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Claims  |
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We claim:
1. A miniaturized total analysis system (.mu.-TAS) comprising a
miniaturized column device comprising:
(a) a substrate having first and second substantially planar opposing
surfaces wherein said substrate is comprised of a material other than
silicon or silicon dioxide, said substrate having a first microchannel
laser-ablated in the first planar surface, wherein said first microchannel
comprises more than one sample handling region;
(b) a cover plate arranged over the first planar surface, said cover plate
in combination with the first microchannel forming a first sample
processing compartment, wherein the sample handling regions define a
sample flow component in fluid communication with a sample treatment
component; and
(c) at least one inlet port and at least one outlet port communicating with
the first sample processing compartment, said inlet and outlet ports
enabling the passage of fluid from an external source through the sample
processing compartment.
2. The .mu.-TAS of claim 1, wherein said first sample processing
compartment comprises a serial arrangement of sample handling regions
which define a serial arrangement of alternating sample flow components
and sample treatment components.
3. The .mu.-TAS of claim 2, further comprising detection means laser
ablated in the substrate, wherein said detection means is in communication
with the first sample processing compartment thereby enabling the
detection of a sample passing through the sample processing compartment.
4. The .mu.-TAS of claim 3, further comprising detection means laser
ablated in the substrate, wherein said detection means is in communication
with the sample flow component thereby enabling the detection of a sample
passing through the sample processing compartment.
5. The .mu.-TAS of claim 3, further comprising access ports in fluid
communication of the sample flow component, thereby enabling the passage
of fluid between an external source and the sample flow component.
6. The .mu.-TAS of claim 2, further comprising access ports in fluid
communication with the sample flow component, thereby enabling the passage
of fluid between an external source and the sample flow component.
7. The .mu.-TAS of claim 2, further comprising:
(a) a reservoir microstructure laser-ablated in the first planar surface,
wherein the cover plate in combination with said microstructure define a
reservoir compartment having an inlet means and an outlet means;
(b) a conducting microchannel laser-ablated in the first planar surface,
wherein the cover plate in combination with said conducting microchannel
defines a sample flow component having first and second ends respectively
in fluid communication with the sample processing compartment and the
reservoir compartment outlet means;
(c) an orifice in divertable fluid communication with the reservoir
compartment inlet means, said orifice enabling the passage of fluid from
an external source into the reservoir compartment; and
(d) a motive means enabling the displacement of a fluid from the reservoir
compartment through the sample flow component and into the first sample
processing compartment.
8. The .mu.-TAS of claim 7, further comprising:
(a) a sample delivery means in fluid communication with the first sample
processing compartment outlet port, said sample delivery means comprising
a mixing chamber in fluid communication and in axial alignment with a
fluid communication means and an outlet nozzle;
(b) a fluid source in divertable fluid communication with the fluid
communication means; and
(c) a post-column collection device comprising a sample receiving means
positioned relative to the outlet nozzle to receive eluent from the nozzle
means.
9. The .mu.-TAS of claim 2, further comprising:
(a) a sample delivery means in fluid communication with the first sample
processing compartment outlet port, said sample delivery means comprising
a mixing chamber in fluid communication and in axial alignment with a
fluid communication means and an outlet nozzle;
(b) a fluid source in divertable fluid communication with the fluid
communication means; and
(c) a post-column collection device comprising a sample receiving means
positioned relative to the outlet nozzle to receive eluent from the nozzle
means.
10. The .mu.-TAS of claim 2, further comprising:
(a) a second microchannel having an inlet port and an outlet port laser
ablated in the second planar surface;
(b) a second cover plate disposed over the second planar surface, said
cover plate in combination with the second microchannel defining a second
sample processing compartment;
(c) conduit means for communicating the outlet port of the first sample
processing compartment and the inlet port of the second sample processing
compartment with each other thereby forming a single continuous sample
processing compartment, said conduit means comprising a laser-ablated
aperture in the substrate, said aperture having an axis which is
orthogonal to the planar surfaces.
11. The .mu.-TAS of claim 10, further comprising detection means comprising
apertures laser-ablated respectively in the first and second cover plates
and arranged in co-axial communication with the conduit means.
12. The .mu.-TAS of claim 11, further comprising access ports in fluid
communication of the sample flow component, thereby enabling the passage
of fluid between an external source and the sample flow component.
13. The .mu.-TAS of claim 10, further comprising access ports in fluid
communication with the sample flow component, thereby enabling the passage
of fluid between an external source and the sample flow component.
14. The .mu.-TAS of claim 10, further comprising:
(a) a reservoir microstructure laser-ablated in the first planar surface,
wherein the cover plate in combination with said microstructure define a
reservoir compartment having an inlet means and an outlet means;
(b) a conducting microchannel laser-ablated in the first planar surface,
wherein the cover plate in combination with said conducting microchannel
defines a sample flow component having first and second ends respectively
in fluid communication with the sample processing compartment and the
reservoir compartment outlet means;
(c) an orifice in divertable fluid communication with the reservoir
compartment inlet means, said orifice enabling the passage of fluid from
an external source into the reservoir compartment; and
(d) a motive means enabling the displacement of a fluid from the reservoir
compartment through the sample flow component and into the first sample
processing compartment.
