obtained with the measuring device 70 can be (temporarily) stored. Furthermore, the memory module 94 can also be used to store other parameters of the device 1, such as status orOperating data of the pumps 20, 21, data of the microfluidic chip 60, sensor data of the various fluid sensors used, and fill levels of the containers 55, 75. With the pump control 97 and the corresponding control lines, for example, the operating direction of the fluid pump 20 (negative pressure or positive pressure) or the control pressure of the control pump 21 can be specified, as well as the corresponding (solenoid) valves 17, 18, 31 can be controlled. A wireless connection device 98 enables a data connection, for example, to the hospital network or to other connection means, so that a user of the device 1 can be informed at any time during the measurement about the status or the presence of measurement results, and / or about the status of the device 1, such as operational readiness or error status, and / or measurement data obtained can be transmitted to a correspondingly accessible patient file.Finally, the electrical supply device 99 provides the electrical supply to the device 1. The electrical supply device 99 can be designed as an accumulator or energy storage device or comprise a plug for connection to a local power supply. Fig. 8 shows an embodiment of the device 1—simplified compared to the previous embodiments—with a direct connection via the interface 5 to the body fluid source 2. The device 1 comprises the fluidics module 40 and a pump 20 integrated in the base module 10, which pumps the body fluid 95 into the fluidics module 40. The fluidics module 40 is designed to accommodate the microfluidic chip 60, which enables the separation of components such as blood cells (erythrocytes, leukocytes) and / or blood serum proteins from the body fluid 95.In this embodiment, the measuring device 70 already monitors the microfluidic chip 60, so that the measurement can already be performed on or in the region of the microfluidic chip 60. In other words, the measurement can be performed in the flow on the microfluidic chip 60. Möller Medical GmbH - 14 - 25.03.2025 möl-48WOP. Möller Medical GmbH - 15 - 25.03.2025 möl-48WOP Finally, with reference to Fig. 11, a flowchart of a method 100 for measuring, influencing, or diagnosing a body fluid 95 is presented. In step 110, the body fluid 95 is introduced into the device 1 or the fluidics module 40. If necessary, step 115 detects whether body fluid is present in the fluidic module 40, for example, by means of one or more flow sensors 53, 59. Step 120 involves bringing the body fluid 95 to the microfluidic chip 60 arranged on or in the fluidic module 40, so that the microfluidic chip 60 can be used to influence 130 the body fluid 95, for example, by separating blood cells, such as erythrocytes and / or leukocytes 96, from the cerebrospinal fluid 95, further, for example, by means of the separation device 80. For this purpose, it can be advantageous if, for example, the detection 115 activates 125 an initially deactivated microfluidic chip 60.In other words, activation 125 of the microfluidic chip 60 can occur in response to a detection 115 in the fluidics module 40. After influencing 130 the property of the body fluid 95, the body fluid 95 is conveyed 135 to a measuring device 70 for the purpose of measuring 140 the same property or another property of the body fluid 95. After the measurement 140 has been performed, the body fluid 95 and / or the components 96 are finally disposed of 150 in the fluidics module 40. Any diagnosis 160 that may occur can then be performed based on the measurement data collected by the measurement 140, for example, by means of the evaluation module 93. Numerous experiments and trials were also conducted within the scope of this description. A prototype of a microfluidic chip was produced that is capable of separating blood cells, such as erythrocytes and / or leukocytes, from cerebrospinal fluid using acoustic forces.Cell manipulation using acoustic forces (acoustophoresis) is based on the generation of acoustic pressure in a microfluidic channel via a piezoelectric element. At a defined frequency, a standing acoustic wave is generated in the channel, with the pressure node(s) located in the center of the channel. The scattering of the acoustic waves by the cells generates a force known as the acoustic rotation force (F). rad) and pushes the cells towards the acoustic pressure node. The blood cells, such as erythrocytes and / or leukocytes, are focused in the center of the channel due to their positive acoustic contrast factor compared to blood plasma and cerebrospinal fluid. The microfluidic chip 60 comprises in particular a base made of silicon and was manufactured, for example, by double-sided photolithography on a silicon wafer with a diameter of 4 inches and a thickness of 500 μm ± 10 μm. The microfluidic channel and the access holes were manufactured by inductively coupled plasma deep reactive ion etching (ICP-DRIE, Bosch process, Estrellas, Oxford Instruments) on the front and back sides with a channel depth of 200 μm ± 5 μm, a channel width of 700 ± 5 μm, and an access hole diameter of 1000 μm.A glass wafer (700 μm thick) was anodically bonded