A microfluidic-based fluid control method, apparatus, and medium
By setting up liquid-gas interface sensing nodes in the microfluidic reagent disk, the system can determine the liquid's position and interface continuity, generate trigger sequences, and control the liquid to advance segment by segment. This solves the problem of unstable control of segmented liquid movement, achieving accuracy and stability in liquid transfer. It is suitable for clinical mass spectrometry, biochemistry, and coagulation testing scenarios.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- ALI BIOTECHNOLOGY TAIZHOU CO LTD
- Filing Date
- 2026-05-15
- Publication Date
- 2026-07-21
AI Technical Summary
In existing microfluidic technologies, the segmented forward control of liquid is unstable. The timing of downstream channel opening does not match the actual liquid arrival, which can easily lead to premature release, delayed release, or crosstalk. Furthermore, there is a lack of a mechanism for blocking and restoring conduction in abnormal sections, resulting in the unstable downstream spread and transport of abnormalities.
By setting a liquid-gas interface sensing node at the flow control node of the microfluidic reagent disk, the liquid arrival and interface continuity are determined, an interface trigger sequence is generated, the liquid is controlled to advance segment by segment, and in case of abnormality, the downstream channel is closed and switched to the buffer branch. After the continuity is restored, the channel is reopened.
It improves the accuracy and stability of fractional liquid transfer, enhances the controllability of abnormal handling, ensures the reliability of subsequent delivery, and is suitable for clinical mass spectrometry, biochemistry and coagulation testing scenarios.
Smart Images

Figure CN122183729B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of fluid manipulation technology, and in particular to a fluid control method, device and medium based on microfluidics. Background Technology
[0002] Microfluidic technology, which delivers, dispenses, measures, and transfers sample and reagent solutions through microscale channels, has been widely applied in reagent trays and instrument systems for clinical mass spectrometry, biochemistry and coagulation testing, menstrual blood testing, and veterinary medical testing. As the integration and automation levels of testing projects continue to increase, microfluidic reagent trays not only need to complete the orderly transfer of multiple liquids within a limited space, but also need to take into account delivery rhythm, interface stability, and coordination of area switching. Therefore, the stable control of the liquid transfer process within microchannels has become an important technical direction for improving the consistency and reliability of testing systems.
[0003] Existing methods have some shortcomings. Some methods mainly rely on preset cycle time or fixed valve control timing to control the liquid segment forward movement. The timing of downstream channel opening is not sufficiently correlated with the actual liquid arrival and interface continuity, which can easily lead to premature release, delayed release, or crosstalk, affecting the stability of segment transportation. In addition, for interfacial discontinuity, air entrainment, or local anomalies during liquid transportation, some solutions lack fixed-point blocking, buffer switching, and conduction restoration mechanisms for abnormal sections, which can easily cause the anomaly to spread downstream or make subsequent transportation unstable after the anomaly is cleared. Summary of the Invention
[0004] In view of the aforementioned existing problems, the present invention is proposed.
[0005] Therefore, this invention provides a microfluidic-based fluid control method to solve the problems of insufficient matching in segmented release and unstable control during abnormal recovery.
[0006] To solve the above-mentioned technical problems, the present invention provides the following technical solution:
[0007] In a first aspect, the present invention provides a microfluidic-based fluid control method, comprising: introducing the sample liquid to be tested and the matching reagent liquid into the corresponding storage chambers of the microfluidic reagent disk, and setting a liquid-gas interface sensing node at the flow control node to determine the liquid arrival status and interface continuity status, and generating an interface trigger sequence; controlling the upstream liquid to advance segment by segment along a predetermined microchannel according to the interface trigger sequence, and opening the corresponding downstream channel after confirming the liquid front is in place and the interface is continuous at the previous sensing node, so that the sample liquid to be tested and the matching reagent liquid complete directional release and sequential transfer, forming a segmented release result; introducing the sequentially transferred liquid into the processing area according to the segmented release result, and identifying interface anomalies during the liquid crossing the processing area, closing the current downstream channel and switching to the corresponding buffer branch when an interface anomaly is identified, so that the sample liquid to be tested and the matching reagent liquid enter an abnormal blockage; restricting the blocked liquid to the buffer branch and the upstream area of the target node according to the liquid residence position corresponding to the abnormal blockage, and reconnecting the corresponding downstream channel after the liquid resumes continuity, so that the sample liquid to be tested and the matching reagent liquid continue to enter the execution area, forming an execution area delivery state.
[0008] As a preferred embodiment of the microfluidic-based fluid control method of the present invention, the specific steps for generating the interface trigger sequence are as follows:
[0009] The sample solution to be tested and the matching reagent solution are respectively introduced into the corresponding liquid storage chamber of the microfluidic reagent disk and are in the state of waiting to be pushed in their respective corresponding flow channels, forming the initial liquid distribution state;
[0010] In the initial liquid distribution state, the interface sensing signal corresponding to the liquid-gas interface sensing node at the flow control node is collected, and the liquid arrival status is determined to form a liquid arrival status record.
[0011] Based on the liquid arrival status record, the interface continuity state between adjacent flow control nodes is determined, and the flow control nodes that satisfy the liquid arrival status and the interface continuity state between adjacent nodes are arranged in sequence according to their positions to generate an interface trigger sequence.
[0012] As a preferred embodiment of the microfluidic-based fluid control method of the present invention, the specific steps for forming the segmented release result are as follows:
[0013] The release order of each segment is determined based on the interface trigger sequence, and the previous flow control node of the current segment to be released is determined as the previous sensing node to obtain the release preparation content.
[0014] Under the release preparation content, the sample liquid to be tested and the matching reagent liquid are advanced, and the interface sensing signals of the previous sensing node and the corresponding flow control node of the current release section are collected to obtain the advancement sensing record.
[0015] Based on the propulsion sensing records, the system determines the position of the liquid front and the continuity of the interface, and opens the corresponding downstream channels.
[0016] The sample solution to be tested and the matching reagent solution continue to enter the next release section, and the directional release and sequential transfer are completed in sequence according to the order of each release section, so as to obtain the segmented release result.
[0017] As a preferred embodiment of the microfluidic-based fluid control method of the present invention, the specific steps for introducing the sample solution to be tested and the matching reagent solution into the abnormal blocking state are as follows:
[0018] Import the sample solution to be tested and the matching reagent solution corresponding to the segmented release result into the processing area, determine the current processing segment, and obtain the processing import result;
[0019] Under the processing and import results, the interface perception signals corresponding to each flow control node in the current processing section are collected and recorded sequentially to obtain the interface perception record;
[0020] Based on the interface perception record, identify the continuous state of the interface and mark the abnormal sections of liquid crossing, and merge them to obtain the abnormal interface conditions.
[0021] The interface anomaly is mapped to the current processing segment, the downstream channel corresponding to the current processing segment is closed, and the current processing segment is switched to the corresponding buffer branch, thus entering an anomaly blocking state.
[0022] As a preferred embodiment of the microfluidic-based fluid control method of the present invention, the specific steps for forming the delivery state of the execution region are as follows:
[0023] Based on the location of the liquid retention corresponding to the abnormal blockage, the blocked liquid will be confined to the buffer branch and the upstream area of the target node, and the downstream channel corresponding to the current processing section will be kept closed.
