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TECHNICAL FIELD
The present invention relates generally to miniaturized planar column
technology for liquid phase analysis, and more particularly to fabrication
of microstructures in novel separation support media using laser ablation
techniques. The microstructures produced under the present invention find
use in any analysis system which is performed on either small and/or
macromolecular solutes in the liquid phase and which may employ
chromatographic or electrophoretic means of separation, or a combination
of both.
BACKGROUND OF THE INVENTION
In sample analysis instrumentation, and especially in separation systems
such as liquid chromatography and capillary electrophoresis systems,
smaller dimensions will generally result in improved performance
characteristics and at the same time result in reduced production and
analysis costs. In this regard, miniaturized separation systems provide
more effective system design, result in lower overhead due to decreased
instrumentation sizing and additionally enable increased speed of
analysis, decreased sample and solvent consumption and the possibility of
increased detection efficiency.
Accordingly, several approaches towards miniaturization for liquid phase
analysis have developed in the art; the conventional approach using drawn
fused-silica capillary, and an evolving approach using silicon
micromachining. What is currently thought of as conventional in
miniaturization technology is generally any step toward reduction in size
of the analysis system.
In conventional miniaturized technology the instrumentation has not been
reduced in size; rather, it is the separation compartment size which has
been significantly reduced. As an example, micro-column liquid
chromatography (.mu.LC) has been described wherein columns with diameters
of 100-200 .mu.m are employed as compared to prior column diameters of
around 4.6 mm.
Another approach towards miniaturization has been the use of capillary
electrophoresis (CE) which entails a separation technique carried out in
capillaries 25-100 .mu.m in diameter. CE has been demonstrated to be
useful as a method for the separation of small solutes. J. Chromatog.
218:209 (1981); Analytical Chemistry 53:1298 (1981). In contrast,
polyacrylamide gel electrophoresis was originally carried out in tubes 1
mm in diameter. Both of the above described "conventional" miniaturization
technologies (.mu.LC and CE) represent a first significant step toward
reducing the size of the chemical portion of a liquid phase analytical
system. However, even though experimentation with such conventional
miniaturized devices has helped to verify the advantages of
miniaturization in principal, there nevertheless remain several major
problems inherent in those technologies.
For example, there remains substantial detection limitations in
conventional capillary electrophoresis technology. For example, in CE,
optical detection is generally performed on-column by a single-pass
detection technique wherein electromagnetic energy is passed through the
sample, the light beam travelling normal to the capillary axis and
crossing the capillary only a single time. Accordingly, in conventional CE
systems, the detection path length is inherently limited by the diameter
of the capillary.
Given Beer's law, which relates absorbance to the pathlength through the
following relationship:
A=.epsilon.*b*C
where:
A=the absorbance
.epsilon.=the molar absorptivity, (l/m,cm)
b=pathlength (cm)
C=concentration (m/l)
it can be readily understood that the absorbance (A) of a sample in a 25
.mu.m capillary would be a factor of 400.times.less than it would be in a
conventional 1 cm pathlength cell as typically used in UV/Vis
spectroscopy.
In light of this significant detection limitation, there have been a number
of attempts employed in the prior art to extend detection pathlengths, and
hence the sensitivity of the analysis in CE systems. In U.S. Pat. No.
5,061,361 to Gordon, there has been described an approach entailing
micro-manipulation of the capillary flow-cell to form a bubble at the
point of detection. In U.S. Pat. No. 5,141,548 to Chervet, the use of a
Z-shaped configuration in the capillary, with detection performed across
the extended portion of the Z has been described. Yet another approach has
sought to increase the detection pathlength by detecting along the major
axis of the capillary (axial-beam detection). Xi et al., Analytical
Chemistry 62:1580 (1990).
