JP6738464B2 - Microfluidic control - Google Patents

Description

Microfluidics has wide-ranging applications, as well as research into small volume fluids and aspects of operation, control, and use of such small volume fluids in various systems and devices (eg, microfluidic chips). Is included. For example, in some cases, the microfluidic chip can be used as a "lab-on-chip", for example, for use in the medical and biological fields to evaluate fluids and their components.

FIG. 3 is a block diagram schematically illustrating a microfluidic device according to an embodiment of the present disclosure. FIG. 3 is a block diagram schematically illustrating a fluid flow sensor associated with a microfluidic device according to one embodiment of the present disclosure. FIG. 6 is a schematic diagram of a fluid flow feedback loop according to an embodiment of the present disclosure. FIG. 3 is a flow diagram that schematically illustrates a cassette housing a microfluidic device according to one embodiment of the present disclosure. FIG. 3 is a block diagram schematically illustrating a microfluidic device according to an embodiment of the present disclosure. FIG. 3 is a block diagram schematically illustrating an attribute sensor of a microfluidic device according to an embodiment of the present disclosure. FIG. 3 is a block diagram schematically illustrating input/output elements of a microfluidic device according to an embodiment of the present disclosure. FIG. 3 is a block diagram schematically illustrating components of a microfluidic device according to an embodiment of the present disclosure. FIG. 3 is a block diagram schematically illustrating a microfluidic inspection system according to an embodiment of the present disclosure. FIG. 8 is a block diagram schematically illustrating a host device of the system of FIG. 7, according to one embodiment of the disclosure. FIG. 8 is a block diagram schematically illustrating a control interface of the system of FIG. 7, according to one embodiment of the disclosure. FIG. 2 is a plan view schematically showing a microfluidic device according to an embodiment of the present disclosure. FIG. 3 is a plan view schematically illustrating a portion of a microfluidic device that includes a channel structure and its associated components, according to one embodiment of the disclosure. FIG. 3 is a plan view schematically illustrating a portion of a microfluidic device that includes a channel structure and its associated components, according to one embodiment of the disclosure. FIG. 3 is a plan view schematically illustrating a portion of a microfluidic device that includes a channel structure and its associated components, according to one embodiment of the disclosure. FIG. 3 is a block diagram schematically illustrating a fluid flow manager according to an embodiment of the present disclosure. FIG. 3 is a block diagram schematically illustrating a microfluidic device including at least one memory according to an embodiment of the present disclosure. FIG. 3 is a plan view schematically illustrating a portion of a microfluidic device that includes a channel structure and its associated components, according to one embodiment of the disclosure. FIG. 3 is a plan view schematically illustrating a portion of a microfluidic device that includes a channel structure and its associated components, according to one embodiment of the disclosure.

The following detailed description refers to the accompanying drawings, which form a part of this specification, which illustrate, by way of illustration, specific embodiments in which the disclosure may be practiced. It will be appreciated that other embodiments may be used and structural or logical changes may be made without departing from the scope of the present disclosure. Therefore, the following detailed description should not be construed in a limiting sense.

At least some embodiments of the present disclosure relate to microfluidic devices used for treatment and evaluation of biological fluids. In some embodiments, such processing and evaluation includes fluid flow control on the microfluidic device. Thus, at least some embodiments of the present disclosure include fluid flow control within and across one or more channel structures of a microfluidic device.

At least some embodiments of the present disclosure provide fluid flow by employing additional fluid actuators in addition to the primary fluid actuators in controlling fluid flow through the channel structures of microfluidic devices. Provides management of flow control. Therefore, such additional fluid actuators may be referred to as redundant in that the primary operation of the microfluidic device does not depend on such additional fluid actuators. Alternatively, such additional fluid actuators are selectively activated to temporarily alter the fluid flow within the microfluidic channel structure. In some embodiments, a substantial reduction in the expected flow velocity within the microfluidic channel structure occurs (eg, when a partial or complete occlusion occurs within the microfluidic channel structure). By strategically locating the additional fluid actuator and selectively actuating the additional fluid actuator when an occlusion occurs, the additional fluid actuator is used to temporarily and at least partially in the fluid flow direction. It is possible to reverse and remove the blockage.

In some embodiments, the second fluid actuator remains passive until a substantial decrease in fluid flow velocity in the first direction occurs, at which point the second fluid actuator is activated. Reverses the fluid flow for a period and intensity suitable to clear the blockage.

In some embodiments, this fluid backflow is limited to the occluded regions, and thus local regions that do not substantially affect or alter the general fluid flow in the main flow direction within the microfluidic channel structure. Occurs in. However, in other embodiments, an additional fluid actuator is used to completely reverse the fluid flow within the microfluidic channel structure to remove the occlusion. In other words, in at least part of the microfluidic channel structure, the general fluid flow is stopped and only the opposite fluid flow acts.

In some embodiments, changes in flow direction and/or flow velocity are detected by a fluid flow velocity sensor within the microfluidic channel structure.

In some embodiments, the additional fluid actuator is deactivated when the additional fluid actuator is actuated to clear the occlusion.

Thus, in some embodiments, fluid flow control is managed by removing obstruction as it occurs, while maintaining general fluid flow throughout the microfluidic channel structure to maintain desired fluid operation. It

In some embodiments, the additional or redundant fluid actuators described above are automatically actuated at regular intervals to create a temporary, local regurgitation that is opposite to the general fluid flow direction. Occurs in the fluid flow to help prevent occlusion and congestion within the microfluidic channel structure. If a blockage occurs despite this preventive condition of the additional fluid actuator, it is possible to activate the additional fluid actuator more selectively until the blockage clears.

Such a configuration ensures robust operation of the microfluidic device and ensures consistent results, making the point-of-care diagnostic test practical for real-world clinical conditions, while at the same time Can be performed with a relatively low cost inspection chip.

Such and further embodiments will be described and illustrated with respect to at least FIGS. 1-17.

FIG. 1 is a block diagram that schematically illustrates a microfluidic device 20 according to one embodiment of the present disclosure. As shown in the figure, the microfluidic device 20 is formed on a substrate 22 and includes a microfluidic channel structure 30. The microfluidic channel structure 30 includes a configuration for moving a fluid within the microfluidic channel, the configuration directing the fluid as desired to perform an inspection or evaluation of the fluid or to perform a reaction process. To operate, it performs various functions such as heating, pumping, mixing, and/or detection.

In some embodiments, the channel structure 30 includes a first fluid actuator 32 and a second fluid actuator 34. Generally speaking, the first fluid actuator 32 is arranged to produce a general fluid flow (37) in a first direction to perform an operation in the channel structure 30. On the other hand, the second fluid actuator 34 is arranged to selectively and temporarily cause an opposite fluid flow (38) within the channel structure 30. In some embodiments, the reverse fluid flow (38) occurs at a scale and location that does not substantially alter the general fluid flow (37).

In some embodiments, the second fluid actuator provides a local (in the opposite direction) reverse fluid flow (independent of the general fluid flow produced by the first fluid actuator 32). Is located in the channel structure 30 at a distance sufficient to separate from the location of the first fluid actuator.

In some embodiments, the second fluid actuator 34 is substantially lower in strength (eg, lower power) than the strength at which the first fluid actuator 32 operates to maintain the general fluid flow through the channel structure 30. , Longer pulse width).

