Chemical apparatus and process disinfecting – deodorizing – preser – Analyzer – structured indicator – or manipulative laboratory... – Means for analyzing liquid or solid sample
Reexamination Certificate
1998-01-30
2001-05-01
Ludlow, Jan (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Analyzer, structured indicator, or manipulative laboratory...
Means for analyzing liquid or solid sample
C422S081000, C422S082050, C422S082090, C204S603000, C204S612000, C356S073100, C356S246000, C356S344000
Reexamination Certificate
active
06224830
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to microfluid total analysis systems, and methods for making such systems.
BACKGROUND OF THE INVENTION
Obtaining good limits of detection when using optical detection has been a challenge in capillary electrophoresis, due to the short path lengths engendered by the small capillary diameter. Increasing the path length of measuring radiation with a detection zone is therefore desirable. Several approaches are known in the art, such as the U-channel described in “Microfabrication of a Planar Absorbance and Fluorescence Cell for Integrated Capillary Electrophoresis Devices”, Zhenhua Liang et al, Analytical Chemistry, vol. 68, no. 6, Mar. 15, 1996, the Z-channel described in European patent application 93203166.9 published May 18, 1994, or an in-channel reflection device in silicon, described in Manz et al, U.S. Pat. No. 5,599,503 issued Feb. 4, 1997.
The U-channel device of Liang et al has the disadvantage that, although it is of simple design, it is hard to manufacture since an optic fiber used to deliver light to the absorbance zone must have a dimension similar to the size of the channel. Sliding such a fiber into a hole in the device is a very difficult task.
In the design of absorbance cells in microfluid devices, it is desirable to reduce the loss of resolution due to the detector volume. Greater detector volume means lower resolution. This arises as follows. If the absorbance zone becomes very long (higher volume), any molecules that absorb the measuring radiation in the entire path length of the absorbance zone are detected. Thus, if the separation of two species of molecules being detected is less than the length of the absorbance zone the signals from the two species overlap and cannot be resolved. The detector length in a microfluid device is limited to about 200 &mgr;m.
Manz et al, who apply principles known from 1942 (White, J. Opt. Soc. Am., 32 (1942) 285) attempt to solve this problem for certain devices by reflecting light off bounding surfaces of a channel, but the disclosed device is not readily manufactured in devices other than silicon and cannot be used very easily for capillary electrophoresis due to the use of the semiconductor silicon. The formation of mirror planes in glass at the sample introduction point is particularly hard to achieve. Other difficulties include alignment difficulty resulting from the use of optical fibers, and the necessity of forming holes through the plates defining the channel. It is an object of this invention to provide a microfluid device with enhanced path length, improved sensitivity, that may be manufactured without great difficulty in a wide variety of materials.
SUMMARY OF THE INVENTION
There is therefore provided an improved absorbance or detection cell for a microfluid device, and in accordance with an aspect of the invention, the absorbance cell comprises a bottom plate having a channel bearing surface in which a channel is defined, the channel having a fluid inlet and fluid outlet, a top plate having a channel facing surface bound to the channel bearing surface of the bottom plate and first and second reflecting elements formed on opposed sides of the channel to form a waveguide through which the channel extends such that radiation propagating along the waveguide makes multiple passes across the channel, the waveguide having a radiation input end and a radiation output end.
According to a further aspect of the invention, electrically non-conducting material of one of the top plate and bottom plate is disposed between the first reflecting element and the channel, the electrically non-conducting material being transparent to measuring radiation. By this aspect, the reflecting element is no longer in contact with buffer solution during analysis, the device becomes easier to manufacture and in addition the reflecting elements may be made laterally extensive to block stray radiation from reaching a detector.
According to a further aspect of the invention, electrically non-conducting material of the top plate is disposed between the first reflecting element and the channel.
According to a further aspect of the invention, electrically non-conducting material of the bottom plate is disposed between the second reflecting element and the channel, the electrically non-conducting material of the bottom plate being transparent to measuring radiation.
According to a further aspect of the invention, the waveguide input end and the waveguide output end are arranged so that measuring radiation enters the waveguide through one of the top plate and the bottom plate and exits the waveguide through the other of the top plate and the bottom plate. By this arrangement, contamination of detected radiation from radiation at the input end of the waveguide is reduced.
According to a further aspect of the invention, the first reflecting element is formed on a first face of a first plate segment, the first face of the first plate segment abuts against a second face of a second plate segment, and together the first and second plate segments form the bottom plate. By this arrangement, the path length of measuring radiation in the bottom plate is reduced.
According to a further aspect of the invention, there is also provided an input aperture in one of the first and second reflecting elements for introduction of measuring radiation into the waveguide, and an output aperture in the other of the first and second reflecting elements for egress of measuring radiation from the waveguide.
According to a further aspect of the invention, the waveguide input end is arranged such that radiation introduced into the waveguide through one of the top plate and bottom plate propagates at an angle &agr; to a normal to the reflecting surfaces as the radiation passes through the one of the top plate and bottom plate by this arrangement, it is not necessary to have a reflecting surface within the waveguide that deflects perpendicular incident light along the waveguide.
According to a further aspect of the invention, the waveguide input end is arranged such that radiation introduced to the waveguide has a free space mode of propagation. Radiation with a free space mode of propagation advantageously allows control of the radiation propagation direction using optical elements such as mirrors and lenses.
According to a further aspect of the invention, the reflecting elements extend laterally to form a shield between a measuring radiation source and a measuring radiation detector.
According to a further aspect of the invention, the channel of a microfluid device used for capillary electrophoresis is coated with polysiloxane.
According to a further aspect of the invention, the fluid inlet of a microfluid device comprises a flat ended capillary inserted through a hole in a first plate, with the flat ended capillary butting up against a surface of a second plate in which a channel is defined with the flat ended capillary centered over the channel.
According to further aspects of the invention, there are provided several methods of making an absorbance cell for a microfluid device.
One such method comprises the steps of providing a channel in a first plate, attaching a second plate to the first plate; and forming a waveguide about the channel with material of one of the first plate and second plate between the waveguide and the channel.
Another such method comprises the steps of:
forming a first reflecting element on a first face of a first bottom plate segment;
bonding a second bottom plate segment to the first face of the first bottom plate segment;
forming a channel in the second bottom plate segment on a side of the second bottom plate segment opposed to the first bottom plate segment;
bonding a top plate to the first bottom plate segment; and
forming a second reflecting element on the top plate, the first and second reflecting elements being formed on opposed sides of the channel to form a waveguide through which the channel extends such that radiation propagating along the waveguide makes multiple passes across the channel, the
Chiem Nghia H.
Harrison D. Jed
Jiang Yutao
McKinnon Graham H.
Ocvirk Gregor
Christensen O'Connor Johnson & Kindness PLLC
Ludlow Jan
The Governors of the University of Alberta
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