[0024] Collect interface perception signals from buffer branches, upstream regions of target nodes, and corresponding flow control nodes in front of the current processing section, and determine the interface continuity between adjacent flow control nodes.
[0025] After the liquid flow is restored, the corresponding downstream channel is reconnected, and the sample solution to be tested and the matching reagent solution continue to enter the execution area, forming the execution area delivery state.
[0026] As a preferred embodiment of the microfluidic-based fluid control method of the present invention, the initial liquid distribution state refers to the residence state of the sample liquid to be tested and the matching reagent liquid in the corresponding storage chamber, the starting position in their respective corresponding flow channels, and the stable residence state at the corresponding liquid-gas interface position.
[0027] As a preferred embodiment of the microfluidic-based fluid control method of the present invention, the propulsion sensing record includes the sequence of acquisition of interface sensing signals, the sequence of signal changes, and the arrival status of the liquid front of the sample liquid and the matching reagent liquid at the previous sensing node and the corresponding flow control node of the current release section.
[0028] As a preferred embodiment of the microfluidic-based fluid control method of the present invention, the interface sensing signal refers to the capacitance change signal generated when the liquid reaches the corresponding flow control node position, which is different from the air occupation state.
[0029] In a second aspect, the present invention provides a computer device including a memory and a processor, wherein the memory stores a computer program, wherein when the computer program is executed by the processor, it implements any step of the microfluidic-based fluid control method as described in the first aspect of the present invention.
[0030] Thirdly, the present invention provides a computer-readable storage medium having a computer program stored thereon, wherein: when the computer program is executed by a processor, it implements any step of the microfluidic-based fluid control method as described in the first aspect of the present invention.
[0031] The beneficial effects of this invention are as follows: By judging the liquid arrival status and interface continuity, and implementing segmented advancement and directional release according to the interface trigger sequence, the corresponding control of the downstream channel opening timing and the actual liquid transmission status is realized, improving the accuracy, continuity and stability of the segmented transfer of the sample liquid and the matching reagent liquid; by identifying interface anomalies in the processing area, closing the current downstream channel and switching to the corresponding buffer branch when an anomaly occurs, and reconnecting the corresponding downstream channel after the liquid resumes continuity, the local blocking and restoration of conduction in the abnormal section is realized, improving the controllability of anomaly handling and the reliability of subsequent delivery. It is applicable to microfluidic reagent trays and instruments in clinical mass spectrometry, biochemical and coagulation testing, menstrual blood testing and pet medical testing. Attached Figure Description
[0032] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the following description of the embodiments will be briefly introduced. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0033] Figure 1 This is a flowchart of a microfluidic-based fluid control method.
[0034] Figure 2 The flowchart for interface-triggered sequence generation and segmented release control.
[0035] Figure 3 Flowchart for handling interface anomaly identification and anomaly blocking.
[0036] Figure 4 Flowchart for resuming continuous liquid transport and executing regional delivery control.
[0037] Figure 5 This is a comparison chart of the matching rate data for the release of vehicles in different viscosity ratios.
[0038] Figure 6 Heat map of section release matching rate under different viscosity ratios and propulsion pressure fluctuations. Detailed Implementation
[0039] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.
[0040] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.
[0041] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.
[0042] Reference Figures 1-6 This is one embodiment of the present invention, which provides a microfluidic-based fluid control method, including the following steps:
[0043] S1. The sample liquid to be tested and the matching reagent liquid are respectively introduced into the corresponding liquid storage chamber of the microfluidic reagent disk, and a liquid-gas interface sensing node is set at the flow control node to judge the liquid arrival status and interface continuity status and generate an interface trigger sequence.
[0044] S1.1. The sample solution to be tested and the matching reagent solution are respectively introduced into the corresponding storage chambers of the microfluidic reagent disk, and the sample solution to be tested and the matching reagent solution are in a state of waiting to be pushed in their respective corresponding flow channels, forming an initial liquid distribution state corresponding to the sample solution to be tested and the matching reagent solution.
[0045] It should be noted that the sample solution to be tested and the matching reagent solution are injected into the corresponding storage chambers of the sample solution and the matching reagent solution, respectively. After injection, the storage chambers of the sample solution and the matching reagent solution are kept closed, so that the sample solution and the matching reagent solution enter their respective corresponding flow channels and remain at their respective starting positions. The liquid-gas interface positions of the sample solution and the matching reagent solution in their respective flow channels are kept stable. The residence state of the sample solution and the matching reagent solution in their respective storage chambers, their starting positions in their respective flow channels, and their stable residence state at their respective liquid-gas interface positions are taken as the initial liquid distribution state corresponding to the sample solution and the matching reagent solution.
[0046] S1.2. Under the initial liquid distribution state, collect the interface sensing signal corresponding to the liquid-gas interface sensing node at the flow control node, and judge the liquid arrival status of the sample liquid to be tested and the matching reagent liquid at each flow control node to form a liquid arrival status record.
[0047] It should be noted that within the microfluidic reagent tray, microchannels are pre-formed that connect the reservoir corresponding to the sample solution to be tested, the reservoir corresponding to the matching reagent solution, and the downstream transport section. The microchannels corresponding to the transport path of the sample solution to be tested and the microchannels corresponding to the transport path of the matching reagent solution are defined as predetermined microchannels.
[0048] In a predetermined microfluidic channel, the main channel inlet, distribution point, metering point, and execution point, used to characterize changes in liquid transport position, are defined as flow control nodes. Liquid-air interface sensing nodes are installed at each flow control node to detect the liquid-air boundary. The execution point refers to the position downstream of the metering point in the predetermined microfluidic channel and corresponding to the subsequent liquid entry into the execution area. The execution point characterizes the positional changes of the sample liquid and the accompanying reagent liquid during the transport phase at the end of the predetermined microfluidic channel. The flow control nodes are deployed based on the liquid state change positions within the predetermined microfluidic channel, including the reservoir outlet and the main channel... The flow control system includes the inlet, distribution, metering, pre-branching, post-merging, buffer branch interface, and execution area inlet. Adjacent flow control nodes form a detection zone capable of independently determining liquid arrival and interface continuity. The number of flow control nodes is determined by the actual structure of the predetermined microchannel corresponding to the sample liquid and matching reagent liquid. The node spacing is determined by the channel length between adjacent functional locations; equal spacing between adjacent nodes is not required. When the predetermined microchannel has a branching or merging structure, the upstream node of the branching point, the inlet nodes of each branch, and the downstream node of the merging point are used as boundary nodes, thus ensuring that subsequent adjacent flow control nodes... and The continuous discrimination between them has a clear structural boundary.
[0049] Capacitive detection electrodes are set on the outside of the predetermined microchannels corresponding to each flow control node, so that when the liquid reaches the corresponding flow control node position, it generates a capacitance change signal that is different from the air-occupied state, and the capacitance change signal is used as the interface sensing signal corresponding to the liquid-gas interface sensing node.