In some embodiments, the fluid actuators 32, 34, when selectively actuated, produce a selectable fluid displacement of generally 0.5 to 15 picoliters and are operable at frequencies in the range of 1 Hz to 100 kHz. it can. In some embodiments, the second fluid actuator 34, when selectively actuated, produces a fluid displacement of up to 100 picoliters and can operate at frequencies of 1 kHz to 100 kHz. Thus, in some embodiments, the second fluid actuator 34 may be operated in a single pulse mode, in which a single small amplitude single nucleating pulse is performed. A single small pulse of backflow is generated to help clear the blockage, but general fluid flow remains substantially unchanged. In some embodiments, the second fluid actuator 34 is operated in a multi-pulse mode, in which a series of spaced, single, small amplitude, single nucleation pulses are performed, and a series of small pulse backflows occurs. It is created to help clear the blockage, but general fluid flow remains substantially unchanged.

In some cases, microfluidic device 20 is referred to as a microfluidic chip or biological test chip.

Further details regarding the role and attributes of the second fluid actuator 34 in fluid flow control of the channel structure 30 are described below.

As shown in FIG. 2A, in some embodiments, the microfluidic channel structure 30 shown in FIG. 1 includes one or more flow sensors 40 that sense a flow velocity 42 and/or a fluid flow direction 44. The information is used to identify unexpected changes in fluid flow, eg, to detect substantial changes (eg, reductions) in the general fluid flow velocity within the microfluidic channel structure 30. Used, but not limited to. In some embodiments, a plurality of fluid flow sensors 40 are spaced from each other and distributed throughout the channel structure 30 to facilitate identification of the exact location of the occlusion.

In some embodiments, the second fluid actuator 34 includes a plurality of second fluid actuators, and which of the plurality of second fluid actuators 34 will result in backflow or a second fluid flow. A determination is made according to the position of each second fluid actuator 34 for the sensed flow at a position corresponding to each of the plurality of flow sensors 40.

2B schematically illustrates a fluid flow control feedback loop 51 according to one embodiment of the present disclosure, at least in connection with the operation of the microfluidic device 20 as described above with respect to FIGS. 1 and 2A and below with respect to FIGS. 10 is a flowchart 50 schematically showing. Fluid flow within the microfluidic channel structure 30 may be sensed, as indicated by block 52 in FIG. 2B. In some embodiments, the fluid flow sensed is generic fluid flow 54B. In some embodiments, the sensed fluid flow is a localized fluid flow 54A within a portion of the microfluidic channel structure 30.

The sensed fluid flow is capable of identifying the velocity 53A and direction 53B of the fluid flow and whether the sensed fluid flow is a general fluid flow 54A or a localized fluid flow 54B. is there.

After sensing the fluid flow in the microfluidic channel structure 30, at block 55 of FIG. 2B, the sensed fluid flow meets or exceeds a predetermined criteria (eg, minimum, maximum, or other parameter). Is determined. For example, to perform a test or operation involving biological particles within the microfluidic device 20, a minimum flow rate or a maximum flow rate may be involved, each of which may be associated with a respective test. Or make the operation easier. In embodiments in which there may be multiple different targeted local fluid flows within the microfluidic channel structure 30, the determination at block 55 is such that each of these multiple local fluid flows is measured by those fluid flows. It is possible to inquire as to whether or not the criteria for a given location are met or exceeded.

If the query at block 55 is answered yes, then path 56A is selected for further fluid flow detection and block 52 is entered. If the answer to the inquiry at block 55 is NO, then path 56B is selected and block 57 is entered to activate the removal pump (eg, the second fluid actuator 34 of FIG. 1) to activate the microfluidic channel structure 30. The expected blockage within is removed and fluid flow is restored to the general operating conditions of the microfluidic channel structure 30 according to the criteria above.

After such removal activity by the second fluid actuator 34, control in loop 51 returns to block 55 for further fluid flow sensing.

The use of the feedback loop 51 makes it possible to maintain consistent and robust operation of the microfluidic device 20.

In some embodiments, at least some of the information regarding the operation of the feedback loop 51 is communicated from the microfluidic device 20 to external components and devices for further processing and control operations regarding the microfluidic device 20.

After providing further information with respect to at least FIGS. 3-9 regarding the apparatus environment in which the microfluidic device 20 can function, more features regarding fluid flow control of the microfluidic channel structure 30 and the second fluid actuator 34 and Further details regarding attributes will be provided with respect to FIGS. 10-15.

FIG. 3 is a block diagram that schematically illustrates a module 60 that includes a microfluidic device 20 (FIGS. 1 and 2) according to one embodiment of the present disclosure. In some cases, the module is called a cassette or container. As shown in FIG. 3, the module 60 includes a housing 61 that at least partially houses and/or supports the microfluidic device 20.

In some embodiments, as shown in FIG. 3, a fluid reservoir 64 is defined within the housing 61 proximate to the microfluidic device 20 and is in fluid communication between the fluid reservoir 64 and the microfluidic device 20. Contact is possible. As shown in FIG. 3, the fluid sample 67 enters the fluid reservoir 64 (via the inlet 62) and mixes with one or more reagents 66 before entering the microfluidic device 20. In some embodiments, the microfluidic device 20 includes its own reservoir, which initially receives the fluid sample (mixed with the reagent 66) from the reservoir 64 before the microfluidic device 20 receives the fluid. Can flow into multiple channels of the.

When the fluid sample 67 is blood, in some embodiments, the one or more reagents 66 are anticoagulants such as ethylenediaminetetraacetic acid (EDTA) and/or buffers such as phosphate buffered saline (PBS). Including liquid. In some embodiments, a suitable blood sample has a volume of about 2 microliters and a reagent has a volume of about 8 microliters, resulting in a volume of 10 microliters processed by microfluidic device 20.

It is further understood that when the fluid sample 67 is whole blood, in some embodiments, the one or more reagents 66 include other or additional reagents for preparing blood for the diagnostic test of interest. Will be done. In some embodiments, such one or more reagents 66 help the sensor identify particular particles for tracking, counting, moving, etc., of the particular particles in a fluid sample. In some embodiments, such one or more reagents 66 bind specific particles in the liquid sample 67 to exclude or filter the specific particles from the fluid sample to provide a specific biological target of interest. It facilitates better separation or concentration of the particles. In some embodiments, manipulation with one or more reagents 66 works in concert with filters and/or other sorting and separation mechanisms to exclude certain biological particles from the sensing area of the microfluidic device 20. It will be done.

In some embodiments, the one or more reagents 66 are suitable for performing nano-particle tagging techniques, magnetic particle sorting techniques, and/or high density particle tagging techniques. Microparticle tagging and/or materials suitable for carrying antibody-antigen binding for materials.

In some embodiments, at least some reagents 66 include a lysing agent, such as (but not limited to) where it is desirable to separate red blood cells prior to performing a white blood cell count or analysis.

Of course, if the fluid sample 67 is a different biological fluid, such as urine, cerebrospinal fluid, rather than blood, one or more reagents 66 may be used to handle such fluids and the desired separation and classification of the components of such fluids. It will include the appropriate type and number of reagents 66 suitable to accomplish.

