A system for accurate measurement of fluids in nanoliters or femtoliters or a reaction system
The microfluidic system using N-ary weights and bubbles solves the problem of insufficient precision in microfluidic manipulation in existing technologies, achieving precise measurement and response control of 1 picoli or femtoliter, improving control accuracy and efficiency, and saving resources.
Patent Information
- Application Number
- CN202511301793.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-12
- Publication Date
- 2025-12-16
- Estimated Expiration
- 2045-09-12
AI Technical Summary
Existing technologies lack sufficient precision in micro-fluid manipulation, especially at picoliter or air-level, resulting in low control accuracy and efficiency, and significant resource waste.
A microfluidic system based on N-ary weight droplets and bubbles is used to generate droplets or bubbles in cross channels and to achieve precise measurement and reaction control of 1 picolit or femtoliter by utilizing shear force and fluid infusion under vacuum or non-vacuum conditions.
It significantly improves the precision and efficiency of micro-fluid manipulation, saves manpower and material resources, and achieves precise measurement and reaction control of 1 picoli or femtoliter.
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Figure CN120771941B_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The application relates to a microfluidic system in the fields of biotechnology, life science and the like, in particular to a N-base picoliter or femtoliter fluid precision taking system or reaction system. BACKGROUND
[0002] In the current world economy, the research and production practice in the fields of biotechnology, life science, chemical industry, medical health and the like all involve microfluids, especially the taking, control or reaction system of picoliter or femtoliter micro reagents, and at present, many fields in the industry generally adopt microliter or nanoliter reagent control for the target objects of micrometer or nanometer size, such as cells, bacteria and genes, which are far smaller than 10 picoliters. As of July 2025, the precision of the pipetting and dispensing equipment sold on the global market is not higher than 10 picoliters. Similar to studying goldfish in a swimming pool, the control precision and efficiency are low, and the resources of manpower and materials are wasted seriously. SUMMARY
[0003] The "N-base weight drop bubble-based picoliter or femtoliter fluid precision taking system and reaction system" of the application can greatly improve the dispensing precision to 1 picoliter or even femtoliter, which is similar to studying the above-mentioned goldfish in a fish tank, can greatly improve the control precision and experimental efficiency, and can significantly save the resources of manpower and materials.
[0004] Based on mature technology: T-shaped or cross-shaped intersection channels with a depth and width of 0-100 um (especially a depth and width of 0-10 um): two immiscible phase fluids generate droplets or bubbles by using shear force; or another method: a plurality of recesses with a volume of 1 picoliter or even femtoliter are pre-set, and the fluids are filled under vacuum or non-vacuum conditions, and then the fluids outside the recesses are cut off by a solid or another immiscible fluid, that is, microdroplets or microbubbles are generated - not limited to the above two methods for generating uniform droplets or bubbles, which can easily realize 1 picoliter or even femtoliter: uniform droplets or bubbles with a particle size, which lay a technical foundation for the application.
[0005] The application provides a N-base picoliter or femtoliter fluid precision taking system or reaction system, which has the following characteristics:
[0006] The fluid is composed of one or more of gas, liquid, solid and the like, and is a collection of substances capable of flowing in a certain space, wherein the solid can be in the form of powder or particles to realize the flowable property.
[0007] The precision of the controlled fluid is picoliter or femtoliter, and the liquid volume range includes but is not limited to: femtoliter, picoliter, nanoliter, microliter, milliliter, liter, kiloliter and the like, especially 1 pL (picoliter) level precision.
[0008] Bubbles, refers to one or more of the three states of matter composed of gas, liquid, solid, can be driven by the movement of the independent material collection, types include but not limited to: droplets, bubbles.
[0009] Fluid carriers, which contain, have or externally connected: channels, flow or pipeline, can accommodate or achieve the function of fluid storage, flow, observation, cultivation, reaction, sorting or control of entity structure (functional structure), instruments, vessels or equipment, including but not limited to: microfluidic chip, biochip, kit, especially including: PDMS, glass, silicon (single crystal silicon or polycrystalline silicon), PMMA, PC, PE, PP, PVC, PLA, PA, PEEK, PTFE, acrylic, plastic or other transparent or translucent material based chip, three-dimensional printing, plastic products, etc.
[0010] The output path of the achievement includes but is not limited to: the achievement output channel inside or outside the fluid carrier, or the achievement output pipeline; the output path of the waste includes but is not limited to: the waste output channel inside or outside the fluid carrier, or the waste output pipeline; the output channel is divided according to its function, including but not limited to: the achievement output channel, the waste output channel.
[0011] The fluid carrier contains several (one or more): bubble array capture sorting unit, also contains at least one input channel, and at least one output channel, two channels are respectively communicated with the aforementioned bubble array capture sorting unit through the input interface and the output interface, respectively realizing the inflow and outflow of fluid.
[0012] The bubble array capture sorting unit is a pipeline type (i.e.: channel or pipeline type) cavity structure that can communicate with the external space, which can be considered as one of the channel and pipeline or its deformation, which can be understood as a special channel, flow channel, pipeline in the fluid carrier, or the deformation structure mentioned above, the size of the cavity inside in the axial direction (i.e. the flow direction of the fluid from the input channel to the output channel) is greater than that in the radial direction (perpendicular to the aforementioned axial direction). The bubble array capture sorting unit is different from the ordinary channel in that the inner wall of the cavity includes but is not limited to: the top surface, the bottom surface, the side wall or other inner wall positions of the inner side of the cavity, which is provided with a plurality of capture points capable of capturing bubbles or trapping fluid. The capture point contains a capture mechanism, and the capture mechanism of the capture point can only accommodate a specified number (one or more) of capture objects corresponding to the group in the size design, and the specified number of capture objects is defined as a package.
[0013] Specific design method: the design method of each package containing a single capture object includes but is not limited to: the width of the capture mechanism cavity of the capture point is 1 to 2 times the diameter of the corresponding group of capture objects, and the range between 1 to 2 times does not include 2 times, and the best is 1 times; the depth of the capture mechanism cavity of the capture point is 0.5 to 1.5 times the diameter of the corresponding group of capture objects, and the best selection in the range between 0.5 to 1.5 times is 1 times; the design method of each package containing multiple capture objects includes but is not limited to: the volume of the capture mechanism cavity of the capture point is 1 times the sum of the volumes of the minimum circumscribed cuboid (or cube) of the specified number of capture objects in the corresponding group.
[0014] The capture mechanism of the capture point includes but is not limited to: pits, grooves, protrusions, dams, rings, islands, gaps, or other structures that can capture, limit, or intercept drops or fluids.
[0015] The capture object of the capture point includes liquid drops, liquid blocks, liquid columns, liquid flows, bubbles, gas flows, or other forms of fluid, especially including: weight drops.
[0016] When the capture mechanism of the capture point is for a corresponding group of single capture objects (including but not limited to: weight drops), the limiting height (i.e.: pit depth, groove depth, protrusion height, or limiting height of other capture point form structure) is not less than 1 / 4 of the diameter of the corresponding group of capture objects (i.e.: 0.25 times the diameter of the corresponding group of capture objects), and not more than 7 / 4 of the diameter of the corresponding group of capture objects (i.e.: 1.75 times the diameter of the corresponding group of capture objects), and the more optimal selection: the limiting height of the capture mechanism of the capture point is not less than 1 / 2 of the diameter of the corresponding group of capture objects (i.e.: 0.5 times the diameter of the corresponding group of capture objects), and not more than 3 / 2 of the diameter of the corresponding group of capture objects (i.e.: 1.5 times the diameter of the corresponding group of capture objects), and the most optimal selection: the limiting height of the capture mechanism of the capture point is the same as the diameter of the corresponding group of capture objects or within ±10% (the error value can be selected within ±0 to 100% according to actual conditions).
[0017] When the capture mechanism of the capture point is for multiple capture objects (including but not limited to: weight drops), the volume of the capture mechanism cavity of the capture point is the sum of the volumes of all specified number of capture objects, or the sum of the volumes of the minimum circumscribed cuboid (or cube) of all specified number of capture objects, or the calculation error of the sum of the two volumes is within ±50%, especially including: within ±10%.
[0018] The weight droplet bubble includes one or more of gas, liquid, solid and other three-state substances, and the forms include but are not limited to: weight liquid droplets, weight bubbles, other forms, a set or multiple sets of series droplet bubbles with accurate volume measurement, and the set is divided into several groups according to the volume difference, each group contains several bags, and each bag contains a fixed number of weight droplet bubbles of the same size in the group, and the particle size of the weight droplet bubble in the same group is uniform, the volume and the number of the weight droplet bubble in each bag are the same, or the error is negligible, or the positive and negative errors are allowed.
[0019] According to the N-ary idea: the bag volume of each group is monotonically sorted (ascending or descending) according to the total droplet volume in the single bag, and in any adjacent group: the ratio of the volume of the weight droplet bubble in the larger bag volume group to the smaller bag volume group is: the effective number of bags in the smaller bag volume group plus 1, and the ratio is an integer or a real number, especially including: the ratio is an integer N (i.e. N in the aforementioned "N-ary") or a real number greater than 1, and in the real number case, the integer part obtained by using the direct truncation method or the "M-removes M+1-enters" method (for example but not limited to: rounding method) is N (i.e. N in the aforementioned "N-ary"), and the real number part discarded by the direct truncation method or the "M-removes M+1-enters" method can be ignored or regarded as an allowed positive or negative error, and M and N are natural numbers.
[0020] The "M-removes M+1-enters" method takes the integer part plus 1 as the integer part of the ratio when the decimal part of the real number is greater than or equal to (M+1) / 10, and takes the integer part directly as the integer part of the ratio when the decimal part is less than M / 10. The "M-removes M+1-enters" method especially includes the "rounding" method.
[0021] In the present application, unless otherwise specified, the capture point or capture mechanism, and the capture object targeted or operated, are all in a matching relationship with the corresponding group.
[0022] In the present application, the prefix "effective" or "effective" before the weight droplet bubble or bag means that the weight droplet bubble with a volume specification that can be controlled to implement fluid distribution meets the requirements, or the bag composed of several weight droplet bubbles does not include: standby, redundancy, does not participate in liquid distribution control, and does not meet the requirements of droplets such as non-specific description. In the present application, the description of the weight droplet bubble refers to the effective weight droplet bubble, and the bag refers to the effective bag.
[0023] In the description of the present application about quantity or numerical value, unless specially stated, the cases such as invalid weight droplet bubbles or invalid packets, which cause the difference of quantity or numerical value calibration, are not considered, and the difference does not exceed the protection scope of the present application. In application, the number of effective packets or effective weight droplet bubbles of each group participating in fluid distribution is not less than the weight droplet bubble demand quantity of the group in this round.
[0024] By controllably selecting a plurality of groups and a specified number of packet weight droplet bubbles in each group, the single packet volume in the group with the smallest packet volume (i.e. the volume of the weight droplet bubbles captured or contained by the capture mechanism of a single capture point in the group with the smallest packet volume) is used as the highest precision, i.e. the smallest scale of the range, and the sum of the weight droplet bubble volumes in the group with the largest packet volume is used as the upper limit. When the smallest packet volume is in the picoliter or femtoliter level, the specified number of precise fluid taking, dividing, sorting, controlling or obtaining with picoliter or femtoliter level precision is realized.
[0025] Based on the plurality of capture points arranged in the fluid carrier, the capture mechanisms of each capture point have the same capacity in the same group and different capacities in different groups (here, the capacity refers to the cavity capacity). The capture mechanism of each capture point in each group can only contain the single packet weight droplet bubble of the corresponding group, and the number and volume of the effective packets in the corresponding group correspond. Therefore, by a plurality of groups and a plurality of packet weight droplet bubbles in each group, the single packet volume in the group with the smallest packet volume is used as the highest precision, i.e. the smallest scale, and the sum of the weight droplet bubble volumes (or volume sum) in the group with the largest packet volume is used as the upper limit. When the smallest packet volume is in the picoliter or femtoliter level, the specified number of precise fluid taking, dividing, sorting, controlling or obtaining with picoliter or femtoliter level precision is realized.
[0026] A plurality of fluid distribution nozzles (or jets) are arranged on the inner wall of the droplet array capture sorting unit between any adjacent capture points and on the side of the capture point closest to the weight droplet bubble input channel, so as to realize that the plurality of distribution nozzles and the single capture point are alternately arranged and spaced apart along the axial direction (i.e. the fluid flow direction) of the fluid flowing through the droplet array capture sorting unit from the input channel to the output channel, and the end close to the weight droplet bubble input channel is a distribution nozzle, and the end close to the weight droplet bubble output channel can be a distribution nozzle or a capture point. That is, there is only one capture point between two distribution nozzles, but there must be a distribution nozzle between two adjacent capture points, and the number can be one or more.
