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Description  |
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BACKGROUND OF THE INVENTION
This invention relates to a probe for monitoring constituents in a bodily
fluid such as blood, and more particularly, the invention relates to a
probe as part of an apparatus for continuously monitoring the constituents
in the blood including, pH, pCO.sub.2 and pO.sub.2, blood electrolytes and
blood pressure.
Over the years, considerable research and development work has been carried
on in the field of monitoring gases but not necessarily restricted to
blood gases. Within the last twenty years or so, attention has been given
to the development of monitoring systems having the following components:
a dye to react with the constituents being monitored, a structure for
holding the dye, a membrane separating the monitored analyte from the dye,
and a system for directing light onto the dye and monitoring the returned
radiation, the intensity of the return radiation being a measure of the
constituent passing through the membrane and contacting the dye.
Two primary systems have been proposed. In the first, a system for
measuring O.sub.2, for example, a fluorescent dye is excited by the
incoming light source to cause it to fluoresce. The wavelength of
fluorescence is different from the wavelength of the incoming light
source. Oxygen will tend to quench the intensity of fluorescence. The
degree of quenching becomes a measure of the pressure of oxygen in the
fluid being monitored.
Another known system employs an absorption based dye. The dye is irradiated
by light of known intensity. The absorption capability of the dye is
affected by the constituent whose presence is being monitored. The
intensity of the incoming light is compared to the intensity of the light
scattered back from the dye to determine the quantity of the constituent
in the blood.
At the present time, there has been no production of a single probe which
is small enough (less than a millimeter in dimension) to be inserted into
a blood vessel for the continuous monitoring of the triad of pH, CO.sub.2
and O.sub.2. The problem appears to be that there has been no practical
design for and method of manufacturing such a tiny device which satisfies
all the criteria for a commercially successful device such as low cost for
disposability, absence of toxicity, capability of being sterilized and the
like.
SUMMARY OF THE INVENTION
It has been an objective of the present invention to provide a tiny probe
having a maximum transverse dimension of about 0.625 mm and thus being
capable of being passed through a 20 gauge catheter cannula whose minimum
internal diameter is 0.711 mm. The probe is connected by optical fibers to
monitoring apparatus and is capable of providing real time information
concerning one or more constituents of blood.
It has been another objective of the invention to provide a probe for the
measurement of blood pressure and mounted on the same probe as that which
measures partial pressures or constituents of blood.
It has been another objective of the invention to provide a probe which is
capable of holding a dye, the dye being accessible through a permeable
substance, and the probe having an optical system capable of interrogating
the dye.
It has been another objective of the invention to provide a method of
manufacturing an integrated optic probe of the type described herein.
These objectives are attained by providing a plastic base, forming one or
more dye wells in the plastic base, forming, in the plastic base,
waveguides that provide light paths to the dye wells and mounting optical
fibers onto the base in optical communication with the waveguides so as to
bring incoming light to the dye wells and to return the radiation from the
dye wells to monitoring apparatus.
The base is formed by a photofabrication process which includes the steps
of forming a block of light-hardenable material, masking the portion of
that material to be removed and subjecting the remainder to light to
harden it. Thereafter, the masked portion is washed away, leaving one or
more dye wells, as desired, and channels in the block connected to the dye
wells, the channels to be subsequently formed as waveguides. A deposit of
optical cement in the channel followed by the optical hardening of it
creates the waveguides to the respective dye wells.
In a preferred form of the invention, a single optical fiber is cemented in
the block and is connected by a main waveguide and branch waveguides to
the dye wells. The dyes selected are fluorescing type dyes and are
immobilized in substances that are selectively permeable to the gases
under observation. A source, capable of producing multiple differing
wavelengths is directed through a multiplexer to the single optical fiber
to excite the dyes. The wavelengths emanating from the fluorescing dye are
returned and their intensities measured to provide a measurement of the
constituents being observed.