In some embodiments, various reaction processes such as, but not limited to, processes for performing molecular diagnostics and related operations as described above are provided, initiated, performed, and/or terminated. For this purpose, one or more reagents 66 are provided.

In some embodiments, a suitable blood sample (ie, fluid sample 67) has a volume of about 2 microliters, a reagent has a volume of about 8 microliters, and 10 microliters processed by microfluidic device 20. Bring the volume of. Therefore, in this configuration, a dilution factor of about 5 is applied to the whole blood fluid sample. In some embodiments, a dilution factor of 5 or greater or less than 5 is applied to whole blood. In some embodiments, such a low dilution factor ensures a high signal-to-noise ratio as the sensing volume of the (subject) fluid passes through the sensing region where the targeted biological particles are counted. Become. In addition, the lower dilution factor results in a smaller total volume of fluid to be processed by the microfluidic device, thus reducing the total test time for a particular fluid sample. In some embodiments, a dilution factor of 10 or less is used.

Depending on the embodiment, larger or smaller than 2 microliter volumes can be used whether the fluid sample 67 is blood or other types of biological fluids. Further, in some embodiments, greater or less than 8 microliter volumes of reagents can be used, whether the fluid sample 67 is blood or other types of biological fluids. In some embodiments, the fluid sample 67 is also diluted with other or additional fluids other than the reagent 66.

FIG. 4A is a block diagram that schematically illustrates a microfluidic device 80 according to one embodiment of the present disclosure. In some embodiments, microfluidic device 80 includes at least some of the same features and attributes as microfluidic device 20 of FIGS. 1-3. In some embodiments, at least some of the components of microfluidic device 80 of FIG. 4A are incorporated within microfluidic device 20 of FIGS. 1-3.

As shown in FIG. 4A, the microfluidic device 80 includes one or more actuators 82 and one or more fluid flow sensors 84, which act as pumps 85A and/or heaters 85B. In some embodiments, actuator 82 includes a resistive element such as a thermal resistance. When driven with high intensity and sufficient pulse width, an actuator 82 causes a nucleation vapor to move fluid within the channel structure 30 to deliver fluid along and through the channel structure 30. It is possible to cause foam formation. A moderate amount of heat can be generated as a by-product. In one embodiment, driving at such high intensities involves relatively short pulse widths and higher power.

However, when driven with significantly lower intensity and insufficient pulse width, actuator 82 cannot act as a pump because there is not enough energy to cause significant fluid displacement. Heat is generated rather than acting as a pump, and the actuator 82 acts as a heater 85B without moving fluid. In one embodiment, such low intensity driving involves relatively long pulse widths and lower power.

In one embodiment, the one or more actuators 82 correspond to the first fluid actuator 32 and the second fluid actuator 34 of FIG.

In some embodiments, microfluidic device 80 includes one or more fluid flow sensors 40 (FIG. 2A) that sense the flow velocity and direction of fluid within microfluidic channel structure 30. In some embodiments, the one or more fluid flow sensors 40 are dedicated sensors for sensing fluid flow and direction. In this sense, the one or more fluid flow sensors 40 are separate and independent of other sensors, such as an attribute sensor (eg, 83 in FIG. 4B). However, in some embodiments, the one or more fluid flow sensors 40 are at least partially implemented via the functionality of an attribute sensor (reference numeral 83 in FIG. 4B). In some embodiments, occluded or diminished fluid flow is at least partially identified by the value (or change in value) of the signal from the impedance sensor indicating the lack of cells flowing near or over the sensor. In some embodiments, the occluded or diminished fluid flow is at least partially identified by detecting the temperature of the silicon substrate rising above a threshold temperature. Upon such identification, the second fluid actuator 34 is operated as a redundant pump to create a reverse flow of fluid.

In some embodiments, the fluid flow sensor 40 (whether it is dedicated or part of an attribute sensor) includes multiple asymmetrically arranged electrodes to estimate flow direction via signal analysis. And/or the residence time of individual cells within the detection zone over a specified period of time is analyzed to determine the flow rate.

The control interface 106 described below can be connected to the electrical interface of the microfluidic device 20,80 to drive and control one or more actuators 82 and one or more fluid flow sensors 40. Is.

In some embodiments, the structure and components of the chip-based microfluidic device 20,80 may include integrated circuit microfabrication techniques (e.g., electroforming, laser ablation, anisotropic etching, sputtering, dry and wet etching, photolithography, Casting, molding, stamping, machining, spin coating, lamination, etc.).

FIG. 4B is a block diagram that schematically illustrates one or more attribute sensors 83 of a microfluidic device, according to one embodiment of the disclosure. In some embodiments, a microfluidic device, such as device 20,80 (FIGS. 1-4A), has one or more attribute sensors 83 for detecting pH, identification of particular biological particles, temperature, cell number, etc. Is further included. In some embodiments, the attribute sensor 83 includes an impedance sensor. In some embodiments, the attribute sensor 83 can function as the flow sensor 40. In some embodiments, the attribute sensor 83 is separate and independent of the dedicated flow sensor 40.

FIG. 5 is a block diagram that schematically illustrates an input/output element 89 of a microfluidic device, such as the microfluidic device 20, 80 of FIGS. 1-4A, according to one embodiment of the invention. The input/output element 89 enables communication of data, power, control signals and the like with an external device, which facilitates the operation of the microfluidic devices 20 and 80, which will be described later with reference to FIGS. Will be further explained.

FIG. 6 is a block diagram that schematically illustrates components 86, 87 of a microfluidic device, according to one embodiment of the present disclosure. In some embodiments, the microfluidic device, such as device 20,80 (FIGS. 1-4C), further includes an inlet/outlet chamber 86 and/or a filter 87. The inlet/outlet chambers allow fluids to enter and exit various portions of the channel structure 30, while the filter 87 separates different components of the fluid (e.g., larger particles as described further below). Not pass through the microfluidic channel structure 30).

FIG. 7 is a block diagram schematically illustrating a microfluidic inspection system 100 according to an embodiment of the present disclosure. As shown, the system 100 includes a cassette 60, a control interface 106 (having a housing 107), and a host device 108. In some embodiments, cassette 60 includes at least some of the same features and attributes as at least cassette 60 described above with respect to FIG. 3, and microfluidic device 20 includes microfluidic device 20 described above with respect to FIGS. , 80 and at least some of the same features and attributes.

As shown in FIG. 7, in addition to at least the microfluidic device 20, the cassette 60 includes power, data, and/or control signals, etc., between the microfluidic device 20 (within the cassette 60) and the control interface 106. And an input/output (I/O) control module 102 for communicating with the host device 108. The control interface 106 then communicates with the host device 108. In some embodiments, the I/O module 102 of the cassette 60 connects with the input/output element 89 of the microfluidic device 80 (FIG. 4A).

In some embodiments, as shown in FIG. 7, the cassette 60 can be removably coupled to the control interface 106, which allows the cassette 60 to be coupled as desired or It can be removed. The control interface 106 can be removably coupled to the host device 108, as described further below. In some cases, control interface 106 is referred to as, or is implemented as, a dongle or connector.

