MICROFLUIDIC DEVICE
20210187504 · 2021-06-24
Inventors
Cpc classification
B01L2400/08
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/0867
PERFORMING OPERATIONS; TRANSPORTING
B01L2400/086
PERFORMING OPERATIONS; TRANSPORTING
B01L2200/14
PERFORMING OPERATIONS; TRANSPORTING
B01L2200/16
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502715
PERFORMING OPERATIONS; TRANSPORTING
B01L2200/0621
PERFORMING OPERATIONS; TRANSPORTING
International classification
Abstract
A microfluidic device (100) comprises: a reaction chamber (102); at least a first and a second supply channel (110a, 110b) for allowing transport of a first fluid and a second fluid, respectively, from a fluid supply source (112a, 112b) into the reaction chamber (102), wherein each of the first and the second supply channels (110a, 110b) comprises a side drain (114a, 114b) connected to the supply channel (110a, 110b) between the fluid supply source (112a, 112b) and the reaction chamber (102), wherein the side drain (114a, 114b) is configured to prevent undesired diffusion of the fluid in the supply channel (110a, 110b) into the reaction chamber (102); at least a first and a second outlet (120a, 120b) connected to the reaction chamber (102) for allowing transport of fluid from the reaction chamber (102), wherein the first and second outlets (120a, 120b) have different dimensions to provide different hydraulic resistance.
Claims
1. A microfluidic device comprising: a reaction chamber; at least a first supply channel and a second supply channel connected to the reaction chamber for allowing transport of a first fluid and a second fluid, respectively, from a fluid supply source into the reaction chamber, wherein each of the first supply channel and the second supply channel comprises a side drain connected to the supply channel between the fluid supply source and the reaction chamber, wherein the side drain is configured to provide a flow away from the supply channel so as to prevent undesired diffusion of the fluid in the supply channel into the reaction chamber; at least a first outlet and a second outlet connected to the reaction chamber for allowing transport of fluid from the reaction chamber when changing the fluid that is to fill the reaction chamber, wherein the first outlet and second outlet have different dimensions so as to provide different hydraulic resistance.
2. The microfluidic device according to claim 1, wherein the microfluidic device comprises a plurality of supply channels, each of the supply channels comprising a side drain, wherein the first and second outlets are separate from side drains of the supply channels.
3. The microfluidic device according to claim 1, wherein the second outlet is arranged farther away from the first supply channel and the second supply channel than the first outlet, wherein the second outlet has a lower hydraulic resistance than the first outlet.
4. The microfluidic device according to claim 1, wherein the device comprises at least three outlets distributed along a side surface of the chamber.
5. The microfluidic device according to claim 3, wherein the at least three outlets are distributed along at least a portion of a perimeter of the reaction chamber, wherein an equal distance is provided between adjacent outlets.
6. The microfluidic device according to claim 1, wherein the reaction chamber defines an area in a plane and the reaction chamber has a small thickness in a direction transverse to the plane, wherein the supply channels and outlets are connected to the reaction chamber in the plane.
7. The microfluidic device according to claim 1, wherein the dimensions of the first outlet and the second outlet are set in dependence of mass diffusion coefficient of the first fluid and the second fluid.
8. The device according to claim 1, wherein the first outlet and the second outlet have different dimensions in at least one of a cross section or length for providing different hydraulic resistance.
9. The microfluidic device according to claim 1, wherein the first outlet and the second outlet are connected to a common main outlet for removing fluid from the device.
10. The microfluidic device according to claim 9, wherein the first outlet and the second outlet are associated with a common outlet for transporting the fluid exiting the reaction chamber through the first and second outlets to the common main outlet.
11. The microfluidic device according to claim 10, wherein each of the first outlet and the second outlet extends along a straight line between the reaction chamber and the common outlet.
12. The microfluidic device according to claim 1, wherein the first supply channel and the second supply channel are connected to the reaction chamber in locations close to each other.
13. The microfluidic device according to claim 1, further comprising a control unit for controlling a flowrate of the first supply channel and the second supply channel.
