WO2011062471A2

WO2011062471A2 - Disposable paraffin microvalve for biomedical applications

Info

Publication number: WO2011062471A2
Application number: PCT/MY2010/000237
Authority: WO
Inventors: Hing Wah Lee; Chia Sheng Daniel Bien
Original assignee: Mimos Bhd
Current assignee: Mimos Bhd
Priority date: 2009-11-20
Filing date: 2010-10-29
Publication date: 2011-05-26
Anticipated expiration: 2012-05-20
Also published as: MY150339A; WO2011062471A3

Abstract

The present invention provides a microfluidic device (100) comprises an adapting unit; a microvalve (120) adapted to removably couple with the adapting unit, the microvalve (120) having a fluid path (124) and a heat sensitive plug (126), the heat sensitive plug (126) is disposed to block the fluid path (124), wherein the microvalve (120) is adapted to be normally-closed by default by the heat sensitive plug (126); and a heater (114) disposed on a position having a close proximity to the heat sensitive plug (126), wherein the heater (114) is operable to melt the heat sensitive plug (126). Once the heat sensitive plug (126) is molten to open the fluid path (124), the fluid path (124) is not re-closable and a replacement microvalve is required for a new use. A microvalve and a method of fabricating the same is also provided herewith.

Description

Disposable Paraffin Microvalve for Biomedical Applications

Field of the Invention

[0001] The present invention relates to microfluidic devices. In particular, the invention relates to a disposable microvalve for the microfluidic device and a method of fabricating the same.

Background

[0002] There is an increasing demand on miniaturized devices, such as microfluidic devices, which are heavily used for biological and biomedical applications, such as Lab-on-Chip (LOC), Point-of-Care, Total Analysis System (TAS), just to name a few. These devices are mainly silicon-based devices because silicon is proven to be excellent for microfabrication, especially for integrated circuit fabrications. However, silicon based devices can be expensive to fabricate, and it has relatively high stiffness, therefore rigid and can easily get crack. Further, the silicon substrates are often available in standard thicknesses, which may not always be available to suit the desire application.

[0003] It is most desirable that microfluidic devices include microvalves for controlling fluid flows. These check valves are typically active devices with include moving parts and operationally consumed power. Due to the complexity in fabrication, these valves are not suitable for disposable microfluidic devices. [0004] LOC for example are getting more common due to its operational advantages on biological or medical syntheses and analyses. LOC usually involve dispensing of fluid in micro or nano-liters into a microfluidic system for biological analyses. Fabrications of such microfluidic system with current micromachining fabrication require growing thin films, photolithography exposure and etching repeatedly. There is a trend on developing reduced cost disposable microfluidic devices. Polymer-based materials such as PD S, SU-8, epoxy or polyimide are preferred over silicon or glass wafer for micromachining fabrications. However, conventional polymer-based microfluidic devices would still require a separate silicon or glass substrate for packaging purposes and they do not integrate with any passive microvalve due to the complications in its fabrication processes to integrate microvalve into microfluidic devices.

Summary

[0005] In one aspect of the present invention, there is provided a microfluidic device comprises an adapting unit; a microvalve adapted to removably couple with the adapting unit, the microvalve having a fluid path and a heat sensitive plug , the heat sensitive plug is disposed to block the fluid path , wherein the fluid path having the microvalve is adapted to be normally-closed by default; and a heater disposed at a close proximity to the heat sensitive plug . The heater is operable to melt the heat sensitive plug , to open the fluid path allowing fluid to flow through, the fluid path not re-closable and a replacement microvalve is required for a new use.

[0006] In one embodiment, the heat sensitive plug comprises paraffin wax.

[0007] In another embodiment, the heater may be disposed on the adapting unit or integrated on the microvalve .

[0008] In a further embodiment, the fluid path comprise at least one inlet and at least one outlet . The microvalve may further comprise a auxiliary chamber defined along the fluid path , wherein the auxiliary chamber having a wider fluid path than the fluid path . Alternatively, the auxiliary chamber is defined beyond the heat sensitive plug along the fluid path .

[0009] In a yet another embodiment, the adapting unit comprises sensors and readout components . For disposable application, the microvalve can be made a polymer-based device, such as PDMS or PMMA.

[0010] It is possible that the microvalve is attachable to the adapting unit via attachment means that include any one of snapping means, inter-locking means, adhesive and slot configurations.