Generally speaking, a fluid sample 67 (FIG. 3) is processed via microfluidics to undergo various functional or reactive processes before being transferred to a detection region within the microfluidic device 20 under control of the control interface 106. Exposed. The microfluidic device 20 provides an electrical output signal representative of sensor data to the control interface 106. A control interface 106 under the control of the host device 108 allows the host device 108 to communicate data to and from the control interface 106 (for thermal management of the substrate 22 and/or from the microfluidic device 20). It is possible to send and receive (including command information for controlling the microfluidic device 20 to obtain sensor data).

FIG. 8 is a block diagram that schematically illustrates a host device 108 (FIG. 7) according to one embodiment of the present disclosure. As shown in FIG. 8, in some embodiments, the host device 108 generally includes a central processing unit (CPU) 110, various support circuits 112, memory 114, various input/output (I/O) circuits 116, and external interfaces. Including face 118. CPU 110 includes a microprocessor. In some embodiments, support circuitry 112 includes cache, power supplies, clock circuits, data registers, and the like. In some embodiments, memory 114 includes random access memory, read only memory, cache memory, magnetic read/write memory, etc., or any combination of such storage devices. In some embodiments, I/O circuitry 116 cooperates with external interface 118 to facilitate communication with control interface 106 via communication medium 119 (shown in FIG. 7). The communication medium 119 can include any type of wired and/or wireless communication protocol, and can include electrical, optical, radio frequency (RF), etc. transfer paths.

In some embodiments, the external interface 118 enables transmission and reception of data to and from the control interface 106 via a USB (Universal Serial Bus) cable. Includes USB controller. It will be appreciated that in some embodiments, other types of electrical, optical, or radio interfaces to the control interface 106 are used to send and receive data and/or power.

In some embodiments, an operating system (OS) 109 and a driver 111 are stored in the memory 114 of the host device 108, as shown in FIG. The OS 109 and driver 111 include instructions that can be executed by the CPU 110 to control the host device 108 and to control the control interface 106 via the external interface 118. The driver 111 provides an interface between the OS 109 and the control interface 106. In some embodiments, host device 108 includes a programmable device that includes machine-readable instructions stored on a non-transitory processor/computer-readable medium (eg, memory 114).

In some embodiments, as shown in FIG. 8, the host device 108 includes a display 120 that allows the OS 120 to provide a graphical user interface (GU1) 122. The user can interact with the OS 109 and the driver 111 using the user interface 122 to control the control interface 106 and display the data received from the control interface 106. It will be appreciated that the host device 108 can be any type of general purpose or special purpose computing device. In one embodiment, the host device 108 is a mobile computing device such as a "smartphone", "tablet".

FIG. 9 is a block diagram that schematically illustrates the control interface 106 according to an embodiment of the present disclosure. In one embodiment, control interface 106 includes controller 134, I/O circuitry 136, and memory 138. The controller 134 includes a microcontroller or microprocessor. In some embodiments, control interface 106 receives power from host device 108, and in some embodiments control interface 106 includes power supply 142.

In some embodiments, memory 138 stores instructions 140 that may be executed by controller 134 to at least partially control microfluidic device 20 and/or to communicate with host device 108. As such, the control interface 106 includes a programmable device including a machine readable 140 stored on a non-transitory processor/computer readable medium (eg, memory 138). In other embodiments, control interface 106 can be implemented using hardware or a combination of hardware and instructions 140 stored in memory 138. For example, in some embodiments, all or part of the control interface 106 is implemented using a PLD (Programmable Logic Device), an ASIC (Application Specific Integrated Circuit), or the like.

In some embodiments, the driver 111 in the memory 114 of the host device 108 and/or the memory 138 of the control interface 106 are machine-readable for implementing and/or operating fluid flow control management of the microfluidic channel structure 30. Store the instruction. In some embodiments, such fluid flow management is at least partially implemented via the fluid flow control manager 350, as described below with respect to at least FIG. 13A.

FIG. 10 is a plan view showing a microfluidic device 160 according to an embodiment of the present disclosure. In some embodiments, microfluidic structure 160 includes at least some of the same features and attributes as at least a microfluidic device (eg, 20,80) described above with respect to FIGS. It is suitable for implementing fluid flow control as described throughout the disclosure.

As shown in FIG. 10, the microfluidic device 160 includes a substrate 22 having a microfluidic channel structure 162 formed therein and an input/output unit 180. As previously mentioned, in some embodiments the substrate comprises a silicon material.

As shown in FIG. 10, the microfluidic channel structure 162 includes an array of microfluidic channel units 166 arranged in fluid communication with a centrally disposed reservoir 164. However, it will be appreciated that the unit 166 is not strictly limited to the particular size, shape, and location shown in FIG. 10, and can exhibit other sizes, shapes, and locations.

In some embodiments, the plurality of microfluidic channel units 166 are generally independent of each other, and the fluid flow velocity and direction of each channel unit 166 is managed independently of each other channel unit 166. It

FIG. 11 is a diagram schematically illustrating a microfluidic structure 200 of a portion of a microfluidic device 20 according to one embodiment of the disclosure, one exemplary each of the plurality of microfluidic channel units 166 of FIG. An embodiment is provided.

As shown in FIG. 11, in some embodiments the microfluidic structure 200 includes a microfluidic channel 202, a first fluid actuator 204, an attribute sensor 206, a nozzle 205 (eg, an outlet), and an inlet 208. FIG. 10 also shows fluid reservoir 214 in communication with fluid reservoir 64 of cassette 60 (FIG. 3). In some embodiments, the channel 202 corresponds to each of the plurality of channels 165 (of the microfluidic channel unit 166) of FIG.

In some embodiments, as further shown in FIG. 11, a mesh filter 212 for filtering particles in the applied fluid sample is disposed within the fluid reservoir 214. The shape of fluid channel 202 in FIG. 10 is shown as being “U-shaped”, but this is not intended as a general limitation on the shape of channel 202. As such, the shape of the channel 202 can include other shapes such as curved shapes, serpentine shapes, cornered shapes, and combinations thereof, some of which are later described in FIGS. 12A, 12B, 14 and It will be further described and illustrated with respect to FIG. Moreover, various portions of channel 202 can vary in width. Further, the channel 202 is not shown to a particular scale or ratio. The width of the channel 202 created on the device can vary from any scale or ratio shown in the drawings of this disclosure. The arrows in the channels indicate exemplary directions of fluid flow through the channels.

Inlet 208 provides an opening for channel 202 to receive fluid. The filter 210 is disposed within the inlet 208 to prevent particles of a particular size in the fluid (depending on the size of the filter 210) from entering the channel 202. In some embodiments, the inlet 208 can have a larger width and volume than the channel 202.

In some embodiments, the attribute sensor 206 is located within the channel 202 near the inlet 208 (eg, closer to the inlet 208 than the pump actuator 204), as shown in FIG. In some embodiments, the attribute sensor 206 is disposed within the entrance 208. In some embodiments, the attribute sensor 206 is an impedance sensor and detects impedance changes as biological particles in the fluid pass through the sensor 206.