In U.S. Pat. No. 5,273,633 to Wang, a further approach to increased
detection pathlengths in CE has been described where a reflecting surface
exterior of the capillary is provided, the subject system further
including an incident window and an exit window downstream of the incident
window. Under Wang, light entering the incident window passes through a
section of the capillary by multiple internal reflections before passing
through the exit window where it is detected, the subject multiple
internal reflections yielding an effective increase in pathlength. While
each of the aforementioned approaches has addressed the issue of extending
the pathlength, each approach is limited in that it entails engineering
the capillary after-the-fact or otherwise increasing the cost of the
analysis.
A second major drawback in the current approach to miniaturization involves
the chemical activity and chemical instability of silicon dioxide
(SiO.sub.2) substrates, such as silica, quartz or glass, which are
commonly used in both CE and .mu.LC systems. More particularly, silicon
dioxide substrates are characterized as high energy surfaces, in that such
materials interact irreversibly with a number of compounds and strongly
adsorb many compounds, most notably bases. The use of silicon dioxide
materials in separation systems is further restricted due to the chemical
instability of those substrates, as the dissolution of SiO.sub.2 materials
increases in basic conditions (at pH's greater than 7.0) due to the
general weakness of the Si--O--Si bond.
To avoid the problems arising from the inherent chemical activity of
silicon dioxide materials, prior separation systems have attempted
chemical modifications to the inner silica surface of capillary walls. In
general, such post-formation modifications are difficult as they require
the provision of an interfacial layer to bond a desired surface treatment
to the capillary surface, using, for example, silylating agents to create
Si--O--Si--C bonds. Although such modifications may decrease the
irreversible adsorption of solute molecules by the capillary surfaces,
these systems still suffer from the chemical instability of Si--O--Si
bonds at pH's above 7.0. Accordingly, chemical instability in SiO.sub.2
materials remains a major problem.
However, despite the recognized shortcomings with the chemistry of
SiO.sub.2 substrates, those materials are still used in separation systems
due to their desirable optical properties. In this regard, potential
substitute materials which exhibit superior chemical properties compared
to silicon dioxide materials are generally limited in that they are also
highly adsorbing in the UV region, where detection is important.
In order to avoid some of the substantial limitations present in
conventional .mu.LC and CE techniques, and in order to enable even greater
reduction in separation system sizes, there has been a trend towards
providing planarized systems having capillary separation microstructures.
In this regard, production of miniaturized separation systems involving
fabrication of microstructures in silicon by micromachining or
microlithographic techniques has been described. See, e.g. Fan et al.,
Anal. Chem. 66(1):177-184 (1994); Manz et al., Adv. in Chrom. 33:1-66
(1993); Harrison et al., Sens. Actuators, B B10(2): 107-116 (1993); Manz
et al., Trends Anal. Chem. 10(5): 144-149 (1991); and Manz et al., Sensors
and Actuators B (Chemical) B1(1-6) :249-255 (1990) .
The use of micromachining techniques to fabricate separation systems in
silicon provides the practical benefit of enabling mass production of such
systems. In this regard, a number of established techniques developed by
the microelectronics industry involving micromachining of planar
materials, such as silicon, exist and provide a useful and well accepted
approach to miniaturization. Examples of the use of such micromachining
techniques to produce miniaturized separation devices on silicon or
borosilicate glass chips can be found in U.S. Pat. No. 5,194,133 to Clark
et al.; U.S. Pat. No. 5,132,012 to Miura et al.; in U.S. Pat. No.
4,908,112 to Pace; and in U.S. Pat. No. 4,891,120 to Sethi et al.
Micromachining silicon substrates to form miniaturized separation systems
generally involves a combination of film deposition, photolithography,
etching and bonding techniques to fabricate a wide array of three
dimensional structures. Silicon provides a useful substrate in this regard
since it exhibits high strength and hardness characteristics and can be
micromachined to provide structures having dimensions in the order of a
few micrometers.
Although silicon micromachining has been useful in the fabrication of
miniaturized systems on a single surface, there are significant
disadvantages to the use of this approach in creating the analysis device
portion of a miniaturized separation system.
