Source: https://patents.justia.com/patent/9677121
Timestamp: 2019-10-23 05:49:49
Document Index: 248772810

Matched Legal Cases: ['§371', 'Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60']

US Patent for Systems and methods for thermal actuation of microfluidic devices Patent (Patent # 9,677,121 issued June 13, 2017) - Justia Patents Search
Justia Patents Liquid ValvesUS Patent for Systems and methods for thermal actuation of microfluidic devices Patent (Patent # 9,677,121)
Nov 21, 2014 - HandyLab, Inc.
This application is a continuation of U.S. application Ser. No. 13/847,415, filed Mar. 19, 2013 and scheduled to issue on Nov. 25, 2014 as U.S. Pat. No. 8,894,947, which is a divisional of U.S. application Ser. No. 11/929,877, filed Oct. 30, 2007 and issued as U.S. Pat. No. 8,420,015 on Apr. 16, 2013, which is a continuation of U.S. application Ser. No. 10/910,255, filed Aug. 2, 2004 and issued as U.S. Pat. No. 7,829,025 on Nov. 9, 2010, which is a continuation-in-part of (a) U.S. application Ser. No. 10/489,404, with a §371(c) date of Mar. 7, 2005 and issued as U.S. Pat. No. 7,674,431 on Mar. 9, 2010, which is a U.S. national stage application of International Application No. PCT/US02/29012, filed Sep. 12, 2002; (b) U.S. application Ser. No. 09/949,763, filed Sep. 12, 2001 and issued as U.S. Pat. No. 6,852,287 on Feb. 8, 2005; and (c) U.S. application Ser. No. 09/819,105, filed Mar. 28, 2001 and issued as U.S. Pat. No. 7,010,391 on Mar. 7, 2006. U.S. application Ser. No. 10/910,255 also claims the benefit of U.S. Provisional Application No. 60/491,264, filed Jul. 31, 2003; U.S. Provisional Application No. 60/491,539, filed Aug. 1, 2003; U.S. Provisional Application No. 60/491,269, filed Jul. 31, 2003, U.S. Provisional Application No. 60/551,785, filed Mar. 11, 2004; and U.S. Provisional Application No. 60/553,553, filed Mar. 17, 2004. The disclosures of all of the above-referenced prior applications, publications, and patents are considered part of the disclosure of this application, and are incorporated by reference herein in their entirety.
In some embodiments, the resistive element has a thermal dissipation constant (DC) and, during the first actuation state, the code can be configured to control the resistive element to dissipate a power k, wherein the ratio k/DC ≧40° C., ≧55° C., or ≧65° C. The ratio may be k/DC<300° C., <250° C., <200° C., <175° C., or <150° C.
A computer-readable medium can be provided with current to operate an electrical energy source to cause an amount of current to flow the resistive element of the second microfluidic device.
The method can also include manufacturing a second microfluidic device defining a microfluidic network including a channel configured to receive a liquid sample therein. Instructing a user to operate the microfluidic device with the channel in thermal contact with a heat source. Instructing the user to introduce a fluidic sample to the channel and providing a computer-readable medium including code configured to actuate the heat source to heat the liquid sample in the channel. The code is configured to actuate an electrical energy source to provide an amount of electrical energy determined on the basis of the amount of electrical energy required. to heat the fluidic sample present in the first microfluidic device to a temperature sufficient to observe the physio-chemical property of the fluidic sample.
Another aspect of the invention relates to a microfluidic system including a microfluidic device defining a microfluidic network including at least one thermopneumatic pressure source. The system also includes at least two thermopneumatically actuated components in gaseous communication with the thermopneumatic pressure source, wherein, pressure within the thermopneumatic pressure source simultaneously actuates each of two thermopneumatically actuated components.
Referring to FIG. 1, an exemplary microfluidic network 110 of a microfluidic device has a sample input module 150 and reagent input module 152 to allow sample and reagent materials, respectively, to be input to device 110. Generally, one or both of input modules 150, 152 are configured to allow automatic material input using a computer controlled laboratory robot Network 110 may also include output ports configured to allow withdrawal or output of processed sample from or by microfluidic network 110.
Material moved or otherwise manipulated and processed by the microfluidic device can be in the form of a microdroplet having upstream and downstream termini typically defined by a liquid gas interface. In some embodiments, the microdroplets have a volume of 25 μl or less, 10 μl or less, 2.5 μl or less, 1 μl or less, 0.5 μl or less, or 0.3 μl or less. Various features of the microfluidic device can be sized to accommodate such microdroplets. For example, channels and chambers can have a width of less than 200 μm and a depth of Jess than 50 μm. In general, the microdroplets have a length that is substantially shorter than a length of the channels through which the microdroplets move.
FIG. 3 illustrates, schematically and not to scale, the general structure of an exemplary integrated microfluidic device. This microfluidic device includes a microfluidic network included three types of sub-assemblies. In particular, this microfluidic network has four separate sub-assemblies: two micro-droplet metering sub-assemblies, metering1 and metering2; one mixing sub-assembly, mixing1; and one reaction/detection sub-assembly, reaction/detection1.