As shown in FIG. 11, in some embodiments, the first fluid actuator 204 (eg, pump) is disposed downstream of the attribute sensor 206 and near the closed end of the channel 202. The first fluid actuator 204 can be a fluid inertial pump actuator that can be implemented using a wide variety of structures. In some embodiments, the first fluid actuator 204 is a thermal resistance that creates nucleating vapor bubbles that create movement of fluid within the channel 202. The displaced fluid is ejected from the nozzle 405, which allows an inertial flow pattern within and/or through the channel 202. In some embodiments, the first fluid actuator 204 is implemented as a piezoelectric element (eg, PZT) that produces movement of fluid within the channel 202 due to electrically induced deflection. Other deflection membrane elements driven by electricity, magnetism, and other forces can also be used to implement the first fluid actuator 204.

Generally speaking, the fluid actuator 204 is placed sufficiently close to the attribute sensor 206 to ensure a high fluid flow velocity near the attribute sensor 206. Although not shown, in some embodiments the first fluid actuator 204 is arranged to cause inertial pumping to push biological particles through the area of the sensor 206, but in some embodiments the first fluid actuator 204 is The actuators 204 are arranged to cause inertial pumping to attract biological particles through the area of the attribute sensor 206, as shown in FIG.

The first fluid actuator 204 is consistent with the previously described microfluidic device (20 in FIGS. 1-2A, 80 in FIG. 4A) when operated at longer pulse widths and intensities. Acts as a heater to heat the fluid in channel 202. As previously mentioned, in such a case, the first fluid actuator 204 is driven in a pulse mode with lower intensity and longer pulse width to provide pulses of heat to the fluid without forming nucleation bubbles. Works with.

In some embodiments, the channel 202 includes two or more first, such that two or more fluid actuators are located within a single channel 202 to control general fluid flow within the channel structure 200. Fluid actuator 204.

FIG. 12A is a schematic plan view of a microfluidic device 240 according to an embodiment of the present disclosure. In some embodiments, microfluidic device 240 includes at least some of the same features and attributes as the general components of microfluidic device 160 (at least as described above with respect to FIG. 10) and channel structure 200 of FIG. ..

As shown in FIG. 12A, in some embodiments, the microfluidic channel structure 240 includes a first branch 241A and a second branch 241B that connect to and communicate with an end 243 (via segment 242E). Includes one channel 242. The first branch 241A includes an inlet 248A and channel segments (ie, portions) 242A, 242C, and the second branch 241B includes an inlet 248B and segments 242B, 242D. The coupling portion 249 is formed at the intersection of the segments 242D, 242C, 242E.

In some embodiments, the first attribute sensor 246A is located within the segment 242D and the second attribute sensor 246B is located within the segment 242E.

The first actuator fluid actuator 244C (similar to the first fluid actuator 32 of FIG. 1) is located in the end 243, and the nozzle 245 (represented by a circle overlaid on the square representing the actuator 244C) is also at the end. It is arranged in the part 243. In operation, the drive of the first fluid actuator 244C draws fluid from the reservoir 214 through the branches 241A, 241B of the channel 242, passes through the attribute sensors 246A, 246B, and then through the nozzle 245. Exit 242.

In some embodiments, at least one fluid flow sensor (F) 250 (or 252) is located within channel 242. In this particular embodiment, fluid flow sensor (F) 250 is shown within channel segment 242D adjacent to attribute sensor 246A, downstream thereof and upstream of coupling 249. In some embodiments, a second fluid flow sensor 252 (or 250) is located within channel 242. In a particular embodiment shown in FIG. 12A, the second fluid flow sensor 252 is located in the channel segment 242C upstream of the coupling 249.

Each branch 241A, 241B includes a respective second fluid actuator 244A, 244B (similar to the second fluid actuator 34) disposed near the first end of the respective segment 242A, 242B.

In operation, the first fluid actuator 244C draws in fluid via the branches 241A, 241B to generate a main flow in the direction indicated by arrow A.

In some embodiments, the occlusion condition is identified by one or both of the flow sensors 250,252 located on the segments 242D,242C, respectively. Although an occlusion condition can potentially occur at any of several locations along the channel 242, in some embodiments the joint 249 presents a more prone site for occlusion, which is the channel This is due to the pair of 90 degree bends formed by the segments 242C, 242D and the momentum of the fluid flow from each of the individual segments 242C, 242D that meet each other.

However, in some cases where an occlusion is formed in channel 242, a first is needed to cause backflow in direction B (opposite direction A) for a temporary predetermined period of time sufficient to clear the occlusion. One or both of the two fluid actuators 244A, 244B are driven. In some embodiments, the main flow produced by the first fluid actuator 244C is maintained while driving the second fluid actuator 244A and/or 244B.

In one embodiment, the blockage near the coupling 249 is resolved by driving only one of the second fluid actuators 244A, 244B, where the one second fluid actuator is involved in the blockage. Fluids and components are drawn in one direction away from coupling 249, while at least a portion of the main flow along direction A is drawn towards end 243 due to the continued drive of first fluid actuator 244C. After the blockage is removed, the one second fluid actuator (one of 244A and 244B) is stopped.

By arranging the pair of second fluid actuators 244A, 244B respectively in different branches, it is possible to determine which of the second fluid actuators 244A, 244B will cause the blockage to be cleared more quickly and effectively. It is possible to select one of the second fluid actuators 244A and 244B.

FIG. 12B is a plan view schematically illustrating a microfluidic device 260 according to an embodiment of the present disclosure. In some embodiments, the microfluidic device 260 includes at least substantially the same features and attributes as the general components of the microfluidic device 160 described above with respect to FIG. 10 and the channel structure 200 of FIG.

As shown in FIG. 12B, in some embodiments, the microfluidic channel structure 260 includes a first channel 262 including a main branch 261A and a second branch 261B extending from the main branch 261A and back to the main branch 261A. including. The main branch 241A includes an inlet 268A and channel segments (ie, portions) 262A, 262B, 262C, 262D, 262H, 262I. The second branch 261B begins at the junction 275 via an inlet 268B extending from the main branch 261A, the second branch 261B further including segments 262E, 262F, 262G, and then again with the segment 262I of the main branch 261A. Join. The connecting portion 275 is located at the intersection of the segments 262D, 262E, 262H.

In some embodiments, the first attribute sensor 266 is located within the segment 262E and the filter 270A is located downstream of the first attribute sensor 266 at the inlet 268B.

In some embodiments, a fluid flow sensor 270 is located in the main branch 261A upstream of the inlet 268B of the second branch 261B to monitor flow parameters near the coupling 275.

The first actuator fluid actuator 264A (similar to the first fluid actuator 32 in FIG. 1) is located within the first segment 262A of the main branch 261A and is diverted by the induced fluid flow from the reservoir 214 to the channel 262. Creating a fluid flow in direction A by causing inertial pumping of the fluid through 261A, forcing the fluid in a first fluid flow direction A. A portion of the fluid flow in main branch 261A is diverted into second branch 261B.

In some embodiments, another first fluid actuator 264B in segment 262G of second branch 261B serves to induce fluid flow in second branch 261B. The narrower the width of the second branch 261B and the filter 270A, the smaller the particles that enter the second branch 261B and the more they pass through the attribute sensor 266 in the segment 262E of the second branch 261B. Large particles that are not sized to enter the second branch 261B will continue to exist in the main fluid flow within the channel segments 262G, 262H.

In some embodiments, at least one fluid flow sensor 270 is located within channel 262. In certain embodiments, fluid flow sensor 270 is shown in channel segment 262D upstream of coupling 275. Although not shown in FIG. 12B, in some embodiments, an additional fluid flow sensor may be channeled to sense overall fluid flow and/or identify local occlusions at locations other than junction 275. It will be appreciated that various locations within 262 can be provided.