[0050] The expression for liquid occupancy determination is,
[0051] ;
[0052] in, Indicates liquid At flow control nodes Place, moment The occupancy discriminant when When, it indicates that the liquid has occupied the corresponding flow control node position, when When the subscript indicates that the liquid does not occupy the corresponding flow control node position; Indicates the type of liquid. When, it indicates the sample solution to be tested. When, it indicates the matching reagent solution; Indicates the flow control node index; Indicates a specific moment in time; Indicates liquid At flow control nodes Place, moment Interface-sensing signals at that time; Indicates liquid At flow control nodes The liquid at that location occupies the reference signal; superscript Indicates "liquid occupies"; Indicates liquid At flow control nodes The air at that location occupies the reference signal; superscript It means "air occupies".
[0053] The liquid occupancy discriminant above and All are absolute differences, used to compare the proximity between the current interface sensing signal and the liquid occupation reference signal and the air occupation reference signal; if the absolute difference between the current interface sensing signal and the liquid occupation reference signal is not greater than the absolute difference between the current interface sensing signal and the air occupation reference signal, it is determined that the liquid has occupied the corresponding flow control node position.
[0054] The liquid occupation reference signal and air occupation reference signal are obtained through the calibration process after the microfluidic reagent disk is assembled. Specifically, an air occupation state and a liquid stable occupation state are formed at the corresponding fluid control node, and the capacitance detection signal at this fluid control node is continuously collected. After removing abrupt changes and averaging the capacitance detection signal, the air occupation reference signal and liquid occupation reference signal are obtained respectively. When the viscosity, ionic strength or detection temperature of the sample liquid and the matching reagent liquid change, the liquid occupation reference signal and air occupation reference signal are corrected according to the blank channel calibration signal and the corresponding liquid calibration signal to make the reference signal correspond to the current detection conditions.
[0055] When acquiring interface sensing signals, capacitance detection signals of each liquid-gas interface sensing node are continuously acquired according to a preset sampling period. The sampling period is determined based on the shortest liquid passage time and valve response time between adjacent flow control nodes, ensuring that at least one effective sample is obtained when the same liquid front passes through adjacent flow control nodes. The continuously acquired capacitance detection signals are smoothed using a sliding window, and the smoothed capacitance detection signals are used for liquid occupancy discrimination. Only when the same flow control node meets the liquid occupancy discrimination conditions within the continuous sampling window is this flow control node marked as being in liquid position. The length of the continuous sampling window and the noise tolerance range are pre-calibrated based on the baseline fluctuation amplitude under air occupancy and the signal fluctuation amplitude under stable liquid occupancy.
[0056] According to the sequential positions of each flow control node in the predetermined microchannel, the interface sensing signals corresponding to each liquid-gas interface sensing node are collected one by one. The interface sensing signals collected at each flow control node are then correlated with the liquid-gas interface positions of the sample liquid and the matching reagent liquid in their respective flow channels. When the interface sensing signal at a flow control node indicates that the sample liquid or the matching reagent liquid has occupied the corresponding flow control node position, the corresponding flow control node is marked as being in liquid position. The expression is as follows:
[0057] ;
[0058] ;
[0059] in, Indicates liquid First arrival at the flow control node Time; Indicates liquid At flow control nodes Liquid arrival determination quantity at the location, when When, it indicates a flow control node. The liquid has been determined to be in place, when When, it indicates a flow control node. Not in place; The infimum operator represents the condition that satisfies... The earliest time; This indicates that no condition was detected within the preset observation time window. Limited time.
[0060] The initial arrival time is determined within a preset observation time window, which is the self-flow control node. The time interval from the start of acquiring interface sensing signals to the end of the maximum observation period, where the maximum observation period is preset based on the flow channel length between adjacent flow control nodes, the liquid calibration propulsion speed, propulsion pressure, and valve response delay; in the actual control program, when When this happens, the flow control node is judged to be in a timeout state and will be... Record it as 0, while keeping the corresponding downstream channel closed, and write the timeout status into the liquid arrival status record.
[0061] When a flow control node fails to detect a condition that satisfies the maximum observation time. When the corresponding interface sensing signal does not indicate that the sample liquid or the matching reagent liquid occupies the corresponding flow control node position, the corresponding flow control node is marked as not in place, and the liquid in place and not in place states are recorded in sequence according to the order of the flow control nodes to form a liquid in place state record.
[0062] S1.3. Combine the liquid arrival status record to determine the interface continuity state between adjacent flow control nodes, and arrange the flow control nodes that meet the liquid arrival status and the interface continuity state between adjacent nodes in sequence according to the order of their positions to generate an interface trigger sequence.
[0063] It should be noted that in the liquid position status record, two adjacent flow control nodes are used as a group of continuous discrimination objects, and the liquid position status corresponding to each group of continuous discrimination objects is compared. When two adjacent flow control nodes are both marked as liquid in position, and during the sequential change of the interface sensing signal at the two adjacent flow control nodes along the predetermined microchannel flow direction, there is no interruption change from liquid occupying the corresponding flow control node position to non-position state, the two adjacent flow control nodes are marked as interface continuous state. For the discrimination of interface continuous state, the instantaneous fluctuation of a single sampling point is not directly determined as an interruption change. When the liquid occupation discrimination quantity between the same adjacent flow control nodes is continuously in the non-position state within the continuous sampling window, or the duration of the non-position state exceeds the pre-calibrated interruption confirmation time, this change is determined as an interruption change. The interruption confirmation time is pre-determined based on the air baseline noise, the signal fluctuation under the stable liquid occupation state, and the controller sampling period, and is used to eliminate misjudgments caused by instantaneous noise. The discrimination expression for interface continuous state is:
[0064] ;
[0065] in, Indicates liquid At adjacent flow control nodes and The interface between them is a continuous discrimination quantity, when When, it indicates a flow control node. With flow control nodes The interfaces between them are continuous, when When this occurs, it indicates that the interface is not continuous; Indicates flow control node The sequence number of the next adjacent flow control node; Indicates For a variable that takes a value, in Within the defined time interval, the liquid occupancy discrimination quantity The minimum value is used to determine the flow control node. Reaching the next adjacent flow control node Whether the liquid remains in an occupied state during the process; Indicates Starting from, with The time interval that marks the end point.
[0066] When either of two adjacent flow control nodes is marked as not in position, or when the interface sensing signal at two adjacent flow control nodes changes sequentially along the predetermined microchannel flow direction and there is an interruption in the change from liquid occupying the corresponding flow control node position to not in position, the two adjacent flow control nodes are marked as having a discontinuous interface.
[0067] Based on the sequential positions of each flow control node in the predetermined microchannel, the flow control nodes marked as being in the liquid-positioned state and satisfying the interface continuity with the preceding flow control node are arranged sequentially. The resulting sequence of flow control nodes is recorded as the interface trigger sequence, expressed as follows:
[0068] ;
[0069] in, Indicates liquid The interface trigger sequence; This represents a sorting operator that sorts the flow control node numbers that meet the conditions in ascending order according to their positions corresponding to the predetermined flow direction of the microchannel. Indicates flow control node The sequence number of the adjacent preceding flow control node; Indicates liquid At adjacent flow control nodes and The interface between them is a continuous discrimination quantity.
