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FIELD OF THE INVENTION
This invention relates to systems using solid materials containing
fluorescent compounds as probes to analyze for the concentration of
chemical substances in fluids.
BACKGROUND OF THE INVENTION
It has previously been proposed to measure the concentration of certain
analytes (chemical substances being analyzed) such as oxygen (O.sub.2) or
nitric oxide (NO), by the quenching of fluorescence. Such a technique is
an indirect measurement since the gas is not measured per se. Instead, the
effect of the gas on fluorescence intensity is measured. Several devices
have been proposed to use fluorescence quenching to measure oxygen. In
such devices, radiation is applied through a fiber optic element or bundle
at the proper radiation frequency to excite the fluorophor. A detector is
provided for determining the intensity of the radiation from the
fluorophor, which is at a different frequency from the incident radiation.
In the presence of oxygen, the radiation from the fluorophor is "quenched"
or reduced, so that the intensity of the output radiation from the
fluorophor is a function of the concentration of oxygen that is present in
the environment surrounding the probe.
Several patents have disclosed this type of system, and three of these
patents are D. W. Lubbers U.S. Pat. No. 4,306,877, granted Dec. 22, 1981,
Richard G. Buckles U.S. Pat. No. 4,321,057, granted Mar. 23, 1982, and J.
I. Peterson, et al. U.S. Pat. No. 4,476,870, granted Oct. 16, 1984.
Additional articles which provide some background in this field include an
article entitled "Chemical Sensors Based on Fiber Optics", by W. Rudolph
Seitz, at pp. 16, 18, 20, 22, 24, 33 and 34, Analytic Chemistry, Volume
56, No. 1, January 1984; and an article entitled "Fiber-Optic Sensors for
Biomedical Applications", by J. I. Peterson, et al. pp. 123-127, Science,
Apr. 13, 1984, Volume 224, No. 4645. A number of texts are known which
disclose sources for energizing fluorescent material, and detectors for
picking up the radiation. These texts which discuss the overall type of
system to which the present probes are applicable, include Principles of
Optics by Max Born and Emil Wolf, Pergamon Press, New York, Third Edition,
1965; Physical Optics by R. W. Wood, Dover Publishing Company, 1967;
Radiation and Optics by John Stone, McGraw-Hill, 1963; and Optics by M. V.
Klein, John Wiley & Sons, 1970.
The patent to R. G. Buckles, U.S. Pat. No. 4,321,057, purports to disclose
structures for measuring the concentration of oxygen by variations in the
output fluorescent intensity from a fluorophor; and also that the
concentration of glucose may be measured through the effect of a catalyst
glucose oxidase on the quenching action of oxygen in reducing the output
radiation from a fluorophor. However, the fluorescent analysis structures
disclosed in the Buckles patent, for example, include sheaths, of two or
more layers of material, and this is typical of the fluorescent analysis
devices which have been proposed heretofore. As a result of the use of
several layers or sheaths, or membranes, the response times would be
relatively long, normally taking in the order of several minutes or more,
before equilibrium and a relatively stable output is obtained.
Accordingly, an important object of the present invention is to decrease
the response time of analyzing apparatus employing fluorescent material to
measure analytes.
Additional objects of the present invention are to provide ease of
fabrication at reduced cost; greater flexibility of design of analyte
detection system, thereby allowing increased optimization for a given
application; and for many applications, superior reliability.
SUMMARY OF THE INVENTION
In general, the present invention involves analysis systems using
homogeneous, solid, composite materials containing fluorescent material,
wherein the fluorescent material is affected by the concentration of the
analytes in the fluid to be analyzed, and the fluorescent radiation
intensity is thereby varied.
In accordance with important aspects of the present invention, the probe is
formed of a matrix of transparent polymeric material which is permeable to
the analyte, and which has the fluorophor and any other essential
materials (e.g., catalysts and reagents) immobilized within the matrix of
the polymeric material; and the polymeric matrix is directly exposed to
the fluid being analyzed. The term "analyte" will frequently be used in
the present specification and claims to refer to a chemical substance in a
fluid, such as oxygen in air, or glucose in blood, where it is desired to
determine the concentration of the chemical substance, such as the oxygen
or glucose.
