U.S. patent number 3,743,103 [Application Number 05/188,830] was granted by the patent office on 1973-07-03 for phase separator for continuous flow operation.
This patent grant is currently assigned to Technicon Instrument Corporation. Invention is credited to Anthony F. Buccafuri, Jack Isreeli, Aaron Kassel.
United States Patent |
3,743,103 |
Isreeli , et al. |
July 3, 1973 |
PHASE SEPARATOR FOR CONTINUOUS FLOW OPERATION
Abstract
A separator for separating multiphase fluid streams. The
separator includes inlet and outlet means having wettable means
positioned within the inlet means to direct the fluid to the outlet
means.
Inventors: |
Isreeli; Jack (Mamaroneck,
NY), Kassel; Aaron (Tarrytown, NY), Buccafuri; Anthony
F. (Pomona, NY) |
Assignee: |
Technicon Instrument
Corporation (Tarrytown, NY)
|
Family
ID: |
22694708 |
Appl.
No.: |
05/188,830 |
Filed: |
October 13, 1971 |
Current U.S.
Class: |
210/532.1;
422/255; 422/82 |
Current CPC
Class: |
G01N
35/08 (20130101); B01D 17/0208 (20130101); B01D
17/045 (20130101); B01D 17/04 (20130101) |
Current International
Class: |
B01D
17/02 (20060101); G01N 35/08 (20060101); B01d
012/00 (); G01n 029/02 () |
Field of
Search: |
;23/230,253
;210/65,83,84,532,533,536,537,538 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Hart; Charles N.
Claims
What is claimed is:
1. A separator for separating phases from a multiphase fluid stream
on a continuous flow basis comprising, an inlet for said
multi-phase stream, first and second outlets, and means in said
separator which are preferentially wettable by one of said phases
to promote phase separation and the accumulation of said one phase
on and around said means and the flow of said phase to a
predetermined one of said outlets, said last-mentioned means
extending generally from said inlet and to said predetermined one
of said outlets, so as to direct said one phase to said
predetermined one of said outlets.
2. A separator as in claim 1 wherein, said multi-phase stream
comprises an aqueous phase and an organic phase, and wherein said
means are preferentially wettable by said organic phase.
3. A separator as in claim 1 wherein, said multi-phase stream
comprises a polar phase and a non-polar phase, and wherein said
means comprise a non-polar surface so as to be preferentially
wettable by said non-polar phase.
4. A separator as in claim 1 wherein, said last-mentioned means
comprises a generally elongate member which is insertable into said
separator to extend generally from said inlet and to said
predetermined one of said outlets.
5. A separator as in claim 2 wherein, said organic phase is heavier
than said aqueous phase, said predetermined one of said outlets is
disposed at a lower level than the other of said outlets.
6. A separator as in claim 2 wherein, said aqueous phase is heavier
than said organic phase, said predetermined one of said outlets is
disposed at a higher level than the other of said outlets.
7. A separator as in claim 1 further comprising, means to introduce
a separating fluid after phase separation to segment the phase
which flows to said predetermined outlet.
8. A separator as in claim 1 further comprising, means to introduce
a separating fluid after phase separation to segment the phase
which flows to the other of said outlets.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a new and improved phase separator for
continuous flow operation.
2. Description of the Prior Art
Although phase separators for continuous flow operation are known,
it may be understood that the same will, in general, be found to
have relatively large hold-up volumes which function to limit the
usefulness thereof in automated analysis apparatus. More
specifically, and for use, for example, in automated analysis
apparatus wherein a series of different samples which constitute an
aqueous phase are formed into a stream and automatically and
successively treated, as by solvent extraction, through interaction
with a solvent phase, it may be understood that the relatively
large hold-up volumes of the included prior art phase separators
will function to unduly limit the sample analysis rate at which
such analysis apparatus may be operated, and will not, in every
instance, provide the complete phase separation as is required to
insure the consistent accuracy of the sample analysis results. Too,
said relatively large hold-up volumes are not particularly
conductive to the required maintenance of sample integrity with
resultant possility of unacceptable inter-sample contamination.