[0070] Interface trigger sequence It is for a single liquid The generated trigger sequence; when At that time, the interface trigger sequence corresponding to the sample liquid to be tested is obtained. ,when At that time, the interface trigger sequence corresponding to the matching reagent solution is obtained. When the sample solution to be tested and the matching reagent solution need to be simultaneously introduced into the same processing area or the same execution area, the liquid ratio requirements will be determined according to the target processing area, target node, and liquid ratio requirements. and The triggering nodes corresponding to the same target node or the same merging node form a joint triggering unit; when one liquid arrives first while the other liquid has not yet arrived, the closed state of the downstream channel corresponding to the liquid that arrived first is maintained until both liquids meet the liquid arrival state and interface continuity state, and then the corresponding downstream channel opening operation is performed.
[0071] S2. Based on the interface trigger sequence, the upstream liquid is controlled to advance segment by segment along the predetermined microchannel. After confirming that the liquid front is in place and the interface is continuous at the previous sensing node, the corresponding downstream channel is opened, so that the sample liquid to be tested and the matching reagent liquid can be released in a directional manner and transferred in sequence, forming a segmented release result.
[0072] S2.1. Based on the interface trigger sequence, determine the release order of the sample solution to be tested and the corresponding reagent solution, and determine the flow control node before the current release segment as the previous sensing node to obtain the release preparation content corresponding to the interface trigger sequence.
[0073] It should be noted that the flow control nodes in the interface trigger sequence, arranged in the predetermined flow direction of the microchannel, are read sequentially, and the flow channel between two adjacent flow control nodes with liquid arrival discrimination function is taken as a release section. For straight flow channels, a release section is directly formed between two adjacent flow control nodes. For bifurcated flow channels, the release section of the corresponding branch is formed by the upstream flow control node at the bifurcation point and the flow control node at the entrance of each branch. For merging flow channels, the corresponding merging release section is formed by the flow control node before and after the merging of each branch. Each release section is not required to be of equal length or have the same corresponding functional position. The division is based on whether independent release discrimination can be achieved through the upstream flow control node, downstream flow control node and corresponding valve control channel.
[0074] Select the current release segment in the segmented release sequence, and determine the flow control node preceding the current release segment as the previous sensing node. Record the correspondence between the current release segment and the previous sensing node, the sequential position of the current release segment in the segmented release sequence, and the correspondence between the sample solution to be tested and the supporting reagent solution and the current release segment. This will yield the release preparation content corresponding to the interface trigger sequence. The release preparation content includes at least the current release segment, the previous sensing node, the closure status of the downstream channel corresponding to the current release segment, and the correspondence between the sample solution to be tested and the supporting reagent solution and the current release segment.
[0075] S2.2 Under the release preparation content, control the sample liquid to be tested and the matching reagent liquid to advance along the predetermined microchannel to the current release section, and continuously collect the interface sensing signals of the previous sensing node and the corresponding flow control node of the current release section to obtain the advancement sensing record.
[0076] It should be noted that a propulsion pressure is applied to the reservoir corresponding to the sample solution and the corresponding reagent solution, causing the sample solution and the reagent solution to move forward along their respective predetermined microchannels towards the current release section, while keeping the downstream channel of the current release section closed. During the forward movement of the sample solution and the reagent solution, the interface sensing signal corresponding to the previous sensing node and the interface sensing signal corresponding to the flow control node of the current release section are continuously collected according to the flow direction of the predetermined microchannel. The order of collection of the interface sensing signals, the order of signal changes, and the arrival of the liquid front of the sample solution and the reagent solution at the previous sensing node and the flow control node of the current release section are recorded to obtain the propulsion sensing record.
[0077] Furthermore, the external driving pressure is predetermined based on the calibrated viscosity of the sample liquid and the matching reagent liquid, the predetermined microchannel cross-sectional size, the channel length between adjacent flow control nodes, and the target propulsion time. When applying propulsion pressure to the corresponding reservoir, a gradual pressurization method is used to ensure that the liquid front smoothly enters the current release section, and the propulsion pressure is maintained or finely adjusted based on the interface sensing signal feedback. When the pressure fluctuation exceeds the pre-calibrated allowable fluctuation range, or when the liquid front fails to reach the corresponding flow control node within the maximum observation time, the pressurization is stopped and the corresponding downstream channel is kept closed. The allowable fluctuation range is determined by the unloaded microchannel test and the calibration propulsion test of liquids with different viscosity ratios.
[0078] S2.3. The propulsion sensing record is judged to confirm the liquid front position at the previous sensing node and the interface continuity between the adjacent flow control nodes of the current clearance section. When the liquid front position is in place and the interface is continuous, the corresponding downstream channel is opened to enable the current clearance section to be released.
[0079] It should be noted that the interface sensing signal corresponding to the previous sensing node in the advance sensing record is compared with the interface sensing signal corresponding to the flow control node of the current release section. When the interface sensing signal at the previous sensing node continuously indicates that the sample liquid to be tested or the matching reagent liquid has occupied the position of the previous sensing node, the previous sensing node is recorded as the liquid front is in place.
[0080] The continuity of the interface sensing signal change process between the previous sensing node and the flow control node corresponding to the current release section is determined. Specifically, when the interface sensing signal at the previous sensing node and the interface sensing signal at the flow control node corresponding to the current release section appear sequentially along the predetermined microchannel flow direction, and there is no interruption change from the liquid occupying the position of the corresponding flow control node to the non-positioned state, the adjacent flow control nodes corresponding to the current release section are recorded as interface continuity.
[0081] Before opening the corresponding downstream channel, the liquid front position at the previous sensing node and the interface continuity between the adjacent flow control nodes of the current release section are maintained and confirmed. When the above state is maintained for a preset time and no liquid front regression from the position to the non-position state is detected, the propulsion pressure is adjusted to the holding pressure and an opening command is sent to the corresponding valve control structure. The actual opening of the corresponding downstream channel is based on the opening state fed back by the valve control structure, thereby avoiding premature release caused by valve response delay, pressure inertia, or liquid front regression.
[0082] After the above confirmation, the downstream channel corresponding to the current section to be released is switched from closed to open, so that the sample solution to be tested and the matching reagent solution can continue to move forward along the opened downstream channel, thereby completing the release of the current section to be released.
[0083] The expression for determining the release of a section is:
[0084] ;
[0085] in, Indicates liquid In the The segment release discrimination quantity on a pending release segment, when When, it indicates a liquid In the The pending passage sections meet the release conditions; Indicates the index of the section to be released; Indicates liquid The The sequence number of the upstream flow control node for each pending passage segment; Indicates liquid The The sequence number of the downstream flow control node for each pending passage segment; This represents a chain multiplication operator that performs a chain multiplication on the interface continuous discrimination quantities of all adjacent flow control node pairs from the upstream flow control node to the downstream flow control node.
[0086] when and When the nodes are adjacent, the product term only includes the interface continuity judgment quantity of adjacent node pairs; when the section to be released contains multiple consecutive flow control nodes, the product term indicates that all adjacent flow control node pairs in the section to be released meet the interface continuity state; when the nodes corresponding to the section to be released are not continuous, the section to be released is divided into multiple continuous sub-segments according to the actual flow channel connection relationship, and the section release judgment is performed separately.
[0087] S2.4 After the current release segment is completed, the sample solution to be tested and the matching reagent solution continue to enter the next release segment corresponding to the interface trigger sequence, and the directional release and sequential transfer are completed in sequence according to the order of each release segment to obtain the segmented release result.