to the silicon wafer (SB6, SÜSS MicroTec, Garching, Germany) and then cut into rectangular chips (11 mm x 58 mm) using a wafer saw (DAD3221, Disco Corporation). The piezoelectric transducer (20 mm x 20 mm x 2 mm, PZ26, Ferroperm Piezoceramics A / S, Kvistgard, Denmark) was bonded to the back of the diced chips using an epoxy resin (H20E, EPO-TEK). Two copper wires (0.25 mm diameter) were bonded to the electrodes of the piezoelectric transducer using silver paste and superglue. The chip was clamped into a holder and sealed with O-rings using three flanged PTFE tubes (1 / 16 inch x 0.75 mm outer and inner diameters), which provide access to the inlet and two outlet ports. A modular in vitro test bench was built to test the microfluidic chip.It includes an interface for connecting the particle separation device and the spectrophotometer, three syringe pumps (Nemesys 290N, low-pressure syringe pump, Cetoni GmbH, Korbussen, Germany), and 0.75 mm diameter tubing. The electronics for operating the piezoelectric transducer include a waveform generator (333500B series, Keysight, CA, USA) and a High Wave 3.2 amplifier (Digitum Elektronik, Nürtingen, Germany). A camera (Toolcraft DigiMicro, Conrad Electronic, Hirschau, Germany) was used for imaging at the bifurcation of the microfluidic chip. In addition, the extended test environment included a laboratory spectrometer (Photometer 4040v5+, Riele, Berlin, Germany) and a centrifuge (Universal 320 & Hematocrit Rotor, Hettich AG, Bäch, Switzerland) to test the same samples in parallel. In this way, tests of the present plasmaphoresis chip can be evaluated and compared with the standard analysis (laboratory centrifuge).The microchips were tested with diluted porcine blood and CSF samples from six aSAH patients. The porcine samples were diluted with phosphate-buffered saline (PBS) to achieve the same hematocrit value as the CSF sample, while the patient samples were not diluted. To remove any air pockets, the entire system—the tubes and the microfluidic chip—is flushed with the sample to be tested, and the residue is collected in a container. After the initial system flush, the flow rate is set to 60 μL / min at the inlet and -15 μL / min at the plasma outlet. At these flow rates, the device could be operated for hours without experiencing stability issues. The flow rates and division ratios could be increased at the expense of operational stability.At a constant flow rate, the piezoelectric transducer is activated, causing the erythrocytes and / or leukocytes to move toward the center of the channel. The input signal for operating the piezoelectric transducer was chosen as a sine wave with a frequency range of 1036–1050 kHz (half the wavelength fitted to the channel width ( / 2 mode)) and a peak-to-peak amplitude of 28 V. The optimal operating point for the active blood particle separation device is determined by applying different voltages and frequencies to the piezoelectric transducer, as well as different flow rates at the inlet and outlet. The resulting efficiency of focusing the blood particles is monitored. The separation of the blood particles is clearly demonstrated in a supplementary video (OxyHbMeter Functional Principle) to be made available online by the applicant, but can also be easily deduced from the further description.In the supplemental video, the fluid flows from left to right and is separated as follows: Waste 96 (separated red blood cells) is extracted in the center at the first outlet 62, and plasma or CSF 95 for CSF Hb detection is located in the two side arms 68. After the entire dead volume in the tubes has been drained, the plasma or CSF 95 is collected in the corresponding syringe. The system continues to operate for approximately 70 minutes until 1 ml of plasma or CSF 95 is collected in the plasma or CSF syringe. The collected plasma or CSF 95 is then analyzed with the spectrophotometer to determine the Hb concentration of the sample. Afterward, the device was cleaned with saline and ethanol to be reused for the next experiment.In the clinical setting, CSF samples from six patients (2) treated for SAH and hydrocephalus at the Neurocritical Care Unit of the University Hospital of Zurich and requiring external ventricular drainage (4) were analyzed. The study was approved by the Local Ethics Committee of the Canton of Zurich, Switzerland, under approval number 2021-01089. Written informed consent was obtained from the legal representatives, as all patients lacked capacity, and the study was conducted in accordance with the Declaration of Helsinki and its amendments. CSF (95) was not collected directly from the patients (2) but from a collection bag (2) containing the CSF (95) drained over the previous 2 to 3 hours. The separation efficiency and hemolysis induced by the microfluidic chip (60) were compared with conventional centrifugation (state-of-the-art).The samples were centrifuged for 15 minutes at 3600 RCF, and the separated CSF was analyzed spectrophotometrically. The measured Hb values ​​of the centrifuged sample served as a baseline to verify the values ​​of the sample separated with the Microfluidic Chip 60. Five cuvette measurements were performed for the spectrometer analysis of both separation methods. Using the latest chip design