14. The microfluidic device according to claim 1, wherein dimensions of cross sections of the side drains are set for controlling a flowrate through the side drains.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0054] The above, as well as additional objects, features and advantages of the present inventive concept, will be better understood through the following illustrative and non-limiting detailed description, with reference to the appended drawings. In the drawings like reference numerals will be used for like elements unless stated otherwise.
[0055]
[0056]
[0057]
DETAILED DESCRIPTION
[0058]
[0059] The microfluidic device 100 may comprise a plurality of reaction chambers 102, which may be connected in an array and different fluids are provided through different channels of the microfluidic device 100.
[0060] The microfluidic device 100 may be formed on a substrate, e.g. a chip, which may include electronic circuitry, for example for controlling flow of fluids in the microfluidic device 100 and for providing sensors for performing measurements or acquiring information relating to reactions occurring in the microfluidic device 100. The flow of fluids in the microfluidic device 100 may be controlled by on-chip valves, but may also or alternatively be controlled by external valves and/or pumps.
[0061] The reaction chamber 102 may have any shape and is shown in
[0062] The reaction chamber 102 may be arranged on the substrate and may be arranged in a plane defined by the substrate such that the shape of the reaction chamber 102 is defined in the plane.
[0063] The reaction chamber 102 may comprise side surfaces 104 that define a perimeter of the reaction chamber 102. The side surfaces 104 together with a top and bottom surface, which may be shared by several structures on the substrate, may define a volume of the reaction chamber 102 in which volume fluids may be received.
[0064] The reaction chamber 102 may be supplied with fluids from a plurality of supply channels 110a, 110b. As shown in
[0065] The supply channels 110a, 110b may be connected to the reaction chamber 102 in the plane defined by the substrate for allowing transport of a respective fluid from a fluid supply source 112a, 112b into the reaction chamber 102. The fluid supply source 112a, 112b may be an inlet into the supply channel 110a, 110b, through which the fluid may be entered into the supply channel 110a, 110b. Fluid supply may be connected to the inlet for providing fluid into the supply channel 110a, 110b. The fluid supply may be configured to always provide supply of the same fluid. However, the fluid supply may be altered such that different fluids may be provided by the fluid supply channels 110a, 110b at different times, e.g. for different set-ups of reactions to be performed in the reaction chamber 102.
[0066] Each supply channel 110a, 110b may further be provided with a side drain 114a, 114b. The side drain 114a, 114b is connected to the supply channel 110a, 110b between the fluid supply source 112a, 112b and the reaction chamber 102.
[0067] The side drain 114a, 114b may be configured to provide a flow away from the supply channel 110a, 110b. This implies that, when the reaction chamber 102 is filled by a first fluid from the first supply channel 110a, the first fluid may exit the reaction chamber 102 through the side drain 110b of the second supply channel 110b. This implies that the first fluid will flow from the reaction chamber 102 to the side drain 110b of the second supply channel 110b and, hence, prevent diffusion of a second fluid from the fluid supply source 112b of the second supply channel 110b into the reaction chamber 102.
[0068] Hence, the side drains 114a, 114b may ensure a high purity of a fluid in the reaction chamber 102. The high purity may further be achieved without a need for valves to stop flow of the second fluid when the reaction chamber 102 is filled by the first fluid.
[0069] The supply of fluids into the reaction chamber 102 may be used e.g. for sequentially filling the reaction chamber 102 with different fluids. Thus, a sequence of reagents may for instance be loaded and washed from the reaction chamber, which may be used in various applications, such as for DNA synthesis.
[0070] The microfluidic device 100 may further comprise a plurality of outlets 120a, 120b, 120c. The outlets 120a, 120b, 120c are connected to the reaction chamber 102 in the plane defined by the substrate for allowing transport of fluid from the reaction chamber 102. Thus, when a first fluid is to be replaced by a second fluid in the reaction chamber 102, the first fluid may exit the reaction chamber 102 through the outlets 120a, 120b, 120c.
[0071] The reaction chamber 102 may be associated with at least two outlets. However, in many embodiments, a large number of outlets 120a, 120b, 120c may be desired in order to facilitate fast replacement of the first fluid by the second fluid, as will be described later.