[0027] The distribution nozzles between adjacent weight droplet bubbles can be shared. With reference to the fluid flowing in the droplet array capture sorting unit, the distribution nozzles can be located on the same side or different sides of the capture point, i.e. including the same side, the opposite side, the adjacent side or other side, and more specific application modes are as follows:
[0028] The shunt nozzle can spray fluid (several kinds of substances in gas, liquid, and solid states: one or more mixtures) into the cavity of the droplet array capture sorting unit, achieving: using the location of the shunt nozzle as a demarcation point, or using a cross-section containing the location of the shunt nozzle (including but not limited to: a cross-section perpendicular to the axial direction of the fluid flowing through the droplet array capture sorting unit and coplanar with the location of the shunt nozzle) as a demarcation interface, driving the fluid (such as droplets, liquid columns, liquid blocks, or other forms of fluid) captured in the cavity of the droplet array capture sorting unit in multiple different directions, by selecting different locations of the shunt nozzle to spray the same or different fluid as the captured object on both sides of the cavity of the droplet array capture sorting unit, it can achieve the precise driving, control, and obtaining of a specific amount or volume of fluid (especially liquid and gas) through the intended output path (including but not limited to: a dedicated result output channel) to the designated destination space.
[0029] Based on the above design, the fluid carrier can change its position, angle, or posture, or rotate, flip, move, or switch channels (i.e. channels or pipelines inside or outside the fluid carrier, or different branches of the channels and pipelines) in different control stages or links to achieve precise and reliable capture, limitation, displacement, distribution, sorting, or control of a specified number of weight droplets. The switching channel method includes but is not limited to: using switches or valves, especially controllable valves, to switch on or off or switch between different channels, different pipelines, or different branches of the channels and pipelines. This process includes one or more of the following links, and when multiple links are used, the timing should be consistent with the link number (i.e. the order of the above processes).
[0030] Link one, weight droplet capture link (fluid carrier posture control).
[0031] Full load of the capture mechanism means that the cavity of the capture mechanism is filled with the rated number of weight droplets, which corresponds to the volume of the cavity. At this time, the weight droplets in the cavity are in a relatively stable state and cannot overflow, and other weight droplets cannot enter. If the number of weight droplets exceeds the rated number of the capture mechanism cavity, it will easily overflow, and if the number is insufficient, it can allow or cause other weight droplets to enter.
[0032] The drop array of the fluid carrier captures the sorting unit, and the capture mechanism of all capture points is full of the required number of weight drop bubbles (i.e. the product of the number of capture points in the drop array capture sorting unit and the number of weight drop bubbles in each package). The minimum sample size is not less than the minimum sample size. The corresponding group of weight drop bubbles is from the similar channel or pipeline cavity of the drop array capture sorting unit entering the drop array capture sorting unit through the input channel. At this time, if the capture mechanism of all capture points in the drop array capture sorting unit is full, the weight drop bubbles flow through the inlet and outlet of the capture mechanism of all capture points in the drop array capture sorting unit in turn, and then flow out through the output channel. If the capture mechanism of a certain capture point is not full, that is, there is a spare in the cavity, the weight drop bubbles enter the capture mechanism and are captured.
[0033] In the above process, before being captured by the capture mechanism of a certain capture point or flowing out of the cavity of the drop array capture sorting unit (flowing to the output channel), the motion direction of the weight drop bubbles is: (1) when the density of the weight drop bubbles is less than the density of the fluid driving the motion of the weight drop bubbles, the motion path of the weight drop bubbles increases monotonically with time (i.e. the path function monotonically increases with time), the position height of the weight drop bubbles monotonically increases, and the angle between the motion direction of the weight drop bubbles and the buoyancy direction ranges from 0 degrees to 90 degrees (a right angle), i.e. the angle is 0 degrees, acute or right angle, and the control effect is best when the angle is acute, especially 45 degrees. The above mechanism can not only make the weight drop bubbles automatically rise along the pipeline type space under the action of buoyancy, but also make the specified number of weight drop bubbles enter the capture mechanism of the capture point and repel or prevent subsequent excess weight drop bubbles from entering by mistake; (2) when the density of the weight drop bubbles is greater than the density of the fluid driving the motion of the weight drop bubbles, the motion path of the weight drop bubbles decreases monotonically with time (i.e. the path function monotonically decreases with time), the position height of the weight drop bubbles monotonically decreases, and the angle between the motion direction of the weight drop bubbles and the gravity direction ranges from 0 degrees to 90 degrees (a right angle), i.e. the angle is 0 degrees, acute or right angle, and the control effect is best when the angle is acute, especially 45 degrees. The above mechanism can not only make the weight drop bubbles automatically descend along the pipeline type space under the action of gravity, but also make the specified number of weight drop bubbles enter the capture mechanism of the capture point and repel or prevent subsequent excess weight drop bubbles from entering by mistake.
[0034] The starting point of the axial vector line segment is the interface between the drop array capture sorting unit and the input channel, and the ending point of the axial vector line segment is the interface between the drop array capture sorting unit and the output channel. The direction of the axial vector line segment and the angle between the horizontal plane and the axial vector line segment define the capture angle, which is 0 degrees or an acute angle. For any capture point: the capture point itself and the cross section of the drop array capture sorting unit wall and the axial vertical fluid flow through the inside of the drop array capture sorting unit, the geometric center of the cross section (the center of the circle if the cross section is circular, and the center point with equal distance from the four sides if the cross section is rectangular) is defined as: the corresponding cross section geometric center, the curve obtained by intersecting the cross section with the drop array capture sorting unit wall is defined as: the capture cross section contour line, and then:
[0035] (1) When the density of the weight drop is less than the density of the fluid driving the movement of the weight drop, the movement direction of the weight drop in the similar channel pipeline type cavity of the drop array capture sorting unit is monotonously upward (the height of the weight drop monotonously increases), or the angle between the movement direction of the weight drop and the buoyancy direction is an acute angle, 0 degrees or a right angle of 90 degrees.
[0036] That is, the ending point of the aforementioned axial vector line segment is not below the starting point; especially when the capture angle is 45 degrees, it is most beneficial for the capture, limiting and control of a specified number of weight drops by the action of buoyancy, and at the same time, the posture of the drop array capture sorting unit is along the buoyancy direction, so that the capture point position is above the corresponding cross section geometric center, including but not limited to: the best position is that the capture point position is at the highest point of the corresponding capture cross section contour line (here, high and low are described based on the vertical buoyancy direction of the horizontal plane).
[0037] (2) When the density of the weight drop is greater than the density of the fluid driving the movement of the weight drop, the movement direction of the weight drop in the similar channel pipeline type cavity of the drop array capture sorting unit is monotonously downward (the height of the weight drop monotonously decreases), or the angle between the movement direction of the weight drop and the gravity direction is an acute angle, 0 degrees or a right angle of 90 degrees.
[0038] That is, the ending point of the aforementioned axial vector line segment is not above the starting point; especially when the capture angle is 45 degrees, it is most beneficial for the capture, limiting and control of a specified number of weight drops by the action of gravity, and at the same time, the posture of the drop array capture sorting unit is along the buoyancy direction, so that the capture point position is below the corresponding cross section geometric center, including but not limited to: the best position is that the capture point position is at the lowest point of the corresponding capture cross section contour line (here, high and low are described based on the vertical buoyancy direction of the horizontal plane).
[0039] After this process, the drop array capture sorting unit captures all capture points in the capture mechanism, and all capture points achieve the capture of a specified number of: one or more weight drop bubbles in the corresponding group, and can prevent subsequent excess weight drop bubbles from entering.
[0040] Step two, clearing the field.
[0041] After the drop array capture sorting unit controlled by the operator captures all capture points and captures a specified number of drops in the corresponding group, under the premise that all capture points stably capture and limit the target of their corresponding group, the input channel, the output channel (avoiding the output channel of the results or branching, such as using the waste liquid channel, here, the output channel of the results refers to the specific pipeline or channel that the operator intends to drive the specified number of fluids to the destination space), using fluid flushing, driving or replacing, etc., to remove the excess fluid outside the capture point that may cause errors in subsequent fluid control or distribution effect: the excess fluid, including: fluid in the form of droplets, liquid flow, particles, bubbles, gas flow or other forms, especially including excess weight drop bubbles that are not captured by the capture point.
[0042] For example, introduce fluids such as gas (especially including inert gas), oil, etc. from the input channel to drive the removal of excess: droplets, liquid flow, particles, bubbles, gas flow or other forms of fluid in the drop array capture sorting unit that are not captured, through other output channels (such as waste liquid channels) that are not results output channels.
[0043] If there are no remaining drops after the drop array capture sorting unit controlled by the operator captures all capture points and captures a specified number of drops in the corresponding group, that is, there are no other drops outside the capture point in the drop array capture sorting unit that may cause errors in fluid distribution, the step can be ignored.
[0044] At this point, the following strategies and methods can be selected (one or more combinations) for subsequent operation:
[0045] (1) Queue reversal distribution strategy:
[0046] The timing can be connected to any of the preceding steps one to step two, followed by:
[0047] Step three, limit step - fluid carrier horizontal attitude control:
[0048] With any point in space as the axis (including but not limited to: a point of the fluid carrier, especially the best point: the middle position of the connecting line of the exit and entrance of the series of capture points capture mechanism), follow the principle of minimum displacement, rotate the fluid carrier, make the flow direction of the droplet array capture sorting unit inside the fluid, from the input channel to the output channel (or the axial direction of the channel or pipeline type cavity of the droplet array capture sorting unit) be: along the horizontal direction, or the angle with the horizontal plane is 0 to 90 degrees, that is, 0 degrees, acute angle or right angle, and to realize reliable restraint and positioning:
[0049] (1) When the density of the weight droplet is less than the density of the fluid outside the weight droplet driving its movement, adopt the buoyancy restraint: the opening direction of the exit and entrance of the capture mechanism of the capture point is perpendicular to the horizontal plane downward (at this time, the best effect) or the angle with the gravity direction is less than the right angle (90 degrees), the opening direction includes but is not limited to: opening downward or obliquely downward; (2) When the density of the weight droplet is greater than the density of the fluid outside the weight droplet driving its movement, adopt the gravity restraint: the opening direction of the exit and entrance of the capture mechanism of the capture point is perpendicular to the horizontal plane upward (at this time, the best effect) or the angle with the buoyancy direction is less than the right angle, the opening direction includes but is not limited to: opening upward or obliquely upward.
[0050] Detailed description of the fluid carrier attitude leveling: for all capture points in the droplet array capture sorting unit being controlled, the leveling effect meets one of the following two situations:
[0051] (1) Buoyancy restraint situation - if the density of the fluid around the droplet is greater than the density of the droplet itself, the buoyancy is used to limit the droplet (capture object) from escaping the capture mechanism of the capture point: if the opening directions of the exit and entrance of the capture mechanism of all capture points in the droplet array capture sorting unit being controlled are the same, make the opening downward, the opening directions of the exit and entrance of the capture mechanism of all capture points are opposite to the buoyancy direction (that is, the same as the gravity direction); if the opening directions of the exit and entrance of the capture mechanism of all capture points in the droplet array capture sorting unit being controlled are different, make as many capture points as possible have the opening direction of the exit and entrance of the capture mechanism downward and opposite to the buoyancy direction (that is, the same as the gravity direction), the implementation method: for each capture point, take the angle between the opening direction of the exit and entrance of the capture mechanism and the gravity direction (the opposite direction of the buoyancy), the sum of the angles of all different capture points in the droplet array capture sorting unit being controlled, the sum of the absolute values, or the sum of the squares, is the smallest, in the attitude leveling process of the buoyancy restraint situation: according to the shortest displacement principle, and at the same time avoid the opening direction of the exit and entrance of the capture point: upward or having upward component (which can cause the capture object to escape from the capture point under the action of the buoyancy), or even if the opening direction of the exit and entrance of the capture point is upward or has upward component, the process time is relatively short, which is not enough to make the capture object escape from the capture point.
[0052] (2) Gravity restraint position limiting situation - if the density of the fluid around the droplet is less than that of the droplet itself, the droplet (the captured object) is restrained from leaving the capture point by gravity: if the opening directions of all the capture point outlets in the droplet array manipulation capture sorting unit are the same, the opening direction is upward, and the opening directions of all the capture point outlets are opposite to the direction of gravity (i.e., the same as the direction of buoyancy); if the opening directions of all the capture point outlets in the droplet array manipulation capture sorting unit are different, as many as possible of the opening directions of the capture point outlets are upward and opposite to the direction of gravity (i.e., the same as the direction of buoyancy), the implementation method is as follows: the included angle between the opening direction of the outlet of each capture point and the direction of buoyancy (the opposite direction of gravity) is calculated, and the sum of the angles of all different capture points in the droplet array manipulation capture sorting unit is the smallest, the sum of the absolute values, or the sum of the squares, and the posture leveling process in the gravity restraint position limiting situation is as follows: the shortest displacement principle is followed, and at the same time, the opening direction of the capture point outlet is avoided to be downward or have a downward component (which can cause the captured object to leave the capture point under the action of gravity), or even if the opening direction of the capture point outlet is downward or has a downward component, the process time is short enough to cause the captured object to leave the capture point.
