This invention relates to the field of microfluidic systems, and more particularly to a method of making a microfluidic device, where the microfluidic device can itself be a platform for making a microfluidic system with multiple components.
Two key components of any fluidic system are valves and pumps. These are the basic mechanisms for creating and controlling fluid flow. In lab-on-chip (LOC) applications, where analytic processes are carried out on a microchip, the need for pumps and valves remains, but new designs are required to fit within the constraints of available microfabrication processes. Unfortunately, current designs for microfabricated valves and pumps impose a significant chip-to-world burden, and this burden impedes progress towards greater miniaturization and integration of LOC systems.
Microfabrication processes, especially those suitable for mass production, are strongly biased towards planar geometries. This flattening of geometries makes traditional macroscopic designs unworkable or inefficient. This has affected the types of valves and pumps that are being used in LOC applications. For this reason many workers in the field have switched from mechanical pumps to other transduction mechanisms, such as electro-osmotic flow (EOF). However, these new mechanisms can have a number of significant drawbacks, such as affecting ion concentrations, which are significant when attempting to perform chemical reactions. For this reason, many groups have continued to use mechanical pumps. In particular, microfluidic “peristaltic” pumps have become very popular. Underlying the operation of peristaltic pumps, which are different in design from their macroscopic counterparts, is the operation of a sequence of active valves. In particular, existing processes actuate the valves and pumps using pneumatic control signals that are generated off-chip. This imposes significant interconnect burdens to the system design.
Even more critical is the fact that existing microfabrication processes support only limited system integration. Fluidic channels, valve, pumps, and aqueous contacts are commonly supported, but all other components are off-chip. A very small portion of the systems' overall complexity is embedded on the chip. This divide essentially creates a barrier to increased integration.
To achieve higher levels of integration, and thus lower costs and improve reliability, the number of off-chip interconnections is significantly reduced. The control signals are generated on-chip (or at least within the same package), thus providing an integrated microelectronic system.
Disclosed herein is a microfabrication process capable of building otherwise standard LOC valves and pumps, which can also accommodate the inclusion of electrostatic actuators. These electrostatic actuators are positioned such that they can replace the pneumatic controls. Instead of the myriad off-chip connections necessary to carry pneumatic signals, the fluidic components can be driven by electrical signals generated on-chip. This approach promotes increased integration of LOC systems, and thus reduces costs and improves reliability.
According to the present invention there is provided a method of making a microfabricated device, comprising: depositing a first metal layer on a substrate to provide a first electrode of an electrostatic actuator; depositing a first structural polymer layer over said first metal layer; depositing a second metal layer over said first structural polymer layer to form a second electrode of the electrostatic actuator; depositing an insulating layer over said first structural polymer layer; planarizing said insulating layer; etching said first structural polymer layer through said insulating layer and said second metal layer to undercut said second metal layer; providing additional pre-formed structural polymer layers, at least one of which has been previously patterned; and bonding said additional structural layers in the form of a stack over said planarized second insulating layer to define at least one microfluidic channel. In this context the microfluidic device can itself be a platform for making a microfluidic system with multiple components.
In another aspect the invention provides a method of making a microfabricated device, comprising depositing a first structural polymer layer over said substrate; depositing an insulating layer over said first structural polymer layer to define a hard mask; planarizing said insulating layer; etching said first structural polymer layer through said insulating layer; providing additional pre-formed structural polymer layers, at least one of which has been previously patterned; and bonding said additional structural layers in the form of a stack over said planarized second insulating layer to define at least one microfluidic channel.
In yet another aspect the invention provides a microfabricated structure, comprising upper and lower electrodes of an electrostatic actuator separated by a first structural polymer layer, wherein the first structural polymer is undercut to expose a gap between the first and second electrodes; and a stack of additional structural polymer layers bonded over said upper electrode to define microfluidic channels.
The layers may be bonded by direct mutual application or laminated together. The term “bonded” is defined to include lamination. It will be also understood that in the case of a layer applied over or on an underlayer, there may be one or more intervening layers.
The invention further provides a microfabricated structure, comprising a substrate; a polymer layer on the substrate, and a planarized inorganic layer applied over the polymer layer; wherein the inorganic layer serves as a hard mask for the polymer layers.