and test setup, in vitro and clinical measurements were performed with diluted blood and CSF patient samples. These experiments served to evaluate the separation efficiency and hemolysis induced by the separation with the Microfluidic Chip 60 compared to conventional centrifugation. A scientific paper to be published soon will further discuss the measurement results in detail, which are not currently relevant to this description.Nevertheless, the contents of this paper, "OxyHbMeter – a novel bedside medical device for monitoring cell-free hemoglobin in the cerebrospinal fluid – proof of principle," are hereby incorporated by reference. Furthermore, the aforementioned study accompanying the present patent demonstrates the fundamental feasibility and (industrial) applicability of the device 1 shown in the present description. Summarizing the study, the results of the microfluidic chip 60 were very close to those of centrifugation. The photograph shown in Fig. 9 shows the microfluidic chip 60 with the piezoelectric element 80 switched on, whereby the resonance frequency of the channel 64 is reached. The erythrocytes 96 of the human sample are concentrated in a narrow band in the center of the channel 64 and therefore exit only through the central outlet 62.The novel bedside monitoring system should enable continuous and non-invasive quantification of CSF without the need to clamp or puncture the CSF drainage system. Compared to daily CSF collection with manual processing of each sample, the OxyHbMeter would offer better user-friendliness, reduce the risk of infection, and enable autonomous measurement of CSF Hb concentration. This method could improve reproducibility and be integrated into an effective warning system, for example, by providing a biomarker to predict DCI. In the tests, which also form the basis of the scientific publication, the flow rates were selected heuristically to achieve stable particle focusing throughout the extraction of plasma or CSF. The device used for this study was Möller Medical GmbH - 17 - 25.03.2025 möl-48WOP. Möller Medical GmbH - 18 - 25.03.2025 möl-48WOP and the fluid properties. The wavelength ( ) results from the channel width (D) and the selected resonance mode (k). To focus the particles in the center of the channel along the channel width—which is utilized for the present application of geometric separation of a component 96 from the body fluid 95—the first mode is used, in which half the wavelength fits within the channel width (k = 1, / 2 mode). The frequency depends on the wavelength and the speed of sound (c0) in the fluid used: c f mit 2Dk Möller Medical GmbH - 19 - 25.03.2025 möl-48WOP List of reference symbols 1 Device 2 Body fluid source 4 Drainage 5 Interface, e.g. connecting line 8 Hose coupling 10 Base part 11 Solenoid valve, “normally closed” 12 Solenoid valve, “normally open” 13 Air inlet 14 Air inlet filter 15 Air outlet 16 Outlet filter 17 First switching valve 18 Second switching valve 20 (external orarranged in the base part) Fluid pump 21 Switching pump 22 Air inlet 23 Inlet filter 24 Pressure sensor 25 Pressure accumulator 28 Pressure sensor 29 Pressure sensor 30 Switching output 31 Switching valve 32 Pressure connection in the base part 33 Control device 34 Control line 36 Air connection 37 Pressure connection in the base part 38 Second pressure connection in the base part 40 Fluidics module 41 Inlet line to the body fluid reservoir 42 Inlet line to the microfluidic chip 43 Inlet line to the measuring device 44 Inlet line from the measuring device to the waste collection volume 45 Inlet line from the microfluidic chip to the waste collection volume 48 Fluidics module housing 49 Housing passage 51 Hose coupling 52 Check valve in the inlet line 53 Flow sensor 54 Liquid detection 55 Body fluid reservoir 56 Liquid level in the body fluid reservoir 57 Level sensor in the body fluid reservoir Möller Medical GmbH - 20 - 25.03.2025 möl-48WOP 58 switching valve, e.g.Solenoid valve 59 Check valve in front of microfluidic chip 60 Microfluidic chip 61 Inlet 62 First outlet opening 63 Second outlet opening 64 Inlet channel 65 Bifurcation 66 Wafer 67 First outlet channel 68 Second outlet channel 69 Flow sensor 70 Measuring device 72 Measuring volume 73 Switching valve, e.g. solenoid valve 74 Sensor, in particular optical sensor 75 Residue receiving volume 76 Fill level sensor in the residue receiving volume 79 Switching valve, e.g. solenoid valve 80 Separation device 82 Pressure connection on or in the fluidic module 83 Second pressure connection on or in the fluidic module 84 Pressure connection line 85 Measuring point in pressure connection line 86 Switching connection 87 Second switching connection 88 Third switching connection 89 Fourth switching connection 90 Flushing device 92 Switching device, switching valve, e.g.Solenoid valve 93 Evaluation module 94 Storage module 95 Body fluid 96 Separated components of the body fluid 97 Pump control 98 Wireless connection device 99 Electrical supply device 100 Procedure 110 Introduction 115 Detection of the body fluid in the fluidics module 120 Supply of the body fluid 125 Activation 130 Influence 135 Further conveyance 140 Measurement 150 Disposal of the body fluid and / or the components in the fluidics module.