In accordance with one specific embodiment of the invention, the polymeric
material may be poly (dimethyl siloxane), commonly known as silicone, for
analyzing for the concentration of oxygen in a gas or liquid. By way of
background, dimethyl siloxane is a monomer, and the designation "poly
(dimethyl siloxane)" is a polymer in which many dimethyl siloxane
molecules are linked together, and the parentheses in this expression have
a chemical, rather than English language significance. The immobilized
fluorophor could be 9,10-diphenyl anthracene. When the fluorophor
immobilized in the silicone is excited, it emits output radiation. The
presence of oxygen will tend to quench the output radiation of the
fluorophor, and will reduce the output radiation. With the polymeric
matrix directly exposed to the gas being analyzed, the response time may
be on the order of about two or three seconds, as more fully disclosed
herein below, as compared with the unreasonably long time period of three
minutes or more which has heretofore limited the use of the prior art
probes of this general type in practical applications.
In accordance with another specific embodiment of the invention, the
concentration of glucose in a fluid, such as blood, may be analyzed by
using poly (hydroxyethyl methacrylate), or PHEMA, having a fluorophor and
catalytic material physically entrapped therein. The catalytic material
may be glucose oxidase, which catalyzes the reaction of glucose and oxygen
to produce gluconic acid and hydrogen peroxide, thereby reducing the
concentration of oxygen within the matrix when glucose is present; and
thereby reducing the quenching action of oxygen which would otherwise take
place. Accordingly, with increasing presence of glucose, there is
increased fluorescent output. As the radiation output intensity is also
dependent on the oxygen concentration in the fluid, this may be
concurrently measured using a companion sensor containing the same
fluorophor, but not the glucose oxidase, in the polymeric matrix.
A preferred fluorophor for immobilization in the PHEMA is 9,10- diphenyl
anthracene. In the second case, as in the first case, the polymeric matrix
chemically or physically immobilizes the materials involved in the
reactions; and no multiple layers, or enclosing membranes are included in
the structure. Such additional layers slow down the detection of the
analyte (oxygen and/or glucose), make manufacture more difficult, increase
cost, or decrease reliability.
From a somewhat different aspect, the present invention utilizes
fluorescent compounds, catalysts and other reagents trapped in polymeric
hosts. The fluorescence intensity of the fluorophor is changed by the
presence of an analyte in fluid environments surrounding the polymeric
host. In the most elementary cases, the analyte reacts directly with the
fluorophor via quenching to reduce the fluorescence intensity. More
generally, catalysts and other reagents can be incorporated into the
polymer host to couple the analyte and fluorophor by any number of
chemical reactions. The disclosed materials are formed of a matrix of
transparent polymeric material that is permeable to the analyte and that
has the fluorophor, catalyst and other essential materials immobilized
within the matrix of the polymer host; the resulting composite material is
directly exposed to an environment containing the analyte.
The use of a polymeric matrix such as silicone or PHEMA which has good
physical strength, as well as the desired transparency and permeability,
is useful in avoiding the need for successive layers and/or membranes that
have increased the response time of prior proposed devices; and the new
composite materials provide for ease of fabrication, reduced cost, and
flexibility in design.
Advantages of the new materials and sensor construction include the
following:
1) The composite material is a single structure, containing the fluorophor,
catalyst, when employed, and possible additional reagents all
homogeneously distributed, and not requiring multiple layers, or membranes
as are found in prior sensors. The single phase is an advantage because it
(a) reduces diffusion path lengths, thereby reducing diffusion time and
significantly decreasing the response time of the sensor, and (b) the
resulting sensor is much easier and cheaper to manufacture, and (c) tends
to be more reliable as a result of its simpler design.
2) Immobilizing the fluorophor in the polymer allows for larger fluorophor
concentration. Higher fluorophor concentrations yield larger initial
fluorescence intensity, thereby providing a larger dynamic range (i.e.,
increasing measurable analyte concentration range).
3) The polymer host and reagents can be chosen for increased selectivity of
the analyte, and therefore decreased interference by other compounds.
4) The analytes, or compounds to be measured, as well as any products from
chemical reactions occurring within the polymer hosts, readily diffuse in
and out of the composite material while the fluorophor, and the catalyst,
and the reagents, when used, do not leach out of the matrix.
5) The transducer/sensors are reversible, allowing continuous real-time
measurement. The oxygen sensor does not consume oxygen, in contrast to
prior art oxygen sensors that utilize electrodes and are currently in use
for oxygen measurement. The glucose sensor consumes small amounts of both
oxygen and glucose, but this does not reduce its effectiveness as a
continuous sensor, since in application the amounts of glucose and oxygen
which are consumed are not limiting factors in the concentration
measurements.