Although the invention is described with reference to a particular orientation, it will be appreciated that this is arbitrary and merely used for convenience of description. The orientation depends on how the device is mounted and is referred to herein as in the vertical orientation for convenience of description.
The polymer layers may be transferred using a transfer bonding process wherein they are first bonded on one side by a weak bond to a carrier, and then bonded on the other side to the underlying layer by a strong bond. Subsequently, the carrier can be removed.
Embodiments of the invention thus provide a process flow for the microfabrication of fluidic components supporting a high level of integration. Using this process, one can fabricate systems containing many different miniature components, and many different types of components, in an integrated manner. The process flow can be carried out in standard high-volume semiconductor manufacturing equipment. The process flow is compatible with CMOS processing, and so can be run as a post-processing step on CMOS wafers.
The invention will now be described in more detail, by way of example only, with reference to the accompanying drawings, in which:—
a to 1t illustrate a process flow for a method in accordance with an embodiment of the invention;
In the following description, in order to simplify the discussion, details relating to CMOS integration have been omitted. The process flow outline of a method in accordance with an embodiment of the invention shown in
One embodiment of the invention will be described below with reference to
In step (a) a layer 12 of 100 nm of Al is deposited by PVD (Plasma Vapor Deposition) on a silicon substrate 10.
In step (b) lithography is performed on the layer of Al 12 to start the fabrication of electrostatic actuators. Processing starts with the deposition of the first metal layer 12. This layer is used to create the bottom electrodes of the electrostatic actuator, but can also be used to make tracks for electrical routing.
In step (c) an insulating layer 14 of 500 nm of Si3N4 is deposited by CVD (Chemical Vapor Deposition).
In step (d) lithography is performed on the Si3N4 layer. The electrostatic actuators operate in “contact mode,” which means that when sufficient voltage is applied, the membrane deflects past the pull-in voltage, and snap down. To prevent electrical shorting, an electrically insulating passivation layer is required, and this is provided by this silicon nitride layer.
In step (e) a spin-coat 16 of 2000 nm of a photopatternable epoxy-based polymer is applied. This layer is used tocreate the gaps between the bottom and top electrodes of the electrostatic actuator. SU-8 or KMPR™ photoresist is suitable for use as the polymer layer, although there are certainly many other suitable candidates. For the process, any polymer than can be spun at the appropriate thickness, etched in a pure O2-plasma, and that provides the necessary dimensional and chemical stability would be a suitable candidate.
In step (f) a layer 18 of 100 nm of Al is applied by PVD.
In step (g) lithography of the Al layer 18 is performed to create the top electrodes. This metal layer is used to fabricate the top electrodes of the electrostatic actuators, but it can also be used to provide tracks for electrical routing.
In step (h) a layer 20 of 1000 nm of SiO2 is applied by low-temperature CVD.
In step (i) CMP (Chemical Mechanical Polishing) of the SiO2 layer 20 is performed down to ˜500 nm. This layer is significant to the process flow, and physically separates the electrical and pneumatic sections of the chip from the fluidic regions. Other materials may be used instead of SiO2, in particular Si3N4 or other inorganic materials. The choice of an inorganic provides good etch-selectivity for patterning. The oxide layer 20 serves two purposes with respect to achieving the overall goals of the microfabrication process. First, this layer is planarized in preparation for later bonding steps. The elimination of topography is important to form void-free bonding. Second, this layer serves as a hard mask for two further processing steps.
In step (j) lithography is performed on the SiO2 layer 20.
In step (k) RIE (reactive ion etching) of the KMPR layer 16 is performed to etch holes through the first KMPR layer 16 to create openings 21 for electrical vias 24 (
In step (l) a PVD layer 22 of 2500 nm of Al is applied. This step fills the vias with metal. This metal provides the conducting paths between the two metal layers, creating the vias.
In step (m) lithography is performed on this Al layer 22. This removes excess metal from regions outside the vias.
In step (n) the vias are potentially capped with a noble metal so that, if exposed to fluid, the vias can also serve as aqueous contacts, and drive electrochemical reactions, electrophoresis, electroosmotic flow (EOF), or other aqueous or other solvent electrical interactions.