[0072] The outlets 120a, 120b, 120c may be distributed along the perimeter of the reaction chamber 102 as defined by the side surfaces 104. Thus, the outlets 120a, 120b, 120c may be distanced from each other in order to facilitate removal of a fluid from the entire volume of the reaction chamber 102.
[0073] The outlets 120a, 120b, 120c may each provide an outlet channel 122a, 122b, 122c which may connect the reaction chamber 102 to a main outlet 124a, 124b, 124c. Fluid may exit the outlet channel 122a, 122b, 122c through the main outlet 124a, 124b, 124c and may be further transported, e.g. to waste or to further analysis of the fluid.
[0074] The outlets 120a, 120b, 120c may be associated with a common main outlet such that the outlet channels 122a, 122b, 122c may end in an interconnected channel, which may further lead to the main outlet. The side drains 114a, 114b may also be associated with the common main outlet.
[0075] The outlets 120a, 120b, 120c may be arranged at different distances from the respective supply channels 110a, 110b. This implies that, for example, a travel distance from a first supply channel 110a to a first outlet 120a is different from a travel distance from the first supply channel 110a to a second outlet 120b and further different from a travel distance from the first supply channel 110a to a third outlet 120c.
[0076] The difference in travel distances may affect how a fluid front propagates through the reaction chamber 102 when the first fluid is to be replaced by the second fluid. Thus, if the fluid front reaches a first outlet 120a first, fluid may be transported between the second supply channel 110b and the first outlet 120a and further exit the reaction chamber 102, without the fluid front of the second fluid propagating to the second and third outlets 120b, 120c, or the fluid front slowly propagating towards the second and third outlets 120b, 120c.
[0077] The outlets 120a, 120b, 120c may therefore be provided with different hydraulic resistances. This implies that a resistance experienced by the second fluid which is to replace the first fluid in the reaction chamber 102 may be different in different directions from the second supply channel 110b. Hence, the fluid front of the second fluid may propagate with different speeds in different directions. This may be utilized such that the reaction chamber 102 may be very quickly filled in the entire volume by the second fluid when fluid replacement is performed. The fluid front may reach the outlets 120a, 120b, 120c simultaneously or approximately simultaneously such that filling of the entire volume of the reaction chamber 102 by the second fluid is facilitated. Hence, the hydraulic resistance of an outlet that is associated with a large travel distance from a supply channel may be set to be low while the hydraulic resistance of an outlet that is associated with a short travel distance from a supply channel may be set to be high. Thus, if the second outlet 120b is arranged farther away from the first supply channel 110a and the second supply channel 110b than the first outlet 120a, the second outlet 120b may be provided with a lower hydraulic resistance than the first outlet 120a.
[0078] The outlets 120a, 120b, 120c may be distributed along at least a portion of the perimeter of the reaction chamber 102. This may imply that, with a difference in hydraulic resistances between the outlets 120a, 120b, 120c, the fluid front of the second fluid may reach the side surfaces 104 of the reaction chamber 102 simultaneously such that the second fluid very quickly fills the reaction chamber 102.
[0079] It should be realized that a shape of the reaction chamber 102, locations in which the supply channels 110a, 110b are connected to the reaction chamber 102 and locations in which the outlets 120a, 120b, 120c may be altered in many different ways while enabling a fast replacement of fluids in the reaction chamber 102. The hydraulic resistances of the outlets 120a, 120b, 120c may be adapted to the shape of the reaction chamber 102 and the travel distances between the supply channels 110a, 110b and the outlets 120a, 120b, 120c in the reaction chamber.
[0080] It should also be realized that the hydraulic resistances need not necessarily be designed such that an optimum speed of replacement of fluids is provided. However, by having different hydraulic resistances of the outlets 120a, 120b, 120c, the speed of replacement of fluids may be improved to a sufficient or acceptable extent. Hence, the hydraulic resistances of the outlets 120a, 120b, 120c need not be set such that the fluid front of the second fluid entering the reaction chamber needs to exactly simultaneously reach the outlets 120a, 120b, 120c. Rather, the fluid front may reach the outlets at quite different times while still ensuring that the speed of replacement of fluids is acceptable.