These sub-assemblies are constructed from elements such as valves, pumps, vents, passages, space to accommodate overflows, reservoirs, inlets, outlets detectors, mixing zones, and the like. For example, sub-assembly metering1 includes inlet1, overflow1, valve1, heater1, and passage1. Similarly, sub-assembly metering2 includes inlet2, overflow2, valve2, heater2, and passage2. The mixing subassembly, mixing1, includes heater1, heater2, valve3, valve4, vent1, vent2, Y-shaped passage3, and passage4. Finally, reaction/detection1 sub-assembly includes valve5, valve6, heater3, and passage5.
First, fluid is introduced into inlet1, for example, by an external robotic device, and flows up to the stable position created by the first hydrophobic region h3 just beyond the widening of passage1. Any excess fluid flows out through port overflow1. Next, DAQ 26 instructs sub-assembly metering 1 to measure a micro-droplet of determined volume from an aliquot of fluid introduced through port inlet1, as described in co-pending application Ser. No. 09/819,105. Sub-assembly metering2 is constructed and operates similarly to extract a measured micro-droplet of fluid from a second fluid sample likewise supplied at inlet 2.
The operation of the DAQ is exemplified by the following description of the control of a simple resistive heat source, such as the resistive heater shown in valve 1 of the microfluidic device depicted in FIG. 3. As shown in FIG. 3, valve 1 includes a resistive heating element 9 that is connected at its terminals 11, 13 to a pair of I/O contacts 12(a) via leads 8. The DAQ activates this resistive heating element by instructing analog multiplexor 48 to connect the output of heat source driver 47 to a pair of I/O contacts 25(a) that are connected to corresponding 1/0 contacts 21(a) of the chip carrier 20, that are connected to corresponding contacts 12(a) of the substrate. It then instructs heat source driver 47 to supply a selected amount of current. The current supplied by driver 47 flows through analog multiplexor 48 and to the resistive heating element 9 via the selected leads 39 and 8.
Current flow directional elements 70 and 71 may be but are not necessarily formed by microfabrication on a substrate with elements R1 and R2. Rather, current flow directional elements 70 and 71 may be disposed at other positions along current path ways that respectively include R1 and R2. Current flow directional elements 70 and 71 are generally disposed in series with R1 and R2.
For a two terminal component, such as the resistive heater RI described above, the system may use two I/O contacts to supply the control signals for operation of the component. Thus, if the number of two-terminal components of system 99 is N, then 2N I/O contacts are sufficient to allow DAQ 26 to independently control each of the components.
In some embodiments, the second actuation states have a duty cycle of no more than about 5%, no more than about 2.5%, no more than about 0.5%, no more than about 0.25%, or no more than about 0.2% and the first actuation states have a duty cycle of no more than 90%, no more than 95%, no more than 97.5%, or no more than 99% During a remaining portion of the duty cycle, if any, the system is neither in the first nor the second duty cycle. This remaining portion may be used to stabilize a circuit that determines an electrical property of the heater/sensor, e.g., a voltage drop thereacross. For example, this circuit may include a diode clamp that is stabilized during the remaining portion of the duty cycle. In some embodiments, during the remaining portion, no current is passed through the heater sensor.
FIGS. 7A, 7B illustrate a technique for reducing the number of 1/0 contacts by structuring the leads that provide current to the heat sources, temperature sensors, or combined heat source/sensors of the microfluidic device so that each lead serves more than one component, while still allowing DAQ 26 to control each thermally actuated component of the microfluidic device independently of others. Specifically, FIGS. 7A, 7B depicts a technique for sharing I/O contacts among three of the two-terminal resistors of a valve structure, such as shown in FIGS. 5A-5B discussed above. The valve operates essentially the same as the valve shown in FIGS. 5A, 5B, except that it uses only four contacts rather than six. In this example, each resistor is connected to a pair of I/O contacts and therefore can be controlled by the DAQ in the same way as described above. Although the other resistors share these I/O contacts, no resistor shares the same pair of contacts with another. Accordingly, the DAQ is able to supply current to any given resistor via the pair of associated contacts, without activating any other resistor.
According to this arrangement, electrical contacts for N resistors can be assigned to R rows and C columns such that the product RC is greater than or equal to N. Typically, R is approximately equal to C, and generally equals C. With this arrangement, resistors assigned to the same row share a common electrical lead and I/O contact 12(a). Similarly, resistors assigned to the same column also share a lead and I/O contact 12(a). However, each resistor has a unique address, corresponding to a unique pair of I/O contacts, (e.g., to its unique row/column combination in the array), Therefore, each resistor is individually actuatable by supplying electric current to the appropriate pair of I/O contacts.