The vias 24 may be filled by depositing an additional metal layer by PVD and then patterning the metal layer so that it only remains in the vias (as described above), or alternatively by electroless deposition.
In step (o) lithography is potentially performed on the SiO2 layer.
In step (p) a RIE (Reactive Ion Etch) is performed on the Al layer 22.
In step (q) an isotropic etch of the KMPR layer 16 is performed to undercut the Al/SiO2 bilayer to create the electrode gaps 25. This completes the fabrication of the electrostatic actuators. Overetch of the KMPR during lithography is not an issue, as the underlying KMPR will be removed either way. Etching of the SiO2 and the Al may be combined.
In step (r) a bond/laminate polymer layer 26 is applied. This second polymer layer is added to the materials stack through bonding or lamination. This avoids in-filling of the gaps previously created, which are necessary for the electrostatic actuators. The second polymer layer is used to form the “floor” of the eventual microfluidic channels. KMPR may be used for all polymer layers, although other materials may be substituted, such as SU-8, dry-films designed for lamination, etc. The layer is patterned prior to bonding. Alternatively, the polymer film may be patterned after bonding or lamination.
In step (s) a third bond/laminate polymer layer 28 is applied. The third polymer layer is used to create the walls for the microfluidic channels. The third polymer layer may be similar to the second polymer layer.
In step (t) the fourth bond/laminate polymer layer 30 is applied. The fourth polymer layer 30 is used to create the roofs for the microfluidic channels and is similar to the other polymer layers.
The process flow outlined above is capable of fabricating many important fluidic components, and is designed to serve as a platform technology for the development of LOC devices.
In another embodiment a fifth structural polymer layer (not shown) is formed under the second structural polymer layer to provide a floor to a lower fluidic channel formed on the underside of the second structural polymer layer. In yet another embodiment a fifth structural layer may be formed over the fourth structural polymer layer to provide a floor of a second microfluidic channel. As sixth structural polymer layer may then be applied over the fifth structural polymer layer to provide the roof for the second microfluidic channel.
A variety of devices that can be made by the described process are illustrated in
For example,
An electrostatic actuator 42, 44 is shown in
An aqueous contact is shown in
A fluidic port is shown in
A pneumatic port is show in
An electrostatic valve is shown in
The addition of a via 72 in the membrane on one side of the valve seat equalizes the pressure across that half of the membrane, converting the structure to a check-valve as shown in
A further addition is to include electrodes to create an electrostatic actuator. This allows the valve to be held open electrostatically, which allows bidirectional flow. This device thus acts as a semi-active check-valve.
It will thus be seen that a variety of different components that can be built using this polymer manufacturing process. An electrostatic actuator for a microfluidic valve can be integrated within a four layers polymer manufacturing process, using two metal layers (and possible vias between them). The overall process perspective shows two microfluidic layers that can cross over, one targeted for fluid transport (top) and one targeted for air displacement (bottom).
The microfabrication process described herein is closely aligned with modern microfabrication methods. The invention uses readily available microfabrication materials using existing fabrication techniques. As a result the novel process is compatible with high-volume manufacturing.
The check-valves described herein can replace the inlet and outlet valves of current LOC pumps, and those pumps will continue to work. The process described herein therefore complements existing LOC practices, and adds values to those processes. For example, the inventive process is compatible with glass-PDMS-glass, glass-PDMS-glass-glass, and SU-8 laminate microfabrication processes. By working with and simplifying existing LOC designs, costs can be reduced.
The microfabrication process described herein permits the elimination of pneumatic connections, which are a limitation of current LOC devices. Because of their relatively large size, pneumatic connections limit the amount of functionality that can be integrated on-chip, increasing overall system costs. Additionally, as a mechanical connection that must be set at time-of-use, pneumatic connections reduce reliability and increase the need for operator training
One of the major limitations of many polymer materials, such as PDMS, used in LOC devices is that any processing or operation of the device is limited to approximately 100° C. to prevent changes in the material properties, such as degradation of the polymer or changes in its mechanical properties. This process described herein does not require the use of PDMS, and can tolerate temperatures as high as 250° C. The assembly process, which typically uses soldering temperatures similar to these temperatures, is therefore compatible with high volume electrical systems manufacturing. The operating temperature of the LOC device itself can also be raised to meet the military standard of 125° C.