Initially, silicon micromachining is not amenable to producing a high
degree of alignment between two etched or machined pieces. This has a
negative impact on the symmetry and shape of a separation channel formed
by micromachining, which in turn may impact separation efficiency.
Secondly, sealing of micromachined silicon surfaces is generally carried
out using adhesives which may be prone to attack by separation conditions
imposed by liquid phase analyses. Furthermore, under oxidizing conditions,
a silica surface is formed on the silicon chip substrate. In this regard,
silicon micromachining is also fundamentally limited by the chemistry of
SiO.sub.2. Accordingly, there has remained a need for an improved
miniaturized separation system which is able to avoid the inherent
shortcomings of conventional miniaturization and silicon micromachining
techniques.
SUMMARY OF THE INVENTION
The present invention relates to a miniaturized planar column device for
use in a liquid phase analysis system. It is a primary object of the
present invention to provide a miniaturized column device laser-ablated in
a substantially planar substrate, wherein said substrate is comprised of a
material selected to avoid the inherent chemical activity and pH
instability encountered with silicon and prior silicon dioxide-based
device substrates.
The present invention is also related to the provision of detection means
engineered into a miniaturized planar column device whereby enhanced
on-column analysis or detection of components in a liquid sample is
enabled. It is further contemplated under the invention to provide a
column device for liquid phase analysis having detection means designed
into the device in significantly compact form as compared to conventional
technology. In one particular aspect of the present invention, it is
contemplated to provide optical detection means ablated in a miniaturized
planar column device and having a substantially enhanced detection
pathlength.
It is a further related object of the present invention to provide a device
featuring improved means for liquid handling, including sample injection,
and to provide a miniaturized column device with means to interface with a
variety of external liquid reservoirs. Specifically contemplated herein is
a system design which allows a variety of injection methods to be readily
adapted to the planar structure, such as pressure injection, hydrodynamic
injection or electrokinetic injection.
It is yet a further related object of the present invention to provide a
miniaturized total chemical analysis system (.mu.-TAS) fully contained on
a single, planar surface. In this regard, a miniaturized system according
to the present invention is capable of performing complex sample handling,
separation, and detection methods with reduced technician manipulation or
interaction. Accordingly, the subject invention finds potential
application in monitoring and/or analysis of components in industrial
chemical, biological, biochemical and medical processes and the like.
A particular advantage of the present invention is the use of processes
other than silicon micromachining techniques or etching techniques to
create miniaturized columns in a wide variety of polymeric and ceramic
substrates having desirable attributes for an analysis portion of a
separation system. More specifically, it is contemplated herein to provide
a miniaturized planar column device by ablating component microstructures
in a substrate using laser radiation. In one preferred embodiment, a
miniaturized column device is formed by providing two substantially planar
halves having microstructures laser-ablated thereon, which, when the two
halves are folded upon each other, define a separation compartment
featuring enhanced symmetry and axial alignment.
Use of laser ablation techniques to form miniaturized devices according to
the present invention affords several advantages over prior etching and
micromachining techniques used to form systems in silicon or silicon
dioxide materials. Initially, the capability of applying rigid
computerized control over laser ablation processes allows microstructure
formation to be executed with great precision, thereby enabling a
heightened degree of alignment in structures formed by component parts.
The laser ablation process also avoids problems encountered with
microlithographic isotropic etching techniques which may undercut masking
during etching, giving rise to asymmetrical structures having curved side
walls and flat bottoms.
Laser ablation further enables the creation of microstructures with greatly
reduced component size. In this regard, microstructures formed according
to the invention are capable of having aspect ratios several orders of
magnitude higher than possible using prior etching techniques, thereby
providing enhanced separation capabilities in such devices. The use of
laser-ablation processes to form microstructures in substrates such as
polymers increases ease of fabrication and lowers per-unit manufacturing
costs in the subject devices as compared to prior approaches such as
micromachining devices in silicon. In this regard, devices formed under
the invention in low-cost polymer substrates have the added feature of
being capable of use as substantially disposable miniaturized column
units.