For the measurement of blood pressure, the invention provides a block
having a cavity therein. The cavity is covered by a cantilevered
diffraction grating and a flexible seal which flexes in response to
changes in blood pressure and thereby causes the diffraction grating to
pivot. Optical fibers and waveguides direct light of two wavelengths onto
the diffraction grating and direct the reflected light back to measuring
apparatus. A ratio of the intensity of the reflected beams provides a
measure of the deflection of the gratings and hence blood pressure.
Intensity is not the only method of determining analyte concentration.
Lifetime decay (phase shift) plus others can be used.
Another feature of the invention resides in the mounting of the blood
pressure monitoring probe on the blood gas monitoring probe. The mounting
is such that, when passed through a cannula, the dye wells on the blood
gas probe will be positioned beyond the cannula and the blood pressure
probe will remain within the cannula. A heparin solution, which is slowly
introduced into the blood stream through the cannula, provides the
communication of the pressure of the blood to the probe within the cannula
.
BRIEF DESCRIPTION OF THE DRAWINGS
The several features and objectives of the invention will become more
readily apparent from the following detailed description taken in
conjunction with the accompanying drawings in which:
FIG. 1 is a diagrammatic elevational view illustrating the invention.
FIG. 2 is a perspective view of the probe and cannula combination.
FIG. 3 is a cross sectional view taken along lines 3--3 of FIG. 2.
FIG. 4 is a diagrammatic view of a portion of the monitoring apparatus.
FIG. 5 is a diagrammatic view of the elements illustrating the process of
manufacturing probes.
FIG. 6 is a diagrammatic cross sectional view of a blood pressure
monitoring probe, and
FIG. 7 is a diagrammatic view of the face of a waveguide onto which the
light from the diffraction grating is reflected.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
General Organization and Operation
As shown in FIG. 1, a cannula 10 is inserted into the blood vessel of a
patient indicated at 11. The cannula has an internal bore 12. Passing
through the bore and partially projecting slightly beyond the cannula is a
probe 15 which is connected by at least one optical fiber 16 to an
instrument 17 whose functions will be described.
Mounted on the probe 15 is a blood pressure probe 20, and two optical
fibers 21 and 22 connected to the instrument 17. Further, a tube 25 is
connected to the blood pressure probe to introduce a reference pressure
into the probe, as will be described below.
As best shown in FIG. 2, the blood gas probe consists of a block 27 in
which three dye wells 28, 29 and 30 are formed. The block 27 is tiny,
having a maximum dimension across the diagonal, in cross section, of about
0.625 mm. Its thickness is about 0.38 mm. and its width is about 0.5 mm.
These dimensions permit the probe to pass through the cannula bore 12
which is about 0.90 mm. in diameter. The tip of the bore where it is
tapered inwardly, as shown at 32, has a maximum diameter of about 0.711
mm. It is necessary to provide spacing between the inside diameter of the
cannula tip and the outside dimensions of the probe to permit the flow of
a heparin solution from an injection site 33 (FIG. 1) to the bloodstream
in the artery to prevent clotting of the blood. Additionally, it may be
necessary from time to time to take blood samples through the injection
site 33.
Each dye well forms a sensor for a specific blood gas. Let it be assumed
that dye well 28 is for sensing oxygen O.sub.2, dye well 29 is for
CO.sub.2 and dye well 30 is for pH. Each dye well contains a dye which is
excited to fluorescence by an incoming beam of a preselected wavelength.
The intensity of the fluorescence is measured. That fluorescence is to be
selectively quenched by the particular blood gas associated with the dye.
The dye well can be covered by a membrane selectively permeable for the
blood gas to be measured or, alternatively and preferably, the dye can be
immobilized in a porous matrix which is selectively permeable to the gas
being measured. For example, the O.sub.2 and CO.sub.2 can be disposed in a
matrix of silicone rubber. The dye for the O.sub.2 is insensitive to
CO.sub.2. The dye for the CO.sub.2 is insensitive to O.sub.2. The silicone
rubber is hydrophobic and will block permeation of water and the larger
gas molecules.
The dye well 30 contains a fluorescing dye embedded in a porous matrix of
acrylamide gel which is hydrophilic and thus permits the passage of water
containing the H ion. The dye contained within the matrix is sensitive
only to the hydrogen ion.