6) The oxygen sensor shows increased stability, increased sensitivity, and
greatly decreased reaction time, compared with other optically based
oxygen sensors.
7) The glucose transducer has the unusual feature of coupling two chemical
reactions within a single solid phase.
8) The composite material does not show memory or hysteresis, and
consequently can readily detect increases and decreases in analyte
concentration. In other words, these materials form the basis for a
reversible sensor.
9) The polymer host, fluorophor, catalysts, and other reagents can be
chosen to provide adequate stability for a given application. The
resulting composite material will not have the drift found in currently
available electrode based chemical sensors.
10) Clinical, non-clinical, and industrial applications can be accommodated
by the appropriate choice of constituent elements.
11) The composite matrix is a single solid phase and as such can be readily
fabricated into a variety of geometries as required for each application.
Other objects, features and advantages of the invention will become
apparent from a consideration of the following detailed description, and
from the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic diagram indicating the processes involved in
heterogeneous catalysis and photophysical reactions, in a polymeric
matrix, illustrating the principles of the invention;
FIG. 2 is a plot of concentration-vs.-normalized time, with the oxygen
concentration being plotted as a direct function of time, the diffusion
coefficient and as an inverse function of the square of the thickness of
the probe;
FIG. 3 is a plot showing the linear nature of the inverse relative
fluorescence intensity, as a function of the partial pressure of oxygen at
several temperatures;
FIGS. 4 and 5 are schematic system diagrams indicating the over-all mode of
operation of fluorescent probe systems which are employed in the sensing
of analyte concentrations;
FIG. 6 is a diagram of an experimental arrangement using lenses employed in
certain tests relating to the present invention;
FIG. 7 is an enlargement, showing the sample holding arrangement employed
in the test system of FIG. 6;
FIG. 8 shows a probe arrangement in which a sphere of transducer material
is secured or fixed to the end of a fiber optic element or bundle;
FIG. 9 shows a cylindrical transducer geometry in which the light is
transmitted through the fiber to the sensor element from one direction,
and output radiation from the fluorophor is transmitted along the fiber
optic element in the same direction;
FIG. 10 shows a similar cylindrical geometry, but one wherein the fiber
optic element or bundle ends at the remote end of the fluorescent probe,
and a single fiber optic bundle both supplies the input radiation in one
direction, and conducts the output radiation away from the probe in the
opposite direction;
FIG. 11 shows an arrangement in which the transducer material is connected
in series with the fiber optics;
FIG. 12 is a schematic showing of a fluorescent probe, which may be of
cylindrical configuration secured to the end of a fiber optic bundle or a
fiber optic element, in which the outer end of the transducer may be
provided with a reflective coating so that the output radiation is
transmitted back along the fiber optic channel;
FIG. 13 shows a shortened cylindrical probe with axial input and radial
output fiber optics;
FIG. 14 shows a slightly different embodiment in which the fiber optic
channels are coupled to a rectangular block of transducer material;
FIG. 15 shows an arrangement similar to that of FIG. 14, but with the
remote surface of the transducer being reflective to send light back down
the single fiber optic channel;
FIG. 16 employs a rectangular transducer with input and output fiber optics
at right angles to one another;
FIG. 17 shows a configuration which is similar to the arrangement shown in
FIG. 11, but includes exterior mechanical supporting elements
interconnecting the two fiber optic channels, without significantly
impairing the accessibility of the transducer;
FIG. 18 shows a fiber optic channel with a cylindrical, in-line, transducer
having a reflective end, and a support element to more firmly secure the
transducer element to the fiber optic channel;
FIG. 19 shows a pair of probes which may be employed together to
simultaneously determine glucose and oxygen levels in a fluid, such as
blood;
FIG. 20 shows a fluorescent probe mounted across a conduit through which
the fluid to be analyzed passes, with fiber optic input and output
channels coupled to the fluorescent probe on each side of the conduit; and
FIG. 21 shows a probe arrangement in which a disc of composite material is
secured or fixed in the radial direction to the end of a fiber optic
element or bundle.
DETAILED DESCRIPTION
Before describing the drawings in detail, a consideration will be given to
certain more general matters relating to the invention.
