IL88967A - Probe incorporating detector materials - Google Patents

Description

PROBE INCORPORATING DETECTOR MATERIALS o'un o nin !? iDn inan OCT OPTICAL CHEMICAL TECHNOLOGIES LTD., Iventors: Dr. A. Bromberg Mr. E. Fal kenstein C:07591 07591SPN 1-1102 January 10 , 1989.

PROBE INCORPORATING DETECTOR MATERIALS, onain ? on mno FIELD OF THE INVENTION The present invention relates generally to a probe incorporating detector materials , and more particularly to a sensing device for use in the manufacture of an optic probe apparatus for quantitative determination of the chemical properties of a medium in situ, which device incorporates light sensitive material chemically bonded to the internal surfaces of porous glass tips of optical fibers, and to optic probe apparatus incorporating such a device.

RELATION TO PRIOR PATENT APPLICATIONS In our prior patent applications listed below, we claimed inter alia a sensing device for use in the manufacture of an optic probe apparatus for quantitative determination of the chemical properties of a medium in situ, the device comprising essentially at least one inorganic (e.g. glass or fused silica) optical fiber means, each of which has at an open end thereof an integral or fused-on porous glass tip, having adsorbed on the internal surface at least one fluorescent or other light sensitive substance. Such device had the advantages over comparative prior art devices of having greater sensitivity, being generally smaller and therefore potentially of greater flexibility and applicability, and in particular being useful for monitoring the chemical properties of the human blood stream in vivo, which was not believed to be practical before. 88967/2 In the present invention, which is to be regarded as an improvement in or modification of the invention of commonly assigned U.S. Patent No. 5.04 , 82, claiming priority from Israel Patent Applications Nos. 84l8l & 84182 (filed October 16 , 1987 ) , and 84531 & 84533 (filed November 19, 1987), the adsorbed light sensitive substance is replaced by at least one chemically bonded light sensitive substance. The chemical bonding imparts greater stability to the product than the physically adsorbed substance, e.g. although the previous product had minimum leakage of light sensitive material,*- in the present product, leakage is zero. The product of the present invention seems also to be more sensitive than the previous product, and this may be due (at least in certain cases) to the fact that in the case of the chemically bound material there is a more substantial difference between the wave-lengths of the incident and emitted light than is the case for the adsorbed material.

BACKGROUND OF THE INVENTION Optic probes for quantitative determination of certain chemical properties of the blood in situ, are known. Thus, in US 447687Ο (Peterson), which issued October 16, 1984, and the contents of which are incorporated by reference herein, there is described such a probe intended for determining the partial pressure of oxygen in the blood or tissue of a living animal. This probe comprises one or two strands of plastic optical fibers terminating in an elongate section of porous polymer tubing which is packed with a fluorescent visible light-excitable dye placed on a porous adsorptive particulate polymeric support. While many compounds which are excited by ultraviolet light are known, and the intensity of the emitted light of such compounds may be sensitive to the presence of oxygen, Peterson used plastic optical fibers, because (inter alia) he regarded the use of inorganic fibers as impractical for the desired purpose because / ■fljoKocm of brittleness. Also, since plastic optical fibers are insufficiently transparent to ultraviolet light, this necessitated the use by him of visible light and of dyes sensitive thereto.

As will be seen from the description herein, and contrary to the teaching of Peterson, the present inventors have found the use of at least certain inorganic optical fibers to be eminently practical for the purposes of the present invention, and brittleness is not a problem. Moreover, the use of a sensitized porous glass tip at the end of such fibers, enables the manufacture of optical probe apparatus which is believed to be considerably more sensitive than that of Peterson. Furthermore, the use according to the present invention of such a tip has the result that the sensor can be much smaller than, and is therefore potentially of greater flexibility and applicability than Peterson's probe. Unpublished experiments by the present inventors have shown that in fact no more than an ambit of about 200 microns of Peterson's probe is the realistic sensitive volume .

In US 4568518 (Wolfbeis), which issued February 4, 1986 (the contents of which are incorporated by reference herein), there is described a flexible sensor element comprising a carrier membrane and an immobilized nertwork structure (especially one based on cellulose) including a fluorescent indicator, and in particular such an indicator for measurement of pH values and for blood gas analysis. Wolfbeis's object appears to be to load the carrier with as much indicator as possible and he takes the view that "all known methods of immobilization pertaining to glass surfaces suffer from the disadvantage that the surface will take up only a relatively small amount of bonded immobilized material in a single layer." Contrary to the teaching of Wolfbeis, however, the present inventors have found that the fact that glass surfaces may only immobilize a relatively small amount of material {in the present invention the relevant material is chemically bonded to internal surfaces of the glass, optimally in a single layer) is to be regarded as an advantage and not a disadvantage.. This is because when much more than a molecular layer of fluorescent material is immobilized on a carrier, the fluorescent molecules under excitation may tend to react physically with each other, the effect of which will be to substantially reduce the number of excited molecules which give the desired information.