An optical channel 35 having branches 36, 37 and 38 is connected to each
dye well. The channel is filled with an optical cement 39 which is
hardened and which, in combination with the block which forms the channel,
creates a waveguide 40 leading to each dye well. The optical fiber 16 is
connected in the channel 35 in abutment with the waveguide to form a
substantially loss-free optical path from the apparatus 17 to the
waveguide and back.
To facilitate the understanding of the operation of the blood gas monitor,
a fairly basic system will be first described.
A light source within the apparatus 17 will be directed through the optical
fiber and waveguide 35 to each dye well to excite the dye contained within
the dye well to fluorescence. Each dye will fluoresce at its own frequency
or wavelength. The intensity of the unquenched fluorescence is known. When
each dye is subjected to the respective blood gas to which it is
sensitive, its intensity of fluorescence will be quenched. The degree of
quenching will be the measure of the partial pressure of the blood gas
under observation. The foregoing system is an over simplification of the
operation of the monitoring apparatus. A more specific description of the
probe and its operation to measure blood gases will be set forth
hereinafter.
THE PROBE
The configuration of the probe is dictated to some extent by the size of
the cannula through which it is passed. The cannula shown in FIG. 2 is
about 50 mm. long and has an inside diameter of about 0.90 mm. The tip 32
is tapered and has a minimum inside diameter of 0.711 mm.
The overall dimensions of the probe are therefore preferred to be 0.38 mm.
thick and 0.5 mm. wide. The length of the probe is slightly greater than
50 mm. so that the probe fills the flexible 50 mm. portion of the cannula
with the three dye wells projecting beyond the tip of the cannula as shown
in FIG. 2. Thus, the dye wells will be exposed to the comparatively rapid
flow of blood (approximately 100 cc. per minute) as contrasted to the very
slow flowing heparin solution of a few drops per minute passing through
the cannula. The blood pressure probe 20, however, is preferably disposed
within the cannula bore as shown. Since the pressure of the heparin
solution within the cannula will be the same as the blood pressure, the
blood pressure probe on the outside of the cannula does not have to be
subjected directly to the blood.
Except for the base 41 which is an aluminum substrate, the block 27 is
substantially entirely formed of a photopolymer film resist, that is, a
monomer which is polymerized by ultraviolet light such as Riston
manufactured by duPont. It will be flexible enough to bend with any
flexure of the cannula in the artery.
Each block is formed with a channel configuration, as shown at 35-38. Each
channel and branch is converted to a waveguide by filling with a
photo-resist or optical cement such as Norland Optical Adhesive
manufactured by Norland Products, Inc. of New Brunswick, N.J. The channel
is of square cross section having a cross-sectional dimension of 0.112 mm.
by 0.112 mm. A single optical fiber having a core diameter of 0.112 mm. is
positioned in the channel 35 and is in abutment with the waveguide formed
by the polymerized Norland material. The positioning of the optical fiber
should be such that its core 42 lies exactly within the confines of the
square waveguide material as shown in FIG. 3 with the cladding 43
projecting beyond the waveguide.
With this configuration, all of the excitation light will pass from the
core into the waveguide without loss. The return light, emitted from the
fluorescing dye, will substantially entirely all return to the core except
for a small loss from the light at the corners of the waveguide which do
not lie in abutment with the fiber core.
The optoelectronic system for interrogating the probe is diagrammatically
illustrated in FIG. 4. As shown there, a source 50 directs light through a
filter and lens system 51 to create five excitation wavelengths .lambda.ex
1-5. A multiplexer 52 transmits those excitation waves to the optical
fiber 16 which in turn directs the waves to the dye wells. Excitation
waves 1 and 2 interact with the dye in dye well 30 which monitors pH.
Waves 3 and 4 interact with the dye and dye well 29 which measures
CO.sub.2. Wave 5 interacts with the dye well 28 which measures the oxygen
O.sub.2.
Each excitation wave creates a corresponding fluorescent wave which is
transmitted through the waveguide 35 and the optical fiber back to the
multiplexer as emitted wavelengths .lambda.em 1-5. These wavelengths are
received by a photocell system 53 which measures their intensities.