The present invention in certain aspects relates to composite materials
comprised of polymer hosts, fluorescent compounds, catalysts, and other
necessary reagents for the detection of particular analytes in
environments surrounding said material. Certain of the fundamental
chemical and photophysical reactions that occur within the composites may
be described by the terms "heterogeneous catalysis" and "fluorescence
quenching".
Heterogeneous catalysis occurs as the analyte diffuses from the environment
into the composite material, reacts with the catalysts immobilized within
the polymer, and the reaction products diffuse out. It is necessary to
employ heterogeneous catalysis when the analyte of interest does not
directly quench a suitable fluorophor. Any number of chemical reactions
can be used to couple the analyte to the fluorophor. The reactions that
are catalyzed must consume or produce a compound that does quench
fluorescence.
Fluorescence is the absorption and prompt reemission of electomagnetic
radiation with change of wavelength, in gases, liquids, and solids.
Fluorophors emit radiation outwardly in all directions. Fluorescence
quenching results when a molecule in an excited state gives up its energy
by a non-radiative transition to a second molecule. The second molecule
must lose this energy in a non-radiative manner. Incident radiation of a
given range of wavelengths is utilized to raise the immobilized
fluorescent component to an excited state. The analyte of interest or
suitable compound produced or consumed during heterogeneous catalysis acts
to absorb the energy from the fluorescent compound. Thus, the fluorescent
compound is reduced to its ground state, light is not emitted and the
overall fluorescence intensity of the composite material is decreased. The
energy absorbed by the quenching molecule is dissipated non-radiatively to
the surrounding polymer host.
Since the catalysts, reagents, and fluorophors are immobilized throughout
the polymer, analytes of interest must dissolve into and diffuse through
the polymer to reach the active sites. Consequently, diffusion of the
analytes within the polymer is an important factor in determining the
response time of sensors utilizing the materials. Another factor affecting
response time is the geometry of the fluorescent probe.
The device sensitivity and specificity is determined by the reactions
occurring within the composite material as well as by the polymer itself.
Since the analyte must diffuse into the polymer host, it is important that
the polymeric matrix be readily permeable to the analyte. The other
constituents of the composite material can be chosen to be specific for a
given analyte in a given application.
The disclosed composites are formed of a matrix of polymeric material that
is transparent in the wavelengths of interest (e.g. the excitation and
emission radiation). The fluorophor, catalyst, and other reagents are
immobilized during the polymerization. Physical and/or chemical
immobilization can be utilized.
DETAILED DESCRIPTION OF THE DRAWINGS
With reference to the drawings, FIG. 1 shows a process illustrating the
principles of the invention, and it will be described both generally, and
in terms of a specific example.
FIG. 1 represents a polymeric matrix 2 which may be a material such as
PHEMA mentioned above, in which a fluorophor 6, also designated by the
letter F, is immobilized. When the fluorescent material is in the excited
state, it is designated by the symbol F*, as compared with a plain "F",
when the fluorophor is not excited by incoming radiation. A catalyst
designated by the letter "C" and reference numeral 4 is also immobilized
within the polymeric matrix 2. One suitable catalyst for a system
involving the detection of glucose concentration is glucose oxidase. The
glucose is the analyte, or the substance being analyzed, and it is
designated in FIG. 1 by the letter A and the reference numeral 10. The
quencher Q is designated by the reference numeral 14, and in this specific
case, it would be oxygen.
Now, in FIG. 1 the fluorophor F is irradiated by input radiation of
suitable intensity and wavelength and many fluorophor molecules are raised
to the excited state F*. The analyte A (for example, glucose) and the
quencher Q (for example, oxygen) diffuse into the permeable polymeric
matrix 2 and encounter the catalyst C (for example, glucose oxidase) and
the excited fluorophor molecules F*. The quencher Q would normally quench
the fluorophor output radiation, and would reduce the over-all output
radiation proportionally to the quencher (oxygen) concentration. However,
the analyte, (glucose) in the presence of the catalyst (glucose oxidase)
combines with the quencher (oxygen), to form reaction products (gluconic
acid and hydrogen peroxide) thus eliminating the quenching action.
Thus, if the concentration of the quencher (oxygen) is known, the increase
in output radiation is a measure of the concentration of the analyte
(glucose). In some cases, the quencher may be the analyte, in which case a
simpler and more direct relationship is obtained. In addition, in some
cases the analyte may react with the catalyst or other reagents to
increase the amount of the quencher, thus further reducing the output
radiation.