[0011] In another aspect of the present invention, there is provided a microvalve for the microfluidic device . The microvalve may comprise a fluid path and a heat sensitive plug , wherein the heat sensitive plug is disposed to block the fluid path , so that the microvalve is closed by default by the heat sensitive plug . The microvalve is adapted to removably couple with an adapting unit of the microfluidic device having a heater disposed on a position associated to the heat sensitive plug , and the heater is operable to melt the heat sensitive plug to open the fluid path.

[0012] In a further aspect, there is provided a method for fabricating a microvalve. The method comprises forming a patterned photoresist layer on a substrate defining a fluid path for the microvalve; forming a first polymer layer on the patterned photoresist layer ; removing the first polymer layer from the substrate with the fluid path formed on the first polymer layer ; forming a second polymer layer sepaiately; forming a third polymer layer on the second polymer layer ; depositing a predetermined amount of paraffin on the third polymer layer ; bonding the first polymer layer defining the fluid path on the third polymer layer . The predetemtined amount of paraffin is adequately deposited to block the fluid path. Brief Description of the Drawings

[0013] This invention will be described by way of non-limiting embodiments of the present invention, with reference to the accompanying drawings, in which:

[0014] FIG. 1A illustrates a schematic cross sectional view of a microfluidic system in accordance with one embodiment of the present invention;

[0015] FIG. IB shows a schematic top view of the microfluidic system 100 of

FIG. 1A;

[0016] FIGs. 2A-2J illustrates a process of forming a microfluidic device in accordance with one embodiment of the present invention;

[0017] FIG. 3 illustrates schematically a microfluidic device connecting a readout device in accordance with one embodiment of the present invention; and

[0018] FIGs. 4A-4D illustrates a schematic operational flow of a microfluidic device in accordance with one embodiment of the present invention.

Detailed Description

[0019] In line with the above summary, the following descriptions of a number of specific and alternative embodiments are provided to understand the inventive features of the present invention. It shall be apparent to one skilled in the art, however that this invention may be practised without such specific details. Some of the details may not be described at length so as not to obscure the invention. For ease of reference, common reference numerals will be used throughout the figures when refen-ing to the same or similar features common to the figures. [0020] FIG. 1A illustrates a schematic cross sectional view of a microfluidic system 100 in accordance with one embodiment of the present invention. Possibly, the microfluidic system 100 is a polymer-based microfluidic device. The microfluidic system 100 comprises an adapting unit 110 and a microvalve 120. The microvalve 120 is adapted for removably attaching on the top of the adapting unit 110, via any attachment means (not shown). Preferably, the attachment means include any snapping means, inter-locking means, adhesive means, simple slotting configuration or the like. Such removable configuration allows the microvalve 120 be removable from the microfluidic system 100 and replaceable with a replacement microvalve 120. The microvalve 120 is thereby disposable for each use. It is desired that the microvalve 120 is relatively simple in structure and cost effective to make so that it is viable for disposable application.

[0021] Still referring to FIG. 1A, the adapting unit 110 comprises an adapter

112 and a heater 114. The adapter 112 is adapted to provide the attachment means for coupling/receiving the microvalve 120 on its top. These attachment means shall allow user to easily remove the used microvalve 120 from the adapting unit 110 and replace with a replacement piece with the least effort required, while able to secure the microvalve 120 on the adapting unit 110 operationally. There exist many of attacliment means for disposable applications, which are well known in the art, and therefore will not be described herein in detail. The main upper surface of the adapter 112 for abutting the microvalve 120 defining a channel to mount the heater 114. The heater 114 is generally connected to a power source (not shown) of the microfluidic system 100. [0022] The microvalve 120 comprises a valve body 122, a fluid path 124, and a plug 126 and a base panel 129. The valve body 122 is generally mounted on the base panel 129, wherein the valve body 122 is also adapted with a matching attachment means for coupling with the adapter 112. The valve body 122 can also be made up by polymer. The fluid path 124 is defined within the valve body 122 with an inlet 127 and an outlet 128 at the two ends of the fluid path 124. The plug 126 is disposed on the fluid path 124 to block the passage. Preferably, the plug 126 is made up of heat sensitive material, such as paraffin. The microvalve 120 is made for one time use only, i.e. disposable, therefore, it is desired that the microvalve 120 be configured as a non- reversible valve. In the present embodiment, the microvalve 120 is made as a normally-closed valve.