FIGS. 9A, 9B, 10A, 10B depict similar arrays for the resistive components used to sense temperature, such as R2 shown in FIG. 5. FIG. 9A depicts one array of leads for supplying current to sensing resistors 110-118. FIG. 9B depicts another set of leads for measuring the voltage across the same resistors. With this structure, the leads that are used to stimulate the “resistive sensors carry no current from the heat source driver 47 because they are electrically isolated from driver 47. Similarly, the leads for sensing the voltage of the resistive sensors 110-118 (FIG. 9B) carry essentially no current because they are isolated from the leads that supply current from drivers 47 and 49(a) (shown in FIGS. 8A, 8B and 9A).
The arrays of FIGS. 9A, 9B, 10A, and 10B include current flow directional elements 215′-223′, which allow current to flow in only one direction through sensing resistors 110-118. Thus, current flow directional elements 215′-223′ preferably allow current to flow in only one direction between the positive terminal of RTD drive or RTD sense and the negative or ground terminal of RID drive or RID sense along a current path that includes one of sensing resistors 110-118. Typically, current flow directional elements 215′-223′ allow current to flow from the positive terminal to the negative terminal or ground terminal of either RTD drive or RTD sense but not from the negative or ground terminal to the positive terminal thereof. Current flow directional elements 215′-223′ may be diodes similar to current flow directional elements 70, 71.
The upper surface of the substrate is polished until smooth. In some embodiments, the surface roughness is reduced to less than about 15%, e.g., less than about 10% of the active regions to be applied. In some embodiments, the top surface is polished to create a smooth surface, e.g., a surface finish of SPI A1/SPI A2/SPI A3, such as for crack-free deposition and lithograph y of thin films.
1. A method of using a microfluidic system, comprising:
providing a first device comprising a first substrate defining a microfluidic network comprising at least one of each of a thermally actuated valve and a thermally actuated reaction chamber;
operatively receiving the first device in a second device, the second device comprising a second substrate defining a plurality of heat sources, each heat source being in thermal communication with a respective one of the thermally actuated valve and the thermally actuated reaction chamber of the first device, wherein at least one of the heat sources is a combined heating and temperature sensing element; and
controlling each heat source of the plurality of heat sources independently.
2. The method of claim 1, further comprising heating a respective one of the thermally actuated valve and the thermally actuated reaction chamber with the combined heating and temperature sensing element.
3. The method of claim 1, further comprising sensing a temperature of a respective one of the thermally actuated valve and the thermally actuated reaction chamber with the combined heating and temperature sensing element.
4. The method of claim 1, further comprising controlling the at least one of each of the thermally actuated valve and the thermally actuated reaction chamber independently of others.
5. The method of claim 1, further comprising heating only a localized region of the microfluidic network so that the heat generated is sufficient to actuate only a single element of the microfluidic network.
6. The method of claim 1, wherein the second device has a substantially lower thermal conductivity than the plurality of heat sources.
7. The method of claim 1, further comprising controlling the heat sources with control circuitry.
8. The method of claim 1, further comprising receiving signals in the second substrate from a data acquisition and control board.
9. The method of claim 1, wherein the combined heating and temperature sensing element comprises a resistive temperature sensor.
10. The method of claim 1, further comprising thermopneumatically actuating the thermally actuated valve.
11. The method of claim 1, further comprising thermal cycling the reaction chamber to perform a polymerase chain reaction.
12. The method of claim 1, wherein the thermally actuated valve comprises a temperature responsive substance.
13. The method of claim 12, wherein the temperature responsive substance is wax.
14. A method of using a microfluidic system, comprising:
heating a thermally responsive substance and moving the thermally responsive substance into a channel of the microfluidic network.
15. The method of claim 14, wherein the temperature responsive substance is wax.
16. The method of claim 14, further comprising thermal cycling the reaction chamber to perform a polymerase chain reaction.
17. A method of using a microfluidic system, comprising:
generating an amount of heat from a first heat source of the plurality of heat sources to actuate a first thermally actuated component but insufficient to actuate a second thermally actuated component.
18. The method of Claim 17, further comprising controlling the microfluidic system by electrical signals or optical signals received from a data acquisition and control board.
19. The method of claim 17, further comprising controlling a heat source of the plurality of heat sources independently of another heat source of the plurality of heat sources.
20. The method of claim 17, further comprising thermal cycling the reaction chamber to perform a polymerase chain reaction.
21. A method of using a microfluidic s stem, comprising:
actuating one of the plurality of heat sources such that current flows in essentially only one direction through the heat source.
22. The method of claim 21, further comprising substantially preventing current flow in a second, opposite direction through the heat source.
23. The method of claim 21, further comprising controlling the heat sources with control circuitry.
24. The method of claim 21, further comprising thermal cycling the reaction chamber to perform a polymerase chain reaction.
7049558 May 23, 2006 Baer
Patent Publication Number: 20150152477
Application Number: 14/550,126
International Classification: B01L 3/02 (20060101); B01L 3/00 (20060101); B01L 7/00 (20060101); G01N 1/40 (20060101); C12Q 1/68 (20060101);