In some embodiments, as shown in FIG. 12B, a second fluid actuator 264C (similar to second fluid actuator 34) is positioned upstream of coupling 275 and flow sensor 270 and proximate thereto. ..

In operation, mainstream flow generally occurs in the direction indicated by directional arrow A in the manner described above.

In some embodiments, the occlusion can be identified via the flow sensor 270. Occlusions can potentially occur at several locations along the channel 262, but in some embodiments the coupling 275 will present a site where occlusions are more likely to occur. This is because of the 90° turn that is made by the channel segments 262D, 262H when coupled to the segment 262E of the second branch 261B, so that the width (W2) of the channel segment of the second branch 261B is that of the main branch 261A. This is because it is narrower than the width (W1) and/or there is a filter 270A in the inlet 268B of the second branch 261B.

According to this non-limiting embodiment in which a blockage is formed in channel 262 near coupling 275, a second fluid actuator 264C (similar to second fluid actuator 34 in FIG. 1) is activated. , A reverse fluid flow is generated having a direction B (opposite direction A) for a temporary period sufficient to clear the occlusion. In some embodiments, the main flow generated by the first fluid actuators 264A, 264B is maintained while the second fluid actuator 264C is driving. After the blockage is cleared, the second fluid actuator 264C is stopped.

In some embodiments, there is another second fluid actuator 264D, which is driven substantially simultaneously with the second fluid actuator 264C. The second fluid actuator 264D is disposed downstream of the coupling portion 275 and the second fluid actuator 264C, and the second fluid actuator 264D is a temporary fluid generated by the second fluid actuator 264C when it is driven. It helps to maintain the mainstream of direction A during reverse flow (of direction B).

FIG. 13A is a block diagram illustrating a fluid flow manager 350 according to one embodiment of this disclosure. In some embodiments, the fluid flow control manager 350 operates in connection with at least some of the same features and attributes as the microfluidic device described above with respect to Figures 1-12B. Generally speaking, in some embodiments, the fluid flow control manager 350 senses the velocity and direction of the fluid flow and selectively reverses the fluid flow via a second or redundant fluid actuator, At least partially managing fluid flow within a microfluidic device channel structure. As shown in FIG. 14, the fluid flow control manager 350 includes a flow parameter module 360 and a fluid drive module 380.

As shown in FIG. 13A, the flow parameter module 360 includes a sensing function 362 having a flow velocity parameter 53A, a direction parameter 53B, a local parameter 54A, a general parameter 54B, and a reference parameter 370, a main function 364, and a removal function 366.

Via the flow sensor 40, the sensing function 362 operates to sense fluid flow within the microfluidic channel structure according to at least the flow velocity parameter 53A (FIGS. 2B and 13A) and the flow direction parameter 53B (FIGS. 2B and 13A). To do. Sensing function 362 can detect fluid flow locally (54A in FIGS. 2B and 13A) and/or generally (54B in FIGS. 2B and 13A). The reference parameter 370 can set a reference for a desired or acceptable flow velocity or flow direction with which sensed flow information will be compared (eg, in block 55 of the feedback loop 51 of FIG. 2B). To

The primary function 364 provides a basic or primary fluid flow pattern implemented within and throughout the microfluidic channel structure 30 implemented via a primary fluid actuator (eg, the primary fluid actuator 32 of FIG. 1). However, the removal function 366 is implemented in at least a portion of the channel structure 30 via an additional fluid actuator (second fluid actuator 34 of FIG. 1) to remove and/or prevent occlusion. Provide a fluid flow pattern (eg, in the opposite direction).

Main function 364 and removal function 366 operate in accordance with flow rate parameter 53A, directional parameter 53B, local parameter 54A, and general parameter 54B, at least as described above with respect to FIG. 2B.

As shown in FIG. 13A, the fluid drive module 380 includes a main function 390 and a removal function 392 having a flow rate parameter 394, a power parameter 396, a pulse width parameter 398, and a position parameter 399. A main function 390 drives the first fluid actuator 32 to produce a main fluid flow action, and a removal function 392 selectively reverses a portion of the fluid flow. The main function 390 and the removal function 392 are performed according to at least the flow velocity parameter 394, the power parameter 396, the pulse width parameter 398, and the position parameter 399 of the fluid actuators that each uses. The flow velocity parameter 394 controls the drive speed of the fluid actuator (32, 34 in FIG. 1, 82 in FIG. 4A), which may range from 1 Hz to 100 kHz, and the power parameter 396 is the power applied to the fluid actuator. Control the amplitude. If the microfluidic channel structure includes more than one fluid actuator (either the first fluid actuator or the second fluid actuator 34), the position parameter 399 is the position of each fluid actuator within the channel structure. It makes it possible to select which fluid actuator to drive based on.

In some embodiments, fluid flow control manager 350 resides in machine-readable instructions stored in memory associated with the controller (eg, memory 138 of control interface 106 and/or memory 114 of host device 108). To do. Through at least the connections and communication paths described above with respect to FIG. 3, the fluid flow control manager 350 maintains a consistent fluid flow within the operating microfluidic channel structure 30 (FIGS. 1-2A), 162 (FIG. 10). To at least partially control the fluid operation of the microfluidic device 20,80,160 to help.

In some embodiments, at least some of the functionality of the fluid flow control manager 350 includes memory (eg, machine readable instructions (as shown in FIG. 13B) on the microfluidic device 20 (eg, to implement such functionality). 352) resides on the microfluidic device 20 (FIGS. 1-12B, 14, 15), where the memory 352 is the memory 114 (FIG. 8) or the memory 138 (FIG. 9). And have at least some of the same features and attributes as. In such an embodiment, the functionality of the fluid flow control manager 350 on the microfluidic device 20 is the functionality of the fluid flow control manager 350 remaining on the control interface 106 (FIG. 9) and/or the host device 108 (FIG. 8). To complement or work with it. In some embodiments, all functionality of fluid flow control manager 350 is stored in memory 352 of microfluidic device 20. In some embodiments, if such memory 352 resides on the microfluidic device 20, the microfluidic device 20 may also include the controller 134 of the control interface 106 (FIG. 9) and/or the controller function of the host device 108 (FIG. 8). (Eg, CPU 110) includes a controller or circuit having a control function that includes at least some of the same functions.

FIG. 14 is a plan view showing a channel structure 400 of a microfluidic device according to an embodiment of the present disclosure. In some embodiments, the microfluidic device including the channel structure 400 has at least the same features and attributes as the microfluidic device 160 (at least described above with respect to FIG. 10) and the overall components of the channel structure 200 of FIG. Including some.

As shown in FIG. 14, in some embodiments, the microfluidic channel structure 400 includes a first channel 402 that includes a first portion 401A, a second portion 401B, and a third portion 401C. The first portion 401A includes inlets 408A, 408B and channel segments 402A, 402B. The second portion 401B includes a segment 402C and a multi-turn segment 402D that includes a series of 90 degree turns and then the end of the second portion 401B. Part segment 402E joins to third part 401C. The third portion 401C includes two oppositely extending segments 402M, 402P, which include attribute sensors 406A, 406B and end segments 402N, 402Q, respectively. Each end segment 402N, 402Q includes a first fluid actuator 404A, 404B and a fluid outlet nozzle 405A, 405B, respectively.