In another aspect of the instant invention, laser-ablation in planar
substrates allows for the formation of microstructures of almost any
geometry or shape. This feature not only enables the formation of complex
device configurations, but further allows for integration of sample
preparation, sample injection, post-column reaction and detection means in
a miniaturized total analysis system of greatly reduced overall
dimensions.
The compactness of the analysis portion in a device produced under to the
present invention, in conjunction with the feature that integral functions
such as injection, sample handling and detection may be specifically
engineered into the subject device to provide a .mu.-TAS device, further
allows for integrated design of system hardware to achieve a greatly
reduced system footprint.
By the present invention, inherent weaknesses existing in prior approaches
to liquid phase separation device miniaturization, and problems in using
silicon micromachining techniques to form miniaturized column devices have
been addressed. Accordingly, the present invention discloses a
miniaturized column device capable of performing a variety of liquid phase
analyses on a wide array of liquid samples.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an exploded view of a miniaturized column device constructed in
accordance with the present invention.
FIG. 2 is a plan view of the interior surface of the miniaturized column
device of FIG. 1.
FIG. 3 is a plan view of the exterior surface of the device of FIG. 1.
FIG. 4 is a cross-sectional side view of the miniaturized column device of
FIG. 1, taken along lines IV--IV and showing formation of a separation
compartment according to the invention.
FIG. 5 is an exploded view of a preferred embodiment of the present
invention including optical detection means.
FIG. 6 is a cross-sectional axial view of the intersection of the
separation compartment and the optical detection means in the miniaturized
column device of FIG. 5.
FIG. 7 is an exploded view of a first side of a miniaturized column device
having microchannels formed on two opposing planar surfaces of a support
substrate.
FIG. 8 is an exploded view of a second side of the column device of FIG. 7.
FIG. 9 is a cross-sectional trans-axial view of the extended optical
detection pathlength in the miniaturized column of FIG. 8 taken along
lines IX--IX.
FIG. 10 is plan view of a miniaturized column device constructed under the
invention having first and second component halves.
FIG. 11 is a pictorial representation of the column device of FIG. 10
showing the folding alignment of the component halves to form a single
device.
FIG. 12 is a cross-sectional axial view of the separation compartment
formed by the alignment of the component halves in the device of FIG. 10.
FIG. 13 is a plan view of a further preferred embodiment of the present
invention having optional micro-alignment means on first and second
component halves.
FIG. 14 is a pictorial representation of the column device of FIG. 13
showing the micro-alignment of the component halves.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Before the invention is described in detail, it is to be understood that
this invention is not limited to the particular component parts of the
devices described or process steps of the methods described as such
devices and methods may vary. It is also to be understood that the
terminology used herein is for purposes of describing particular
embodiments only, and is not intended to be limiting.
In this specification and in the claims which follow, reference will be
made to a number of terms which shall be defined to have the following
meanings:
The term "substrate" is used herein to refer to any material which is
UV-adsorbing, capable of being laser-ablated and which is not silicon or a
silicon dioxide material such as quartz, fused silica or glass
(borosilicates). Accordingly, it is contemplated under the present
invention to form miniaturized column devices in suitable "substrates"
such as laser ablatable polymers (including polyimides and the like) and
in laser ablatable ceramics (including aluminum oxides and the like).
The term "liquid phase analysis" is used to refer to any analysis which is
done on either small and/or macromolecular solutes in the liquid phase.
Accordingly, "liquid phase analysis" as used herein includes
chromatographic separations, electrophoretic separations, and
electrochromatographic separations.
In this regard, "chromatographic" processes generally comprise preferential
separations of components, and include reverse-phase, hydrophobic
interaction, ion exchange, molecular sieve chromatography and like
methods.
"Electrophoretic" separations refers to the migration of particles or
macromolecules having a net electric charge where said migration is
influenced by an electric field. Accordingly electrophoretic separations
contemplated under the invention include separations performed in columns
packed with gels (such as polyacrylamide, agarose and combinations
thereof) as well as separations performed in solution.