[0088] It should be noted that the subsequent release segments following the current release segment in the interface trigger sequence are identified, and the flow control node preceding the subsequent release segment is designated as the previous sensing node. The sample solution to be tested and the corresponding reagent solution continue to move forward along the corresponding downstream channel after opening, allowing them to sequentially enter the subsequent release segments. A progress sensing record is generated for the subsequent release segments, the liquid front arrival status at the previous sensing node is determined, and the interface continuity between adjacent flow control nodes corresponding to the subsequent release segments is determined. When the liquid front is in place and the interface is continuous, the downstream channel corresponding to the subsequent release segment is opened, so that the subsequent release segment is released. According to the order of each release segment in the interface trigger sequence, the advance perception record is formed for each release segment in sequence. The liquid front is in place at the previous perception node, and the interface continuity between the adjacent flow control nodes corresponding to each release segment is determined. When the liquid front is in place and the interface is continuous, the corresponding downstream channel is opened until each release segment corresponding to the interface trigger sequence has completed directional release and sequential transfer, and the segmented release result is obtained.
[0089] Furthermore, when the predetermined microchannel lengths or the number of flow control nodes of the sample solution to be tested and the matching reagent solution are inconsistent, instead of directly corresponding the two liquids with the same segment index, a joint release unit is established according to the target processing area, target node, or confluence node; let the first... Each joint release unit includes the release section corresponding to the sample solution to be tested. The corresponding release section for the matching reagent solution The result of the joint release is expressed as follows:
[0090] ;
[0091] in, Indicates the first The combined release results of the sample solution and the matching reagent solution in each combined release unit, when When, it indicates the first In each joint release unit, both the sample solution to be tested and the matching reagent solution meet the release conditions of the corresponding section. When this occurs, it indicates that at least one liquid has not yet met the release conditions for the corresponding section, and the corresponding downstream channel remains closed; Indicates the sample solution to be tested in the first... The segment release discrimination quantity corresponding to the segment to be released in each joint release unit; Indicates the matching reagent solution at the first The segment release discrimination quantity corresponding to the segment to be released in each joint release unit; Indicates the sample solution to be tested; This indicates the matching reagent solution.
[0092] Figure 5 The data shown are simulation example data obtained based on the microfluidic reagent disk structure and fluid control process of this embodiment. During the simulation, the predetermined microchannel structure, flow control node layout, valve control channel position, interface trigger sequence generation rules, and segment release discrimination rules are kept consistent. Only the viscosity ratio between the sample liquid to be tested and the matching reagent liquid is changed. The segment release matching rate is calculated as the proportion of the number of release segments that meet the actual liquid front arrival state, interface continuity state, and corresponding downstream channel opening timing to the total number of release segments participating in the discrimination. Characteristic peak position A and characteristic peak position B are the local peak positions in the segment release matching rate curve. The point with the largest difference is the sampling position with the largest difference in matching rate between curves with different viscosity ratios.
[0093] Figure 5 The values "viscosity ratio = 1.00", "viscosity ratio = 1.10", "viscosity ratio = 1.20", "viscosity ratio = 1.30", and "viscosity ratio = 1.40" represent simulation results obtained under different viscosity ratio conditions for the sample liquid and the matching reagent liquid, respectively, using the control method of this embodiment. All curves were obtained under the same microfluidic reagent disk structure, the same predetermined microchannel, the same flow control node arrangement, and the same interface trigger sequence control logic, only changing the relative flow resistance conditions of the sample liquid and the matching reagent liquid. Figure 5It is evident that under different viscosity ratios, the segment release matching rate remains at a high level overall. This indicates that by judging the liquid arrival status and interface continuity, and implementing segment-by-segment advancement and directional release based on the interface trigger sequence, this embodiment can maintain a good matching relationship between the opening timing of the corresponding downstream channel and the actual liquid transmission status. The enlarged partial view further shows that, near characteristic peak A, characteristic peak B, and the point of maximum difference, although there are certain differences in the segment release matching rate under different operating conditions, the overall change is continuous and no obvious instability occurs. This indicates that this embodiment can still maintain good segment release accuracy, continuity, and stability under different liquid operating conditions.
[0094] Figure 6 The propulsion pressure fluctuation range indicates the degree of deviation of the actual propulsion pressure from the reference propulsion pressure during the propulsion process. The reference propulsion pressure is the pressure value that enables the liquid to stably pass through adjacent flow control nodes, determined through calibration propulsion tests under the corresponding viscosity ratio conditions. The actual propulsion pressure is the pressure value applied to the corresponding reservoir in real time during the liquid propulsion process. The larger the propulsion pressure fluctuation range, the more obvious the deviation of the actual propulsion pressure from the reference propulsion pressure. Figure 6 Each horizontal column corresponds to a different propulsion pressure fluctuation range condition, and each vertical row corresponds to a different viscosity ratio condition. Under each combination of viscosity ratio and propulsion pressure fluctuation range, the segment release matching rate is calculated according to the same liquid arrival discrimination, interface continuity discrimination, and segment release discrimination rules.
[0095] Figure 6 The vertical rows correspond to different viscosity ratio conditions, and the horizontal columns correspond to different propulsion pressure fluctuation amplitude conditions. The propulsion pressure fluctuation amplitude is expressed as a relative amplitude in percentage form, and the value range is [missing information]. Figure 6 The horizontal columns show consistent propulsion pressure fluctuations. The color intensity indicates the segment release matching rate of this embodiment under the corresponding parameter combinations. A color closer to a high value indicates a higher segment release matching rate, while a color closer to a low value indicates a lower segment release matching rate. Figure 6 It is evident that, under most combinations of viscosity ratios and propulsion pressure fluctuations, the segment release matching rate remains within a high range. This indicates that this embodiment is not only effective under a single operating condition, but can maintain good segment-by-segment propulsion and directional release effects over a wide range of operating conditions through liquid arrival status judgment, interface continuity status judgment, and interface trigger sequence control. Meanwhile, the local color changes also indicate that when the viscosity ratio increases or the propulsion pressure fluctuation amplitude intensifies, the segment release matching rate will decrease to a certain extent, further demonstrating the adaptability of this embodiment to changes in operating conditions and its performance change trend.
[0096] It should also be noted that existing technologies typically use preset driver programs, fixed propulsion rhythms, or fixed valve control timings to segmentally deliver liquids and switch channels in a microfluidic reagent tray. This solution, however, determines the segment release sequence through an interface trigger sequence and, in conjunction with propulsion sensing status, judges the liquid front arrival status and interface continuity status. When the liquid front arrives and the interface is continuous, the corresponding downstream channel is opened to achieve directional release and sequential transfer of the sample liquid and matching reagent liquid. This allows the channel opening timing to match the actual liquid flow state, effectively reducing problems such as premature release, delayed release, empty release, cross-flow release, and transmission instability. It improves the accuracy, continuity, and reliability of segmented propulsion, enhances the precision of microfluidic fluid control, and provides a guarantee for the stability of subsequent liquid delivery.
[0097] S3. Based on the segmented release results, the sequentially transferred liquid is introduced into the processing area, and interface anomalies are identified during the liquid's passage through the processing area. When an interface anomaly is identified, the current downstream channel is closed and switched to the corresponding buffer branch, so that the sample liquid to be tested and the matching reagent liquid enter the abnormal blocking.