The measurement systems for pH, O.sub.2 and CO.sub.2 are similar. A single
source is filtered to provide excitation wavelengths. A multiplexer will
sequence those wavelengths to excite the dye at different intervals of
time. The fluorescence will be at a third wavelength. The intensity of the
fluorescence created by the first wavelength will be different from the
intensity of the fluorescence when excited by the second wavelength. The
intensity of the fluorescing wavelength produced by each excitation
wavelength will change with changes in concentration of CO.sub.2 or pH.
However, the intensity produced by one excitation wavelength will change
at a rate different from the intensity produced by the other excitation
wavelength. The ratio of those two intensities, assuming no variation in
the intensity of the source, will be a measure of the pH and will remain
constant regardless of losses occurring in the system. It is contemplated
that the ratios of emitted intensities will be measured to determine pH
and CO.sub.2, CO.sub.2 being essentially a pH measurement as is well known
in the art.
The measurement of oxygen partial pressure cannot be done in that fashion.
Instead, the oxygen-sensitive dye is excited by a single wavelength and
the rate of decay of the emitted wave is measured. As a preliminary, it
will have been determined, for the specific dye and excitation wavelength,
what the rate of decay will be for different oxygen pressures. For
example, if the pressure of oxygen is high, the rate of decay will be
faster than if the pressure of oxygen is low. Thus, the instrument can be
programmed to measure the length of time for the intensity of the emitted
fluorescence to drop a preselected number of units of intensity. The time
for decay, for one level of oxygen pressure, from one specified point to a
lower specified point will always be the same regardless of losses in the
system. Thus, when the decay times are known for the various levels of
oxygen pressure, determining the decay time for an unknown blood will
produce the desired information.
All of this apparatus is housed in a microprocessor-based instrument 17
that provides the necessary calculations and presents real time readouts
of pH, pO.sub.2, pCO.sub.2 and blood pressure, as will be described
hereinafter.
THE PROCESS OF MANUFACTURE OF THE GAS PRESSURE PROBE
One of the advantages of the present invention is the low cost for
producing probes. The low cost is obtained through the integrated optic
design of the probe which admits of mass production techniques as
disclosed hereinafter.
As shown in FIGS. 5, in the simultaneous manufacture of multiple probes a
Riston layer 60 is mounted on an aluminum substrate 41. The Riston layer
is subjected to ultraviolet light to harden it. These layers are in plan
100 mm by 200 mm and thus capable of making 800 probes having dimensions
of 50.times.0.5 mm.
A second Riston layer 62 is applied to the Riston layer 60. It is 0.112 mm.
thick which is the desired depth of each dye well and associated
waveguide.
A mask 63 is applied to the Riston layer 62, the mask defining the dye
wells 28, 29 and 30 and channels 35-38 to be formed for each probe. Since
each probe is approximately one-half mm. wide, approximately 400 elements
can be masked on one-half the strip and 400 elements masked on the other
half of the strip. The thus masked strip is subjected to ultraviolet light
to polymerize all unmasked portions of the strip. After exposure and
hardening, the unhardened monomer is washed out with a solution with
1,1,1-trichlorethane leaving the dye wells and channels.
A photo-resist optical cement (Norland) is inserted in the dye wells and
associated channels just formed.
A second mask is placed over the strip to mask each of the three dye wells
and the length of channel 35 leading to the channel branches 36-38. With
the strip thus masked, it is subjected to ultraviolet light. Again, the
uncured optical cement is rinsed away. The cured or hardened cement forms
the waveguide 40 leading from the optical fiber (to be inserted later) to
the dye well. The strip is now ready for the introduction of the dyes. One
system for introducing the dye and matrix, that is the gas permeable
immobilizing material, into the wells consists simply of masking the
entire surface of the strip except for the selected dye well (pH, for
example). The dye and matrix is then spread over the surface so that it
will get good penetration into each well. The excess is wiped off.
The matrix is cured in situ. This may be done by subjecting it to
ultraviolet light where the matrix is a substance which can be cured by
ultraviolet light. Alternatively, a hardener can be injected by a stepping
apparatus of known design.