"Electrochromatographic" separations refers to combinations of
electrophoretic and chromatographic techniques.
The term "motive force" is used to refer to any means for inducing movement
of a sample along a column in a liquid phase analysis, and includes
application of an electric potential across any portion of the column,
application of a pressure differential across any portion of the column or
any combination thereof.
The term "surface treatment+ is used to refer to preparation or
modification of the surface of a microchannel which will be in contact
with a sample during separation, whereby the separation characteristics of
the device are altered or otherwise enhanced. Accordingly, "surface
treatment+ as used herein includes: physical surface adsorptions; covalent
bonding of selected moieties to functional groups on the surface of
microchannel substrates (such as to amine, hydroxyl or carboxylic acid
groups on condensation polymers); methods of coating surfaces, including
dynamic deactivation of channel surfaces (such as by adding surfactants to
media), polymer grafting to the surface of channel substrates (such as
polystyrene or divinyl-benzene) and thin-film deposition of materials such
as diamond or sapphire to microchannel substrates.
The term "laser ablation" is used to refer to a machining process using a
high-energy photon laser such as an excimer laser to ablate features in a
suitable substrate. The excimer laser can be, for example, of the F.sub.2,
ArF, KrCl, KrF, or XeCl type.
In general, any substrate which is UV absorbing provides a suitable
substrate in which one may laser ablate features. Accordingly, under the
present invention, microstructures of selected configurations can be
formed by imaging a lithographic mask onto a suitable substrate, such as a
polymer or ceramic material, and then laser ablating the substrate with
laser light in areas that are unprotected by the lithographic mask.
In laser ablation, short pulses of intense ultraviolet light are absorbed
in a thin surface layer of material within about 1 .mu.m or less of the
surface. Preferred pulse energies are greater than about 100 millijoules
per square centimeter and pulse durations are shorter than about 1
microsecond. Under these conditions, the intense ultraviolet light
photo-dissociates the chemical bonds in the material. Furthermore, the
absorbed ultraviolet energy is concentrated in such a small volume of
material that it rapidly heats the dissociated fragments and ejects them
away from the surface of the material. Because these processes occur so
quickly, there is no time for heat to propagate to the surrounding
material. As a result, the surrounding region is not melted or otherwise
damaged, and the perimeter of ablated features can replicate the shape of
the incident optical beam with precision on the scale of about one
micrometer.
Although laser ablation has been described herein using an excimer laser,
it is to be understood that other ultraviolet light sources with
substantially the same optical wavelength and energy density may be used
to accomplish the ablation process. Preferably, the wavelength of such an
ultraviolet light source will lie in the 150 nm to 400 nm range to allow
high absorption in the substrate to be ablated. Furthermore, the energy
density should be greater than about 100 millijoules per square centimeter
with a pulse length shorter than about 1 microsecond to achieve rapid
ejection of ablated material with essentially no heating of the
surrounding remaining material. Laser ablation techniques, such as those
described above, have been described in the art. Znotins, T. A., et al.,
Laser Focus Electro Optics, (1987) pp. 54-70; U.S. Pat. Nos. 5,291,226 and
5,305,015 to Schantz et al.
The term "injection molding" is used to refer to a process for molding
plastic or nonplastic ceramic shapes by injecting a measured quantity of a
molten plastic or ceramic substrate into dies (or molds). In one
embodiment of the present invention, miniaturized column devices may be
produced using injection molding.
More particularly, it is contemplated to form a mold or die of a
miniaturized column device wherein excimer laser-ablation is used to
define an original microstructure pattern in a suitable polymer substrate.
The microstructure thus formed may then be coated by a very thin metal
layer and electroplated (such as by galvano forming) with a metal such as
nickel to provide a carrier. When the metal carrier is separated from the
original polymer, an mold insert (or tooling) is provided having the
negative structure of the polymer. Accordingly, multiple replicas of the
ablated microstructure pattern may be made in suitable polymer or ceramic
substrates using injection molding techniques well known in the art.