In FIG. 1 the letter "R" designates additional reagents which may be
included in the polymeric matrix, to improve probe operation for specific
applications. One example of such reagents for medical applications are
the fibrinolytic enzymes (e.g. urokinase and streptokinase) which prevent
the formation of blood clots on the matrix, that might otherwise impair
the permeability of the probe, and its usefulness as a measuring tool.
FIG. 2 shows sample results of several experiments which evaluated the
diffusion coefficient, D, of oxygen in PDMS at several temperatures and
fluorophor (9,10-diphenyl anthracene) concentrations. For a given sample,
FIG. 2 may be viewed as a plot of oxygen concentration vs. normalized
time. In the ranges evaluated, D was not a function of initial or final
oxygen concentration or of fluorophor concentration. The diffusion
coefficient is a function of temperature, obeying an Arrhenius relation.
The figure shows how the concentration of oxygen, initially zero within
the fluorophor/silicone composite matrix varies with the diffusion
coefficient (D), time (t), and thickness "l" in a sample when exposed to
an environment that has oxygen present. Shown are sample data for four
temperatures and two fluorophor concentrations, as well as the theoretical
curve for these experimental conditions. A measure of the device response
time at a given temperature is the 92.4% concentration point 17 where
Dt/l.sup.2 =1.0. For example, at T =37.degree. C., D=5.times.10.sup.-5
cm.sup.2 /s. At this temperature, for a planar sample 100 microns thick,
the 92.4% saturation value is achieved in 2 seconds. At 20.degree. C., D
=3.2.times.10.sup.-5 cm.sup.2 /s, and for a 100 microns thick sample, the
time to achieve 92.4% saturation is 3.1 seconds. Cylindrical or spherical
samples would achieve the 92.4% saturation more rapidly. These relatively
short time periods are in contrast to the response time periods for
multiple sheath or other similar probe geometries using membranes, of
three minutes or more. Thus, by using a geometry in which the permeable
transparent polymer matrix as described above is directly exposed to the
material being measured, a decrease in response time of one or two orders
of magnitude may be achieved, from three minutes or 180 seconds down to
about 3 seconds.
FIG. 3 graphically illustrates experimental results indicating that the
relative fluorescence intensity varies linearly with the partial pressure
of oxygen surrounding the composite. At a given oxygen partial pressure
the concentration of oxygen within the material decreases with increases
in temperature. This is demonstrated by the decreasing slopes of the lines
with increasing temperature. The slope of a line at a given temperature is
representative of the composite matrix sensitivity. Data were taken with
increasing and decreasing oxygen concentrations and showed no signs of
hysteresis. These experiments were conducted over a three month period,
and no fluorophor or polymer degradation was apparent during this period
of time.
FIG. 4 shows an overall system of the type which is involved in the present
invention. A light source 22 supplies light through the filter 24 to a
fiber optic bundle or light channel 26 which is normally provided with an
exterior coating or sheath 28. Light from the fiber optic channel 26 is
applied to a fluorescent probe 30.
The fluorescent probe 30 is located within an environment 32 in which it is
desired to measure the concentration of oxygen, glucose, or other analyte
which will affect the output fluorescence from the fluorescent probe 30.
An additional fiber optic element 34 conducts illumination from the probe
30 through the filter 35 to the light intensity detector 36. Although the
channel 34 is shown extending at right angles from probe 30, it could of
course be at any angle (i.e., 0.degree. to 180.degree.) with respect to
input channel 26. A change in output at the light intensity detector 36
indicates that the concentration of the analyte being detected within the
environment 32 is changing. Thus, for example, oxygen has the property
that it tends to quench or reduce the fluorescent output of many
fluorophors. Accordingly, as the concentration of oxygen increases,
assuming that the probe 30 is illuminated with a constant level of light
from source 22, the amount of radiation transmitted from the probe 30 to
the light detector 36 from the fiber optic probe 34 will be significantly
reduced. The level of the light detected by the light intensity detector
36 may be calibrated to indicate the concentration of oxygen within the
environment 32, to give an accurate indication of the oxygen
concentration, as noted above in connection with FIG. 3, for example.