OBJECTS OF THE INVENTION
It is, accordingly, an object of this invention to provide a new
and improved phase separator for cintinuous flow operation having a
very small hole-up volume.
Another object of this invention is the provision of a phase
separator as above including means to promote complete phase
separation.
Another object of the invention is the provision of a phase
separator as above which, when utilized with a stream of a series
of different samples, includes means to preserve sample integrity
and inhibit inter-sample contamination.
A further object of this invention is the provision of a phase
separator as above which is particularly adaptable for use in an
automated, continuous flow sample anslysis system which functions
to determine the morphine level in a succession of different urine
samples at a particularly high analysis rate.
SUMMARY OF THE DISCLOSURE
As disclosed herein, the new and improved phase separator for
continuous flow operation of the invention takes the form of a
fitting of a suitably inert material in the nature of glass having
a body portion, an inlet for a multi-phase stream which includes
aqueous and organic phases, and first and second outlets for said
phases. Means which are preferentially wettable by said organic
phase to promote phase separation and the accumulation of said
organic phase and flow thereof to the outlet therefor are provided
and take the form of a generally elongate member which is
insertable into said separator to extend generally between said
inlet and the outlet for said organic phase. For use in those
instances wherein the organic is the heavier of the phases, the
outlet therefore is disposed at a lower level than the aqueous
phase outlet, while the reverse is true for instances wherein the
aqueous phase is the heavier to thereby, in either event, take full
advantage of the natural separational effects of gravity. Means may
be included to segment one of the resultant separated phase streams
with a suitable separating fluid when the separator is used in
automated, sample analysis systems.
An application of the separator of the invention in an automated
analysis system directed toward the determination of the morphine
levels in a stream of different urine samples on a continuous flow
basis is disclosed to clearly illustrate the advantages provided by
the separator.
DESCRIPTION OF THE DRAWINGS
The above and other objects and significant advantages of the
invention are believed made clear by the following detailed
description thereof taken in conjunction with the accompanying
drawings wherein:
FIG. 1 is a longitudinal cross-sectional view taken through a first
embodiment of the phase separator of the invention;
FIG. 2 is a cross-sectional view taken along line 2--2 of FIG.
1;
FIG. 3 is a longitudinal cross-sectional view taken through a
second embodiment of the phase separator of the invention;
FIG. 4 is a longitudinal cross-sectional view taken through a third
embodiment of the phase separator of the invention;
FIG. 5 is a longitudinal cross-sectional view taken through a
fourth embodiment of the phase separator of the invention; and
FIG. 6 is a schematic flow diagram illustrating a utilization of
the phase separator of the invention in an automated sample
analysis system.
DETAILED DESCRIPTION OF THE INVENTION
Referring now to FIGS. 1 and 2, a first embodiment of a new and
improved phase separator for organic-aqueous phase separation in
continuous flow analysis is indicated generally at 10 and comprises
an inlet 12 and outlets 14 and 16. The separator 10 is preferably
made of glass. An insert 18 of a material which is preferentially
wet by said organic phase is disposed as shown within the separator
by friction fit, and the insert includes a nib or the like 20 to
maintain the same positioned substantially as depicted. For use
with a polar aqueous phase and a non-polar organic phase, the
insert 18 is made of a suitable material in the nature of Teflon or
polyethylene having a non-polar surface.
A stream 22 of alternating, substantially immiscible organic and
aqueous (O and A) liquid phase segments, in which said organic
phase is the heavier, is flowed as by pumping into separator inlet
12 through conduit 24. For a typical continuous flow utilization of
the separator 10, the stream 22 will preferably be segmented as
shown by a suitable separating fluid in the nature of air, and will
consist of successive treated samples of an aqueous phase, a solute
from which has been extracted into an organic solvent phase by
preferential partitioning during flow through a mixing coil or the
like as well understood by those skilled in the continuous flow
solvent extraction art.