[0053] The process control time between the present stage and the previous and subsequent stages will not cause any error in the position of the captured target such as the weight droplet, or the error can be ignored or allowed as a positive or negative error. For the case of including a flow separation nozzle, when the flow separation nozzle (or nozzle) next to it is crossed, i.e., the flow separation nozzle and the specified number of weight droplets are alternately and spaced arranged, and both ends of the arrangement are flow separation nozzles, the position state sequence has not changed, then the present stage three can be omitted.
[0054] Stage four, weight droplet position limiting and capture releasing stage (fluid carrier posture control):
[0055] Determination of the flip axis: when the entry and exit positions of the capture mechanisms of the current round of the same group of capture points (or their common feature points - so-called common feature points, i.e. the same type of feature points, including but not limited to: spatial center point, geometric center point, entry (center point or two side corner positions), bottom (center point or two side corner positions), side wall (center point or two side corner positions), corner, or points with a fixed distance from these points, or the projection of the entry, bottom, and side of the capture mechanism cavity of the capture point on a certain plane, taking the endpoints, midpoints, or N-equal points of the line segment) are collinear: take the straight line, parallel line, or acute-angled line containing the entry and exit positions of the current round of the same group of capture points as the flip axis. When the entry and exit positions of the current round of the same group of capture points are not collinear: take the entry and exit positions of each capture point in the current round of the same group to the straight line with the smallest sum or sum of squares of distances, and the value is the smallest. Then the straight line is the maximum fitting line of the multiple point positions. Select the maximum fitting line, or its parallel line, or the line with an acute angle with it as the flip axis.
[0056] The flip axis is parallel to the horizontal plane or has an acute angle with the horizontal plane.
[0057] Along the above-mentioned flip axis, the drop array capture sorting unit is flipped by the fluid carrier according to the shortest displacement principle, with an angle of 90 degrees to 270 degrees, and the optimal control is to flip 180 degrees. Each package of drop weight captured in the current round of the same group of capture points can be separated from the capture point by the action of gravity or buoyancy, and at the same time, the following characteristics are not changed: there is one or more shunt nozzles between any two adjacent package drop weights, and on the side of the package drop weight input channel of the capture point closest to the input channel, there are several shunt nozzles that can spray fluid. Here, the number of package drop weights in each package is one or more, and it is the capture mechanism of the same capture point from the previous link.
[0058] During the process or after the completion, each package of mass droplet adheres to the inner wall of the cavity of the droplet array capture sorting unit under the action of gravity or buoyancy. The adhesion point of each package of mass droplet can be provided with or without a limiting point, a limiting groove or other limiting mechanism. The principle mechanism is similar to the capture point, which is located on the other side wall of the channel than the wall surface of the capture point capture mechanism. It can slightly limit the position of each package of droplet, and at the same time, it will not completely hinder the axial movement of the droplet along the droplet array capture sorting unit. The limiting mechanism, such as the limiting point, the limiting groove or other types, forms include but are not limited to: pits, grooves, protrusions, dams, rings, islands, gaps or other structures that can capture, limit or intercept droplets or fluids. However, the limiting height of the limiting point, the limiting groove or other limiting mechanisms for limiting objects (a package of mass droplet, containing one or more mass droplets) is not more than the diameter of a single mass droplet, especially including but not limited to: not more than the radius of the mass droplet (half of the diameter), which is used for limiting and positioning the droplet during the turning process or after the turning to prevent the position error from affecting the final fluid distribution control accuracy.
[0059] Link five, mass droplet distribution link:
[0060] In the droplet array capture sorting unit, one or more: fluid distribution nozzles (or nozzles) that can spray fluid are arranged on both sides of any two mass droplets, or on the side of the output channel other than the mass droplet closest to the output channel. That is, the distribution nozzle and the specified number of mass droplets are alternately arranged and spaced apart. In addition, a plurality of distribution nozzles (or nozzles) are arranged between any adjacent capture points and on the side of the mass droplet input channel closest to the capture point.
[0061] After the foregoing link, by selecting different positions of the distribution nozzle, the same or different fluid (gas, liquid, solid, any one of the three substances, or a mixed fluid of multiple substances, especially including: a fluid that is soluble or insoluble with the captured object) is sprayed to both sides along the channel or pipeline type internal cavity of the droplet array capture sorting unit. That is, the fluid of a specified number or capacity required by the user, including but not limited to droplets such as droplets, liquid columns, liquid blocks, bubbles, gas flows, and other forms of fluid, can be driven to a specified destination space position through the intended or specific output path (including but not limited to a dedicated result output channel), thereby achieving precise driving, distribution and control of the liquid, gas or other types of fluid.
[0062] One or more droplet array capture sorting units are jointly operated, and the control target of strategy 1: the queue turning and distribution method is achieved, that is, the sorting, driving or obtaining of a specified number of mass droplets.
[0063] In the strategy method (two) on-demand selection of spray strategy, (three) redundant delete convergence strategy, all use the clear row hole to participate in the control.
[0064] The captured bubble array controlled by the sorting unit: all capture points as a reference, the output path and the waste output path are located on the opposite side of the input channel and can be independently controlled. Both can be different branches of the same output channel, or they can be independently connected with the bubble array capture sorting unit cavity at different positions. From the perspective of the weight of the bubble, the path of its movement is: entering from the input channel, flowing through all capture points and their capture mechanism entrances and exits (if the capture mechanism is empty, the number of weight bubbles suitable for the cavity space will enter, and subsequent weight bubbles will only "slide through" the capture mechanism entrance and exit), and finally flowing out through the output path or the waste output path with the help of gravity or buoyancy, or by setting a controllable valve in the channel.
[0065] In the stage of entering the bubble array capture sorting unit and being captured by the captured point:
[0066] Method one: close the output path, and only open the waste output path in the output path.
[0067] Or method two: adjust the attitude of the fluid carrier, under the action of gravity or buoyancy, make the waste output path closer to the outlet weight bubble at the entrance, or the direction of the outlet weight bubble flow at the entrance is smaller than the direction of the gravity or buoyancy used to drive the weight bubble, so that the waste output path is a more favorable motion route for the weight bubble to enter:
[0068] (1) When the density of the weight bubble is smaller than the surrounding fluid that drives its movement, adjust the attitude of the fluid carrier, use buoyancy to make the waste output path directly connected with the output interface of the bubble array capture sorting unit, and the angle between the waste output path and the buoyancy at the connection is smaller than that of other channels: the best way is that the waste output path and the buoyancy direction are the same, that is, the angle between them is 0;
[0069] (2) When the density of the weight bubble is larger than the surrounding fluid that drives its movement, adjust the attitude of the fluid carrier, use gravity to make the waste output path directly connected with the output interface of the bubble array capture sorting unit, and the angle between the waste output path and the gravity at the connection is smaller than that of other channels: the best way is that the waste output path and the gravity direction are the same, that is, the angle between them is 0.
[0070] After the weight droplet enters the droplet array capture sorting unit and completes the full-scale capture of all capture points, and other uncaptured limit droplets are removed, one method is to close the waste output path, and only the achievement output path is open in the output path; or another method is to adjust the posture of the fluid carrier, under the action of gravity or buoyancy, to make the achievement output path closer to the outlet of the weight droplet, or the droplet flow direction at the inlet is smaller than the angle between the driving weight droplet gravity or buoyancy direction, compared with other paths, so that the achievement output path is a more favorable motion route for the weight droplet to enter:
[0071] (1) When the density of the weight droplet is smaller than the surrounding fluid driving its movement, adjust the posture of the fluid carrier, use the buoyancy to make the achievement output path directly connected at the output interface of the droplet array capture sorting unit, and the angle between the achievement output path and the buoyancy at the connection is smaller than that of other channels: the best way is that the achievement output path is the same as the direction of the buoyancy, that is, the angle between them is 0;
[0072] (2) When the density of the weight droplet is larger than the surrounding fluid driving its movement, adjust the posture of the fluid carrier, use the gravity to make the achievement output path directly connected at the output interface of the droplet array capture sorting unit, and the angle between the achievement output path and the gravity at the connection is smaller than that of other channels: the best way is that the achievement output path is the same as the direction of the gravity, that is, the angle between them is 0.
[0073] The said clear hole: used for actively discharging or removing the captured objects in the capture mechanism of the capture point, or used for preventing the target reagent or other fluids (gas, liquid, solid, etc. : one or more mixtures of three states of matter) remaining or adsorbing on the bottom or side wall of the capture mechanism cavity, the "clear hole" sprays fluid through the hole, for example but not limited to: oil, gas and other immiscible droplets, for flushing and flushing in the capture mechanism or other forms of capture point, to remove the remaining substances (including but not limited to: weight droplets or their residual parts) in the capture mechanism cavity, in addition to the clear hole, vibration or other methods can also be used alone or in combination: the surface of the capture mechanism cavity of the capture point is deformed, so that it has but is not limited to: hydrophobic (not hydrophilic), oleophobic (not oleophilic) properties; or use knocking, vibration, ultrasonic wave and other methods to remove the residual part after fluid distribution, so as to not affect the next fluid distribution.
[0074] The "clear hole" can be arranged on the bottom or side wall of the capture mechanism cavity, and the hole diameter (or the longest line segment in the interface) size should be less than 500um, which can be reduced to less than 10um, especially less than 3um, the small cross-section hole design can effectively prevent the reverse error of the substances in the capture mechanism cavity into the "clear hole" by surface tension or other fluid characteristics.
[0075] The direction of the fluid material ejected from the clear-out hole includes, but is not limited to, one or a combination of the following: (1) the ejection direction is parallel to the bottom surface of the capture mechanism cavity, (2) the ejection direction forms an acute angle with the bottom surface of the capture mechanism cavity, (3) the ejection direction forms a right angle or an obtuse angle with the bottom surface of the capture mechanism cavity.
[0076] (ii) On-demand selected ejection strategy:
[0077] A clear-out hole is arranged in the bottom, side wall, or other part of the cavity of each capture point capture mechanism. Each clear-out hole of each capture point is connected to an independent input channel or external pipeline, and can controllably eject fluid into the capture mechanism cavity, so as to realize the discharge of the captured object (including but not limited to: droplet containing cells, bacteria, and other biological particles) from the capture mechanism.
[0078] Step three, the process steps before step three in the preceding (i) queue flipping and sorting strategy, that is, after the corresponding group of weight droplets enter the droplet array capture sorting unit, complete the full-quantity capture of all capture points, and remove other droplets that are not captured and limited (i.e. after the preceding clearing step), the waste output path is closed, and only (only) the achievement output path is opened in the output path. A certain number of weight droplets are selected from the capture points in the droplet array capture sorting unit, and are driven to the outside of the corresponding capture mechanism by controllable ejection of fluid from the corresponding clear-out hole.
[0079] Specific method: with the achievement output channel (or the driven target position) as the reference, the fluid is sequentially ejected from the clear-out hole of the corresponding capture mechanism in the order from far to near on the path, and the captured object (such as the weight droplet) is driven to sequentially escape from the capture point (capture mechanism), and the captured object ejected later can be prevented from entering the empty capture point of the captured object ejected earlier, thereby avoiding errors or mistakes.
[0080] Step four, the specified number of weight droplets driven away enter the cavity of the droplet array capture sorting unit, and are then driven to the specified target space position through the only open achievement output path in the output path under the driving of the input channel fluid or by gravity or buoyancy before the waste output path is closed.
[0081] One or more droplet array capture sorting units are jointly operated according to the above principle, and the control target of the on-demand selected ejection method (strategy 2) is achieved: the sorting, driving, or obtaining of a specified number of weight droplets.
[0082] (iii) Excess deletion convergence strategy:
[0083] Step 3, after the preceding step 1, the flow path of the preceding step 2, that is, after the corresponding group of weight droplets enters the droplet array capture sorting unit and completes the full-quantity capture of all capture points, and after the other uncaptured limit droplets are removed, first, the output path is closed, and only (only) the waste output path in the output path is opened. A specified number of capture points corresponding to the clear hole jet fluid, and the specified number of weight droplets are deleted through the waste output path.
