U.S. patent number 5,116,495 [Application Number 07/455,502] was granted by the patent office on 1992-05-26 for capillary chromatography device.
This patent grant is currently assigned to OttoSensors Corporation. Invention is credited to Otto J. Prohaska.
United States Patent |
5,116,495 |
Prohaska |
May 26, 1992 |
**Please see images for:
( Certificate of Correction ) ** |
Capillary chromatography device
Abstract
The invention describes a new fabrication procedure of a
capillary chromatography device with at least one sensor unit. The
device contains at least one capillary column which is formed
between a carrier and a cover layer, and which has at least one
inlet and one outlet opening for a carrier phase and/or the sample.
In addition, the invention describes a capillary chromatography
device with at least one sensor, where the capillary columns with
inlet and outlet openings and, if necessary, additional inlet,
outlet and detector chambers, are formed between a carrier and a
cover layer, which is deposited onto the carrier surface.
Inventors: |
Prohaska; Otto J. (Cleveland
Heights, OH) |
Assignee: |
OttoSensors Corporation
(Cleveland, OH)
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Family
ID: |
26791211 |
Appl.
No.: |
07/455,502 |
Filed: |
December 22, 1989 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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96137 |
Sep 11, 1987 |
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Current U.S.
Class: |
210/198.2;
210/198.3; 210/656; 210/658; 422/70; 73/61.52; 96/101 |
Current CPC
Class: |
G01N
30/6095 (20130101); G01N 30/38 (20130101); G01N
30/461 (20130101); G01N 30/6034 (20130101); G01N
30/466 (20130101) |
Current International
Class: |
G01N
30/60 (20060101); G01N 30/00 (20060101); G01N
30/38 (20060101); G01N 30/46 (20060101); B01D
015/08 () |
Field of
Search: |
;73/61.1C,866,864.83,864.84 ;210/658,656,198.2,198.3
;422/70,68.1,82.01,82.03 ;55/386 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
Other References
Patent and Trademark Office Translation of Japan Kokai
No-60-230058, PTO-4179, Aug. 1990, pp. 1-10. .
Snyder, Introduction to Modern Liquid Chromatography, John Wiley
& Sons Inc., New York (1979) pp. 125, 126, 227, 519-522 and
625. .
A Gas Chromatographic Air Analyzer Fabricated on a Silicon Wafer,
Terry, IEEE Transactions of Electronic Devices vol. ED-26, No. 12,
Dec. 1979 pp. 1880-1886. .
The Wall-Jet Electrochemical Detector in Normal HPLC Gunasingham et
al.; Analytical Chemistry Symposia Series, vol. 17, Chemical
Sensors 1983 pp. 561-565. .
Acetylcholine and Choline in Neuronal Tissue Measured by HPLC with
Electrochemical Detection; P. E. Potter, J. Neurochem vol. 41 No.
1, 1983, pp. 188-194. .
Capillary Liquid Chromatography in Field Flow Fractionation-Type
Channels; J. C. Gidding; J. Chromatography 255 (1983) pp. 359-379.
.
Liquid Chromatography in Open-Tubular Columns; Jorgenson, J.
Chromatography, 255 (1983) pp. 335-348. .
Theoretical Aspects of LS with Packed and Open Small-Bore Columns;
Knox, J. Chromatography Science, vol. 18, Sep. 1980 pp.
453-461..
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Primary Examiner: Therkorn; Ernest G.
Attorney, Agent or Firm: Calfee Halter & Griswold
Parent Case Text
This is a continuation of Ser. No. 096,137, filed Sep. 11, 1987 now
abandoned.
Claims
I claim:
1. A capillary chromatography device for separating the components
of a sample, said device comprising:
means defining a capillary column for conducting the sample
therethrough, the cross-section of said capillary column having a
width less than or equal to 1 millimeter and a height less than or
equal to 1 millimeter;
at least one inlet and at least one outlet for conducting the
sample into and out of said capillary column;
at least one sensor located in said capillary column for measuring
a characteristic of the sample;
said means defining a capillary column including first and second
walls, said first wall comprising a substrate and said second wall
comprising a cover layer having opposite portions sealingly adhered
to a surface of said substrate and partially upwardly bent portions
therebetween, said cover layer having a thickness in the range of
0.50 micrometers to 3 micrometers and being formed of a material
selected from the group of materials consisting of SiO.sub.x,
SiO.sub.x N.sub.y, SiN.sub.y, TiO.sub.x, and TaO.sub.x, and
TaO.sub.y, and where x can vary between 1 and 2 and where y can
vary between 1 and 5.