15. The .mu.-TAS of claim 14, further comprising:
(a) a sample delivery means in fluid communication with the first sample
processing compartment outlet port, said sample delivery means comprising
a mixing chamber in fluid communication and in axial alignment with a
fluid communication means and an outlet nozzle;
(b) a fluid source in divertable fluid communication with the fluid
communication means; and
(c) a post-column collection device comprising a sample receiving means
positioned relative to the outlet nozzle to receive eluent from the nozzle
means.
16. The .mu.-TAS of claim 10, further comprising:
(a) a sample delivery means in fluid communication with the first sample
processing compartment outlet port, said sample delivery means comprising
a mixing chamber in fluid communication and in axial alignment with a
fluid communication means and an outlet nozzle;
(b) a fluid source in divertable fluid communication with the fluid
communication means; and
(c) a post-column collection device comprising a sample receiving means
positioned relative to the outlet nozzle to receive eluent from the nozzle
means.
17. A .mu.-TAS device comprising:
(a) a support body formed from a substrate comprised of a material other
than silicon or silicon dioxide, said support body having first and second
component halves each having substantially planar interior surfaces;
(b) a first microchannel laser-ablated in the interior surface of the first
support body half and a second microchannel laser-ablated in the interior
surface of the second support body half, wherein said first and second
microchannels are arranged so as to provide the mirror image of the other;
(c) a sample processing compartment formed by aligning the interior
surfaces of the support body halves in facing abutment with each other
whereby the microchannels define said sample processing compartment and
wherein said sample processing compartment comprises sample handling
regions which define a sample flow component in fluid communication with a
sample treatment component; and
(d) at least one inlet port and at least one outlet port communicating with
the sample processing compartment, said ports enabling the passage of
fluid from an external source through the sample processing compartment.
18. The .mu.-TAS of claim 17, wherein said sample processing compartment
comprises a serial arrangement of sample handling regions which define a
serial arrangement of alternating sample flow components and sample
treatment components.
19. The .mu.-TAS of claim 18, further comprising detection means laser
ablated in the substrate, wherein said detection means is in communication
with the sample processing compartment thereby enabling the detection of a
sample passing through the sample processing compartment.
20. The .mu.-TAS of claim 19, further comprising detection means laser
ablated in the substrate, wherein said detection means is in communication
with the sample flow component thereby enabling the detection of a sample
passing through the sample processing compartment.
21. The .mu.-TAS of claim 19, further comprising access ports in fluid
communication of the sample flow component, thereby enabling the passage
of fluid between an external source and the sample flow component.
22. The .mu.-TAS of claim 18, further comprising access ports in fluid
communication with the sample flow component, thereby enabling the passage
of fluid between an external source and the sample flow component.
23. The .mu.-TAS of claim 18, further comprising:
(a) a reservoir microstructure laser-ablated in the first planar surface,
wherein the cover plate in combination with said microstructure define a
reservoir compartment having an inlet means and an outlet means;
(b) a conducting microchannel laser-ablated in the first planar surface,
wherein the cover plate in combination with said conducting microchannel
defines a sample flow component having first and second ends respectively
in fluid communication with the sample processing compartment and the
reservoir compartment outlet means;
(c) an orifice in divertable fluid communication with the reservoir
compartment inlet means, said orifice enabling the passage of fluid from
an external source into the reservoir compartment; and
(d) a motive means enabling the displacement of a fluid from the reservoir
compartment through the sample flow component and into the sample
processing compartment.
24. The .mu.-TAS of claim 23, further comprising:
(a) a sample delivery means in fluid communication with the sample
processing compartment outlet port, said sample delivery means comprising
a mixing chamber in fluid communication and in axial alignment with a
fluid communication means and an outlet nozzle;
(b) a fluid source in divertable fluid communication with the fluid
communication means; and
(c) a post-column collection device comprising a sample receiving means
positioned relative to the outlet nozzle to receive eluent from the nozzle
means.
25. The .mu.-TAS of claim 18, further comprising:
(a) a sample delivery means in fluid communication with the sample
processing compartment outlet port, said sample delivery means comprising
a mixing chamber in fluid communication and in axial alignment with a
fluid communication means and an outlet nozzle;
(b) a fluid source in divertable fluid communication with the fluid
communication means; and
(c) a post-column collection device comprising a sample receiving means
positioned relative to the outlet nozzle to receive eluent from the nozzle
means. |
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Claims |
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Description |
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TECHNICAL FIELD
The present invention relates generally to miniaturized planar column
technology for liquid phase analysis. More particularly the invention
relates to a miniaturized total analysis system (.mu.-TAS) fabricated in
novel separation support media using laser ablation techniques. The
.mu.-TAS disclosed herein finds use in the liquid phase analysis of either
small and/or macromolecular solutes.
BACKGROUND
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. Chromatogr.