[0084] Step 4, after the above steps, the waste output path is closed, and the output path is opened. The remaining weight droplets in the droplet array capture sorting unit are driven by the controllable jet fluid in the clear hole, or after the droplet array capture sorting unit is flipped, the remaining weight droplets are driven by gravity or buoyancy, or the remaining weight droplets are driven by the input channel fluid. After the remaining weight droplets enter the cavity of the droplet array capture sorting unit, they are driven to the specified destination space through the only open output path.
[0085] Because the number of weight droplets deleted in the previous stage can be arbitrarily selected, the remaining weight droplets after deletion are also indirectly arbitrarily selected. Therefore, one or more droplet array capture sorting units can be jointly operated, and the control target of strategy 3: waste deletion remainder method is achieved, that is, the sorting, driving or obtaining of a specified number of weight droplets.
[0086] The weight droplets can or can not contain biological particles. Through sensors or image recording equipment, the shape, state, and quantity of the biological particles can be obtained, and the storage, culture, monitoring, incubation, sorting, or reaction of the biological particles can be achieved.
[0087] In addition to liquid, the composition of the weight droplets can also contain or dissolve gaseous or solid substances, especially active or inactive biological particles, including but not limited to cells, bacteria, viruses, proteins, secretions, genes, micro-organs, micro-tissues, micro-organisms, or organisms, and the whole or part of each type.
[0088] In the case of containing biological particles, the system biological particles include cells, bacteria, viruses, proteins, secretions, genes, micro-organs, micro-tissues, micro-organisms, or organisms, and the whole or part of each type.
[0089] In the present application, the cavity of the droplet array capture sorting unit, except for the channel part after the capture point (capture mechanism) and the limit point (limit mechanism), is called the main channel, the main passage, or the trunk.
[0090] Firstly: Each capture point, through its capture mechanism, captures one and only one weight droplet, the main channel (or main passage) runs along a straight line parallel to the horizontal plane, or the angle between the main channel and the horizontal plane is an acute angle.
[0091] More optimal design: (1) When the density of the weight droplet is smaller than the surrounding fluid driving its movement, the main channel runs horizontally or monotonously upward, and the angle between the upward movement direction of the weight droplet in the main channel and the horizontal plane ranges from 0 to 90 degrees, especially including an acute angle; (2) When the density of the weight droplet is larger than the surrounding fluid driving its movement, the main channel runs horizontally or monotonously downward, and the angle between the downward movement direction of the weight droplet in the main channel and the horizontal plane ranges from 0 to 90 degrees, especially including an acute angle.
[0092] A multi-lateral limiting mechanism is adopted, including but not limited to: capture mechanism (or capture facility), limiting mechanism (or limiting facility), i.e. on different sides of the droplet array capture sorting unit cavity, a plurality of capture mechanisms (or capture facilities) are arranged, or a plurality of limiting mechanisms (or limiting facilities) are arranged, or both types are arranged, to achieve reliable capture or limiting of the control target.
[0093] The capture mechanism (or capture facility) of the capture point is a deep limiting mechanism: the width of the capture mechanism cavity of the capture point is between 1 to 2 times the diameter of the capture object, and the ratio range does not include 2 times, and the best is 1 times, but the best choice of the ratio is: equal to 1 times; the depth of the capture mechanism cavity of the capture point is between 1 / 4 to 7 / 4 times the diameter of the capture object, including: between 0.5 to 1.5 times the diameter of the capture object, and the best choice of the ratio is 1 times, and the design method for each package of multiple capture objects includes: the volume of the capture mechanism cavity of the capture point is 1 times the volume of the specified number of: specific capture object volume and, or the volume of the specified number of capture object circumscribed minimum cuboid (or cube) volume and.
[0094] The limiting point, limiting slot or other limiting mechanism (or limiting facility) is a shallow limiting mechanism: the principle mechanism is similar to that of the capture point, which can slightly limit the position of each package of droplets, while not completely blocking its axial movement along the droplet array capture sorting unit, and the limiting mechanism, such as limiting point, limiting slot or other types, forms including but not limited to: pit, groove, protrusion, dam, ring layer, island, gap or other structures that can capture, limit or trap droplets or fluid, but the limiting height of the limiting point, limiting slot or other limiting mechanism to the limiting object (a package of weight droplets containing one or more weight droplets) is not greater than the diameter of a single weight droplet, especially including but not limited to: not greater than the radius of the weight droplet (half of the diameter), located on the other side wall of the channel other than the wall where the capture mechanism of the capture point is located, used for limiting and positioning the droplet during and after the turning process, to prevent position errors from affecting the final fluid distribution control accuracy.
[0095] The method for generating, producing or preparing the weight droplet, comprising several of the following:
[0096] Method 1: fluid shearing method.
[0097] Several, especially two: immiscible fluids, at the intersection of cross-channels with three or more branches, generating droplets such as droplets or bubbles by fluid shear force, cross-channel types include: T-shaped, cross-shaped, where one fluid is a liquid, surfactant can be added to achieve stable generation of smaller droplets.
[0098] During the generation of the weight droplet, its parameters can be observed in real time, and the fluid flow rate can be adjusted in real time according to the error, or the particle size screening device, including: sorting chip, filter or other screening device, which has a certain size of screen hole or screen gap according to its own, can screen the target with particle size larger than the screen hole and smaller than the screen hole. First, according to the desired diameter size, select a screen hole smaller than the desired size by a certain value, filter out droplets smaller than the desired size, then select a screen hole larger than the desired size by a certain value, filter out droplets larger than the desired size, then get the weight droplet with the above certain value as the positive and negative error of the particle size, that is, realize the screen hole size filtering.
[0099] Method 2: solid flow flat pit method.
[0100] The chip contains several droplet preparation spaces, and the droplet preparation space is provided with several specific size pits. The pit is an open cavity structure surrounded by a plane or a curved surface, and its shape is a sphere, a polyhedron, or a part of the above shape, especially including: hemispherical, bowl-shaped, groove-shaped, and its cavity volume is designed to be the desired droplet volume, or the error is within ±50% of the expected droplet volume, especially including: within ±10%, and the best error is 0%.
[0101] If there is gas or other substances in the droplet preparation space, which will affect the subsequent droplet preparation, all or part of the gas or other substances in the droplet preparation space can be removed first, especially including: vacuumizing, sub-vacuumizing or making the preparation space gas thin. If there is no gas or other substances in the droplet preparation space, or although there is, but can be ignored or does not affect the subsequent link, the above removal operation is not required, or the step is ignored.
[0102] Fluid A used for bubble preparation is introduced into the droplet preparation space. When all the pit cavities are filled with the fluid A, another fluid B that is not soluble with the fluid A used for bubble preparation is selected (including but not limited to: fluid A is water phase solution, fluid B is oil phase, oil phase includes but not limited to: heavy oil with higher density than water, 7100, FC40, or light oil with lower density than water, such as fluorinated oil). When the density of fluid A used for bubble preparation is greater than fluid B, the direction of the pit opening in the droplet preparation space is adjusted to 0 or acute angle with the direction of buoyancy. When the density of fluid A used for bubble preparation is less than fluid B, the direction of the pit opening in the droplet preparation space is adjusted to 0 or acute angle with the direction of gravity. Fluid B is introduced into the droplet preparation space through a specific interface, and the excess fluid A in the droplet preparation space and the space outside the pit cavity is removed. The process controls the pressure relationship between the inside and outside of the droplet preparation space to remove the excess material outside the pit cavity, while the amount of fluid A in the pit cavity does not change or changes by an acceptable amount. To minimize the error in this case, the pit shape can be designed with a smaller opening and a larger depth-to-width ratio, especially with a depth-to-width ratio greater than 1.
[0103] Alternatively, a solid piston (including a baffle or other solid device) is selected, and the surfaces of the solid piston are flush with the pit opening surfaces in the droplet preparation space. After all the pit cavities are filled with the fluid A, the solid piston is pushed into the droplet preparation space. The solid piston can occupy the space outside all the pit cavities and remove all the material outside the pit opening. Then, the solid piston is removed, and another fluid that is not soluble with the fluid A used for bubble preparation is introduced into the space outside the pit opening through a separate interface. When the solid piston is completely removed from the pit opening, the droplets are quickly, accurately, and batch-produced according to the size of the pit cavity.
[0104] In the above-mentioned methods, the pit cavities are filled with the fluid used for bubble preparation, and the outside of the pit cavity is filled with another fluid that is not soluble with the fluid used for bubble preparation. At this time, the direction of the droplet preparation space is adjusted, especially the pit opening direction is rotated by 90-270 degrees, and the optimal rotation is 180 degrees, or vibration is applied, so that the bubble is separated from the pit cavity and enters the external fluid that is not soluble with it. The part of the fluid and the generated droplet are driven together to move to any target space through the channel or pipeline.
[0105] Method 3: Bubble cutting method.
[0106] Droplet splitting method, expected to improve the accuracy, reduce the volume of the package or the volume of the weight droplet, especially when the volume is in picoliter or femtoliter level, the above method 1 or 2, can be achieved by reducing the volume or size of the droplet generation mechanism, including but not limited to: use of fine channels, small pits. In addition, alone or in combination with the above method (method 1 or 2): using droplet splitting method (such as using T-shaped or Y-shaped channel splitting method), the droplet is evenly divided into multiple sub-droplets, and smaller size droplets are prepared.
[0107] The control method of the present application includes but is not limited to: some of the following anti-backflow and anti-path error measures:
[0108] (1) Anti-backflow and anti-path error measure 1: serpentine channel.
[0109] Input and output channels adopt curved paths. All input or output channels are designed to contain several turning parts greater than 45 degrees to prevent target objects (such as droplets) from moving in reverse and causing errors or mistakes. Under the action of buoyancy or gravity, the droplets are stopped at the extreme value point position with the horizontal plane as the reference.
[0110] If the density of the fluid around the droplet that is not soluble with the droplet is greater than that of the droplet itself, the droplet is stopped at the extreme high value point (or maximum value point) with the horizontal plane as the reference by using buoyancy, so that the droplet cannot or is difficult to overcome the buoyancy and move in reverse to the main channel for fluid distribution; if the density of the fluid around the droplet that is not soluble with the droplet is less than that of the droplet itself, the droplet is stopped at the extreme low value point (or minimum value point) with the horizontal plane as the reference by using gravity, so that the droplet cannot or is difficult to overcome the gravity and move in reverse to the main channel for fluid distribution.
[0111] Curved serpentine structure can be realized by chip internal channel or external pipeline.
[0112] (2) Anti-backflow and anti-path error measure 2: valve at the inlet and outlet.
[0113] One-way valve (uncontrollable or controllable) or two-way valve (input and output bidirectional controllable) is arranged at the inlet and outlet of the channel.
[0114] After the target object completes the directional flow intended by the user in the channel, the controllable valve is closed, or the uncontrollable valve is relied on to prevent the target object from flowing in reverse and avoid causing control errors.
[0115] With the help of different fluid density and mutually insoluble stratification mechanism, the method of collecting, collecting, fusing or processing the weight droplet can be multi-layer protected to prevent evaporation and pollution, including but not limited to some of the following:
[0116] (1) "Pointed roof type" (using buoyancy): "Pointed roof type" collection space or container, including but not limited to: by plane, curved or irregular surface composed of a structure of space decreasing from bottom to top, such as cone, triangle, after the weight drop into the bubble, by pre-set (in the collection space or container) or drive it: the density of the heavy fluid is greater than that of the weight drop, through the different fluid density and mutual insoluble stratification mechanism, automatically limited to: the top of the space or container closed structure, between the heavy fluid and the weight drop, and achieve automatic convergence, multi-layer protection.
[0117] (2) "Sandwich type": "Sandwich type" collection space or container, including but not limited to: by plane, curved or irregular surface composed of a structure, such as vertical tube container, after the weight drop into the bubble, by pre-set (in the collection space or container) or drive it: at least two kinds of fluid with density greater and less than that of the weight drop, through the different fluid density and mutual insoluble stratification mechanism, the weight drop is automatically limited between the at least two kinds of fluid with density greater and less than that of the weight drop, and achieves automatic convergence, protection from top to bottom.
[0118] (3) "Inverted triangular basement type" (using gravity): "Inverted triangular basement type" collection space or container, including but not limited to: by plane, curved or irregular surface composed of a structure of space decreasing from top to bottom, such as inverted cone, inverted triangle, after the weight drop into the bubble, by pre-set or drive it: the density of the light fluid is less than that of the weight drop, through the different fluid density and mutual insoluble stratification mechanism, automatically limited to: the bottom of the space or container closed structure, between the light fluid and the weight drop, and achieve automatic convergence, multi-layer protection.