2. A capillary chromatography device as set forth in claim 1
wherein said substrate includes at least one groove etched therein
for increasing the cross section of said capillary column.
3. A capillary device as set forth in claim 2 wherein the
cross-sectional area of said groove is substantially less than the
cross-sectional area of said capillary column.
4. A capillary chromatography device as set forth in claim 1
wherein said capillary column includes on its inner surface a
separation enhancing layer.
5. A capillary device as set forth in claim 1 wherein said sensor
is located between said inlet and said outlet.
6. A capillary device as set forth in claim 1 wherein said
substrate and said cover layer together define a splitting system
which includes an output opening whereby said sample may enter the
capillary column through said inlet and a portion of said sample
may travel through the capillary column and the remaining portion
may travel through said output opening.
7. A capillary device as set forth in claim 1 wherein said cover
layer determines the inner shape of said capillary column.
8. A capillary device as set forth in claim 1 wherein the height of
said bent cover portions determines the height of said capillary
channel.
9. A capillary device as set forth in claim 1 wherein said inlet
and said outlet are formed by openings in the substrate.
10. A capillary chromatography device as set forth in claim 1
wherein said capillary column has the shape of a spiral.
11. A capillary chromatography device as set forth in claim 1
wherein said capillary column has the shape of a double helix.
12. A capillary chromatography device as set forth in claim 1
wherein said capillary column has a bifilar shape.
13. A capillary chromatography device as set forth in claim 1, 10,
11, or 12 wherein the cross-section of said capillary column
changes continuously along the length of said capillary column.
14. A capillary chromatography device as set forth in claim 1, 10,
11, or 12 wherein the cross-section of said capillary column
changes abruptly along the length of said capillary column.
15. A capillary chromatography device as set forth in claim 1
wherein said substrate and said cover layer define a plurality of
capillary columns extending parallel to each other.
16. A capillary chromatography device as set forth in claim 1
wherein said substrate and said cover layer define a plurality of
capillary columns extending in different directions and merging
into each other.
Description
The aim of the invention, is to describe a process which allows the
fabrication of even complexly designed capillary chromatography
devices in a simple manner and in high quantities. This process can
be achieved in that removeable, i.e., dissolvable, substance, i.e.
photoresist, is applied with the shape of the capillary columns,
with widths of less than 1 .mu.m and up to 1 mm, heights of up to 1
mm preferably 0.5 .mu.m to 3 .mu.m, as well as the shape of
possible additional inlet, outlet and detector chambers and in that
the removable substance as well as the carrier is covered by a
cover layer of at least 0.5 .mu.m, preferably 3 .mu.m thickness,
which is formed either by evaporation, and/or sputtering and/or
plasma enhanced chemical vapor deposition (PECVD) methods or by
spinning, dropping, dipping, or electrolytic methods. Afterwards,
the removeable substance is dissolved through the inlet and/or
outlet openings and the resulting cavities between the substrate
and the cover layer are forming the capillary columns, the inlet,
the outlet and the detector chambers for the carrier phase and/or
the sample. The essential advantage of this invented process is
that there is no etching procedure necessary to form the columns
whereas the device configuration can be achieved by deposition of
one or several out of a series of specific cover layers on almost
any substrate or carrier layer. The device has new applications
since the substrate and the cover layer can be at least a magnitude
smaller than the devices formed by known procedures. In addition,
complicated structure designs can be achieved which cannot be
obtained by using conventional methods, such as etching or
mechanical treatment. It is advantageous to form indentations in
the carrier or carrier layer, i.e. by etching, before the
deposition of the removeable substance in order to increase the
cross section of the capillary column.