Incidentally, the general arrangement as shown in FIG. 4 is known, and the
present invention deals primarily with special types of probes which
provide very fast reaction time for the system, in the order of one-tenth
or one-hundredth, for example, of the time of response of prior proposed
arrangements.
Referring now to FIG. 5 of the drawings, the system is similar to that of
FIG. 4, and includes light source 22, filter 24, detector 36 and its
associated filter 35, all for determining the concentration of analyte
within the environment 32. In the arrangement of FIG. 5, however, the
probe 42 both receives illumination and transmits illumination back
through the shielded fiber optic channel 44. A light splitter 46 which may
include a partially silvered surface 48, permits the direction of
illumination from the light source 22 to the fiber optic channel 44, and
directs a substantial portion of the light returning toward the left in
the fiber optic channel 44 to the detector 36. Incidentally, the output
illumination from the fluorophor included in the probe 42, is normally at
a different radiation frequency than the excitation frequency supplied by
the light source 22. Accordingly, the filter 35 will be suitable for
detecting the radiation from the fluorophor in probe 42, and stray
radiation of other frequencies will be rejected. In this regard, filter 24
blocks light of the frequencies radiated by the excited fluorophor in
probe 42 to increase the sensitivity of the system. The fiber optic probes
will normally be arranged and used so that significant levels of stray
radiation and illumination of the radiated frequency of the probe will not
be picked up at the detectors 36.
FIGS. 6 and 7 show schematically, the test arrangements which were employed
in the course of testing sample specimens which were prepared. The
arrangement of FIG. 6 is also of interest as indicating the use of lenses
instead of direct coupling to the fiber optic channels. Thus, for some
system applications the fiber optics could even be eliminated. As
indicated in FIG. 6, the test arrangements included a light-tight sample
compartment 52, enclosing a masked cuvette 54 containing the sample to be
tested, and two fiber optic bundles 56 and 57 which extended into the
chamber 52. Lenses 58 and 60 were associated with the fiber optic bundles
56 and 57, respectively, in order to maximize coupling between the bundles
and the sample within the cuvette 54.
The sample holder for one set of tests is shown in FIG. 7: the cuvette was
one centimeter by one centimeter square and had walls which were one
millimeter in thickness. A one centimeter cube of silicone 62 containing
fluorophor was formed in the bottom of the cuvette, just above the riser
block 64. Layers of opaque masking tape 66 and 68 were spaced apart by
approximately one millimeter to expose the central portion of the
silicone/fluorophor sample. Input radiation of the proper excitation
wavelength was supplied to the space between the two masks 66 and 68, as
indicated by the arrows 70. Gas containing oxygen was supplied to the
upper surface of the sample 62, and the light intensity emitted from the
sample 62 was measured, by a detector coupled to the fiber optic bundle 57
shown in FIG. 6, with the over-all system being generally as shown in FIG.
4.
An important feature of the present invention involves the nature of the
probe shown at 30 in FIG. 4, 42 in FIG. 5 and at 62 in FIG. 7. It is
desirable that the material selected be readily permeable to the analyte
which is being detected, that it be transparent at the excitation and
emission wavelengths, so that the light may readily penetrate the probe,
and the output radiation transmitted therefrom. In most medical
applications, it is normally desirable that the probe be biologically
compatible. More generally, it is also desirable that the material have
sufficient structural integrity so that it may be directly exposed to the
material being sensed. In this way, a much shorter response time may be
achieved. It has been determined that silicone or PDMS, poly (dimethyl
siloxane), forms an excellent host matrix for the fluorescent probe.
Another advantage of PDMS is the ability to readily incorporate the
fluorophor. Solvents for the various fluorophors, such as benzene,
toluene, and xylene, are also soluble in PDMS and evaporate completely
from it.
A variety of curing agents are available for silicone, some with amine
curing where the agent evaporates. In the experiments employed in
connection with the present invention, poly (dimethyl siloxane) gel,
R-2602, was used with amine curing agent CAT-05 obtained from
McGhan-Nusil. The most commonly used vulcanizing agents for the curing of
silicone rubbers are organic peroxides. Used in very low concentrations
(in the order of 0.1 to 1.0 weight percentages), the function of the
peroxides is to provide free radicals, produced as the peroxides reach
their decomposition temperature. The unsaturated bonds capture hydrogen
atoms from methyl groups of adjacent linear molecules, causing
crosslinkings. In this way the silicone gel becomes a true resilient
rubber.