The microfabrication process described herein is compatible with typical CMOS manufacturing processes, and therefore allows the monolithic integration of both technologies. Further, the use of electrostatic actuation for valves and pumps makes integration of active elements with the supporting electronics relatively straightforward. One major advantage of semiconductor manufacturing processes is the ability to integrate multiple types of devices (components) within the same process. Designers then assemble these components in a myriad of ways to create a wide range of possible systems. The process described herein allows the integration of various type of electrostatic actuators, active valves and pumps, but also some passive components such as metallic vias between the metal layers, aqueous contacts, fluidic ports, electrical pads, pneumatic ports or fluidic/pneumatic vias. In a similar manner, the process provides a wide enough range of fundamental components to provide designers flexibility in the final system design.
Number | Name | Date | Kind |
---|---|---|---|
5216273 | Doering et al. | Jun 1993 | A |
5380396 | Shikida et al. | Jan 1995 | A |
5876675 | Kennedy | Mar 1999 | A |
5901939 | Cabuz et al. | May 1999 | A |
5914507 | Polla et al. | Jun 1999 | A |
6136212 | Mastrangelo et al. | Oct 2000 | A |
6351054 | Cabuz et al. | Feb 2002 | B1 |
6368562 | Yao | Apr 2002 | B1 |
6521188 | Webster | Feb 2003 | B1 |
6590267 | Goodwin-Johansson et al. | Jul 2003 | B1 |
6626417 | Winger et al. | Sep 2003 | B2 |
6666658 | Takeuchi et al. | Dec 2003 | B2 |
6679279 | Liu et al. | Jan 2004 | B1 |
6767194 | Jeon et al. | Jul 2004 | B2 |
6794723 | Takeuchi et al. | Sep 2004 | B2 |
6802489 | Marr et al. | Oct 2004 | B2 |
6807892 | Biegelsen et al. | Oct 2004 | B2 |
6810713 | Hahn et al. | Nov 2004 | B2 |
6837476 | Cabuz et al. | Jan 2005 | B2 |
6838304 | Ikeda et al. | Jan 2005 | B2 |
6934435 | Kane | Aug 2005 | B2 |
6946315 | Ikeda et al. | Sep 2005 | B2 |
6986500 | Giousouf et al. | Jan 2006 | B2 |
7060227 | Staats | Jun 2006 | B2 |
7075162 | Unger | Jul 2006 | B2 |
7081189 | Squires et al. | Jul 2006 | B2 |
7156487 | Chou et al. | Jan 2007 | B2 |
7168675 | Cabuz et al. | Jan 2007 | B2 |
7195465 | Kane et al. | Mar 2007 | B2 |
7222639 | Bonne et al. | May 2007 | B2 |
7232109 | Driggs et al. | Jun 2007 | B2 |
7258774 | Chou et al. | Aug 2007 | B2 |
7328882 | Wang et al. | Feb 2008 | B2 |
7351303 | Liu et al. | Apr 2008 | B2 |
7419638 | Saltsman et al. | Sep 2008 | B2 |
7474180 | Bintoro et al. | Jan 2009 | B2 |
7524464 | Ahn et al. | Apr 2009 | B2 |
7550810 | Mignard et al. | Jun 2009 | B2 |
7600533 | Tai et al. | Oct 2009 | B2 |
7611673 | Kartalov et al. | Nov 2009 | B2 |
7691623 | Jobst et al. | Apr 2010 | B2 |
7741123 | Pease et al. | Jun 2010 | B2 |
7799553 | Mathies et al. | Sep 2010 | B2 |
7832429 | Young et al. | Nov 2010 | B2 |
7842248 | McAvoy et al. | Nov 2010 | B2 |
20040151629 | Pease et al. | Aug 2004 | A1 |
20040188648 | Xie et al. | Sep 2004 | A1 |
20040209354 | Mathies et al. | Oct 2004 | A1 |
20050092662 | Gilbert et al. | May 2005 | A1 |
20050098750 | Sobek | May 2005 | A1 |
20050161327 | Palmieri | Jul 2005 | A1 |
20050223783 | Spivak | Oct 2005 | A1 |