Claims

Möller Medical GmbH - 21 - 25.03.2025 möl-48WOP Patent Claims 1. Device (1) adapted for measuring and / or influencing a property of a body fluid (95), in particular cerebrospinal fluid, provided in a fluidic module of the device, the device comprising the fluidic module (40), a reusable base part (10), adapted or configured to receive the fluidic module on or in the base part, an interface (5, 51), in particular designed as a connecting tube (5) or a tube coupling (8), adapted for connecting the device to a body fluid source (2), in particular a patient, wherein the body fluid source comprises a body fluid, the body fluid being guideable into the fluidic module by means of the interface, a microfluidic chip (60) arranged on or in the fluidic module, adapted to influence the property of the body fluid. 2.Device (1) according to the preceding claim, wherein the device is prepared or configured as a mobile device and / or as a point-of-care diagnostic device.

3. Device (1) according to at least one of the preceding claims, wherein the property of the body fluid (95) is or comprises at least one of the following: the presence of foreign bodies or foreign substances (96) in the body fluid, the presence of particles, suspended particles, or cells (96) such as blood cells and / or blood serum proteins in the body fluid, the presence of hemoglobin or a derivative thereof in the body fluid, and / or the bilirubin level in the body fluid.

4. Device (1) according to at least one of the preceding claims, wherein influencing the property of the body fluid comprises separating particles, suspended particles, or cells from the body fluid. 5.Device (1) according to at least one of the preceding claims, further comprising a measuring device (70) arranged in or on the fluidics module (40) for determining the property of the body fluid (95).

6. Device (1) according to the preceding claim, wherein the measuring device (70) is configured to detect or quantify hemoglobin or a derivative thereof in the body fluid (95).

7. Device (1) according to one of the two preceding claims, wherein the measuring device (70) further comprises an optical sensor (74), in particular a spectrophotometer, arranged in or on the fluidics module (40).

8. Device (1) according to at least one of the preceding claims, further comprising a body fluid reservoir (55) arranged in or on the fluidics module (40), which reservoir is arranged in particular upstream of the microfluidic chip (60). 9.Device (1) according to the preceding claim, wherein the body fluid reservoir (55) comprises a fill level sensor (57) or a fill level indicator.

10. Device (1) according to at least one of the preceding claims, further comprising at least one switchable valve (58, 73, 79, 92), in particular a solenoid valve, in the fluidics module (40), in particular arranged downstream of the body fluid reservoir (55).

11. Device (1) according to at least one of the preceding claims, further comprising a residue receiving volume (75) arranged in or on the fluidics module (40). Möller Medical GmbH - 22 - 25.03.2025 möl-48WOP 12. The device (1) according to the preceding claim, wherein the residual material receiving volume (75) comprises a reservoir.

13. The device (1) according to at least one of claims 11 or 12, wherein the residual material receiving volume (75) is connected to the microfluidic chip (60), such that residual materials from the body fluid (95) can be discharged from the microfluidic chip directly into the residual material receiving volume.

14. The device (1) according to at least one of claims 11 to 13, wherein the residual material receiving volume (75) is connected to the measuring device (70) according to claim 4, such that volumes of the body fluid (95) measured by the measuring device can be discharged into the residual material receiving volume.Device (1) according to at least one of claims 11 to 14, wherein the residual material receiving volume (75) comprises a fill level sensor (76) or a fill level indicator for displaying the fill level of the residual material receiving volume, so that, in particular when a maximum fill level is reached, information can be output or the fluidics module (40) can be replaced with a new fluidics module.

16. Device (1) according to at least one of the preceding claims, further comprising a flushing device (90) arranged in or on the fluidics module (40).

17. Device (1) according to at least one of the preceding claims, further comprising a check valve arranged on the inlet side of the fluidics module (40), in particular upstream of the body fluid reservoir (55).