These sequences of operation are repeated until all three dye wells are
filled and the matrices are cured.
Alternatively, the dye wells can be filled with the dye and an immobilizer
and thereafter covered with a membrane selectively penetrable by the gas
to be measured.
Having completed the insertion of the dye, the strip is then sawed into
individual probes. Automatic handling equipment can be provided to deliver
probes one at a time to an operator station where the operator places an
optical fiber 16 in the available channel and secures with optical cement.
The optical cement is thereafter cured by ultraviolet light to complete
the formation of the probe.
An example of set of dyes and immobilizing matrix is as follows:
______________________________________
Immobi- Exci-
Dye Blood lizer tation
Well Gas Dye Matrix Waves
______________________________________
28 O.sub.2 fluoranthene or
silicone
.lambda.5
coramene rubber
29 CO.sub.2 (HOPSA)
8-hydroxy-1,3,6-py-
silicone
.lambda.3
rene tri sulfonic acid
rubber .lambda.4
30 pH(HOPSA) 8-hydroxy-1,3,6-py-
Acrylamide
.lambda.1
rene tri sulfonic acid
gel .lambda.2
______________________________________
In the foregoing description of the blood gas probe, there has been
disclosed a single fiber probe that interrogates three dye wells each
using a fluorescing dye. It should be understood that the invention is
equally applicable to systems employing multiple fibers for communicating
with respective dye wells such as electrolytes, that the invention is
applicable to systems for measuring other blood constituents, and the
invention is applicable to systems wherein absorption based dyes are
employed to measure the analytes of interest.
BLOOD PRESSURE MONITOR
The blood pressure monitor is shown in FIG. 6.
The blood pressure probe includes the block 27. Preferably, the block is
mounted on the blood gas probe, but it can be a separate unit. The block
27 contains waveguides 71 for two incoming beams and waveguide 72 for two
outgoing beams. Each waveguide is connected to a respective optical fiber
21, 22. Wave guide 71 is terminated in a 45.degree. mirror surface 75. An
optical diffraction grating 77 is mounted above the mirror surface 75 in a
cavity 78. The grating is mounted on a beam 79 which is cantilevered from
a position 80 on the block 70. A flexible seal 81 overlies the grating and
seals the cavity 78. A source of reference pressure, from tube 25, is
connected to the cavity 78 to maintain the cavity at the desired reference
pressure such as atmospheric pressure.
The pressure of the blood acts against the flexible seal 81 and causes the
grating to flex inwardly. The angular displacement of the grating, flexing
inwardly, is a measure of the blood pressure applied to the flexible seal.
In the operation of the blood pressure probe, two beams of wavelength
.lambda.1 and .lambda.2 are directed through the waveguide 71. Those two
beams impinge upon the grating 77. Because of their different wavelengths,
the beams will exit from the diffraction grating at differing angles
.phi.1 and .phi.2 for .lambda.1 and .lambda.2, respectively. As shown in
FIG. 7, 85 represents the face of the waveguide 72 upon which the beams
impinge and are reflected off the grating. Depending upon the amount of
angular shift imparted to the respective beams by the grating, which is in
turn dependent upon their wavelengths, the beams will cover greater or
lesser portions of the face of the waveguide 72. Thus, varied respective
intensities of the beams are transmitted to the instrument 17 (FIG. 1)
which provides a measure of the intensity of the beam of wavelength
.lambda.1 and compares it to the intensity of the beam of wavelength
.lambda.2. The ratio of the intensity of .lambda.1 as compared to
.lambda.2 will be a measure of the amount of deflection of the grating 77
and, hence, blood pressure.
Each probe would be calibrated with a calibration number, or an identifying
electronic tag, attached to it and as it was applied to the monitor. A
gain adjustment in the monitor would have to be made to accommodate
variations in the calibration of the probes one to the other.
From the above disclosure of the general principles of the present
invention and the preceding detailed description of a preferred
embodiment, those skilled in the art will readily comprehend the various
modifications to which the present invention is susceptible. Therefore, we
desire to be limited only by the scope of the following claims and
equivalents thereof:
* * * * *
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