The invented capillary chromatography device is characterized in
that the surface of the substrate or carrier layer as well as a
removeable substance, which is deposited onto the substrate or the
carrier layer and which has the shape of the inside of the
capillary columns, inlet, outlet, and dectector chambers, and which
was evaporated, sputtered, using PECVD or electrolytical methods,
or spun on, dipped in or dropped on, consisting i.e. of photo
resist, is covered by a covered layer consisting of SiO.sub.x,
SiO.sub.x, N.sub.y, TiO.sub.x, Ta.sub.y O.sub.y, where x varies
between 1 and 2 and y varies between 1 and 5, or consisting of
other inorganic or organic substances, such as polymers or other
substances with similar mechanical or electrical qualities and
which forms the capillary columns, the inlet, outlet and detector
chambers together with a substrate when the removeable substance is
removed. The wall thickness of the cover layer is at least 0.5
.mu.m, preferably 3 .mu.m. The inside of the columns and chambers
can be covered with polar or unpolar layers in order to improve
substance separation. The capillary columns are preferably of
rectangular cross section with a height between less than one
micrometer and more than 1 mm, preferably 3 .mu.m, the widths
between less than 1 .mu.m and more than 1 mm. The sensors can be
formed by electrochemical or physical sensors, UV, florescense,
refraction detectors, spectrometers, etc.
A product is achieved by the invented fabrication method which can
be made very precisely since it is very easy to cover the inside
walls of the capillary chromatography columns with evaporated or
chemically deposited separation enhancing layers. The fabrication
process allows the design of almost any shape desired for optimised
performance of columns and chambers, which can split up or combine,
etc., a design which is hardly or not at all achievable by
presently known etching techniques.
These capillary chromatography devices are especially useful for
liquid chromatography measurements. The detector system at the end
of the column can be preferably designed as an electrochemical cell
which can be integrated into the system by a chamber type design so
that the carrier phase and the sample can be finally disposed
through an outlet opening. Another possibility of the invented
design is that the sensors are arranged within the capillary
columns, improving recording procedures. Depending on the
application, it can be advantageous to form the columns meander,
spiral, double helix or bifilar like, and/or change the cross
section of the columns along its continously and/or discontinously.
It also can be advantageous to design the capillary column of a
group of columns, arranged to be parallel, next to and/or above
each other, and/or to split up into a multitude of columns and/or
is combine out of a multitude of columns, and/or to allow
connections among the columns in order to improve the mixture
and/or separation between carrier phase and sample and sample
components. Otherwise thus very small capillary chromatography
devices can be arranged within the very small area and designed
especially for very specific measurements with that invented
fabrication procedure whereas otherwise long capillary columns or
sets of columns would have to be made in the conventional way.
It is also space reducing as soon as two detector systems are
arranged in series connection or two capillary chromatography units
are integrated onto one substrate or as soon as at least two
integrated capillary chromatography devices are connected in
series.
The invention also permits the fabrication of columns which can be
supplied through at least two different inlet openings, or chambers
can be combined, or various columns leading to at least two
detector systems, can be supplied through one inlet opening or
chamber, where an inlet or outlet opening is directly etched into
the column or it's chamber-type establishment.
The special advantages of the invented capillary chromatography
devices and its fabrication process is not only that it can be
inexpensively reproduced in a compact, reproducible form by means
of thin-film technology equipment, but that also well defines
capillary columns of micrometer or submicrometer sectional
dimensions can be achieved and reproduced with high precision, in
contrary to commonly used procedures (see J. C. Giddings, G. P.
Chang, M. N. Myers, J. M. Davis, K. D. Coldwell: Capillary liquid
chromatography in field flows fraction-action-type channels. J.
Chromatography, 225, 359-379, 1983). Theoretical considerations
showed that capillary columns of cross sectional dimmensions in the
range of micrometers achieve extremely high separation qualities at
very short retention times (see J. H. Knox: Theoretical Aspects of
LC with packed and open small-hole columns. J. Chromotographic
Sciences, 18, 453-463, 1980; and J. W. Jorgenson, E. J. Guthrie:
Liquid chromatography in open-tubular columns. J. Chromotography,
255, 335-348, 1983). The invented devices therefore represent high
resolution, time saving instruments.