18. Device (1) according to at least one of the preceding claims, wherein the microfluidic chip (60) has an inlet channel (64) and / or a bifurcation (65). 19.Device (1) according to at least one of the preceding claims, wherein the microfluidic chip (60) has a separation device (80) for separating particles, particles, or cells from the body fluid (95).

20. Device (1) according to at least one of the preceding claims, wherein the separation device (80) comprises at least one piezoelectric component, in particular a piezoelectric transducer.

21. Device (1) according to the preceding claim, wherein the separation device (80) is configured to provide sound pressure, in particular for providing acoustophoresis.

22. Device (1) according to at least one of the preceding claims, further comprising a gas bubble detection and / or separation device arranged upstream of the microfluidic chip (60) for identifying and / or separating gaseous components from the body fluid (95). 23.Device (1) according to at least one of the preceding claims, wherein the interface (5, 51), in particular designed as the connecting tube, is adapted for connection to an external ventricular drainage (4).

24. Device (1) according to at least one of the preceding claims, wherein the interface (5, 51), in particular designed as the connecting tube (5), is adapted for direct connection to the fluidics module (40). Möller Medical GmbH - 23 - March 25, 2025 möl-48WOP 25. Device (1) according to at least one of the preceding claims, wherein the fluidic module (40) is adapted for connection to the interface (5, 51) or comprises the latter, wherein the interface is in particular designed as the connecting hose (5).

26. Device (1) according to at least one of the preceding claims, wherein the fluidic module (40) comprises a hose coupling (51) for connection to the connecting hose (5).

27. Device (1) according to at least one of the preceding claims, further comprising a fluid detector (54) arranged on or in the fluidic module (40) adapted to determine the presence of body fluid (95) in the fluidic module.

28. Device (1) according to at least one of the preceding claims, the base part (10) comprising a pump (20) for providing an overpressure and / or a negative pressure. 29.Device (1) according to the preceding claim, configured such that the pump (20) can be connected to the fluidics module (40), so that an overpressure and / or a negative pressure can be provided in the fluidics module.

30. Device (1) according to at least one of claims 28 or 29, wherein the pump (20) can be connected to the fluidics module (40) by means of at least one pressure connection coupling (30, 37, 38).

31. Device according to at least one of claims 28 or 30, wherein only one pressure connection coupling (82) is provided on the fluidics module for connecting the pump (20) to the fluidics module (40), and via which one pressure connection coupling, in particular both overpressure and negative pressure can be delivered to the fluidics module. 32.Device according to at least one of claims 28 to 31, wherein, for connecting the pump (20) to the fluidics module (40), a plurality of at least two pressure connection couplings (30, 37, 38, 82, 83, 86, 87, 88, 89) are provided on the base part (10) and the fluidics module (40), so that, in particular, the negative pressure can be delivered to the fluidics module separately from the positive pressure.

33. Device (1) according to at least one of the preceding claims, further comprising a control pressure connection coupling (30, 86, 87, 88, 89) for controlling a compressed air-controlled device in the fluidics module (40).

34. Device (1) according to at least one of claims 28 to 33, wherein the positive pressure and / or the negative pressure can be used to influence a fluid flow in the fluidics module (40). 35.Device (1) according to at least one of claims 28 to 34, wherein the body fluid (95) can be sucked in by means of negative pressure, in particular from a ventricular drainage (4) or a body fluid source (2) into the body fluid reservoir (55).

36. Device (1) according to at least one of claims 28 to 35, wherein the body fluid can be conveyed further in the fluidics module (40) by means of positive pressure, in particular from the body fluid reservoir (55) to the microfluidic chip.

37. Device (1) according to at least one of claims 28 to 36, wherein the body fluid reservoir (55) can be subjected to the negative pressure and / or the positive pressure, so that by applying negative pressure, the body fluid (95) can be conveyed from the connecting tube (5) into the body fluid reservoir (55) and / or by applying positive pressure, the body fluid (95) stored in the body fluid reservoir (55) can be conveyed in the direction of the microfluidic chip (60).Device according to at least one of the preceding claims, wherein the base part (10) is further adapted to accommodate a control module (33) adapted to control the further conveyance of the body fluid (95) in the fluidic module (40) and / or to control the measuring device (70), wherein. Möller Medical GmbH - 24 - 25.03.2025 möl-48WOP Control commands of the control module can be transmitted to the fluidics module via the at least one pressure connection and / or via electrical contacts.