The term "LIGA process" is used to refer to a process for fabricating
microstructures having high aspect ratios and increased structural
precision using synchrotron radiation lithography, galvanoforming, and
plastic molding. Under a LIGA process, radiation sensitive plastics are
lithographically irradiated at high energy radiation using a synchrotron
source to create desired microstructures (such as channels, ports,
apertures and micro-alignment means), thereby forming a primary template.
The primary template is then filled with a metal by electrodeposition
techniques. The metal structure thus formed comprises a mold insert for
the fabrication of secondary plastic templates which take the place of the
primary template. In this manner highly accurate replicas of the original
microstructures may be formed in a variety of substrates using injection
or reactive injection molding techniques. The LIGA process has been
described by Becker, E. W., et al., Microelectric Engineering 4 (1986) pp.
35-56. Descriptions of numerous polymer substrates which may be injection
molded using LIGA templates, and which are suitable substrates in the
practice of the subject invention, may be found in "Contemporary Polymer
Chemistry", Allcock H R and Lampe, F. W. (Prentice-Hall, Inc.) New Jersey
(1981).
Accordingly, the invention concerns formation of miniaturized column
devices using laser ablation in a suitable substrate. It is also
contemplated to form column devices according to the invention using
injection molding techniques wherein the original microstructure has been
formed by an excimer laser ablation process, or where the original
microstructure has been formed using a LIGA process.
More particularly, microstructures such as separation compartments,
injection means, detection means and micro-alignment means may be formed
in a planar substrate by excimer laser ablation. A frequency multiplied
YAG laser may also be used in place of the excimer laser. In such a case,
a complex microstructure pattern useful for practicing the invention may
be formed on a suitable polymeric or ceramic substrate by combining a
masking process with a laser ablation means, such as in a step-and-repeat
process, where such processes would be readily understood by one of
ordinary skill in the art.
In the practice of the invention, a preferred substrate comprises a
polyimide material such as those available under the trademarks
Kapton.RTM. or Upilex.RTM. from DuPont (Wilmington, Del.), although the
particular substrate selected may comprise any other suitable polymer or
ceramic substrate. Polymer materials particularly contemplated herein
include materials selected from the following classes: polyimide,
polycarbonate, polyester, polyamide, polyether, polyolefin, or mixtures
thereof. Further, the polymer material selected may be produced in long
strips on a reel, and, optional sprocket holes along the sides of the
material may be provided to accurately and securely transport the
substrate through a step-and-repeat process.
Under the invention, the selected polymer material is transported to a
laser processing chamber and laser-ablated in a pattern defined by one or
more masks using laser radiation. In a preferred embodiment, such masks
define all of the ablated features for an extended area of the material,
for example encompassing multiple apertures (including inlet and outlet
ports), micro-alignment means and separation chambers.
Alternatively, patterns such as the aperture pattern, the separation
channel pattern, etc., may be placed side by side on a common mask
substrate which is substantially larger than the laser beam. Such patterns
may then be moved sequentially into the beam. In other contemplated
production methods, one or more masks may be used to form apertures
through the substrate, and another mask and laser energy level (and/or
number of laser shots) may be used to define separation channels which are
only formed through a portion of the thickness of the substrate. The
masking material used in such masks will preferably be highly reflecting
at the laser wavelength, consisting of, for example, a multilayer
dielectric material or a metal such as aluminum.
The laser ablation system employed in the invention generally includes beam
delivery optics, alignment optics, a high precision and high speed mask
shuttle system, and a processing chamber including mechanism for handling
and positioning the material. In a preferred embodiment, the laser system
uses a projection mask configuration wherein a precision lens interposed
between the mask and the substrate projects the excimer laser light onto
the substrate in the image of the pattern defined on the mask.