[0119] If the collected droplets contain substances such as surfactants that prevent mutual fusion, such as desired droplet fusion, one or more of the following methods can be used to destroy the surface activity of the droplets or weaken the effect of the droplet surfactant, and then achieve droplet fusion: shaking, high temperature above 60 degrees Celsius (especially including high temperature above 100 degrees Celsius), low temperature below 20 degrees Celsius (especially including low temperature below 0 degrees Celsius), ultrasonic waves, electric field, etc. In particular, a non-DC high-frequency electric field with a voltage higher than 1V can controllably control the fusion of droplets.
[0120] Then: multiple rounds of the same or different precise quantitative fluids are driven into the same or different target spaces in the form of weight droplets, wherein the multiple rounds of the same or different weight droplets are driven into the same target space and converge, mix or fuse, which can achieve the mechanism of storage, incubation, culture, reaction or interaction, i.e. a precise quantitative micro-reaction system is achieved. The micro-reaction system is protected or controlled by the above method ("pointed roof type", "sandwich type", or "inverted triangular basement type") and does not have negative phenomena such as evaporation, reduction, loss, etc.
[0121] The abandoned weight droplet flowing out through the non-product export channel can be recycled and re-injected into use through the input channel.
[0122] The weight droplet can contain solid particles in addition to liquid or gas, such as active or inactive biological particles, including but not limited to cells, bacteria, viruses, proteins, secretions, genes, micro-organs, micro-tissues, micro-organisms, or organisms, and the whole or part of each type, and through sensors or image recording equipment, obtain biological particle characteristic information, such as but not limited to fluorescence signal, Raman signal, impedance, shape, state, quantity, etc., to achieve storage, culture, monitoring, incubation, sorting, or reaction applications for biological particles.
[0123] The description of the principles of the weight droplet, the weight droplet, and the weight bubble of the present application is applicable to each other, that is, they are the same in control principle and similar in form.
[0124] According to the N-ary idea, the optimized design method is that the weight droplets in each group are divided into multiple packages, and the number of weight droplets in each package can be one or multiple. The following describes the case where each package contains only one weight droplet, and the single package and single weight droplet concepts are the same (the case where each package contains multiple weight droplets is the same as the following).
[0125] The number of weight droplets in different groups can be the same or different.
[0126] When the above groups are monotonically sorted (ascending or descending) according to the volume or capacity, the volume ratio of different adjacent droplet groups can be the same or different.
[0127] That is, "N" in the "N-ary" can be a constant value or a variable value, and it is more convenient in applications to be a constant N-ary, especially a constant decimal.
[0128] The weight droplets are divided into different groups according to their volume, and the weight droplets in the same group have the same volume or an error within ±z% (where z is a real number between 0 and 100), which can be ignored or allowed.
[0129] All groups are monotonically sorted (ascending or descending) according to the volume or capacity, and the volume or capacity ratio of the two groups of weight droplets in any adjacent group: the larger volume group compared to the smaller volume group is a positive integer or a positive real number (where the decimal part is ignored, accepted or allowed as an error), and the volume or capacity ratio is taken as an integer N, and the number of smaller droplets participating in fluid distribution or control is N-1.
[0130] For example: the different groups of weight drops are arranged in ascending order from small to large volume, and three adjacent groups are selected: assume a, b, and c groups, the volume ratio of b group to a group is Nba, and the volume ratio of c group to b group is Ncb, then the number of weight drops participating in fluid distribution or control is: the number of a group is Nba-1, and the number of b group is Ncb-1. Here, Nba and Ncb can be the same or different in value.
[0131] In any adjacent group, the volume ratio of large volume group to small volume group can be 0 or not (i.e. forming an error) but can be ignored or allowed as a positive or negative error. The volume of the same group of weight drops is the same, or the error is within ±z% (where z is a real number between 0 and 100), which can also be ignored or allowed as a positive or negative error.
[0132] Assuming that the maximum volume of the group participating in fluid distribution or control is Vmax, the number is Nmax, and the minimum volume of the group is Vmin, arranged in ascending order of volume, the adjacent groups of weight drops satisfy: the volume of the large volume group divided by the volume of the small volume group, or the ratio, is rounded to an integer by "cutting method" or "rounding method", and the number of small weight drops participating in fluid distribution or control is 1 more than the rounded value.
[0133] The above same group of weight drops are arranged in linear (including straight line, curve, broken line, combination of the above, or other linear) or non-linear, with equal or unequal spacing, and a number of (one or more) fluid diversion nozzles are arranged on both sides of any weight drop. The fluid diversion nozzles between adjacent weight drops can be shared. Selecting a specific position of the fluid diversion nozzle (one side of the weight drop at the specific position) to spray fluid into the specific pipeline space, the specified number of weight drops can be driven to the target space along the same path through the diversion nozzle of the sprayed fluid in the specific pipeline space to the target position (or output channel), which is called achievement drop. During this process, the remaining weight drops on the opposite side of the achievement output channel of the above-mentioned fluid diversion nozzle are called waste drops, which are driven by the fluid sprayed by the above-mentioned diversion nozzle along a different motion path to other spaces, without interfering with or causing errors to the achievement drops.
[0134] In the same round of fluid distribution operation, if there are other groups, then the above method is used to operate in parallel or in sequence, and the same operation is performed on the different groups of result droplets to gather them in the same position space. That is, the result droplets of fluid distribution of all groups participating in the same round of fluid distribution are gathered in the same space, which realizes obtaining a specified non-negative integer (or natural number, positive integer) number of fluids (liquid or gas) with the minimum weight droplet volume or capacity as the precision (minimum scale).
[0135] The specific pipeline space has a linear or nonlinear extension mode, including but not limited to a straight line, an arc line, a spiral line, or other curved lines.
[0136] In the capture mechanism at the capture point, in the case of capturing a single weight droplet, the number of each group can be controlled by several methods as follows:
[0137] (1) A nozzle is arranged in the capture point (capture mechanism) to spray a specified number of capture objects (weight droplets) by spraying fluid.
[0138] (2) Several packages of weight droplets (the number of weight droplets in each package is one or more) in the same group are arranged in a single column in a pipeline type space in a straight line, a curved line, a broken line, or an irregular line. Nozzles are arranged on both sides of each package of weight droplets (adjacent weight droplets can share one or several nozzles). By selecting several nozzles at different positions, the fluid can be sprayed to drive all weight droplets in the group to the two sides of the pipeline type space, with the selected nozzle position as the boundary. On one side as the target path, the number of packages of driven weight droplets is a specified value, which realizes the highest precision (which can be understood as the smallest scale of measurement) of the volume of a single package of weight droplets captured by a single capture mechanism in the minimum capture volume group, and captures, limits, selects, and drives or obtains a specified number of packages of weight droplets.
[0139] That is, the above Vmin is used as the precision, and (Vmax * Nmax - Vmin) is used as the maximum value to obtain a continuous or arbitrary value of precise fluid quantity, which realizes a precise quantitative fluid quantity taking system, a reaction system, and a control method based on N-weight droplets.
[0140] In the present application, the description of liquid droplets or weight liquid droplets is applicable to gas bubbles or weight gas bubbles, and the same or similar methods are used for the two substances, which are within the protection scope of the present application. BRIEF DESCRIPTION OF DRAWINGS
[0141] Figure 1 Figure 1 is a schematic diagram of a three-group combined decimal liquid distribution system with a 1 picoliter level precision according to an embodiment of the present application.
[0142] Figure 2 For the second embodiment of the present application: the principle and flowchart of the queue flip sorting method.
[0143] Figure 3 For the third embodiment of the present application: the principle and flowchart of the on-demand selection and waste deletion method.
[0144] Figure 4 For the fourth embodiment of the present application: the principle and flowchart of the fixed flow flat pit method droplet generation and separation. DETAILED DESCRIPTION
[0145] The following embodiments of the present application are only one of the specific forms of the present application, and the purpose of giving is to describe the present application in more detail, not to limit the scope of the present application, nor to limit the application form of the present application.
[0146] The operation steps of each embodiment involve different postures of fluid carriers (such as microfluidic chips), and the right side of the principle, flowchart or flowchart is marked with the direction of gravity G.
[0147] Embodiment 1: Three sets of combined decimal separation system with 1 picoliter precision, as shown in Figure 1
[0148] The separation system is composed of three droplet array capture sorting units (i), (j), (h), etc. The capture points and their capture mechanisms in each droplet array capture sorting unit are equally spaced and collinear. The corresponding separation nozzle is located on the opposite side of the position between the two capture mechanisms, and the layout is shown in the figure.
[0149] Figure 1 The fluid flow direction is indicated by the arrow: the left side is the input port, and the right side is the output port. Each droplet array capture sorting unit corresponds to a group of uniform size weight droplets. The droplet array capture sorting unit, the volume of a single weight droplet is 1 picoliter, 10 picoliters, and 100 picoliters, respectively. When each group of weight droplets enters the corresponding droplet array capture sorting unit through the input port, they move monotonously upward at a 45-degree angle with the horizontal plane (the direction of gravity is indicated by G in the figure, at a 45-degree angle with the horizontal plane). Because the density of the weight droplets is less than that of the external driving fluid, they are captured by the capture point capture mechanism (rectangular or semicircular in the figure) arranged above the inner wall under the action of buoyancy. Each capture point only captures a single weight droplet without vacancy. Then, the same driving fluid as before is introduced through the three left inlet ports to remove all remaining droplets outside the capture mechanism in the droplet array capture sorting unit, completing the clearing process. Then, the middle position (the 5th capture point) of each group of capture mechanisms or other spatial points is used as the axis to rotate, so that all capture point capture mechanisms open downward in the same direction as gravity (i.e., the direction of gravity changes to vertical downward in the figure). Then, the axis is the line shared by all capture points (or the center points of the capture mechanism entrances and exits) in the middle (j) group, or the line shared by other groups of capture points, or the parallel line. The three droplet array capture sorting units are rotated 180 degrees synchronously (the direction of gravity changes to vertical upward in the figure). All the weight droplets captured by the capture points are released from the capture mechanism, but they are in a state of force balance under the combined action of buoyancy and the horizontal wall above them. The (h) group is provided with an arc-shaped limiting mechanism (limiting slot) between adjacent diversion nozzles to achieve an auxiliary limiting function for the weight droplets. There are several diversion nozzles between any two weight droplets. At this time, any serial number of diversion nozzles in each droplet array capture sorting unit can be selected synchronously or sequentially to achieve directional diversion of a specified number of weight droplets to the right side, and after the three paths converge, a precise liquid separation of any integer value with a highest precision of 1 picoliter and a maximum value of 999 picoliters (i.e., a highest limit of 1 nanoliter) is obtained. For example, to obtain 678 pL of liquid, select Kh6, Kj7, and Ki8 as three diversion nozzles to spray fluid to both sides, respectively, to obtain h1-h6, 6 large droplets of 100 pL, j1-j7, 7 medium droplets of 10 pL, and i1-i8, 8 small droplets of 1 pL. After the three output paths converge, all droplets can be merged to obtain 678 pL of liquid accurately. The number 678 can be replaced by any integer between 0 and 999.
[0150] Example Two: The principle and flowchart of the queue flip sorting method are shown in Figure 2
[0151] In this example, the weight droplets are water-based weight droplets, and the external driving fluid is a heavy fluid containing a surfactant: heavy oil, which has a higher density than the water-based weight droplets and is not soluble with them.
[0152] The droplet array capture sorting unit of the microfluidic chip is connected with the weight droplet input channel S, the driving oil input channel R, the waste output channel Q, and the result output channel V, respectively, and the layout and direction are as shown in Figure 2
[0153] Figure 2 In step (a), the axial direction of the droplet array capture sorting unit is as shown by the arrow in the figure: along the 45-degree angle upward and downward (uphill) based on the horizontal plane. If the weight droplets mistakenly enter the channel R and the channel V, they all need to have the same downward: speed or displacement component as gravity. However, because the density of the weight droplets is smaller than that of the surrounding heavy oil, the assumption is not true or difficult to be true under the action of buoyancy, thereby avoiding the mistaken entry of the channel R and the channel V to a certain extent.
[0154] The two-phase liquid of the mutually insoluble heavy oil and water passes through the cross-shaped intersection channel to generate a specific size of the “water-in-oil” type weight droplet under the action of shear force, enters the droplet array capture sorting unit through the channel S, and travels along the axial direction of the droplet array capture sorting unit as shown by the arrow in the channel under the joint action of the heavy oil and the buoyancy, and is discharged through the channel Q. During the process, a total of 9 capture points i9-i1 are encountered along the way. The capture mechanism cavity of each capture point can and can only accommodate the entry of a single weight droplet. If a capture point is empty, the first weight droplet to arrive will automatically enter the capture mechanism of the capture point under the driving action of the buoyancy or the heavy oil. Because the diameter of the weight droplet is the same as the depth and width of the capture mechanism cavity, the circumscribed cube volume of the weight droplet and the cavity volume of the capture mechanism have an error within ±50%, other weight droplets cannot enter the capture point again, and even if they reach the entrance of the capture point, they will also “slide past”.