As the stream 22 enters the separator 10, the non-polar surface of
the insert 18 will be preferentially wet by the non-polar solvent
phase, to the substantial exclusion of the polar aqueous phase,
thereby causing the solvent phase to coalesce and pool at and on
said insert. This preferential wetting, in conjunction with the
natural separational effects of gravity on said solvent phase, will
cause the same to follow the insert to the lower portion of the
separator 10 for flow therefrom through outlet 16.
A very small portion of the organic phase, plus substantially all
of the aqueous phase and the air will flow by difference from the
separator through outlet 14. Segmentation of the resultant organic
phase stream for wash purposes and for maintaining sample integrity
in a continuous flow separation system may be readily effected by
the introduction of a suitable separating fluid in the nature of
air to said stream as indicated through capillary 26, although it
is believed clear that such segmentation is not essential to
efficient phase separation. In the same manner, it is believed
clear that the incoming stream 22 need not be air-segmented for
efficient operation of the separator 10.
A second embodiment of the separator is indicated at 30 in FIG. 3
and comprises an inlet 32, outlets 34 and 36, and the insert 18.
The separator 30 is for use when the aqueous phase is the heavier,
and would be particularly applicable for hase separation following
the back-extraction of a solute from the organic to aqueous phases
on a continuous flow basis. As the stream 22 enters the separator
30, the solvent phase again preferentially wets and follows the
insert 18, to the substantial exclusion of the aqueous phase for
flow by difference, with the air and a very small portion of the
aqueous phase, from the separator 30 through outlet 34. The
substantial majority of the aqueous phase will, meanwhile, collect
as shown under the influence of gravity in the lower portions of
the separator 30 for flow therefrom through outlet 36.
Air-segmentation of the resultant aqueous phase may again be
effected through a capillary as here indicated at 38.
A third embodiment of the separator is indicated at 40 in FIG. 4
and comprises an inlet 42 and outlets 44 and 46. The insert, here
indicated at 48, comprises nibs 50 and 52 for positioning. A
debubbler is indicated at 54 and in included only when the incoming
stream 56 is air-segmented. The separator 40 is for use when the
organic phase is the lighter in, for example, a continuous flow
solvent extraction process as described with regard to FIG. 1. As
the stream 56 enters the separator 40, the organic phase will
preferentially wet and follow the insert 48 with the result that
the major portion thereof, as air segmented if required through
capillary 58, will flow from the separator through outlet 44. The
aqueous phase with a very small portion of the organic phase will
flow by difference from the separator through outlet 46.
A fourth embodiment of the separator is indicated at 60 in FIG. 5
and comprises an inlet 62 and outlets 64 and 66. The insert, here
indicated at 68, comprises nibs 70 and 72 for positioning within
the separator as shown. A debubbler is indicated at 74 and is
included only when the incoming stream 76 is air-segmented. The
separator 60 is for use when the aqueous phase is the lighter and
would be particularly applicable for phase separation following
back-extraction of a solute to the lighter aqueous phase on a
continuous flow basis. As the stream 76 enters the separator 60,
the organic phase will preferentially wet and follow the insert 68
with the result that substantially all of said organic phase, with
a very small portion of the aqueous phase will flow by difference
from the separator through outlet conduit 66. The ligher aqueous
phase will meanwhile remain substantially above the preferentially
wetted insert 68 for flow from the separator, as air-segmented if
desired through capillary 76, through outlet 64.
"Purging" of each of the disclosed separator embodiments prior to
the utilization thereof may, of course, be readily effected by the
initial flow therethrough, for a sufficient period of time, of the
phase which preferentially wets the insert to insure the absence of
any of the other phase in the separator prior to the commencement
of operation.