It will be readily apparent to one of ordinary skill in the art that laser
ablation may be used to form miniaturized separation channels and
apertures in a wide variety of geometries. Any geometry which does not
include undercutting may be provided using ablation techniques, such as
modulation of laser light intensity across the substrate, stepping the
beam across the surface or stepping the fluence and number of pulses
applied to each location to control corresponding depth. Further,
laser-ablated channels or chambers produced according to the invention are
easily fabricated having ratios of channel depth to channel width which
are much greater than previously possible using etching techniques such as
silicon micromachining. Such aspect ratios can easily exceed unity, and
may even reach to 10.
In a preferred embodiment of the invention, channels of a semi-circular
cross section are laser ablated by controlling exposure intensity or by
making multiple exposures with the beam being reoriented between each
exposure. Accordingly, when a corresponding semi-circular channel is
aligned with a channel thus formed, a separation chamber of highly
symmetrical circular cross-section is defined which may be desirable for
enhanced fluid flow through the separation device.
As a final step in laser ablation processes contemplated by the invention,
a cleaning step is performed wherein the laser-ablated portion of the
substrate is positioned under a cleaning station. At the cleaning station,
debris from the laser ablation are removed according to standard industry
practice.
As will be appreciated by those working in the field of liquid phase
analysis devices, the above-described method may be used to produce a wide
variety of miniaturized devices. One such device is represented in FIG. 1
where a particular embodiment of a miniaturized column device is generally
indicated at 2. Generally, miniaturized column 2 is formed in a selected
substrate 4 using laser ablation techniques. The substrate 4 generally
comprises first and second substantially planar opposing surfaces
indicated at 6 and 8 respectively, and is selected from a material other
than silicon which is UV absorbing and, accordingly, laser-ablatable.
In a particular embodiment of the invention, the miniaturized column device
2 comprises a column structure ablated on a chip, which, in the practice
of the invention may be a machinable form of the plastic polyimide such as
Vespel.RTM.. It is particularly contemplated in the invention to use such
a polyimide substrate as, based on considerable experience with the
shortcomings of fused silica and research into alternatives thereof,
polyimides have proved to be a highly desirable substrate material for the
analysis portion of a liquid phase separation system.
In this regard, it has been demonstrated that polyimides exhibit low
sorptive properties towards proteins, which are known to be particularly
difficult to analyze in prior silicon dioxide-based separation systems.
Successful demonstrations of separations with this difficult class of
solutes typically ensures that separation of other classes of solutes will
be not be problematic. Further, since polyimide is a condensation polymer,
it is possible to chemically bond groups to the surface which may provide
a variety of desirable surface properties, depending on the target
analysis. Unlike prior silicon dioxide based systems, these bonds to the
polymeric substrate demonstrate pH stability in the basic region (pH
9-10).
Referring now to FIGS. 1-3, the substrate 4 has a microchannel 10
laser-ablated in a first planar surface 6. It will be readily appreciated
that, although the microchannel 10 has been represented in a generally
extended form, microchannels formed under the invention may be ablated in
a large variety of configurations, such as in a straight, serpentine,
spiral, or any tortuous path desired. Further, as described in greater
detail above, the microchannel 10 may be formed in a wide variety of
channel geometries including semi-circular, rectangular, rhomboid, and the
like, and the channels may be formed in a wide range of aspect ratios. It
is also noted that a device having a plurality of microchannels
laser-ablated thereon falls within the spirit of the present invention.
Referring particularly to FIGS. 1 and 4, a cover plate 12 is arranged over
said first planar surface 6 and, in combination with the laser-ablated
microchannel 10, forms an elongate separation compartment 14. Cover plate
12 may be formed from any suitable substrate such as polyimide, the
selection of the substrate only being limited by avoidance of undesirable
separation surfaces such as silicon or silicon dioxide materials.
Under the invention, cover plate 12 may be fixably aligned over the first
planar surface 6 to form a liquid-tight separation compartment by using
pressure sealing techniques, by using external means to urge the pieces
together (such a | | |