39. Device (1) according to at least one of the preceding claims, wherein the base part (10) is further configured to accommodate an evaluation module (93) for evaluating the data obtained with the fluidics module (40), in particular the measuring device (70), and for providing a diagnostic result regarding the property of the body fluid (95).

40. Device (1) according to at least one of the preceding claims, wherein the base part (10) is further configured to accommodate a storage module (94) for storing the measurement data obtained with the fluidics module (40), so that, in particular, the measurement can be continued without interruption even when the fluidics module is replaced. 41.Device (1) according to at least one of the preceding claims, wherein the base part (10) is further configured to accommodate a pump controller (97) for controlling the pump (20) arranged in the base module, wherein the pump controller can be supplied with sensor data from the fluidics module for the control.

42. Device (1) according to at least one of the preceding claims, wherein the base part (10) is further configured to accommodate a wireless connection device (98) for connecting, for example, to a hospital network for data exchange therewith.

43. Device (1) according to at least one of the preceding claims, wherein the base part (10) is further configured to accommodate an electrical supply device (99) comprising a power connection and / or an energy storage device. 44.Device (1) according to at least one of the preceding claims, wherein the base part (10), in particular with the control module (33) according to the preceding claim, is configured to close the access upon detection of an error in the body fluid delivery, i.e., in particular, to act in response to the fluid detector (54) according to the preceding claim 27, and / or to act on a control valve arranged in the fluidic module (40) or on the ventricular drainage (4) according to claim 23 to shut off the fluid flow. 45.Fluidics module (40) for a device (1), in particular according to at least one of the preceding claims, the fluidics module comprising an interface (5, 51), in particular designed as a connecting hose (5) or a hose coupling (51) adapted to connect the fluidics module to a body fluid source (2), in particular a patient, or a drainage (4), such that the body fluid can be guided into the fluidics module through the connecting hose or the hose coupling, a microfluidic chip (60) arranged on or in the fluidics module adapted to influence a property of the body fluid. 46.Microfluidic chip (60), in particular adapted for use in a device (1) for measuring and / or influencing a property of a body fluid, the microfluidic chip comprising an inlet channel (64), a bifurcation (65), a first (62) and a second (63) outlet opening, a separation device (80) for separating a portion of the body fluid (95), in particular particles, particles or cells (96), in the region of the bifurcation from the body fluid, so that the portion of the body fluid can be supplied to the first outlet opening and a purified body fluid can be supplied to the second outlet opening. Möller Medical GmbH - 25 - 25.03.2025 möl-48WOP 47. The microfluidic chip (60) according to the preceding claim, wherein the separation device (80) is configured to guide the portion of the body fluid (95), in particular by means of acoustophoresis, into a central portion of the inlet channel (64), and wherein the purified body fluid escapes into a lateral region of the inlet channel, so that in the region of the bifurcation (65) and with the application of a fluid flow, the portion of the body fluid is guided to the first outlet opening (62) and the purified body fluid is guided to the second outlet opening (63) of the microfluidic chip.

48. The microfluidic chip (60) according to at least one of claims 46 or 47, the separation device (80) comprising a piezoelectric transducer.

49. The microfluidic chip (60) according to at least one of claims 46 to 48, wherein the microfluidic chip comprises a glass wafer. 50.Method (100) for diagnosing a body fluid (95), in particular cerebrospinal fluid, in particular using the device (1) and / or the fluidics module (40) and / or the microfluidics chip (60) according to at least one of the preceding claims, comprising the steps of introducing (110) the body fluid into a fluidics module (40), conveying (120) the body fluid to a microfluidics chip (60) arranged in or on the fluidics module for influencing a property of the body fluid, in particular for separating blood cells (96) from the body fluid, by means of or in the microfluidics chip, conveying (135) the body fluid to a measuring device (70) arranged in or on the fluidics module for determining the same or another property of the body fluid, conveying the body fluid out of the measuring device and into a residue receiving volume (75) arranged in the fluidics module. 51.Method (100) according to the preceding claim, further comprising the step of beginning the conveying of the body fluid (95) in the fluidics module (40) as soon as a body fluid reservoir (55) arranged in the fluidics module is sufficiently supplied with the body fluid (95).

52. Method (100) according to at least one of claims 50 or 51, wherein the steps of conveying the body fluid (95) are carried out by means of a conveying pump (20) arranged in a base module (10).

53. Method (100) according to at least one of claims 50 to 52, wherein the device is a mobile device and the method is a point-of-care diagnostic method.

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