[0023] For the purpose of this invention, one desirable heat sensitive material that can be used as the plug is paraffin. Paraffin is insoluble in most liquids, it will not affect the characteristics and properties of the fluid sample. Generally, paraffin wax (i.e. solid paraffin) is used to block the fluid path. Paraffin wax has a relatively low melting point that is suitable for the present invention, typically about 55°C-57°C is sufficient to result the paraffin start changing its phase into liquid to achieve the objective of the present invention.

[0024] To achieve the functionality of the microfluidic system 100, the heater 114 is placed at a close proximity to the plug 126 so that the microfluidic system 100 can be activated operationally through melting the plug 126. Once the heater 114 is powered, the heat emitted from the heater 114 transmits through the base panel 129 and the valve body 122 to heat up the heat sensitive material. Once the heat sensitive material melts, the passage of the fluid path 122 is opened accordingly. The heat sensitive material then flows alongside the sidewall of the fluid path 122 in a same direction as the fluid flowing through the fluid path 122.

[0025] FIG. IB shows a schematic top view of the microfluidic system 100 of

FIG. 1A. The fluid path 124 further comprises an auxiliary chamber 130 beyond the plug 126. The auxiliary chamber 130 defines a relatively larger cavity than that of the fluid path 122.

[0026] FIGs. 2A-2J illustrates a process of forming a micro valve in accordance with one embodiment of the present invention. In FIG. 2A, there is provided a substrate 202. A patterned photoresist layer 204 is formed on top of the substrate 202. The photoresist layer 204 is patterned to define a fluid path for the microvalve. The patterned photoresist layer 204 can be formed by spin coating of SU-8 photoresist layer 204, for example. As shown in FIG. 2B, a layer of polymer 206, such as Polydimethylsiloxane (PDMS), can then be poured onto the patterned photoresist layer 204 covering thereon. Once the layer of polymer 206 is cured, it is then removed from the substrate 202 with the photoresist layer's pattern formed on the polymer 206 as shown in FIG. 2C. Subsequently, as shown in FIG. 2D, the patterned polymer 207 is then subjected to mechanical drill to form an inlet 208 and an outlet 209.

[0027] In the above embodiment, the photoresist layer 204 is patterned to form a single path fluid passage with one inlet and one outlet. It is understood to a skilled person that the photoresist layer 204 may be patterned in any other form that suit the intended applications. For example, it is possible to form a pattern that consists of one or more inlets channeling into one outlet for mixing few types of fluid, wherein each inlet is provided. [0028] Referring now to FIG. 2E, a sacrificial release oxide 214 is grown on a substrate 212. About 0.5μηι of thickness can be used although other thickness is also possible. As shown in FIG. 2F, a layer of polymer 216, such as polyimide, is sputtered onto the sacrificial release oxide 214, and is cured subsequently. It is well known in the art that polyimide is used in the initial layer because can be easily sputtered to ensure uniform deposition of the layer 216 and it also has good adhesion with thermal oxide surface. A good uniformity is essential for etching process in the later part. Thereafter, a further layer of polymer 218, such as poly-dimethyl siloxane (PDMS) or poly-methyl methacrylate (PMMA), is deposited on top as shown in FIG. 2G. As shown in FIG. 2H, an adequate amount of paraffin 219 is deposited through evaporation and Iifting-off on the polymer 218.

[0029] In the above embodiment, thermal evaporation with lifting-off method is one of the methods that can be used for depositing the paraffin. It is understood that other methods, such as spin coating, manual coating with paraffin pallets, that are well known in the art may be desired.

[0030] Referring now to FIG. 21 that the patterned polymer 207 (of FIG. 2D) is attached to the paraffin deposited polymer substrate. Once attached, the pattern defining the fluid path on the polymer 207 forms a canal/passageway between the inlet 208 and outlet 209. In this process, both the patterned polymer 207 and the paraffin deposited polymer substrate are activated in oxygen plasma with a plasma reactive-ion etching (RIE) process. Then, the two polymers are being pressed together for bonding and also to remove air resided therein. Effectively, the pressure for pressing the two polymers can be applied from center and outwardly applied. About 50N of pressure over about two minutes may be desired for bonding the two polymers to form a bonded structure 230. The bonded structure 230 comprises a paraffin microvalve 232 at the top and a polymer substrate 234 beneath it.

[0031] The bonded structure 230 is then subjected to sacrificial oxide etching using Hydrofluoric Acid (HF) to detach the paraffin microvalve 232 from the polymer substrate 234. The detached paraffin microvalve 232 is shown in FIG. 2J. The detached paraffin microvalve 232 forms a disposable microvalve in accordance with one embodiment of the present invention.