Of particular advantage with regard to each of the disclosed
separator embodiments is the fact the hold-up volume, or volume
thereof which must be filled for each phase separation, is
substantially minimal, whereby the operational rates of the
separators in terms of the number of treated samples which may be
processed thereby per unit time is maximized. Too, the
substantially complete separation provided with regard to the
separated phase of interest is, of course, of particularly
significant advantage as should be obvious.
A utilization of the separation of the invention in a system for
the automated fluorometric determination of the morphine levels in
urine samples to determine drug use on the part of the urine donors
is illustrated schematically in FIG. 6 and, briefly described,
comprises the supply of a continuous air-segmented stream of
successive urine sample segments buffered to appropriate pH (the
aqueous phase), generally alternating segments of a heavier solvent
mixture (the organic phase), and appropriately spaced segments of a
suitable wash liquid, respectively, to and through a suitable
mixing coil 78 to effect the extraction of the free morphine base
solute from the buffered urine sample segments to the adjoining
solvent mixture segments through preferential solute partitioning.
Following this, the stream is flowed through the separator 10 of
FIG. 1 for separation of the organic phase as described, and which
now contains the morphine solute of interest, and immediate
re-segmentation of this phase with air through capillary 26 to
thereby maintain sample integrity and inhibit inter-sample
contamination.
Thereafter, a buffer solution at the same appropriate pH is added
to the organic phase and the resultant stream flowed through mixing
coil 82 to effect a "cleansing" of the organic phase by
wash-extraction or back-extraction of amino acids and like
compounds indiginous to urine therefrom into the buffer solution
aqueous phase. Separation of the organic phase from this buffer is
then effected in separator 10' and is followed as indicated by the
re-segmentation with air of the solvent phase.
A strongly alkaline solution is then added as indicated to the
solvent phase stream and the resultant stream flowed through a
mixing coil 86 to effect back-extraction of the morphine solute
into this newly added alkaline solution aqueous phase. Following
this, the resultant stream is flowed through the separator 60 of
FIG. 5, wherein the same is de-bubbled by debubbler 74 and the
organic phase and a very small portion of the aqueous phase flowed
to waste by difference through outlet 66, while the major portion
of said aqueous phase, now containing the morphine solute of
interest, is immediately re-segmented with air and flowed from
separator 60 to and through pump 88.
A buffer at the appropriate pH is then added to the aqueous phase
and the same divided as indicated into two streams. A
pseudo-morphine solution to dimerize the morphine is added to one
of said streams, and distilled water added to the other to provide
a blank channel, whereupon said streams are simultaneously applied
to and analyzed in fluorometers 90 and 92. The results of these
analayses are applied as indicated to a strip chart recorder to
provide a readily readable and reproducible record of the morphine
level in each of said urine samples.
A general discussion of the methodology involved in the
determination of morphine levels in urine samples is provided in
the article "Automated Analysis for Drugs in Urine" by D. V.
Blackmore, et al., as published in CLINICAL CHEMISTRY, Volume 17,
No. 9, of 1971; and such article is hereby incorporated by
reference herein.
Utilization as described of the separator of the invention in an
automated analysis system may be understood to make possible the
operation of said system at a rate of between 40 and 60 samples per
hour with the same clarity of analysis results as could be provided
by such system utilizing the separators of the prior art at a
maximum rate of between only 10 and 20 samples per hour.
Although disclosed as comprising a separately formed preferentially
wettable insert, it is believed clear that the separator of the
invention could, alternatively, be fabricated with said insert
formed as an integral part thereof.
Too, and although disclosed by way of illustrative example as
applied to the determination of morphine levels in urine samples,
it is believed clear that the phase separator of the invention is
by no means limited thereto, but rather, is advantageously
utilizable for the phase separation function in a very wide variety
of other and different applications.
While we have shown and described the preferred embodiment of our
invention, it will be understood that the invention may be embodied
otherwise than as herein specifically illustrated or described, and
that certain changes in the form and arrangement of parts and in
the specific manner of practicing the invention may be made without
departing from the underlying idea or principles of this invention
within the scope of the appended claims.
* * * * *