[0098] S3.1. Import the sample solution to be tested and the matching reagent solution corresponding to the segmented release result into the processing area, and determine the current processing segment corresponding to the processing area to obtain the processing import result.
[0099] It should be noted that, within the predetermined microfluidic channel, the flow channel section located downstream of the corresponding reservoir of the sample solution to be tested and the corresponding reservoir of the matching reagent solution, and upstream of the processing area, which is used to receive the sample solution to be tested and the matching reagent solution for segmented release and sequential transfer, is defined as the release and transfer section; the flow channel section within the predetermined microfluidic channel used to receive the sample solution to be tested and the matching reagent solution after sequential transfer and for subsequent identification of abnormal interface states is defined as the processing area.
[0100] The sample solution and reagent solution corresponding to the segmented release result continue to move forward along the corresponding opened downstream channel until they enter the processing area from the release transfer section. The flow direction of the sample solution and reagent solution after entering the processing area is kept consistent with the transfer direction corresponding to the interface trigger sequence. The flow channel segment between the start and end positions of the processing area in the predetermined microchannel is defined as the current processing segment. The case where the sample solution and reagent solution enter the current processing segment and continue to be transferred along the current processing segment is recorded as the processing import result.
[0101] S3.2. Under the processing and import results, continuously collect the interface sensing signals corresponding to each flow control node in the current processing section, and record the interface sensing signals sequentially according to the forward movement direction of the sample liquid to be tested and the matching reagent liquid to obtain the interface sensing record.
[0102] It should be noted that, under the processing and import results, the interface sensing signals corresponding to each flow control node sequentially set along the predetermined microchannel flow direction in the current processing section are continuously collected. This allows the interface sensing signals collected at each flow control node to characterize the interface changes of the sample liquid and the matching reagent liquid during their forward movement within the current processing section. The interface sensing signals collected at each flow control node are arranged sequentially according to the forward movement direction of the sample liquid and the matching reagent liquid within the current processing section. The order of appearance and change of the interface sensing signals at each flow control node, as well as the corresponding positional relationship of the flow control node within the current processing section, are correlated to establish a correspondence between the interface sensing signals at each flow control node within the current processing section and the transmission process of the sample liquid and the matching reagent liquid within the current processing section. Finally, the interface sensing signals and their corresponding positional relationships at each flow control node within the current processing section, arranged according to the forward movement direction, are collected to obtain the interface sensing record.
[0103] The appearance of the interface sensing signal refers to the smoothed interface sensing signal entering the liquid-occupied state range from the air-occupied state range and continuously meeting the liquid occupation discrimination condition within the continuous sampling window; the order of changes in the interface sensing signal refers to the order in which the liquid occupation discrimination condition is first met at different flow control nodes; the time resolution of the signal change at each flow control node is determined by the sampling period, and the sampling period and continuous sampling window are pre-calibrated by the controller refresh period, valve response time, and shortest passage time of adjacent nodes.
[0104] S3.3. The interface perception record is judged to identify the interface continuity between adjacent flow control nodes in the current processing section, and the sections with abnormal liquid crossing are marked and merged to obtain the interface abnormality.
[0105] It should be noted that the interface sensing signals at each flow control node in the interface sensing record, arranged according to the forward movement direction of the sample liquid and the matching reagent liquid, are compared adjacently, and the flow channel section between two adjacent flow control nodes is used as the continuity discrimination section. When the interface sensing signals at two adjacent flow control nodes appear sequentially along the predetermined microchannel flow direction, and there is no interruption change from the liquid occupying the corresponding flow control node position to the non-positioned state, the area between the two adjacent flow control nodes is recorded as interface continuity.
[0106] When the interface sensing signals at two adjacent flow control nodes do not appear sequentially along the predetermined microchannel flow direction, or when an interruption occurs between two adjacent flow control nodes, where the liquid occupies the position of the corresponding flow control node and changes to an unoccupied state, the corresponding flow channel segment is marked as an interface discontinuity segment. The interface discontinuity segment is further verified by combining the interruption duration, signal back-off direction, the order of adjacent node arrival, and changes in propulsion pressure. When the discontinuous state reaches the preset interruption confirmation time, and after excluding misjudgments caused by single sampling noise and transient signal loss, the corresponding flow channel segment is determined as a liquid crossing abnormal segment.
[0107] Furthermore, when the upstream flow control node maintains a liquid-occupied state while the downstream flow control node fails to reach its position within the maximum observation time, the corresponding flow channel segment is recorded as a liquid discontinuity anomaly; when an air occupancy signal briefly appears between adjacent flow control nodes and is subsequently restored to a liquid occupancy signal, the corresponding flow channel segment is recorded as an air-entrapment anomaly; when the downstream flow control node regresses its state before the upstream flow control node, the corresponding flow channel segment is recorded as a backflow anomaly; when the interface sensing signal changes slowly and the propulsion pressure remains within the allowable range, the corresponding flow channel segment is recorded as a viscous stagnation anomaly; the liquid discontinuity anomaly, air-entrapment anomaly, backflow anomaly, and viscous stagnation anomaly identified in the current processing segment are merged to obtain the interface anomaly situation.
[0108] S3.4. Assign the interface anomaly to the current processing section, close the downstream channel corresponding to the current processing section, and switch the current processing section to the corresponding buffer branch to stop the sample solution and the matching reagent solution from continuing to transfer downstream, thereby entering the anomaly blocking stage.
[0109] It should be noted that the liquid crossing abnormal section corresponding to the interface abnormality is matched with the corresponding flow channel section in the current processing section, and the corresponding flow channel section in the current processing section is determined as the abnormal corresponding section; the downstream channel corresponding to the abnormal corresponding section is switched from the open state to the closed state, so that the connection between the sample liquid to be tested and the matching reagent liquid in the abnormal corresponding section and the downstream flow channel is cut off, and the sample liquid to be tested and the matching reagent liquid no longer move downstream along the abnormal corresponding section.
[0110] While sealing the downstream channel corresponding to the abnormal section, the propulsion pressure of the upstream liquid storage chamber corresponding to the abnormal section is reduced to the maintenance pressure or the propulsion pressure is stopped, so that the liquid front is no longer driven downstream by the continuous propulsion pressure; when there is still residual pressure in the abnormal section, the local pressure in the abnormal section is released through the corresponding buffer branch, and the blocked liquid is kept in the abnormal section, the buffer branch and the upstream area of the target node.
[0111] The buffer branch is a branch flow channel set on the side of the current processing section and connected to the current processing section through a micro-valve. Its capacity is not less than the residual liquid volume that can be contained between the abnormal corresponding section and the nearest upstream closed position. Each current processing section is provided with at least one buffer branch. If there are multiple buffer branches in the current processing section, the buffer branch located downstream of the abnormal corresponding section and closest to the abnormal corresponding section is selected first. When the liquid volume contained in the corresponding buffer branch reaches the calibrated upper limit, the downstream channel of the current processing section is kept closed, and the current liquid transmission status is recorded as the full-load blockage status.