[0032] FIG. 3 illustrates schematically a microfluidic device 300 connecting a readout device 350 in accordance with one embodiment of the present invention. The microfluidic device 300 is used in an automated biological analysis system. The microfluidic device 300 comprises an adapting unit 310 and a disposable microvalve 320. The adapting unit 310 is adapted to receive the disposable microvalve 320 as an attachment. The disposable microvalve 320 has substantially the same configuration as the microvalve 100 of FIG. 1A, thus references of the parts in FIG. 1A is also adapted herein for simplicity. The adapting unit 310 and the disposable microvalve 320 are configured in a matching manner for proper functionality. The adapting unit 310 comprises a channel 312, a micro-heater 314, a photodetector 316, a pump 318 and two conduits 319. The channel 312 is configured at substantially the center of the microfluidic device 300 for receiving and securing the disposable microvalve 320 therein. The microheater 314 is integrated on the adapting unit 310 exposing on the outer surface of the channel 312, so that when the disposable microvalve 320 is mounted thereon, it is in direct contact with the microheater 314. Further, the microheater 314 is located correspondingly to be in close proximity to the plug 126 of the microvalve 320. Similarly, the conduits 319 are adapted to fit with the inlet 127 and the outlet 128 of the disposable microvalve 320 respectively. The conduit 319 for fitting with the inlet 127 is further in fluid communication with the pump 318. The photodetector 316 may further be integrated in the adapting unit 310 by the (outlet) conduit 319. The photodetector 316 is provided to detect fluid reaction at a region of interest. Depending on the application, other detectors or sensors may be integrated into the microfluidic device. Preferably, these detectors or sensors are not provided on the disposable microvalve.

[0033] Operationally, the pump 318 is activated to pump liquid into the fluid path of the disposable microvalve 320. The disposable microvalve 320 is made normally-closed by default, and therefore, the liquid is block by the plug 126. The microheater 314 is then activated to melt the plug 126, and once molten,

[0034] It is to be noted that the adapting unit 310 is served as cartridge for loading the disposable microvalve 320. Practically, the adapting unit 310 is reusable and the disposable microvalve 320 is only for one-time usage only. With such configurations, fabrications of the disposable microvalve 320 become much simpler and therefore low manufacturing cost without compromising the overall functionalities of the microfluidic device because the adapting unit is fabricated individually/separately. It is possible that the adapting unit 310 is integrated with other components, such as sensors and etc., as required.

[0035] FIGs. 4A-4D illustrates a schematic operational flow of a microfluidic device in accordance with one embodiment of the present invention. As shown in FIG. 4A, the microfluidic device comprises two inlets 401 and 402 channeling fluid into one outlet 409. Each of the inlets 402, before joining into one, leads to an individual fluid path that comprises its own plug 403 (404) and an auxiliary chamber 405 (406). The plugs 403 and 404 cause the respective fluid path to be in a normally-closed configuration. Accordingly, even when the pump is activated, fluid entering the fluid path through the respective inlets is blocked by the plugs 403 (404). Each of the plug 403 (404) is provided with a heater 403' (404'). Under such arrangement, the plugs 403, 404 can be activated at two distinct timings, when necessary.

[0036] Referring now to FIG. 4B, the heater 403' and 404' are activated simultaneously through applying an adequate voltage to the heaters. Heat emitted from the heaters is transmitted to the plugs 403 and 404 through the polyimide layer causing the plugs 403 and 404 to melt gradually. Due to the fluid pressure, the molten plugs 403 and 404 to flow towards the auxiliary chambers 405 and 406 at high viscosity as shown in FIG. 4C. At FIG. 4D, as the molten plugs 403 and 404 flow away from the heater towards the auxiliary chamber 405 and 406 along its side surface due to a capillary action, an opening is formed, and thus, the fluid path is opened. Meanwhile, as the molten plugs departs from the heating region, the molten plugs 403 and 404 start to solidify. Eventually, the plugs 403 and 404 reside at the sidewall of the respective auxiliary chamber 405, 406 while allowing the liquid to pass through the auxiliary chambers 405 and 406.

[0037] In an alternative embodiment, the heater may be integrated on the disposable microvalve with necessary wirings and contacts pads, embedded therein. Once the disposable microvalve is used, the heater is disposed together with the microvalve.

