Monolithic nanofluid sieving structures for DNA manipulation

Semiconductor device manufacturing: process – Making device or circuit responsive to nonelectrical signal

Reexamination Certificate

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C438S050000, C438S053000, C438S800000

Reexamination Certificate

active

06753200

ABSTRACT:

BACKGROUND OF THE INVENTION
The present invention relates, in general, to methods of fabricating fluidic devices and to structures produced by such methods, and more particularly to processes including the removal of sacrificial layers for fabricating multi-level fluidic devices integrally with other devices on a substrate for interconnecting such devices.
The emerging field of fluidics has the potential to become one of the most important areas of new research and applications. Advances in genomics, chemistry, medical implant technology, drug discovery, and numerous other fields virtually guarantee that fluidics will have an impact that could rival the electronics revolution.
Many fluidic applications have already been developed. Flow cytometers, cell sorters, pumps, fluid switches, capillary electrophoresis systems, filters, and other structures have been developed using a variety of materials and techniques in a wide range of applications, including protein separation, electrophoresis, mass spectrometry, and others, have been developed. One of the goals of workers in this field is to develop a “total analysis system” wherein various structures are integrally formed on a single substrate, and for this purpose a variety of techniques, rag from silicon micromachining to injection molding of plastics, have been developed. All of these prior techniques, however, have in common that fluid capillaries are formed by bonding or lamination of a grooved surface to a cap layer, and in cases where multiple layers are present, these result from bonding together multiple substrates. Unfortunately, the drive to develop complex fluidic devices in the environment of a total analysis system has been hindered by the inherent difficulties with lamination-based fabrication techniques. As more devices are integrated onto a single substrate, the connection of the devices requires that connecting fluidic tubes cross over each other. With bonding technology, two capillaries cannot cross without lamination of a second wafer to the basic substrate. Further, the second wafer must be thick, resulting in large aspect ratio vertical interconnects, and ultimately resulting in a limit on miniaturization. If such devices were to reach mass production, alignment and bonding technology to handle the complex assembly would have to be developed, and whatever technology is employed would in all likelihood require costly redevelopment with each generation of smaller more complex fluidic devices.
One major application of fluidic devices is in the fabrication of artificial gel media, which has been a topic of interest for some years for scientific and practical reasons. Artificial gels differ from conventional polyalcrylamide or agarose gels currently used for DNA separation in that the sieving matrix in an artificial gel can be defined explicitly using nanofabrication, rather than relying on the random arrangement of long-chain polymers in the conventional gel. As such, the dimensions and topology of the artificial gel sieving matrix can be controlled and measured precisely. This makes it possible to test theories of DNA electrophoresis with fewer free variables. Artificial gels also have advantages over conventional gels in that conventional gels are expensive and require skilled operators to prepare them immediately before use, whereas artificial gels can be integrated with mass-produced microfabricated chemical processing chips and shipped in a ready-to-use form.
However, previous methods for fabricating artificial gels involved bonding a top layer, either glass or a pliable elastomeric material, to a silicon die with columnar obstacles micromachined into the surface. Such methods have been successful for structures with fluid gap heights as small as 100 nm, but it is difficult to establish a uniform and predictable fluid gap between a silicon floor and a glass or elastomeric top layer. An elastomer layer, and in many cases even a glass layer, can flow between the retarding obstacles in the fluid gap, either dosing the gap entirely or creating large variations in the gap height. Both methods are sensitive to particulate contamination to the extent that a single particle can render an entire device unusable.
SUMMARY OF THE INVENTION
It is, therefore, an object of the invention to provide a method for fabricating multiple fluidic devices as a monolithic unit by the use of a sacrificial layer removal process wherein fluidic devices with one or more layers can be fabricated by successive application and patterned removal of thin films. Some of these films are permanent, and some are sacrificial; that is, they will be removed before the fabrication is complete. When the sacrificial layers are removed, the empty spaces left behind create a “working gap” for the fluidic device which can be virtually any shape, and which can be configured to perform a number of different functions.
Another object of the present invention is to produce nano-fabricated flow channels having interior diameters on the order of 10 nm. Such nanometer-scale dimensions are difficult to attain with conventional micro-fluidic fabrication techniques, but the present invention facilitates fabrication at this scale while at the same time providing integration of such flow channels with other devices. These devices can provide fundamental insights into the flow of fluids in nano-constrictions and are useful in studying the behavior of biological fluids with molecular components similar in size to the cross-section of the channel. The process of the present invention permits the dimensions of the flow channels to be adjusted, for example to manipulate and analyze molecules, viruses, or cells, and the process has the potential of producing structures which will reach currently unexplored areas of physics and biology.
Another object of the invention is to provide a multi-level fluid channels fabricated on a single substrate with fluid overpasses and selective vertical interconnects between levels. Multi-level fabrication is a requirement for any complex fluid circuit, where fluid channels interconnect multiple devices on a single substrate, for without multiple levels, interconnection of large numbers of devices is either impossible or requires tortuous interconnect pathways. Lee available level of sophistication of microfluidic devices is tremendously improved by the capabilities provided by the present invention.
Briefly, the present invention is directed to procedures and techniques for overcoming the inherent difficulties and limitations of prior art laminar bonding approaches to fluidics fabrication and integration of components. In one aspect of the invention, these difficulties are avoided in the fabrication of a monolithic fluidic device by utilizing a shaped sacrificial layer which is sandwiched between permanent floor and ceiling layers, with the shape of the sacrificial layer defining a working gap. When the sacrificial layer is removed, the working gap becomes a fluid channel having the desired configuration. This approach eliminates bonding steps and allows a precise definition of the height, width and shape of interior working spaces, or fluid channels, in the structure of a fluidic device. The sacrificial layer is formed on a substrate, is shaped by a suitable lithographic process, for example, and is covered by a ceiling layer. Thereafter, the sacrificial layer is removed with a wet chemical etch, leaving behind empty spaces between the floor and ceiling layers which form working gaps which may be used as flow channels and chambers for the fluidic device. In such a device, the vertical dimension, or height, of a working gap is determined by the thickness of the sacrificial layer film, which is made with precise chemical vapor deposition (CVD) techniques, and accordingly, this dimension can be very small.
In order to provide access to the sacrificial layer contained in the structure for the etching solution which is used to remove the sacrificial layer, one or more access holes are cut through the ceiling layer, with the wet etch removing

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