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 path length through the
following relationship:
A=.di-elect cons.*b*C
where:
A=the absorbance
.di-elect cons.=the molar absorptivity, (1/m*cm)
b=path length (cm)
C=concentration (m/1)
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 path length cell as typically used in UV/V is
spectroscopy.
In light of this significant detection limitation, there have been a number
of attempts employed in the prior art to extend detection path lengths,
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 path length 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 path lengths 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 path length. While
each of the aforementioned approaches has addressed the issue of extending
the path length, 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 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 pHs greater than 7.0).
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 pHs 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. Chrom. 33:1-66 (1993);
Harrison et al., Sens. Actuators, 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).
State-of-the-art chemical analysis systems for use in chemical production,
environmental analysis, medical diagnostics and basic laboratory analysis
must be capable of complete automation. Such a total analysis system (TAS)
(Fillipini et al (1991) J. Biotechnol. 18:153; Garn et al (1989)
Biotechnol. Bioeng. 34:423; Tshulena (1988) Phys. Scr. T23:293; Edmonds
(1985) Trends Anal. Chem. 4:220; Stinshoff et al. (1985) Anal. Chem.
57:114R; Guibault (1983) Anal. Chem Symp. Ser. 17:637; Widmer (1983)
Trends Anal. Chem. 2:8) automatically performs functions ranging from
introduction of sample into the system, transport of the sample through
the system, sample preparation, separation, purification and detection,
including data acquisition and evaluation. Miniaturized total analysis
systems have been referred to as ".mu.-TAS."
Recently, sample preparation technologies have been successfully reduced to
miniaturized formats. Gas chromatography (Widmer et al. (1984) Int. J.
Environ. Anal. Chem. 18:1), high pressure liquid chromatography (M uller
et al. (1991) J. High Resolut. Chromatogr. 14:174; Manz et al.. (1990)
Sensors & Actuators B1:249; Novotny et al., eds. (1985) Microcolumn
Separations: Columns, Instrumentation and Ancillary Techniques (J.
Chromatogr. Library, Vol. 30); Kucera, ed. (1984) Micro-Column High
Performance Liquid Chromatography, Elsevier, Amsterdam; Scott, ed. (1984)
Small Bore Liquid Chromatography Columns: Their Properties and Uses,
Wiley, N.Y.; Jorgenson et al. (1983) J. Chromatogr. 255:335; Knox et al.
(1979) J. Chromatogr. 186:405; Tsuda et al. (1978) Anal. Chem. 50:632) and
capillary electrophoresis (Manz et al. (1992) J. Chromatogr. 593:253; Manz
et al. Trends Anal. Chem. 10:144; Olefirowicz et al. (1990) Anal. Chem.
62:1872; Second Int'l Symp. High-Perf. Capillary Electrophoresis (1990) J.
Chromatogr. 516; Ghowsi et al. (1990) Anal. Chem. 62:2714) have been
reduced to miniaturized formats.
Capillary electrophoresis has been particularly amenable to miniaturization
because the separation efficiency is proportional to the applied voltage
regardless of the length of the capillary. Harrison et al. (1993) Science
261:895-897. A capillary electrophoresis device using electroosmotic fluid
pumping and laser fluorescence detection has been prepared on a planar
glass microstructure. Effenhauser et al. (1993) Anal. Chem. 65:2637-2642;
Burggraf et al. (1994) Sensors and Actuators B20:103-110. In contrast to
silicon materials (see, Harrison et al. (1993) Sensors and Actuators
B10:107-116), polyimide has a very high breakdown voltage, thereby
allowing the use of significantly higher voltages.
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 total analysis 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 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 path length.
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 sample processing 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 sample processing 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
according to 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 total analysis system capable of performing a variety of
liquid phase analyses on a wide array of liquid samples.
BRIEF DESCRIPTION OF THE FIGURES
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 sample
processing 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 sample
processing compartment and the optical detection means in the miniaturized
column device of FIG. 5.
FIG. 7A 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. 7B is an exploded view of a second side of the column device of FIG.
7A.
FIG. 8A is a pictorial representation of a first side of a preferred
embodiment of the miniaturized column device of FIG. 7A which is
constructed from a single flexible substrate.
FIG. 8B is a pictorial representation of a second side of the column device
of FIG. 8A.
FIG. 9 is a cross-sectional trans-axial view of the extended optical
detection path length in the miniaturized column of FIG. 8 taken along
lines IX--IX.
FIG. 10 is plan view of a miniaturized column device constructed according
to 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 sample processing
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.
FIG. 15 is a diagram of an exemplary .mu.-TAS.
FIG. 16A, 16B, and 16C are illustrations of a .mu.-TAS having a
laser-ablated reservoir compartment as an integral microstructure on the
substrate.
FIG. 17A is a cross-section of the .mu.-TAS of FIG. 15 showing
laser-ablated microstructures for communicating a sample droplet formed by
a pressure pulse to a post-column sample collection device having
laser-ablated sample droplet receiving microwells. FIG. 17B is a
cross-section of the .mu.- | | |