[0081] The hydraulic resistance of an outlet 120a, 120b, 120c may depend on dimensions of the outlet 120a, 120b, 120c. Thus, by having different dimensions of the first outlet 120a, the second outlet 120b and the third outlet 120c, the hydraulic resistance of the outlets 120a, 120b, 120c may differ.
[0082] The outlets 120a, 120b, 120c may for instance have a circular cross section. Thus, dimensions of the cross section may differ in that a diameter of the cross section of the outlets 120a, 120b, 120c differ and the hydraulic resistances may correspondingly differ. According to an alternative, the outlets 120a, 120b, 120c may have rectangular (e.g. square) cross sections. Thus, dimensions of the cross section may differ in that a width or height of the cross section of the outlets 120a, 120b, 120c differ and the hydraulic resistances may correspondingly differ.
[0083] The length of the outlet channel 122a, 122b, 122c may alternatively or additionally differ between the outlets 120a, 120b, 120c such that the hydraulic resistances may correspondingly differ.
[0084] The first supply channel 110a and the second supply channel 110b may be connected to the reaction chamber 102 in locations close to each other.
[0085] This implies that the fluids from the supply channels 110a, 110b may enter the reaction chamber in locations close to each other, such that a travel distance between outlets 120a, 120b, 120c and the supply channels 110a, 110b is similar for all the supply channels 110a, 110b. Hence, the differences in travel distances through the reaction chamber 102 associated with the outlets 120a, 120b, 120c may be similar for all supply channels 110a, 110b such that the hydraulic resistance of the outlets 120a, 120b, 120c may be suitable for replacement of fluids in the reaction chamber 102 regardless through which supply channel 110a, 110b the fluid to be entered into the reaction chamber 102 is supplied.
[0086] According to an embodiment, a separation between the locations in which the first supply channel 110a and the second supply channel 110b are connected to the reaction chamber 102 is less than 25 μm, preferably less than 10 μm. Such small separation distances may easily be achieved using semiconductor fabrication technology for manufacturing of the microfluidic device 100.
[0087] Referring now to
[0088] In the embodiment shown in
[0089] The outlets 120a-120m may be associated with a common outlet busbar 126, which is used for transporting fluid from the outlet channels to a common main outlet 124. The outlet busbar 126 may thus transport the fluid, regardless of where the fluid exits the reaction chamber 102 to the common main outlet 124, such that a single main outlet 124 need to be provided for the reaction chamber 102. Thus, the microfluidic device 100 need not have a complex structure including many long outlet channels, even though the reaction chamber 102 has many outlets 120a-120m. It should be realized that the outlets 120a-120m need not necessarily be connected to a single main outlet but may rather be connected to a plurality of main outlets, wherein the number of main outlets is smaller than the number of outlets 120a-120m from the reaction chamber 102, such as two main outlets.
[0090]
[0091] The hydraulic resistances of the outlets 120a-120m are set in order to promote that the fluid front of the second fluid entering the reaction chamber 102 propagates quickly towards all outlets 120a-120m.
[0092]
[0093]
[0094]
[0095]
[0096] Referring again to
[0097] The control unit 130 may thus control the flowrates which may control that a desired fluid is maintained in the reaction chamber 102 and which may control replacement of fluids within the reaction chamber 102.
[0098] The control unit 130 may provide control signals to pumps and/or valves associated with the first supply channel 110a and the second supply channel 110b for controlling the flowrates.
[0099] The control unit 130 may be provided on a common substrate with the microfluidic device 100 such that a self-contained microfluidic device 100 may be provided on the substrate. According to an alternative, the control unit 130 may be provided externally to the substrate.
[0100] The control unit 130 may receive input, such as manual input, for triggering replacement of fluids. Alternatively, the control unit 130 may comprise instructions for providing a timed sequence of fluids within the reaction chamber 102 and the control unit 130 may automatically process these instructions for controlling the fluids within the reaction chamber 102.
[0101] The control unit 130 may be implemented as a processing unit, such as a central processing unit (CPU), which may execute the instructions of one or more computer programs in order to implement functionality of the control unit 130.