[0155] Figure 2 In step (b), according to the above principle, the capture mechanisms of all capture points (a total of 9 capture points i9-i1) of the droplet array capture sorting unit all capture only one weight droplet without emptying, and there are still a number of uncaptured weight droplets outside the capture mechanism.
[0156] Figure 2 In step (c), the channel S stops injecting the weight droplets, the heavy oil is input through the channel R to drive all uncaptured weight droplets outside the capture points in the droplet array capture sorting unit, and the uncaptured weight droplets are excluded through the channel Q, so that the outside of the capture points is cleared, and each capture point captures only one weight droplet.
[0157] Figure 2 In step (d), the microfluidic chip is rotated with the middle i5 capture point as the axis, so that the axial direction of the droplet array capture sorting unit is parallel to the horizontal plane, and the opening of each capture mechanism is in the same direction as the gravity.
[0158] Figure 2 Middle step (e): Rotate the microfluidic chip 180 degrees with the i1-i9 capture point connection line (i.e. all capture points are collinear) as the axis, so that each captured weight droplet is released from the corresponding capture mechanism, and under the action of buoyancy, it adheres to the side wall on the opposite side of the capture mechanism of the droplet array capture sorting unit to reach a stable equilibrium state. At this time: there are shunt nozzles on both sides of each weight droplet and between every two adjacent weight droplets, and the shunt nozzles and the weight droplets are arranged alternately.
[0159] Figure 2 Middle step (f): Open any one of the shunt nozzle valves Ki0-Ki9 (all valves Ki0-Ki9 are closed before), and here we assume that Ki3 is selected. The heavy oil or other fluid injected through Ki3 into the cavity of the droplet array capture sorting unit flows to both sides after entering the cavity.
[0160] Figure 2 Middle step (g): Open the shunt nozzle valve Ki3, and under the combined action of the driving of the heavy oil or other fluid and the buoyancy, the i1-i3 corresponding three weight droplets are pushed into the result channel V, and then enter the target space through the channel or pipeline. The space is pre-installed with a light fluid (which can also be pre-installed with two fluids with different densities that are not soluble with the weight droplets) that is smaller in density than the weight droplets and not soluble with them, plus the driving heavy fluid (heavy oil), the weight droplets are protected in the middle of the two fluid layers: limiting volatilization or contact with air.
[0161] And the i4-i9 six weight droplets are recycled through the channel S (the channel R needs to be closed at this time) or deleted through the channel R under the reverse driving of the shunt nozzle valve Ki3.
[0162] The above Ki3 can be replaced by any one of Ki0-Ki9, and then 0-9 weight droplets can be selected and driven into the result channel V, that is, the application of the "queue reversal sorting method" is realized. Multiple droplet array capture sorting units as in the design of Example One: operate in parallel or sequentially and then collect the separation results, which can achieve large-scale precise separation based on the smallest weight droplet as the highest precision.
[0163] Example Three: The principle and flowchart of the on-demand selection and ejection method and the waste deletion and remainder method are shown in Figure 3 .
[0164] In this embodiment, the weight droplet is taken as a water-phase weight droplet, and the external driving fluid is a light fluid: light oil, which has a density smaller than the weight droplet and is not soluble with it, including but not limited to: silicon oil with a density < water.
[0165] The droplet array capture sorting unit of the microfluidic chip is connected with: a waste output channel Q controlled by a controllable valve Kq, and a result output channel V controlled by a controllable valve Kv, and instead of a flow dividing nozzle, a series of clear and drain holes controlled by valves are arranged at the capture mechanism of each capture point, such as the bottom center, the bottom corner or the bottom of the side wall (shown in the bottom corner in the figure), which can actively remove the weight droplets or other fluids in the capture mechanism. When the clear and drain holes spray fluids into the cavity of the capture mechanism, they can also act as a repulsion mechanism to prevent the weight droplets from entering. In addition to the above, the system structure design is the same as that of the second embodiment.
[0166] Figure 3 Step (a): close the result output channel V by Kv, and open the waste output channel Q by Kq, then inject the "water-in-oil" type weight droplets into the droplet array capture sorting unit through the channel S, under the joint action of light oil and gravity, the weight droplets travel downward (downhill) at an angle of 45 degrees with the horizontal plane along the axial direction of the droplet array capture sorting unit, and finally are discharged through the channel Q. Since the channel R is upward at this time, the weight droplets cannot overflow through the channel R because their density is greater than that of the surrounding light oil.
[0167] Figure 3 Step (b): all capture mechanisms of the capture points of the droplet array capture sorting unit are not empty, and each capture mechanism only captures one weight droplet, and the remaining several weight droplets that are not captured are outside the capture mechanism.
[0168] Figure 3 Step (c): stop injecting weight droplets through the channel S, and input light oil through the channel R to drive all the weight droplets that are not captured outside the capture points in the droplet array capture sorting unit to be discharged through the channel Q, and the outside of the capture points is cleared, and each capture point only captures one weight droplet.
[0169] Figure 3 Step (d): close the waste output channel Q by Kq, at this time, the posture of the microfluidic chip can remain unchanged (the opening direction of the capture mechanism of all capture points: 45 degrees obliquely upward with the horizontal plane), or the opening direction of the capture mechanism of the capture points can be made to have an angle of 90 to 180 degrees with the direction of gravity.
[0170] Figure 3 Step (e): open the result output channel V by Kv, and open a plurality of corresponding clear and drain holes by selecting some of Ki1 to Ki9 (Ki1 to Ki9 are all closed before), here it is assumed that Ki1, Ki2, Ki3 and Ki6 are opened, then the weight droplets corresponding to i1, i2, i3 and i6 are sprayed out and separated from the capture mechanism of the corresponding capture point.
[0171] Figure 3Step (f): the chip posture is unchanged, or the opening direction of the capture mechanism is the same as the gravity or an acute angle, and the light oil (no weight droplet) is injected into the channel R or the channel S for driving, combined with the action of gravity, and enters the "inverted triangular basement type" target space through the achievement output channel V. The space is pre-installed with a liquid with a smaller density than the light oil and not soluble with the light oil. In addition, the light oil driven by the previous process is also injected, and the weight droplet is protected under at least one insoluble liquid: the evaporation or pollution is limited, that is, the "on-demand selection and ejection method" is realized.
[0172] In Example Three, if the waste output channel Q is not closed in step (d) above and is still open, and the achievement output channel V is not opened in step (e), the other steps and methods remain unchanged, then the i1, i2, i3, i6 corresponding to the weight droplets selected in the previous process are deleted through the waste output channel Q. After that, the waste output channel Q is closed, and the achievement output channel V is opened. Then all the clear holes are opened directly to remove all the remaining weight droplets from their capture mechanisms, while preventing the misentry of the captured mechanisms during the travel process, or: through the similar rotation and inversion method of Example Two, the remaining captured weight droplets are removed from their limiting mechanisms under the action of gravity. Finally, the collection of the remaining weight droplets i4, i5, i7, i8, i9 is realized through the injection of fluid (without weight droplets) in the input channel R or the input channel S for driving, or combined with the action of gravity. The number and position of the remaining weight droplets can be modified according to the needs of the user, that is, the "waste deletion and remaining collection method" is realized.
[0173] Example Four: Liquid droplet generation and liquid separation principle and flow diagram of solid flow flat pit method, as shown in Figure 4
[0174] In this embodiment, the weight droplet selects a water phase solution, and the external auxiliary generation liquid droplet and the driving fluid are: heavy oil (hereinafter referred to as heavy oil) with a density greater than the water phase solution and not soluble with the water phase solution, containing a surfactant.
[0175] The droplet array capture sorting unit of the microfluidic chip is connected with the water phase solution input channel S, the heavy oil input channel L, the liquid droplet recovery channel R, the waste output channel Q, and the achievement output channel V respectively, and the on-off control is realized through Ks, Kl, Kr, Kq, and Kv. The layout and direction are as shown in Figure 4
[0176] Figure 4 Middle step (a): The bubble array capture sorting unit is placed horizontally along its axial direction, and the cavity is pre-vacuumed, sub-vacuumed or made the internal gas thin through several channels, and the capture mechanism is opened vertically upward (opposite to the direction of gravity). Then, Ks is opened, Kl is closed, Kr is closed, Kq is opened, Kv is closed, and the aqueous solution is filled into the cavity of the bubble array capture sorting unit through the input channel S. In this posture, the microfluidic chip can prevent bubbles from remaining in the capture mechanism (the strategy can also be used: pre-extract all or part of the gas).
[0177] Figure 4 Middle step (b): Ks, Kl, Kr, Kq, Kv, etc. are closed, and the capture mechanism i1 to i9 outlet is connected with the rotation axis (the line is parallel to the axial direction of the bubble array capture sorting unit), which is rotated by 180 degrees, so that the capture mechanism is opened vertically downward (same as the direction of gravity).
[0178] Figure 4 Middle step (c): Kl is opened, Kq is opened, Kl, Kr, Kv, etc. are closed, and heavy oil is input through channel L to fill all spaces in the cavity of the bubble array capture sorting unit except the capture mechanism cavity.
[0179] Figure 4 Middle step (d): Ks, Kl, Kr, Kq, Kv, etc. are closed, and the same rotation axis as step (b) is rotated by 180 degrees, so that the capture mechanism is opened vertically upward (opposite to the direction of gravity).
[0180] Figure 4 Middle step (e): The aqueous solution in the capture mechanism of each capture point is separated from the corresponding capture mechanism under the action of buoyancy, and is limited in the arc-shaped limiting groove on the opposite side wall of the capture mechanism in the form of a droplet. The depth of the arc-shaped limiting groove is less than the radius of the droplet. At this time: between any two adjacent weight droplets.
[0181] Figure 4 Middle step (f): Kr and Kv are both opened, and Ks, Kl, Kq are all closed. At this time: there are branch flow nozzles on both sides of each weight droplet and between every two adjacent weight droplets. The branch flow nozzles are arranged alternately with the weight droplets, and the two ends are branch flow nozzles. Then, steps (f) to (g) in Example Two can be followed: open Kin, n is an integer between 0 and 9, which is any branch flow nozzle valve in Ki0 to Ki9 (all valves Ki0 to Ki9 are closed before this process in this embodiment), and spray the fluid into the cavity of the bubble array capture sorting unit. After entering the cavity of the bubble array capture sorting unit, the fluid flows to both sides.
[0182] Figure 4Middle step (g): open the valve Kin, under the combined action of the drive of the heavy oil or other fluid injected through it and the buoyancy, the n droplets of the right side of Kin are jointly pushed into the channel V, and then enter the target space through the channel or pipeline: "turret type" container. Due to the action of buoyancy, the heavy oil (i.e. heavy fluid) with a density greater than that of the droplet of the weight, which drives its travel, is located at the bottom of the container, which plays a protective role to limit volatilization or contact with air, while the 9-n droplets of the left side of Kin are recycled or discarded through the channel R in the opposite direction of the movement of the previous n droplets of the weight.
Claims
1. A precise measurement system or reaction system for N-ary picoliter or femtoliter fluids, characterized in that: Fluid vehicles include: physical structures or devices that enable fluid storage, flow, observation, cultivation, reaction, sorting, or control. A droplet is an independent collection of substances that can move under the influence of a fluid and consists of one or more of the three states of matter: gas, liquid, and solid. Types include: droplets and bubbles. A weighted bubble is a series of one or more groups of bubbles with precise volume measurement. These groups are divided into several categories based on their volume differences. Each group contains several packets, and each packet contains one or more weighted bubbles of the same size and a fixed quantity within that group. The weighted bubbles within the same group have uniform particle size. Following an N-ary system, the volume of each packet is calculated based on all the bubbles within it. The packets are then monotonically sorted (ascending or descending). In any adjacent group, the ratio of the volume of the weighted bubbles in a single packet between the group with the larger packet volume and the group with the smaller packet volume is equal to the number of valid packets in the smaller packet volume group plus 1. This ratio is an integer N not less than 2 or a real number greater than 1. The integer part of the real number, obtained directly or by rounding down M+1, is N. Here, M and N are both natural numbers. The decimal part of the real number or any missing carry-over value is considered as an allowable positive or negative error. Several sets of capture points are set in the fluid carrier. The capture mechanism capacity of the capture points is the same in the same group and different in different groups. In each group, the capture mechanism of the capture point can only accommodate the single bag of weight droplets of the corresponding group, and corresponds to the number and volume of effective bags in the corresponding group. Then, by controllably selecting several groups, and controllably selecting a specified number of bags of weight droplets in each group, the following can be achieved: the single bag volume in the group with the smallest bag volume is used as the highest accuracy, i.e., the smallest scale, and the sum of the weight droplet volumes of the group with the largest bag volume (number of bags + 1) is used as the upper limit. When the smallest bag volume is a picoliter or a femtoliter, the specified quantity of fluid with picoliter or femtoliter accuracy can be accurately measured, divided, sorted, controlled, or obtained.