[0038] The aforesaid provides a solution that is viable for disposable applications because the disposable part, i.e. microvalve, is relatively easy to fabricate and therefore low cost. The microfluidic system is configured to separate the microvalve from the other components, such as the sensor components (i.e. photodetectors), readout electronics or the like which are relatively costly and complicated to fabricate.

[0039] The aforesaid polymers, such as PDMS and SU-8 are provided by way of example, not limitations. It is understood to a skilled person that other types of compatible polymers may also be desired as long as they are compatible for bonding with polyimide.

[0040] Further, the polyimide layers mentioned above can also be deposited via any recognized methods/processes, such as spin coating. Standard industrial-grade polyimide sheets that are available in the market can also be laminated or bonded to the substrate with adhesives.

[0041] The present invention concerns a disposable device suitably used for biochemistry analysis, drug delivery, agriculture, environmental monitoring, microanalyser systems and others. The disposable device can be fabricated in a micro scale using conventional surface micromachining (SMM). In particular, the present invention provides a disposable microvalve that is made normally-closed for operationally controlling fluid flow. The microvalve can be activated (i.e. opened) by melting the plug via heating elements (i.e. heaters).

[0042] While specific embodiments have been described and illustrated, it is understood that many changes, modifications, variations and combinations thereof could be made to the present invention without departing from the scope of the invention.

Claims

1. A microfluidic device ( 100) comprising:

an adapting unit;

a microvalve (120) adapted to removably couple with the adapting unit, the microvalve (120) having a fluid path (124) and a heat sensitive plug (126), the heat sensitive plug (126) is disposed to block the fluid path (124), wherein the fluid path having the microvalve (120) is adapted to be normally-closed by default; and

a heater (1 14) disposed at a close proximity to the heat sensitive plug (126), wherein the heater (114) is operable to melt the heat sensitive plug (126), to open the fluid path (124) allowing fluid to flow through, the fluid path (125) not re-closable and a replacement microvalve is required for a new use.

2. The microfluidic device (100) according to claim 1, wherein the heat sensitive plug (126) comprises paraffin wax.

3. The microfluidic device (100) according to claim 1, wherein the heater (1 14) is disposed on the adapting unit.

4. The microfluidic device (100) according to claim 1, wherein the heater (114) is integrated on the microvalve (120).

5. The microfluidic device (100) according to claim 1, wherein the fluid path (124) comprise at least one inlet (127) and at least one outlet (128).

6. The microfluidic device (100) according to claim 1, wherein the microvalve (120) further comprises a auxiliary chamber (130) defined along the fluid path (124), wherein the auxiliary chamber (130) having a wider fluid path than the fluid path (124).

7. The microfluidic device (100) according to claim 6, wherein the auxiliary chamber (130) is defined beyond the heat sensitive plug (126) along the fluid path (122).

8. The microfluidic device (100) according to claim 1, wherein the adapting unit comprises sensors and readout components (350).

9. The microfluidic device (100) according to claim 1, wherein the microvalve (100) is a polymer-based device.

10. The microfluidic device (100) according to claim 9, wherein the microvalve (120) includes any one of PDMS and PMMA.

l l . The microfluidic device (100) according to claim 1 , wherein the microvalve (120) is attachable to the adapting unit via attachment means that include any one of snapping means, inter-locking means, adhesive and slot configurations.

12. A microvalve (120) for the microfluidic device (100). the microvalve (120) comprising:

a fluid path (124) and a heat sensitive plug (126), wherein the heat sensitive plug (126) is disposed to block the fluid path (124), so that the microvalve (120) is closed by default by the heat sensitive plug (126),

wherein the microvalve (120) is adapted to removably couple with an adapting unit of the microfluidic device (100) having a heater (1 14) disposed on a position associated to the heat sensitive plug (126), wherein the heater (114) is operable to melt the heat sensitive plug (126) to open the fluid path.

13. A method for fabricating a microvalve, the method comprising:

forming a patterned photoresist layer (204) on a substrate (202) defining a fluid path for the microvalve;

forming a first polymer layer (206) on the patterned photoresist layer (204); removing the first polymer layer (206) from the substrate (202) with the fluid path formed on the first polymer layer (206);

forming a second polymer layer (216) separately;

forming a third polymer layer (218) on the second polymer layer (216);

depositing a predetermined amount of paraffin (219) on the third polymer layer

(218) ;

bonding the first polymer layer (206) defining the fluid path on the third polymer layer (218),

wherein the predetermined amount of paraffin (219) is adequately deposited to block the fluid path.