An essential additional advantage over known devices is that the
columns, the splitting systems as well as the detector units can be
formed between the substrate and the cover layer which is partially
bent upwards, it forms the columns and chambers, since the cover
layers adhere strongly to the substrate and form a strong seal and
at the same time enable the establishment of the column-chamber
system in one fabrication step, as soon as the removeable substance
is defined with respect to the detector system and the detector
connections as well as the possible inlet and outlet orifices
through the substrate.
Additional advantages are in that the columns inside walls can be
covered by various layers, i.e. aluminum oxide, carbon, etc., in
order to increase the separation efficiency and in that the length
and cross sectional dimensions can be varied in very defined
manners, columns can be combined and split up, inlet and outlet
chambers can be added and devices can be combined in an on-chip
integrated way, achieving certain, well defined measurement
qualities.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1a shows the top view of a capillary chromotography device and
FIG. 1b a cross section of the device.
FIG. 2a shows a capillary column composed of a set of small columns
and FIG. 2b a cross section of such a column set.
FIGS. 3, a, b, c and d shows various possible capillary column
device designs.
FIG. 4 shows a possible combination of several capillary column
devices.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In FIGS. 1a and b is shown that the cover layer (4) is bent upwards
with respect to a substrate (7) in such a way that at least one
capillary column (6) is formed between the cover layer (4) and the
substrate (7). The cover layer (4) forms together with the
substrate (7) also a splitting system (9) with the result that the
carrier phase and/or the sample (12) can enter through an inlet
opening, which is placed in this case through the substrate (7),
and in part can go through the capillary column (6) and in part can
go through the output opening (2), which in this case is placed
through the substrate (7). The splitting-system is advantageous for
the quantification of the very small sample volume in the range of
nanoliters. The cover layer (4) also can form a detector unit (10)
together with the substrate (7) in defining measurement chambers
which contain the sensors (5). the carrier phase as well as the
sample (12) penetrates through the outlet orifice (3), which in
this case is formed by a hole through the substrate.
Technological fabrication procedures and materials are used for the
invented capillary chromatography devices which are similar to the
ones which had been developed for integrated circuits, or thin-film
probes, however, different process parameters are required in some
cases in order to obstain certain layer qualities. Thin-film
sensors are integrated, if appropriate, in the detector system (10)
forming i.e. electrochemical sensors (5), improving and simplifying
the measurements. The splitting-system (9) is also formed, when
appropriate, by the cover layer (4) and the substrate (7), at the
same time as the capillary columns (6) and the detector systems
(10) are formed. The splitting-systems improves and simplifies the
column filling process since the sample (12) enters through the
inlet orifice (1) and proceeds through the capillary column (6) to
the sensors (5), exiting through the outlet opening (3) and the
sample (12) also moves through the wider splitting-channel (9')
exiting through the outlet orifice (2), without exiting the
capillary column (6) or the detector system (10).
FIG. 2b shows a rectangular cross section of the capillary columns
(6), which is formed in that the cover layer (4) which is deposited
onto the substrate (7) is bent upwards. In order to increase the
separation qualities of the capillary columns (6) they can be
modified inside by polar or unpolar layers (8). Engraved
identations, that is the capillary columns (6) enlarging groves
(11), which i.e. are etched into the substrate (7) can increase the
cross sectional area of the capillary columns (6); the cross
sectional dimensions may range from submicrometer values up to
millimeter values.
The capillary column (6) can be designed in the shape of a meander,
spiral, double helix or bifilar on top of the substrate (7).
Examples are shown in FIG. 3 a, b, c, and d. The cross section of
the capillary columns (6) can be kept constant over the total
length of the column or can be changed continously or abruptly.
FIG. 2a shows that the capillary column (6) can also be designed as
a column system which can show columns running in parallel and/or
single columns splitting up and/or converging of several columns to
one column and/or interconnections among the columns in order to
obtain additional mixture or separation effects.
A combination of several capillary chromatography units, preferably
by integration on one insulating substrate (7), is shown in FIG. 4,
as an example where the capillary column (6) is supplied through
several splitting systems (9) and ends in various detector systems
(10). This, for instance, enables the possibility to add carrier
phases and/or samples (12) at arbitrary times and at arbitrary
locations in a capillary column (6) and broadens the application
range of the integrated capillary chromatography device.
* * * * *