[0112] The calibrated upper limit of capacity is determined based on the geometric volume of the buffer branch, the allowable liquid filling ratio within the branch, and the volume of residual liquid that may enter the buffer branch in the corresponding abnormal section. The geometric volume of the buffer branch is determined by its length and cross-sectional dimensions. The allowable liquid filling ratio within the branch is used to maintain a stable space at the gas-liquid interface. The volume of residual liquid is determined based on the flow channel volume between the corresponding abnormal section and the nearest upstream closure position. When the volume of liquid already contained in the buffer branch reaches the calibrated upper limit of capacity, no more liquid will be introduced into the buffer branch, and the downstream channel corresponding to the current treatment section will remain closed.
[0113] After the downstream channel corresponding to the abnormal section is closed, the disconnected state of the abnormal section and the corresponding buffer branch is switched to the connected state, so that the sample liquid to be tested and the matching reagent liquid located in the abnormal section are transferred from the downstream transmission direction of the current processing section to the corresponding buffer branch, and the sample liquid to be tested and the matching reagent liquid are kept in a restricted position in the corresponding buffer branch and the downstream front of the current processing section, thus entering the abnormal blockage.
[0114] It should also be noted that existing technologies typically handle anomalies by continuously transporting the liquid and then shutting down the entire system, cutting off the flow, or triggering an alarm. However, these methods are not ideal for timely identification of the abnormal section, which can easily allow the abnormal liquid to continue spreading downstream. This solution, on the other hand, introduces the liquid into the treatment area, collects interface sensing signals to identify abnormal interface conditions, and then closes the corresponding downstream channel and switches to the corresponding buffer branch for blocking. This enables pinpoint identification and local blocking of abnormal sections, reduces the spread of the abnormality, and improves the stability, controllability, and reliability of liquid transport within the treatment area.
[0115] S4. Based on the liquid residence location corresponding to the abnormal blockage, the blocked liquid is restricted to the buffer branch and the upstream area of the target node. After the liquid continuity is restored, the corresponding downstream channel is reconnected, so that the sample liquid to be tested and the matching reagent liquid can continue to enter the execution area, forming the execution area delivery state.
[0116] S4.1. Based on the liquid retention location corresponding to the abnormal blockage, the blocked liquid is restricted to the buffer branch and the upstream area of the target node, and the downstream channel corresponding to the current processing section is kept closed, so that the sample liquid to be tested and the matching reagent liquid remain in a restricted position.
[0117] It should be noted that the sample solution and reagent solution corresponding to the abnormal blockage are kept within the corresponding buffer branch, and the flow control node corresponding to the entrance of the execution area is determined as the target node. The flow channel section downstream of the current processing section and located between the corresponding downstream channel and the target node is determined as the upstream area of the target node. While keeping the abnormal section connected to the corresponding buffer branch, the downstream channel corresponding to the current processing section is kept closed, so that the sample solution and reagent solution do not continue to move downstream in the current processing section. The sample solution and reagent solution that have entered the corresponding buffer branch remain in the corresponding buffer branch, and the sample solution and reagent solution located in the upstream area of the target node remain in the buffer branch. Thus, the blocked liquid is confined to the buffer branch and the upstream area of the target node.
[0118] S4.2 After the blocked liquid is confined to the buffer branch and the upstream area of the target node, the interface sensing signals of the buffer branch, the upstream area of the target node and the corresponding flow control node in front of the current processing section are continuously collected to determine the interface continuity between adjacent flow control nodes and restore the continuity of the liquid.
[0119] It should be noted that after the blocked liquid is confined to the buffer branch and the upstream area of the target node, the downstream channel corresponding to the current processing section is kept closed, and the propulsion pressure of the corresponding liquid storage chamber is reduced to the holding pressure. By short-term static placement, low-amplitude pulse propulsion, and temporary storage in the buffer branch, the air-entrained or intermittent liquid is confined to the buffer branch and the upstream area of the target node. The interface sensing signals corresponding to each flow control node in the buffer branch, the interface sensing signals corresponding to each flow control node in the upstream area of the target node, and the interface sensing signals corresponding to the flow control node at the front of the current processing section are continuously collected, and the interface sensing signals at each flow control node are compared sequentially according to the flow direction of the predetermined microchannel. When the liquid occupancy state is met between adjacent flow control nodes within the continuous sampling window, and there is no interruption change from liquid occupancy to non-occupancy state, the liquid state is determined to be restored to continuous state.
[0120] S4.3 After the liquid is restored to continuity, the corresponding downstream channel is reconnected so that the sample liquid to be tested and the matching reagent liquid can continue to enter the execution area from the buffer branch and the upstream area of the target node, forming the execution area transport state.
[0121] It should be noted that the corresponding buffer branch is connected to the current processing section through a branch microvalve, and a reconnection interface is set in the upstream area of the target node, so that the buffer branch can receive the liquid in the abnormal corresponding section when abnormal interruption occurs, and reconnect to the predetermined microchannel when the delivery is restored; during abnormal interruption, the downstream channel corresponding to the current processing section is closed and the branch microvalve is opened; after the liquid is restored to continuity, the branch microvalve is closed or switched to the reconnection state, and the downstream channel corresponding to the current processing section is reopened, so that the sample liquid to be tested and the matching reagent liquid continue to enter the execution area along the upstream area of the target node.
[0122] After the liquid flow is restored, the downstream channel corresponding to the current processing section is switched from closed to open, and the connection between the abnormal section and the corresponding buffer branch is switched from open to closed. This allows the sample liquid and reagent liquid to return to the downstream transport direction of the predetermined microchannel from the corresponding buffer branch and the upstream area of the target node. The flow channel section located downstream of the target node, used to receive the sample liquid and reagent liquid after the restored transport, is defined as the execution area. The sample liquid and reagent liquid pass through the target node sequentially and continue to enter the execution area, while maintaining the flow direction of the sample liquid and reagent liquid in the execution area consistent with the flow direction of the predetermined microchannel. After the sample liquid and reagent liquid enter the execution area, the downstream channel corresponding to the current processing section remains open, the abnormal section and the corresponding buffer branch remain closed, and the sample liquid and reagent liquid continue to be transported along the execution area, forming the execution area transport state.
[0123] It should also be noted that the formation of the delivery status in the execution area is jointly determined by the restoration of the delivery path and the interface sensing results within the execution area. Specifically, when no liquid crossing anomalies occur again between adjacent flow control nodes on the restored delivery path for the sample liquid and the matching reagent liquid, and the sample liquid and the matching reagent liquid reach the inlet flow control node of the execution area and the downstream confirmation flow control node within the execution area used to confirm the effective delivery volume, respectively, it is determined that the sample liquid and the matching reagent liquid have been restored to continuity and have effectively entered the execution area. When there is still an interface discontinuity in the restored delivery path, or when either liquid has not yet reached the downstream confirmation flow control node within the execution area, it is not determined that the delivery status of the execution area is complete, and the acquisition, holding, or blocking control of the corresponding channel continues to be maintained.
[0124] This embodiment also provides a computer device applicable to the microfluidic-based fluid control method, including: a memory and a processor; the memory is used to store computer-executable instructions, and the processor is used to execute the computer-executable instructions to implement the microfluidic-based fluid control method proposed in the above embodiment.