[0102] The control unit 130 may alternatively be implemented as firmware arranged e.g. in an embedded system, or as a specifically designed processing unit, such as an Application-Specific Integrated Circuit (ASIC) or a Field-Programmable Gate Array (FPGA), which may be configured to implement functionality of the control unit 130.
[0103] The control unit 130 may also comprise a memory or have access to a memory for storing instructions.
[0104] Referring now to
[0105]
[0106] The design of a reaction chamber 102 may be initiated by setting a desired rinsing time and size and shape of the reaction chamber 102 and connections to the supply channels 110a, 110b as design inputs.
[0107] The rinsing time T.sub.R is a total time required to replace the fluid in the reaction chamber 102 with another fluid and can be divided into travel time T.sub.t which is the time at which the fluid front arrives at sides of the reaction chamber 102 and diffusion time T.sub.D which is the time required for the first fluid to flow out of the reaction chamber 102 through the outlets 120a-120l by diffusion
T.sub.R=T.sub.t+T.sub.D (equation 1)
[0108] Based on the design inputs, a number of the outlets 120a-120l may be determined by dividing the perimeter of the reaction chamber 102 over an interval length between two adjacent outlets L.sub.s. The interval length can be calculated using the following equations
where L.sub.D is a diffusion length as illustrated in
[0109] Having determined a number of outlets 120a-120l to be used, the flowrates in the channels of the microfluidic device 100 and the dimensions of channels may be determined through a plurality of equations, which define an equation system for solving the flowrates and setting the dimensions.
[0110] The flowrate in the side drains 114a, 114b can be determined using the following equation
where Q.sub.s is the flowrate in the side drain 114a, 114b, D is the mass diffusion coefficient of the first fluid into the second fluid, A.sub.s is a cross-sectional area of the side drain and
is a gradient of the concentration of the undesired fluid in the supply channel 110a, 110b which can be calculated either analytically or using numerical simulation. It should be noted that the concentration of the undesired fluid should go to zero at the connection between the supply channel 110a, 110b into the reaction chamber 102 for a supply channel 110a, 110b that transports an undesired fluid.
[0111] The flowrate in the outlets 120a-120l can be estimated from the equation
where Q.sub.i is a flowrate, A.sub.i is a cross-sectional area and L.sub.ti (as illustrated in
[0112] The supply channel flowrate (Q.sub.inlet) is equal to the sum of the side drain flowrate and the outlet flowrates
Q.sub.inlet=m*Q.sub.s+Σ.sub.i=1.sup.nQ.sub.i (equation 6)
where m is a number of supply channels 110a, 110b and n is the number of outlets 120a-120l.
[0113] Further, the hydraulic resistance (R.sub.h) of each component of the microfluidic device can be described by setting the equivalent resistance network illustrated in
where R.sub.h is the hydraulic resistance of a rectangular shaped channel of height h, width w and length l.
[0114] Having set a desired rinsing time as a design input and using the above equations 2-7, suitable dimensions of the outlets 120a-120l, the side drains 114a, 114b and the flowrate to be applied to the supply channels 110a, 110b may be determined.
[0115] However, it should be realized that even though appropriate characteristics of the microfluidic device 100 may be analytically determined, it may not be necessary to determine the design of the microfluidic device 100 in this manner. Rather, a simple approach may be used, wherein outlets 120 are distributed along a perimeter of the reaction chamber 102 and provided with hydraulic resistances inversely dependent on a distance from the supply channels 110a, 110b. In such manner, a microfluidic device 100 having adequate characteristics for replacement of fluids in the reaction chamber 102 may be achieved.
[0116] Further, it should be noted that, in the above equations, the mass diffusion coefficient of the first fluid into the second fluid is included. Hence, the microfluidic device 100 may be designed to be adapted for use with particular fluids. However, the mass diffusion coefficient may be similar for various fluids and hence the microfluidic device 100 may be designed with a default value of the mass diffusion coefficient and the microfluidic device 100 may still be suitable for use with many different fluids.
[0117] In the above the inventive concept has mainly been described with reference to a limited number of examples. However, as is readily appreciated by a person skilled in the art, other examples than the ones disclosed above are equally possible within the scope of the inventive concept, as defined by the appended claims.