2. The N-ary picoliter or femtoliter fluid precision measuring system or reaction system according to claim 1, characterized in that: Fluid carrier, internally or externally connected: multiple channels, and containing several: droplet array capture and sorting units; The droplet array capture and sorting unit is a channel or pipeline type cavity structure that can communicate with the external space. Its internal cavity dimensions are greater than its radial dimensions in the same axial direction as the internal fluid flow direction. The inner wall of the bubble array capture sorting unit cavity is provided with several capture points along the axial direction that can capture bubbles or trap fluid. The capture mechanism contained in the capture point is designed to accommodate only a specified number of capture objects in a corresponding group. The specified number of capture objects is defined as a package. The design method for each package containing a single corresponding group of captured objects includes: the width of the capture mechanism cavity at the capture point is between 1 and 2 times the diameter of the corresponding group of captured objects, the range of 1 to 2 times including 1 times but not including 2 times; the depth of the capture mechanism cavity at the capture point is between 0.5 and 1.5 times the diameter of the corresponding group of captured objects. The design method for each package containing multiple corresponding groups of captured objects includes: the volume of the capture mechanism cavity at the capture point is the sum of the volumes of the specified number of captured objects in the corresponding group, or the sum of the volumes of the smallest circumscribed cuboid or cube. Based on the above design, at different control stages or links, the fluid carrier can accurately and reliably capture, limit, displace, distribute, sort or control a specified number of weight drops by changing its own position, angle or posture, or by switching channels or pipelines located inside or outside the fluid carrier, or different branches of channels or pipelines.
3. The N-ary picoliter or femtoliter fluid precision measuring system or reaction system according to claim 2, characterized in that: The fluid is composed of one or more substances in the three states of gas, liquid, and solid. Fluid carriers are functional structures, appliances, vessels, or instruments that have or are connected to channels, flow paths, or pipes and can be used for fluid flow. Categories include microfluidic chips, biochips, and reagent kits. It includes at least one input channel and at least one output channel. Both channels are connected to the bubble array capture and sorting unit via the input interface and the output interface, respectively. The output channel types include: result output channel and waste output channel. Output path, including internal or external connections of the fluid vehicle: output channel or output pipeline; Waste output paths, including those inside or outside the fluid vehicle: waste output channels or waste output pipelines; The control process includes one or more of the following steps: Step 1, Weight Bubble Capture: In the droplet array capture and sorting unit of the fluid carrier, the capture mechanisms at all capture points are fully loaded with the required number of corresponding weight droplets, no less than that number. After entering the droplet array capture and sorting unit through the input channel, the direction of movement of the weight droplets before being captured or flowing to the output channel is as follows: (1) When the density of the weight bubble is less than the density of the external driving fluid, the movement path of the weight bubble is monotonically upward with time, and the angle between the direction of movement and the direction of buoyancy is 0 to 90 degrees. (2) When the density of the weight bubble is greater than the density of the external driving fluid, the movement path of the weight bubble is monotonically downward with time, and the angle between the direction of movement and the direction of gravity is 0 to 90 degrees. After this process is completed, in the bubble array capture and sorting unit, the capture mechanism of all capture points can capture one or more weight bubbles in a specified number of corresponding groups, and can prevent the entry of subsequent excess weight bubbles; Step Two: Clearing the Area In the controlled bubble array capture and sorting unit, under the premise that all capture points achieve stable capture and limit of their corresponding capture targets, excess weight bubbles outside the capture points are removed by fluid flushing, dispersing or replacing through the input channel and waste output channel. If all capture points capture the specified number of bubbles from a bag of weights in the corresponding group, and there are no other bubbles outside the capture points that could cause fluid distribution errors, then this step can be ignored.
4. The N-ary picoliter or femtoliter fluid precision measuring system or reaction system according to claim 3, characterized in that: On the inner wall of the bubble array capture and sorting unit, between any adjacent capture points, and on the side of the weight bubble input channel of the capture point closest to the weight bubble input channel, several flow-splitting nozzles that can spray fluid are provided. Taking the fluid flowing inside the bubble array capture and sorting unit as a reference, the flow-splitting nozzles can be located on the same side or opposite side of the capture point. The flow-splitting nozzles can spray fluid, so that the fluid captured in the cavity of the bubble array capture and sorting unit can be driven in multiple different directions with its position as the dividing point. Strategy 1: Queue flipping and distribution method: Following step one or step two above, the control process includes one or more of the following steps: Step 3, Limiting Step: Taking any point in space as the axis, following the principle of minimum displacement, the fluid carrier is rotated so that the angle between the axial direction of the bubble array capture sorting unit and the horizontal plane is 0 degrees or an acute angle, and: (1) when the density of the weight bubble is less than that of its external driving fluid, buoyancy is used to restrain it: the angle between the opening direction of the capture mechanism and the direction of gravity is less than a right angle; (2) when the density of the weight bubble is greater than that of its external driving fluid, gravity is used to restrain it: the angle between the opening direction of the capture mechanism and the direction of buoyancy is less than a right angle; If the process time between the steps before and after this step will not cause any error in capturing the target position, or the error is negligible, or the existence of positive or negative errors is allowed, then step three can be omitted. Step four, the release of the weight after the bubble stops: Determination of the flip axis: For capture points in the same group in the current round: capture mechanism entrance and exit or their common feature points, (1) when the positions are collinear, take the collinear, or parallel, or the straight line with an acute angle to it as the flip axis, (2) when the positions are not collinear: take the maximum fitting line - the sum of the distances from the capture mechanism entrance and exit positions of each capture point in the same group in the current round to the straight line or the sum of the squares of the distances, the minimum value of the maximum fitting line, or parallel, or the straight line with an acute angle to it as the flip axis; Along the aforementioned flipping axis, which is parallel to or forms an acute angle with the horizontal plane, the droplet array capture and sorting unit flips the fluid carrier at an angle between 90 and 270 degrees according to the principle of shortest displacement. The optimal control is: flipping 180 degrees allows several bags of weight droplets captured in the same group in the current round to break free from the constraint of the capture point by means of gravity or buoyancy, while not changing the following characteristics: there are one or more diversion nozzles between any two adjacent bags of weight droplets, and at the same time, there are several diversion nozzles that can spray fluid on the side of the weight droplet input channel closest to the capture point of the weight droplet input channel; In each package here, there is one or more weight droplets, which are from the same capture point in the previous stage; During or upon completion of this process, each pack of weights adheres to the inner wall of the bubble array capture and sorting unit cavity under the action of gravity or buoyancy. The attachment point of each pack of weights may or may not be equipped with a limiting mechanism, including a limiting point and a limiting groove, the limiting height of which shall not exceed the diameter of a single weight bubble. Step 5, Weight Distribution: By selecting different locations for the diversion nozzles, and spraying fluids that are either compatible or incompatible with the captured object along the channels or internal cavities of the droplet array capture and sorting unit, it is possible to drive a specific quantity or volume of fluid, located at the selected diversion nozzle position as the dividing point and closer to the intended output path, to the designated destination space via the intended output path, thereby achieving precise driving, distribution, and control of quantitative fluid. One or more bubble arrays capture sorting units, and similarly, they work together to achieve the control objective of Strategy 1: queue flipping sorting method: sorting, driving, or acquiring a specified number of weight bubbles.
5. The N-ary picoliter or femtoliter fluid precision measuring system or reaction system according to claim 3, characterized in that: In step four, the step of releasing the weight after the bubble is limited, the following limiting mechanism may or may not be provided: a pit, groove, protrusion, dam, ring, island, or gap, whose limiting height is not greater than the diameter of a single weight bubble; Output path, including internal or external connections of the fluid vehicle: output channel or output pipeline; Waste output paths, including those inside or outside the fluid vehicle: waste output channels or waste output pipelines; Using all capture points in the controlled bubble array capture and sorting unit as a reference, the result output path and the waste output path are both located on the opposite side of the input channel and can be controlled to open or close. They can be different branches of the same output channel or they can be independently connected to the cavity of the bubble array capture and sorting unit. Strategy 2: Select the ejection method as needed. After the corresponding set of weights and bubbles enter the bubble array capture and sorting unit and complete the full-capacity capture of all capture points, and clear other uncaptured limit bubbles, close the waste output path and open only the result output path in the output path, or adjust the attitude of the fluid carrier so that, under the action of gravity or buoyancy, the inlet of the result output path is closer to the outflowing weight and bubbles, or the angle between the flow direction of the bubbles at the inlet and the direction of gravity or buoyancy used to drive the weight and bubbles is smaller, so that, compared with other paths, the result output path is a movement route that is more conducive to the entry of weight and bubbles. Each capture point has a cleaning hole at the bottom or side wall of the capture mechanism cavity, which can controllably eject fluid to discharge the captured object from its capture mechanism. Select any number of capture points in the bubble array capture sorting unit, spray fluid through the corresponding cleaning holes, and with the target position as a reference, drive the specified number of weight bubbles to the outside of the capture mechanism in order from far to near along the path. Then, driven by the fluid introduced into the input channel, or by gravity or buoyancy, when the waste output path is closed, move to the specified target position through the only open result output path in the output path. One or more bubble arrays capture sorting units, and similarly, they work together to achieve strategy 2: select the control target of the ejection method on demand: sorting, driving or obtaining a specified number of weight bubbles; Strategy 3: Discard, delete, and take the remainder method: After the weight droplets enter the droplet array capture and sorting unit and complete the full-capacity capture at all capture points, and remove other uncaptured limit droplets, the result output path is closed, and the only open waste output path is opened. By controlling the ejection of fluid from the corresponding cleaning holes of several specified capture points, the specified number of weight droplets are all deleted through the waste output path. After this process is completed, the waste output path is closed, and the result output path is opened. The remaining weight droplets in the droplet array capture and sorting unit are driven by the controllable ejection of fluid from the cleaning holes, or by flipping the droplet array capture and sorting unit and using gravity or buoyancy, or by using the fluid introduced through the input channel, so that all the remaining weight droplets are driven to the specified destination space through the only open result output path. Since the number of weight bubbles deleted in the previous stage can be arbitrarily selected, the number of remaining weight bubbles after deletion can be indirectly selected. Thus, one or more bubble arrays capture and sorting units, and similarly, they work together to achieve the control objective of Strategy 3: the discard deletion and remainder method: the sorting, driving and or obtaining of a specified number of weight bubbles.
6. The N-ary picoliter or femtoliter fluid precision measuring system or reaction system according to any one of claims 1 to 5, characterized in that: The design method for each package containing a single corresponding group of captured objects includes: the width of the capture mechanism cavity at the capture point is preferably 1 times the diameter of the corresponding group of captured objects; the depth of the capture mechanism cavity at the capture point is preferably 1 times the diameter of the corresponding group of captured objects. Capture phase: (1) When the density of the weight bubble is less than the density of the external driving fluid, the movement path of the weight bubble is monotonically upward with time, and the optimal angle between the direction of movement and the direction of buoyancy is 45 degrees. (2) When the density of the weight bubble is greater than the density of the external driving fluid, the movement path of the weight bubble is monotonically downward with time, and the optimal angle between the direction of movement and the direction of gravity is 45 degrees. Limiting process: With any point in space as the axis, following the principle of minimum displacement, the fluid carrier is rotated so that the angle between the axial direction of the bubble array capture sorting unit and the horizontal plane is 0 degrees or an acute angle, and: (1) when the density of the weight bubble is less than that of its external driving fluid, buoyancy restraint is adopted: the optimal angle between the opening direction of the capture mechanism and the gravity direction is 0 degrees; (2) when the density of the weight bubble is greater than that of its external driving fluid, gravity restraint is adopted: the optimal angle between the opening direction of the capture mechanism and the buoyancy direction is 0 degrees. The capture mechanism at the capture point can capture, limit, or intercept droplets or fluids, and its forms include: pits, grooves, protrusions, dams, concentric circles, islands, and gaps. A multi-sided limiting mechanism is adopted, that is, a capture mechanism or a limiting mechanism is set on different sides of the cavity of the bubble array capture and sorting unit to achieve reliable capture or limiting of the target to be manipulated. The width of the cavity of the capture mechanism or capture facility at the capture point is between 1 and 2 times the diameter of the captured object; the depth of the cavity is between 1 / 4 and 7 / 4 times the diameter of the captured object. In the design method of multiple captured objects per package, the volume of the cavity of the capture mechanism at the capture point is within the specified quantity range: the sum of the volumes of individual captured objects, or the sum of the volumes of the smallest external cuboid or cube of the individual objects, or the calculation error of the sum of the two volumes mentioned above is within ±50%. Limiting mechanisms or facilities, including limiting points and limiting grooves, operate on a principle similar to capture points. They are located on other side walls of the channel, different from the capture point capture mechanism, and can slightly restrict the position of each pack of bubbles. They can take the form of pits, grooves, protrusions, dams, layers, islands, or gaps. The limiting height of the object being limited is not greater than the diameter of a single weight bubble. They are used to limit and position the bubbles during or after flipping to prevent positional errors from affecting the final fluid distribution control accuracy.
