Integrated microfluidic element

Chemical apparatus and process disinfecting – deodorizing – preser – Control element responsive to a sensed operating condition

Reexamination Certificate

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C156S060000, C156S087000, C156S099000, C156S108000, C216S002000, C422S091000, C422S105000

Reexamination Certificate

active

06322753

ABSTRACT:

The present invention relates to integrated microfluidic elements and a method for the manufacture thereof. Such elements are often composed of two juxtaposed plates bonded together, wherein one plate has an etched structure or pattern of channels on the surface facing the other plate to form sealed microchannels.
Glass substrates have in recent years been used in the manufacture of miniaturized analytic electrophoresis instrumentation with micromachining techniques (Harrison, D. J.; Fluri, K., Seiler, K.; Fan, Z.; Effenhauser, C. S.; Manz, A.,
Science
, 261 (1993) 895-897. Effenhauser, C. S.; Manz, A.; Widmer, H. M.,
Anal. Chem
., 65 (1993) 2637-2642. Seiler, K.; Harrison, D. J.; Manz, A.;
Anal. Chem
., 65 (1993) 1481-1488. Jacobson, S. C.; Hergenröder, R.; Koutny, L. B.; Ramsey, J. M.,
Anal. Chem
., 66 (1994) 2369-2373. Effenhauser, C. S.; Paulus, A.; Manz, A.; Widmer, H. M.,
Anal. Chem
., 66 (1994) 2949-2953. Seiler, K.; Fan, Z. H.; Fluri, K.; Harrison, D. J.,
Anal. Chem
., 66 (1994) 3485-3491. Jacobson, S. C.; Koutny, L. B.; Hergenroder, R.; Moore, A. W.; Ramsey, J. M.,
Anal. Chem
., 66 (1994) 3472-3476).
The insulating glass material permits the use of high voltages which can accomplish fast and efficient separations and its transparency allows for sensitive on-column optical sample detection.
Bonding of planar structures is an important step necessary in the manufacture of micro-instrumentation. For utilization of microfabricated flow channels in analytical techniques such as electrophoresis, chromatography, flow injection analysis or field-flow fractionation, the bond between the structures should preferably be direct. Thus, adhesives should be avoided that can clog the capillaries and negatively effect the efficiency or the liquid flow pattern. Accordingly, an etched structure in for example glass is by preference sealed to another glass plate by fusion bonding at a temperature that permits fusion while not deforming the glass parts, to produce uniformly assembled channel structures.
It is difficult to manufacture large bonded assemblies without irregularities, since the demand on the substrate material in terms of planarity, smoothness and cleanness increases with the area of the substrate. Furthermore, it is usually essential that the surfaces are connected under extreme clean room conditions, so that particle contamination can be eliminated at their interface. Void formation often occurs in the process cycle when bonding starts at the same time at various locations. Once a void is generated the trapped gas cannot be exhausted from its confinement.
The glass material most commonly used in micromachining laboratories is polished substrates of Pyrex Corning 7740, due to its compatibility with silicon in terms of thermal expansion. This expensive material is extensively used for anodic bonding to silicon in the manufacture of microsensors (Cozma, A.; Puers, B.
J. Micromech. Microeng
. 5 (1995) 98-102). However, details on glass-glass fusion bonding of micromachined structures are very sparse in the literature. The reported bonding process is characterized by a low yield which often involves repeated cycles ((Harrison, D. J.; Fluri, K., Seiler, K.; Fan, Z.; Effenhauser, C. S.; Manz, A.,
Science
, 261 (1993) 895-897), including the use of weights placed over poorly bonded regions (Fan, Z.; Harrison, D. J.
Anal. Chem
66 (1994) 177-184). Recently, the yield has been improved by the use of sophisticated polishing and cleaning instrumentation (Fluri, K.; Fitzpatrick, C.; Chiem, N.; Harrison, D. J.
Anal. Chem
68 (1996) 4285-4290), available only in specialized micromachining laboratories.
For sample detection purposes, many applications require that one of the glass substrates is very thin (0.15 -0.20 mm), e.g. when using high numerical aperture microscope objectives. An important example of such an application where a high degree of magnification is required is the direct observation of DNA polymer motion by fluorescence microscopy. Bonding thin glass introduces additional problems mainly due to that the commercially available thin cover glass often is manufactured by a drawing process and therefore not very planar. Raley et al. reported on a etch-back technique where first two thicker sheaths of Corning 7740 were bonded together and subsequently thinning one of the sheaths by etching and several grinding steps (Raley, N. F.; Davidson, J. C.; Balch, J. W.
Proc. SPIE-Int. Soc. Opt. Eng
. 2639 (1995) 40-45). Their best glass-glass bonding results were reported to be in the order of a 85% area coverage for 5×5 cm to 5×18 cm glass specimens with a original thickness of 800 &mgr;m. However, the etch-back technique is anticipated to depend on how well the etching process can be optimized.
The present invention has for its main object to provide new techniques for the provision of integrated microfluidic elements where the problems encountered with the prior art as illustrated above are eliminated or at least greatly reduced.
Another object of the invention is to provide a method for the manufacture of integrated microfluidic elements, wherein entrapment of gas between the plates to be bonded together can be avoided.
Yet another object of the invention is to provide a method for such manufacture, wherein the problems encountered in the bonding of two plates of different thermal coefficents of expansion together will be largely avoided.
Still another object of the invention is to provide integrated microfluidic elements free of undesirable voids and less vulnerable to inconsistencies in thermal coefficients of expansion.
For these and other objects which will be clear from the following disclosure the invention provides for a method for the manufacture of an integrated microfluidic element composed of two juxtaposed plates bonded together, wherein at least one plate has an etched structure or pattern of channels on the surface facing the other plate to form sealed microchannels. This method is characterized by forming, distributed over the etched surface of said one plate outside of said etched structure or pattern, micro spacers or posts
11
, and by forming walls surrounding said channels
9
, said walls
9
having a height equal to that of said spacers or posts
11
and then bonding the two plates
3
,
5
together to form said element.
The plates can be bonded together by fusion bonding at an increased temperature which does not exceed the softening temperature of the plates.
The plates may also be bonded together by field assisted bonding methods. The bonding techniques used are not critical to the invention and any conventional bonding method can be used. An example of such conventional bonding method is anodic bonding of a glass plate to a silicon substrate.
The plates used can be constituted by materials used in the art, such as ordinary glass, silicon, quartz, diamond, carbon, ceramics or polymers. Particularly useful materials are glass, quartz and silicon.
It is particularly preferred in the method of the invention to form also the spacers or posts and the walls simultaneously with the forming of the structure of pattern of channels by etching.
According to an alternative method the etching can be carried out in two steps, a first step to form the channels and a second step to form the spacers or posts. By such alternative method the depth of the etched sections can be varied.
In some cases it is desired to impart special properties to the channels formed, and here the juxtaposed surfaces of the plates are covered by a thin layer before bonding the plates together. Such layer can be formed e.g. by chemical vaporization deposition (CVD), and the layer can be constituted by any desired material, such as silicon nitride, metals, glass etc.
Access to the channels formed in the microfluidic element of the invention is suitably obtained by the formation of holes in either or both of the two plates in positions coinciding with the channels.
To obtain optimal performance of the microfluidic element of the invention it is preferred that the contact surfac

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