[0125] The computer device can be a terminal, comprising a processor, memory, communication interface, display screen, and input devices connected via a system bus. The processor provides computing and control capabilities. The memory includes non-volatile storage media and internal memory. The non-volatile storage media stores the operating system and computer programs. The internal memory provides an environment for the operation of the operating system and computer programs stored in the non-volatile storage media. The communication interface is used for wired or wireless communication with external terminals; wireless communication can be achieved through Wi-Fi, carrier networks, NFC (Near Field Communication), or other technologies. The display screen can be an LCD screen or an e-ink screen. The input devices can be a touch layer covering the display screen, buttons, a trackball, or a touchpad on the computer device's casing, or an external keyboard, touchpad, or mouse.
[0126] This embodiment also provides a storage medium storing a computer program that, when executed by a processor, implements the microfluidic-based fluid control method as proposed in the above embodiments. The storage medium can be implemented by any type of volatile or non-volatile storage device or a combination thereof, such as Static Random Access Memory (SRAM), Electrically Erasable Programmable Read-Only Memory (EEPROM), Erasable Programmable Read Only Memory (EPROM), Programmable Read-Only Memory (PROM), Read-Only Memory (ROM), magnetic storage, flash memory, magnetic disk, or optical disk.
[0127] In summary, this invention improves the accuracy, continuity, and stability of segmented transfer of sample liquids and reagent solutions by: judging the liquid arrival status and interface continuity, and implementing segmented advancement and directional release based on the interface trigger sequence; and by identifying interface anomalies within the processing area, closing the current downstream channel and switching to the corresponding buffer branch when an anomaly occurs, and reconnecting the corresponding downstream channel after the liquid continuity is restored. This achieves local blocking and restoration of conduction in abnormal sections, improving the controllability of anomaly handling and the reliability of subsequent delivery. It is applicable to microfluidic reagent trays and instruments in clinical mass spectrometry, biochemical and coagulation testing, menstrual blood testing, and pet medical testing.
[0128] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.
Claims
1. A microfluidic-based fluid control method, characterized in that, include: The sample solution to be tested and the matching reagent solution are respectively introduced into the corresponding liquid storage chambers of the microfluidic reagent disk, and a liquid-gas interface sensing node is set at the flow control node to determine the liquid arrival status and interface continuity. The specific steps are as follows: The sample solution to be tested and the matching reagent solution are respectively introduced into the corresponding liquid storage chamber of the microfluidic reagent disk and are in the state of waiting to be pushed in their respective corresponding flow channels, forming the initial liquid distribution state; In the initial liquid distribution state, the interface sensing signal corresponding to the liquid-gas interface sensing node at the flow control node is collected, and the liquid arrival status is determined to form a liquid arrival status record. Based on the liquid arrival status record, the interface continuity state between adjacent flow control nodes is determined, and the flow control nodes that satisfy the liquid arrival status and the interface continuity state between adjacent nodes are arranged in order to generate an interface trigger sequence. According to the interface trigger sequence, the upstream liquid is controlled to advance segment by segment along the predetermined microchannel. After the liquid front is confirmed to be in place and the interface is continuous at the previous sensing node, the corresponding downstream channel is opened, so that the sample liquid to be tested and the matching reagent liquid can be released in a directional manner and transferred in sequence, forming a segmented release result. Based on the segmented release results, the sequentially transferred liquid is introduced into the processing area, and interface anomalies are identified during the liquid's passage through the processing area. When an interface anomaly is identified, the current downstream channel is closed and switched to the corresponding buffer branch, so that the sample liquid to be tested and the matching reagent liquid enter the abnormal blocking. Based on the location of the liquid stoppage corresponding to the abnormal blockage, the blocked liquid will be confined to the buffer branch and the upstream area of the target node. After the liquid continuity is restored, the corresponding downstream channel will be reconnected, allowing the sample liquid to be tested and the matching reagent liquid to continue to enter the execution area, forming the execution area delivery state.
2. The microfluidic-based fluid control method as described in claim 1, characterized in that, The specific steps to generate the segmented release result are as follows: The release order of each segment is determined based on the interface trigger sequence, and the previous flow control node of the current segment to be released is determined as the previous sensing node to obtain the release preparation content. Under the release preparation content, the sample liquid to be tested and the matching reagent liquid are advanced, and the interface sensing signals of the previous sensing node and the corresponding flow control node of the current release section are collected to obtain the advancement sensing record. Based on the propulsion sensing records, the system determines the position of the liquid front and the continuity of the interface, and opens the corresponding downstream channels. The sample solution to be tested and the matching reagent solution continue to enter the next release section, and the directional release and sequential transfer are completed in sequence according to the order of each release section, so as to obtain the segmented release result.
3. The microfluidic-based fluid control method as described in claim 1, characterized in that, The specific steps for preventing the abnormal entry of the test sample solution and the matching reagent solution are as follows: Import the sample solution to be tested and the matching reagent solution corresponding to the segmented release result into the processing area, determine the current processing segment, and obtain the processing import result; Under the processing and import results, the interface perception signals corresponding to each flow control node in the current processing section are collected and recorded sequentially to obtain the interface perception record; Based on the interface perception record, identify the continuous state of the interface and mark the abnormal sections of liquid crossing, and merge them to obtain the abnormal interface conditions. The interface anomaly is mapped to the current processing segment, the downstream channel corresponding to the current processing segment is closed, and the current processing segment is switched to the corresponding buffer branch, thus entering an anomaly blocking state.
4. The microfluidic-based fluid control method as described in claim 1, characterized in that, The specific steps for establishing the execution area delivery status are as follows: Based on the location of the liquid retention corresponding to the abnormal blockage, the blocked liquid will be confined to the buffer branch and the upstream area of the target node, and the downstream channel corresponding to the current processing section will be kept closed. Collect interface perception signals from buffer branches, upstream regions of target nodes, and corresponding flow control nodes in front of the current processing section, and determine the interface continuity between adjacent flow control nodes. After the liquid flow is restored, the corresponding downstream channel is reconnected, and the sample solution to be tested and the matching reagent solution continue to enter the execution area, forming the execution area delivery state.
5. The microfluidic-based fluid control method as described in claim 1, characterized in that, The initial liquid distribution state refers to the residence state of the sample liquid to be tested and the matching reagent liquid in the corresponding storage chamber, the starting position in their respective corresponding flow channels, and the stable residence state at the corresponding liquid-gas interface position.
6. The microfluidic-based fluid control method as described in claim 2, characterized in that, The propulsion sensing record includes the sequence of acquisition of interface sensing signals, the sequence of signal changes, and the arrival status of the liquid front of the sample liquid and the matching reagent liquid at the previous sensing node and the corresponding flow control node of the current release section.
7. The microfluidic-based fluid control method as described in claim 1, characterized in that, The interface sensing signal refers to the capacitance change signal generated when the liquid reaches the corresponding flow control node position, which is different from the air occupation state.
8. A computer device comprising a memory and a processor, wherein the memory stores a computer program, characterized in that, When the processor executes the computer program, it implements the steps of the microfluidic-based fluid control method according to any one of claims 1 to 7.
9. A computer-readable storage medium having a computer program stored thereon, characterized in that, When the computer program is executed by the processor, it implements the steps of the microfluidic-based fluid control method according to any one of claims 1 to 7.
Citation Information
Patent Citations
Structures for precisely controlled transport of fluids
US20020114738A1
Slug control during thermal cycling
US20120058460A1