With regard to the fluorophor, any of a number of fluorophors may be
employed, and typical aromatic hydrocarbons which may be employed include
anthracene; decacyclene; perylene; rubrene; 9-methyl anthracene;
9,10-diphenyl anthracene; 9,10-dichloro anthracene; and tetracene. Each
compound possesses an excitation spectrum in the near ultra-violet or low
visible wavelength range, and an emission spectrum in the low to
mid-visible wavelength range. These excitation and output frequencies are
known for each of these compounds, and the filters 24 and 35, for example,
in FIGS. 4 and 5, are chosen in order to pass the indicated frequencies.
Reference will now be made to the additional drawings associated with the
present patent specification, many of which show specific probe
geometries. It is to be emphasized that FIGS. 8 through 21 show various
geometries to indicate that virtually any type of geometry may be
employed. Thus, the fact that the probe consists of a single composite
matrix leads to great flexibility in the final design of the probe.
Furthermore, rapid response time is achieved by directly exposing the
polymeric matrix containing the fluorophor (and in some cases the
catalyst, and/or reagents) to the fluid containing the analyte. Emphasis
is placed on the lack of multiple layers or coatings and on the new
materials consisting of, for example, a transparent permeable polymeric
matrix, including homogeneously distributed fluorophor and catalyst.
FIG. 8, for example, shows a simple fluorescent probe which includes a
sphere of transducer material 78 mounted on a fiber optic element or
bundle 80, which is provided with an external coating or sheath 82.
Incidentally, in the present drawings, all of the fiber optic elements or
bundles have external coatings or sheaths, as is normal with fiber optics.
The radiation for exciting the fluorescent material included in the
transducer material 78 is sent from left to right down the fiber optic
channel 80, and the excited radiation at a different frequency from the
element 78 is transmitted back from right to left through the fiber optic
channel 80, in a manner similar to the system of FIG. 5 of the drawings.
In FIG. 9 of the drawings, a fiber optic channel 84 supplies exciting
energy to the fluorescent transducer 86 which is cylindrical in
configuration. The transducer 86 is mounted on a section 88 of the fiber
optic element or bundle which is free from the external shielding 90 which
encloses the fiber optic element or bundle 84, on either side of the
transducer member 86. The system with which the arrangement of FIG. 9
would be used, would be similar to that shown in FIG. 4 of the drawings in
which the fiber optic elements are only employed for the one-way
transmission of radiation, rather than for transmitting light in both
directions.
In FIG. 10 of the drawings a transducer assembly is shown including the
fluorescent transducer 92 mounted on one end of the fiber optic bundle or
element 94. As in the case of prior embodiments, the fiber optic element
94 is provided with a coating or sheath 96 except in the area where it is
enclosed by the transducer 92. The radiation excited within the transducer
92 at a different frequency from the incident radiation will be
transmitted from right to left through the fiber optic element or bundle
94, in the geometric configuration shown in FIG. 10. If desired, the
right-hand end of the fiber optic element and the fluorescent transducer
may be coated with reflecting material 96 to increase the reflection of
the excited radiation from right to left along the fiber optic channel 94.
However, it may be noted that the difference in index of refraction of the
fiber optic element or bundle and that of the transducer portion as
compared with air, will mean that a substantial portion of the energy is
reflected from right to left. Accordingly, the reflecting material,
although helpful, is not necessary.
In the arrangement of FIG. 11 two sheathed fiber optic channels 102 and 104
are connected in series with a fluorescent transducer 106. With this
arrangement as shown in FIG. 11, the incident exciting radiation is
supplied from left to right in fiber 102, and is transmitted to the
detector at a different frequency on light fiber 104. Incidentally,
optical and/or mechanical coupling arrangements, known per se, may be
employed in each case at the interface between the fiber optic channel and
the probe.
FIG. 12 is an arrangement similar to that of FIG. 11, wherein the shielded
light fiber 108 transmits energy at one frequency to excite the
fluorescent material in the transducer 110, but the radiation from the
fluorescent material at a different frequency is transmitted back from
right to left in the fiber optic element 108. If desired, reflective
material 112 may be provided at the outer end of the transducer 110.
In each case, care must be taken to insure that interfering variable stray
radiation is either not picked up by the fiber optic element or through
the transparent transducer 106 or 110, or that it is filtered out by the
filters pr | | |