7. The N-ary picoliter or femtoliter fluid precision measuring system or reaction system according to any one of claims 1 to 5, characterized in that: The method for generating, producing, or preparing the weight droplets includes several of the following: Method 1: Fluid shearing method: Multiple immiscible fluids converge at a cross channel with three or more branches, generating droplets by fluid shear force. When there are three cross channels, the droplets are T-shaped; when there are four cross channels, the droplets are cross-shaped. If one of the fluids is a liquid, a surfactant can be added to achieve the stable generation of smaller droplets. During the process of generating weight droplets, its parameters can be observed in real time, and the fluid flow rate can be adjusted in real time according to the error. Alternatively, particle size screening devices, including sorting chips and filters, can be used. These devices have sieve holes or slits of specific sizes that can separate target objects with particle sizes larger or smaller than the sieve holes. First, based on the desired diameter, a sieve hole smaller than the desired size is selected to filter out droplets smaller than the desired size. Then, a sieve hole larger than the desired size is selected to filter out droplets larger than the desired size. This results in droplets with a particle size error of the aforementioned specific value, thus achieving sieve hole particle size filtration. Method 2: Solidification leveling method: The chip contains several droplet fabrication spaces, each with a specific size recess. The recess is an open cavity structure enclosed by a plane or curved surface. Its shape is a sphere, a polyhedron, or a part of the aforementioned shapes. The cavity volume is designed to be the desired droplet volume. The droplet preparation space is placed horizontally. The cavity is evacuated to a vacuum or sub-vacuum beforehand, or the internal gas is made rarefied. This step can be ignored if it does not affect subsequent steps. Fluid A, used for droplet preparation, is introduced into the droplet preparation space. When all the pit cavities are filled with fluid A, another fluid B, which is immiscible with fluid A, is selected. When the density of fluid A is greater than that of fluid B, the angle between the opening direction of the pit in the droplet preparation space and the buoyancy direction is 0 or an acute angle through direction conversion or posture adjustment. When the density of fluid A is less than that of fluid B, the angle between the opening direction of the pit in the droplet preparation space and the gravity direction is 0 or an acute angle through direction conversion or posture adjustment. Fluid B is introduced into the droplet preparation space through a specific interface, and it removes excess fluid A from the space outside the pit cavities within the droplet preparation space. This process controls the relationship between the pressure inside and outside the droplet preparation space, so as to remove excess material from the space outside the pit cavities while the amount of fluid A in the pit cavities does not change, or the change is negligible and acceptable. To reduce the error in this case, the pit shape can be designed with a smaller opening and a larger cavity depth and width. Alternatively, a solid piston can be selected, with several faces flush with the opening surfaces of the pits in the droplet preparation space. After all the pit cavities are filled with fluid A, the solid piston is pushed into the droplet preparation space. With all the pit openings as boundaries, it can occupy the space outside all the pit cavities and push away all the material in the space outside all the pit openings. Then, while removing the solid piston, another fluid that is immiscible with fluid A used to prepare droplets is introduced into the space outside the pit openings from a separate interface. When the solid piston is withdrawn from all the pit openings, the rapid, accurate, and batch production of droplets is achieved according to the size of the pit cavities. In the above methods, the cavity of the pit is filled with the fluid used to prepare the droplet, and the outside of the pit cavity is another fluid that is insoluble with it. At this time, by changing the direction or adjusting the posture of the droplet preparation space, or by applying vibration, the droplet can be detached from the pit cavity and enter the external fluid that is insoluble with it. Driving this part of the fluid, together with the generated droplet, can move together through the channel or pipe to any destination space. Method 3: Bubble splitting method, aiming to improve accuracy and reduce the volume of the package or the volume of the bubble drop. Method 1 or 2 above can be achieved by reducing the volume or size of the bubble generation mechanism, including: using fine channels or small pits; Alternatively or in combination with the above methods: using the bubble-splitting method, a bubble can be split into multiple sub-bubbles to prepare small-sized bubbles.
8. The N-ary picoliter or femtoliter fluid precision measuring system or reaction system according to any one of claims 1 to 5, characterized in that: This includes several of the following measures to prevent backflow and path error: (1) Serpentine channel, with input and output channels using curved paths. (2) Channel entrance and exit settings: uncontrollable or controllable one-way valves, or bidirectional controllable two-way valves; The capture mechanism or capture facility at the capture point, the width of the cavity, is optimally chosen to be 1 times the diameter of the captured object; the depth of the cavity is optimally chosen to be 1 times the diameter of the captured object; for the design method of multiple captured objects per package, the volume of the cavity of the capture mechanism at the capture point is within the specified number range: the sum of the volumes of individual captured objects, or the sum of the volumes of the smallest circumscribed cuboid or cube of the individual objects, or the calculation error of the sum of the two aforementioned volumes is within ±10%; The limiting mechanism includes: pits, grooves, protrusions, dams, rings, islands, and gaps, and its limiting height is not greater than the radius of the weight's droplet. Weighted bubble formation, a fluid shearing method in the generation, production or preparation of weighted bubbles, uses two immiscible fluids that converge at an intersection with three or more branches to generate bubbles by fluid shearing force. In the solid-flow leveling pit method, in order to remove excess material from the space outside the pit cavity while keeping the amount of fluid A in the pit cavity unchanged or with negligible and acceptable change, the shape of the pit can be designed to make the depth-to-width ratio of the cavity greater than 1 in order to reduce the error in this case. The cavities of the pits are filled with a fluid used to prepare droplets, and the outside of the pit cavities is filled with other fluids that are immiscible with it. In particular, this includes rotating the opening direction of the pits by 90-270 degrees. To improve accuracy, especially when the volume is in the picoliter or liter, Method 1 (fluid shearing method) or Method 2 (solid flow leveling method) can be achieved by reducing the volume or size of the bubble generating mechanism, including using fine channels or small pits.
9. The N-ary picoliter or femtoliter fluid precision measuring system or reaction system according to any one of claims 1 to 5, characterized in that: Limiting mechanisms or limiting facilities include: limiting points and limiting grooves. The principle and mechanism are similar to the capture point. They are located on other side walls of the channel that are different from the capture point. They can slightly limit the position of each pack of bubbles. The forms include: pits, grooves, protrusions, dams, layers, islands, and gaps. The limiting height of the limiting object is not greater than the radius of the weight bubble. It is used to limit and position the bubbles during or after flipping to prevent positional errors from affecting the final fluid distribution control accuracy. The cavities of the pits are filled with the fluid used to prepare the droplets, and the outside of the pit cavities is filled with other fluids that are immiscible with it. In this case, it is especially optimal to rotate the opening of the pit by 180 degrees. Based on volume or capacity, the groups are monotonically sorted, that is, when arranged in ascending or descending order, the volume ratio of different adjacent groups of droplets is the same or different, and N is a constant or variable value. The method for collecting, pooling, fusing, or processing the weight droplets, utilizing a stratification mechanism of fluids with different and immiscible densities, includes several of the following: (1) "Glazed roof type", utilizing buoyancy: The "Glazed roof type" collection space or container contains a structure with decreasing space from bottom to top, consisting of a flat, curved or irregular surface. After the weight droplets enter, they are automatically confined between the top closed structure of the space or container and the aforementioned heavy fluid through a layering mechanism of different fluid densities and immiscibility, by means of a pre-set or driving heavy fluid with a density greater than that of the weight droplets, and achieve automatic convergence to prevent negative impacts such as volatilization and pollution. (2) "Sandwich type": A "sandwich type" collection space or container contains a structure composed of a flat, curved or irregular surface. After the weight droplet enters, with the help of at least two fluids with densities greater and smaller than the weight droplet respectively, which are pre-placed in the collection space or drive it, the weight droplet is automatically confined between the aforementioned at least two fluids with densities greater and smaller than the weight droplet respectively, through a stratification mechanism of different fluid densities and immiscibility, and achieves automatic convergence. It is protected from both top and bottom to prevent negative impacts such as volatilization and pollution. (3) "Inverted Triangle Basement Type", utilizing gravity: The "Inverted Triangle Basement Type" collection space or container contains a structure with decreasing space from top to bottom, consisting of a plane, curved surface or irregular surface. After the weight droplets enter, they are automatically confined between the bottom closed structure of the space or container and the aforementioned light fluid through a layering mechanism of different fluid densities and immiscibility, by means of a pre-placed or driving light fluid with a density lower than that of the weight droplets. This achieves automatic convergence and prevents negative impacts such as volatilization and pollution. It contains at least one light fluid with a density lower than that of the collected weight droplets. This light fluid is pre-placed in the receiving space or container. After the weight droplets enter, they are automatically confined at the bottom tip of the "Inverted Triangle Basement Type" with decreasing space from top to bottom, and achieve automatic convergence. The weight droplets are then confined in the middle layer between the bottom closed structure of the space or container and the aforementioned light fluid, preventing negative impacts such as volatilization and pollution. If the collected bubbles contain substances that prevent them from merging, and if it is desired that the bubbles merge, one or more of the following methods can be selected: by vibration, high temperature above 60 degrees Celsius, low temperature below 20 degrees Celsius, ultrasound, electric field, or by using a special agent to remove surface activity, the surface activity of the bubbles can be destroyed or the effect of the bubble surfactant can be weakened, thereby achieving the merging of the bubbles. Then: Multiple rounds of identical or different precisely quantified fluids, in the form of weighted droplets, are driven to the same or different target spaces. Among them, multiple rounds of identical or different weighted droplets are driven to the same target space and merge, mix or fuse, which can realize the mechanism of storage, incubation, cultivation, reaction or interaction, that is, realize a precisely quantified micro-reaction system. This micro-reaction system is protected or controlled by the above-mentioned "pointed roof type", "sandwich type" or "inverted triangular basement type" methods, and no negative phenomena such as volatilization, reduction or loss will occur.
10. The N-ary picoliter or femtoliter fluid precision measuring system or reaction system according to any one of claims 1 to 5, characterized in that: In addition to liquids or gases, droplets may also contain active or inactive biological particles. The categories of biological particles include: cells, bacteria, viruses, proteins, secretions, genes, microorganisms, microtissues, microorganisms or organisms, as well as whole or part of the aforementioned types. The biological particles are used to obtain characteristic information, including: fluorescence signals, Raman signals, impedance, shape, state and quantity, through sensors or imaging equipment. This enables the storage, cultivation, monitoring, incubation, sorting or reaction of biological particles. If the collected bubbles contain substances that prevent them from merging, and if it is desired that the bubbles merge, a non-DC high-frequency electric field with a voltage higher than 1V can be selected to control the merging of the bubbles. The descriptions of weight droplets, weight liquid droplets, and weight bubbles are all applicable to each other, that is, they are similar in their control principle and form. According to the N-ary system concept, in the fluid precision measurement system, reaction system and its control method, the number of weight droplets in different groups may be the same or different. Based on volume or capacity, the groups are monotonically sorted, that is, when arranged in ascending or descending order, the volume ratios of different adjacent groups of droplets are the same or different, and N is a constant or variable value. Assume that the weights involved in fluid distribution or control have the following characteristics: the largest group has a weight volume or capacity of Vmax and a quantity of Nmax; the smallest group has a weight volume or capacity of Vmin. They are arranged in ascending order of volume or capacity. The weights in adjacent groups satisfy the following condition: the volume ratio between the weights in the large volume group and the weights in the small volume group is rounded down. If the ratio contains a decimal, it is rounded down using either the "truncated" or "rounded" method. The rounded value is one more than the quantity of weights in the small volume group. This enables the precise measurement of fluid quantities, either continuously or arbitrarily, using Vmin as the accuracy and Vmax*Nmax-Vmin as the maximum value. This realizes a precise quantitative fluid measurement system, reaction system, and control method based on N-ary weights and bubbles.
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