20060014083 | Carlson | Jan 2006 | A1 |
20060180779 | Allen et al. | Aug 2006 | A1 |
20080087855 | Wang et al. | Apr 2008 | A1 |
20090056822 | Young et al. | Mar 2009 | A1 |
20090256218 | Mignard et al. | Oct 2009 | A1 |
Number | Date | Country |
---|---|---|
1 314 472 | May 2003 | EP |
2 022 753 | Feb 2009 | EP |
0109598 | Feb 2001 | WO |
Entry |
---|
van der Wouden et al., Field-effect control of electro-osmotic flow in microfluidic networks, Colloids and Surfaces A: Physicochemical and Engineering Aspects, vol. 267, Issues 1-3, Oct. 5, 2005, pp. 110-116. |
Gong et al., Direct-referencing two-dimensional-array digital microfluidics using multilayer printed circuit board, Journal of microelectromechanical systames, vol. 17, No. 2, Apr. 2008, p. 257-264. |
Paul et al., Lamination-based rapid prototyping of microfluidic devices using flexible thermoplastic substrates, Electrophoresis 2007, 28, p. 1115-1122. |
H.T.G. van Lintel et al., “A piezoelectric micropump based on micromachining of silicon”, Sensors and Actuators, vol. 15, No. 2, pp. 153-167 (1988). |
E. Stemme and G. Stemme, “A valveless diffuser/nozzle-based fluid pump”, Sensors and Actuators A. vol. 39, No. 2, pp. 159-167 (1993). |
T. Ohori et al., “Partly disposable three-way microvalve for a medical micro total analysis system (μTAS)”, Sensors and Actuators A. vol. 64, No. 1, pp. 57-62 (1998). |
S. Böhm et al., “A plastic micropump constructed with conventional techniques and materials”, Sensors and Actuators A. vol. 77, No. 3, pp. 223-228 (1999). |
T.T. Veenstra et al., “Use of selective anodic bonding to create micropump chambers with virtually no dead volume”, Journal of the Electrochemical Society, vol. 148, No. 2 pp. G68-G72 (2001). |
D.C. Duffy et al., “Microfabricated centrifugal microfluidic systems: Characterization and multiple enzymatic assays”, Analytical Chemistry, vol. 71, No. 20, pp. 4669-4678 (1999). |
N.T. Nguyen et al., “MEMS-Micropumps: A Review”, Journal of Fluids Engineering, vol. 124, No. 2, pp. 384-392 (2002). |
W.H. Grover et al., “Monolithic membrane valves and diaphragm pumps for practical large-scale integration into glass microfluidic devices”, Sensors and Actuators B, vol. 89, No. 3, p. 315-323 (2003). |
C.K. Fredrickson and Z.H. Fan, “Macro-to-micro interfaces for microfluidic devices”, Lab on a Chip, vol. 4, No. 6, pp. 526-533 (2004). |
A. Groisman and S.R. Quake, “A microfluidic rectifier: Anisotropic flow resistance at low Reynolds numbers”, Physical Review Letters, vol. 92, No. 9, pp. 094501-1 to 094501-4 (2004). |
C.-H. Wang and G.-B. Lee, “Automatic bio-sampling chips integrated with micro-pumps and micro-valves for disease detection”, Biosensors and Bioelectronics, vol. 21, No. 3, pp. 419-425 (2004). |
P. Liu et al. “Integrated Portable Polymerase Chain Reaction-Capillary Electrophoresis Microsystem for Rapid Forensic Short Tandem Repeat Typing” Analytical Chemistry, vol. 79, No. 5, pp. 1881-1889 (2007). |
C. Zhang et al., “Micropumps, microvalves, and micromixes with PCR microfluidic chips: Advances and trends”, Biotechnology Advances, vol. 25, No. 5, pp. 483-514 (2007). |
Number | Date | Country | |
---|---|---|---|
20130034467 A1 | Feb 2013 | US |