In operation, actuation of the first fluid actuators 404A, 404B induces a fluid flow from the reservoir 214 into the segments 402A, 402B of the first portion 401A and then the second portion 401B and the third portion 401C. After passing through the respective attribute sensors 406A and 406B, the nozzles 405A and 405B exit.

In some embodiments, at least one fluid flow sensor (F) is disposed within channel 402. In the particular embodiment shown in FIG. 14, at least one fluid flow sensor (F) is shown in the second portion 401B upstream of the attribute sensors 406A, 406B. Further, in some embodiments, as shown in FIG. 14, a plurality of flow sensors (F) are included within channel 402 and distributed along the length of portions 401A, 401B, 401C of channel 402. .. In one embodiment, at least some of the plurality of flow sensors (F) are located at or near a portion of the plurality of 90 degree turns along the channel segment 402D of the second portion 401B.

In some embodiments, a second fluid actuator 404D (similar to second fluid actuator 34 in FIG. 1) is disposed upstream of attribute sensors 406A, 406B between a pair of flow sensors (F).

In some embodiments, another second fluid actuator 404C is located at the joint 413 of the channel segments 402A, 402B, 402C all upstream of the plurality of flow sensors (F).

In operation, a main flow occurs in the direction indicated by directional arrow A and the first fluid actuators 404A, 404B induce fluid flow through channel 402 in the manner previously described.

In some embodiments, it is possible to identify the occlusion via at least some of the plurality of flow sensors (F) located within each segment 402D of the second portion 401B. In some embodiments, the occlusion can be identified via the flow sensor (F) near the coupling 413 for substantially the same reason as described above for coupling 249 in FIG. 12A. As previously mentioned, occlusions can be identified at other locations within channel 402.

If an occlusion is formed in channel 402, one or both of the second fluid actuators 404C, 404D are actuated for a temporary period sufficient to clear the occlusion (opposite direction A). ) An opposite fluid flow with direction B is produced. In some embodiments, the main flow produced by the first fluid actuators 404A, 404B is maintained while driving the second fluid actuators 404C, 404D. It will be appreciated that in some embodiments only one of the second fluid actuators 404C, 404D is included within the microfluidic channel structure 400.

After the blockage is removed, the particular second fluid actuator 404C and/or 404D is deactivated.

FIG. 15 is a plan view showing a channel structure 500 of a microfluidic device according to an embodiment of the present disclosure. In some embodiments, a microfluidic device that includes a channel structure 500 has at least substantially the same features and characteristics as the microfluidic device 160 (at least as described above with respect to FIG. 10) and the overall components of the channel structure 200 of FIG. Contains attributes.

As shown in FIG. 15, in some embodiments, the microfluidic channel structure 500 includes a first channel 502 that includes a first portion 501A, a second portion 501B, and a third portion 501C. The first portion 501A includes inlets 508A, 508B and channel segments 502A, 502B that are coupled together via a common segment 502C. The second portion 501B includes a multi-turning segment 502E that includes a series of 90 degree turns, which is then coupled to the third portion 501C. The third portion 501C includes two oppositely extending segments 502K, 502L, which are respectively attribute sensors 506B, 506A and channels 502M, 502N downstream of the sensors 506B, 506A. including.

In operation, actuation of the first fluid actuators 504A, 504B induces a fluid flow from the reservoir 214 to the segments 502A, 502B of the first portion 501A and then through the second portion 501B and the third portion 501C. Fluid passes through the respective attribute sensors 506A, 506B.

In some embodiments, at least one fluid flow sensor (F) is disposed within channel 502. In the particular example shown in FIG. 15, a fluid flow sensor (F) 513A is shown in the third portion 501C downstream of the attribute sensor 506A. It will be appreciated that in some embodiments, a similar fluid flow sensor (F) can be located downstream of the attribute sensor 506B.

In some embodiments, the channel 502 can include an additional fluid flow sensor located at least some of the locations in the embodiments described above with respect to at least FIGS. 1-14. ..

In operation, main flow occurs in the direction indicated by the directional arrow A and the first fluid actuators 504A, 504B induce fluid flow through the channel 502 in the manner previously described.

In some embodiments, the occlusion can be identified by at least a portion of the flow sensor (F) located in the respective segment 502L within the third portion 501C of the channel 502. As mentioned above, other occlusions can potentially be identified elsewhere in the channel 502 by means of appropriately located fluid flow sensors (F).

If an occlusion is formed in the channel 502 (eg, near the attribute sensor 506A), the reverse with direction B (opposite direction A) for a temporary period sufficient to clear the occlusion. Second fluid actuator 504C is driven to generate a fluid flow of In some embodiments, the main flow caused by the first fluid actuators 504A, 504B is maintained while driving the second fluid actuator 504C. After removing the blockage, the second fluid actuator(s) 504C is stopped.

At least some embodiments of the present disclosure provide fluid flow control of a microfluidic channel structure that includes one or more additional or redundant fluid actuators to remove and/or prevent the formation of occlusions. To do.

While particular embodiments have been illustrated and described herein, various alternative and/or equivalent embodiments may be substituted for the particular embodiments illustrated and described without departing from the scope of the present disclosure. It is possible. This application is intended to cover any adaptations or variations of the specific embodiments discussed herein.

Below, the exemplary embodiment which consists of a combination of various structural requirements of this invention is shown.
1. Board,
A microfluidic channel structure formed on the substrate, the microfluidic channel structure including a reservoir and a first channel extending from the reservoir.
First and second fluid actuators disposed in the first channel, the first fluid actuator being in a first position and from the reservoir into the first channel. Selectively producing a general fluid flow in the direction of, the second fluid actuator being in a second position and substantially altering the general fluid flow in the first direction. A first and a second fluid actuator selectively producing a reverse fluid flow having a second opposite direction.
2. 2. The biological test chip according to item 1, further comprising an attribute sensor disposed in the first channel, and the second position is upstream of the attribute sensor.
3. The biological test chip according to item 1, further comprising an attribute sensor disposed in the first channel, and the second position is downstream of the attribute sensor.
4. An attribute sensor disposed in the first channel,
At least one fluid flow sensor disposed within the first channel to detect a substantial decrease in the flow velocity of the fluid flow in the first direction, the at least one fluid flow sensor A distance from the at least one attribute sensor and independent of the at least one attribute sensor,
The biological test chip according to item 1 above.
5. The biological test chip of claim 4, wherein the at least one fluid flow sensor comprises a plurality of flow sensors distributed between the first location and the second location.
6. The second fluid actuator includes a plurality of second fluid actuators, and a determination of which of the plurality of second fluid actuators produces the second fluid flow is determined by the plurality of flow sensors. The biological test chip according to the preceding paragraph 5, which is performed according to the respective positions of the second fluid actuator with respect to the fluid flow detected at the respective corresponding positions.
7. The second fluid actuator remains in a passive state until an unexpected substantial decrease in the flow velocity of the fluid flow in the first direction occurs, and when the substantial decrease occurs, the second fluid actuator The biological test chip of claim 1, wherein the fluid actuator produces a reverse fluid flow with a selective duration and intensity sufficient to ameliorate the substantial reduction.
8. Board,
A microfluidic channel structure on the substrate,
A first fluid actuator for producing a first fluid flow in a first direction in the microfluidic channel structure;
A second fluid actuator for producing a second fluid flow in the microfluidic channel structure in an opposite second direction;
At least one fluid for detecting whether a substantial change in at least one of a flow velocity and a direction of the first fluid flow in the microfluidic channel structure occurs during the operation of the first fluid actuator. Equipped with a flow sensor,
Biology, wherein the second fluid actuator remains inactive until the substantial change is determined and returns to inactivity when the target flow velocity and direction of the first fluid flow is restored. Microfluidic device.
9. The at least one fluid flow sensor comprises a plurality of fluid flow sensors distributed in spaced relation to one another throughout the microfluidic channel structure, and the second fluid actuator comprises a plurality of second fluid actuators; A determination of which of the plurality of second fluid actuators produces the second fluid flow is determined by a respective second fluid flow sensor sensed at a respective corresponding location of the plurality of fluid flow sensors. 9. The biological microfluidic device according to item 8, which is performed according to the position of the fluid actuator.
10. The first fluid actuator is capable of being driven at a first level to produce a flow velocity and direction sufficient to establish the general fluid flow, and the second fluid actuator is 9. The biological microfluidic device of clause 8, capable of being driven at a second level that is substantially less than the first level to produce two fluid flows. ..
11. The preceding paragraph, which includes an input/output module that communicates feedback loop information regarding the sensed fluid flow to allow an external controller to initiate a command signal to selectively cause a second fluid flow. The biological microfluidic device according to.
12. In the above paragraph 8, the microfluidic channel structure includes a series of microfluidic channel units that are independent of each other, and the flow velocity and direction of the fluid flow for each channel unit are managed independently of each other channel unit. The described biological microfluidic device.
13. Board,
A microfluidic channel structure formed on the substrate, the microfluidic channel structure including a reservoir and a first channel extending from the reservoir.
At least two fluid actuators disposed within said first channel,
A first fluid actuator in a first position that produces a general fluid flow in a first direction from the reservoir into the first channel;
At least two second fluid actuators in a second position that automatically cause, at regular intervals, a reverse fluid flow local to the opposite second direction to prevent occlusion. A biological test chip comprising a fluid actuator.
14. The first fluid actuator can be driven at a first level to generate a flow velocity and direction sufficient to establish the general fluid flow, and the second fluid actuator can 14. The biological test chip of paragraph 13, which is capable of being driven at a second level that is substantially lower than the first level to produce a localized reverse fluid flow.
15. At least one fluid flow sensor for detecting at least one of a substantial change in a flow velocity and/or a direction of the general fluid flow in the microfluidic channel structure;
When the second fluid actuator senses a substantial change in the flow velocity and direction of the general fluid flow, the second fluid actuator has a higher power and a higher power sufficient to restore the flow velocity and direction of the general fluid flow. Driven selectively by pulse width,
The biological test chip according to item 13 above.

Claims (15)

Board,
A microfluidic channel structure on the substrate,
A first fluid actuator for producing a first fluid flow in a first direction in the microfluidic channel structure;
A second fluid actuator that produces a second fluid flow in an opposite second direction within the microfluidic channel structure;
At least one fluid for detecting whether a substantial change in at least one of a flow velocity and a direction of the first fluid flow in the microfluidic channel structure occurs during the operation of the first fluid actuator. Equipped with a flow sensor,
The second fluid actuator remains inactive until the substantial change is determined, is activated when the substantial change is determined, and is a target of the first fluid flow. Return to inactivity when flow and direction recover,
Biological microfluidic device. 2. The biological microfluidic device of claim 1, wherein the primary operation of the biological microfluidic device is dependent on the first fluid actuator and not the second fluid actuator. The biological microfluidic device of claim 1 or claim 2, wherein the at least one fluid flow sensor comprises at least one of a dedicated sensor and a portion of an attribute sensor. The at least one fluid flow sensor comprises a plurality of fluid flow sensors distributed in spaced relation to one another throughout the microfluidic channel structure, and the second fluid actuator comprises a plurality of second fluid actuators; A determination of which of the plurality of second fluid actuators produces the second fluid flow is determined by a respective second fluid flow sensor sensed at a respective corresponding location of the plurality of fluid flow sensors. The biological microfluidic device according to any one of claims 1 to 3, which is performed according to the position of the fluid actuator. The first fluid actuator can be driven at a first level to produce a flow velocity and direction sufficient to establish a general fluid flow, and the second fluid actuator can be driven by the second fluid actuator. Biological according to any one of claims 1 to 4, wherein it is possible to drive at a second level which is substantially smaller than said first level to produce two fluid flows. Microfluidic device. 6. The biological microfluidic device of claim 5, wherein the second fluid flow is generated on a scale that does not substantially alter the general fluid flow. The second fluid actuator is disposed at a predetermined location within the microfluidic channel structure, the predetermined location of the first fluid actuator being a distance sufficient to provide a localized second fluid flow. 7. The biological microfluidic device of any of claims 1-6, spaced from the location. An input/output module for communicating feedback loop information regarding the sensed fluid flow to enable an external controller to initiate a command signal to selectively cause the second fluid flow. The biological microfluidic device according to any one of claims 1 to 7. The microfluidic channel structure includes a series of microfluidic channel units that are independent of each other, and the flow velocity and the direction of the fluid flow for each microfluidic channel unit are managed independently of each other microfluidic channel unit. 9. The biological microfluidic device according to any one of claims 1 to 8. Board,
A microfluidic channel structure formed on the substrate, the microfluidic channel structure comprising a reservoir and a first channel extending from the reservoir.
At least two fluid actuators disposed in said first channel,
A first fluid actuator in a first position, producing a general fluid flow in a first direction from the reservoir into the first channel;
At least two second fluid actuators in a second position that automatically cause temporary reverse fluid flow in regular second intervals in opposite second directions to prevent occlusion. A biological test chip comprising a fluid actuator. 11. The biological test chip of claim 10, wherein the primary operation of the biological test chip is dependent on the first fluid actuator and not the second fluid actuator. The first fluid actuator is capable of being driven at a first level to produce a flow velocity and direction sufficient to establish the general fluid flow, and the second fluid actuator is The biological test chip according to claim 10 or 11, which can be driven at a second level that is substantially lower than the first level to generate a temporary reverse fluid flow. .. 13. The biological test chip of any one of claims 10-12, wherein the temporary reverse fluid flow is generated on a scale that does not substantially alter the general fluid flow. The second fluid actuator is positioned at a predetermined location within the first channel, the predetermined location being at a distance sufficient to provide a localized and temporary reverse fluid flow. The biological test chip according to any one of claims 10 to 13, which is separated from the position of the actuator. At least one fluid flow sensor for detecting whether a substantial change in at least one of a flow velocity and a direction of the general fluid flow in the microfluidic channel structure is provided,
Upon detecting a substantial change in at least one of the general fluid flow velocity and direction, the second fluid actuator is sufficient to restore the general fluid flow velocity and direction. Driven selectively with high power and pulse width,
The biological test chip according to any one of claims 10 to 14.

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