In European Patent ^Application No. 0214768 (Hirschfeld) , published March 18, 1987. the contents of which are incorporated herein by reference, physical and chemical properties of a sample fluid are monitored by measuring an optical signal generated by a fluorescent substance and modulated by an absorber substance. In practice, both fluorescent and absorber substances may be adsorbed on or/and covalently bonded 88967/2 to glass in the form of porous or sintered glass, or a colored filter glass may be used alternatively as substrate, the substrate in each case being attached by adhesive to one end of a fiber optic. There is no suggestion in this European Patent Application either that the fluorescent substance may be used in absence of the absorber substance, or that the device of the invention may be used for the measurement of chemical properties of the blood in situ, although the same inventor in U.S. Patent No. Ί, 599 , 901 , which issued July 15 , I986 (and the contents of which are incorporated by reference herein) described a method for direct measurement of arterial blood pressure measuring the intensity of emissions from (inter alia) the surface of a plastic bubble coated with a fluorescent composition and attached to the end of a fiber optic. Moreover, the teaching of the use of porous glass in EP 021^7 8 is restricted to the use of commercially available material which is attached by adhesive to the fiber optic; any concept of attachment in any other manner, or of formation of the porous glass sensor element in situ is completely absent.

In principle, the present invention provides an optical probe device, of which the essential elements are (except for an optional surface polymeric film) virtually completely fabricated from suitable inorganic materials such as glass and/or fused silica without the aid of adhesive for bonding the sensor, and, having chemically bonded to the internal surface thereof one or more light sensitive substances, may be potentially more sensitive than comparable prior art sensors. The sensor element is also much smaller than hitherto, and this enables the device to be used in situations, especially in relation to monitoring the chemical properties of the human blood stream in vivo, which it is believed were not from a practical standpoint possible before the advent of the present invention.

It will be seen infra that the present invention makes use of inter alia substantially non-porous glasses ("parent glasses") which are convertible to porous glasses. Both parent glasses and porous glasses are well known in the art. When parent glasses, which may be certain borosilicate glasses, are heat-treated there results an interconnected separation of phases, one of which may be leached by aoid (or in certain cases even by water) to leave an insoluble mainly silica phase (in fact, a porous glass) which could be consolidated by heating into a dense, clear glass known in the trade as "Vycor" . Since it is the porous glass which is a desirable carrier for chemically bonding at least one light sensitive substance in accordance with the present invention, any such consolidation step as is used to produce "Vycor" glass is of course omitted herein. Composition ranges for parent glasses, which are to be regarded as illustrative only, are: (1) SiO 55-7Ο. Na 0 10-0.1, B 0 balance to make 100%; 2 2 2 3 (2) SiO 55-70, K 0 9-0.1, B 0 balance to make 100%; 2 2 2 3 (3) Al 0 Q.l- , SiO [55 minus 1.25 Al 0 content] up to 70, 2 3 2 3 Na 0 10-0.1 [minus 0.17 x Al 0 content], B 0 balance to make 2 2 3 2 3 100%; ( ) SiO 55-75, alkalis 5-15, oxides of Fe, Co, Ni 5-15, B 0 2 2 3 15-302.

Literature references to porous glasses are also included in the above-cited European Patent Application.

In GB II90583 (Bergman), published May 6, 1970, there is described a gas detector for measuring or monitoring the partial pressure of a gas (in particular, oxygen) , containing a matrix support for luminescent material v The matrix, which in practice is used in the form of a thin film or disc, may be made of "porous Vycor-type glass". No details are provided of how such glass is obtained. In his illustrated embodiment, a sintered metal cylinder contains the matrix, an ultraviolet glow lamp, filters and photoelectric cells. The atmosphere to be monitored either diffuses through the wall of the cylinder, or is led through the apparatus by inlet and outlet pipes. This patent is not concerned with the use of fiber optics, with a detector element of such a size that it may constitute or be attached to the tip of a fiber optic, or with monitoring the chemical properties of the human blood stream in vivo.

In Weetall and Filbert, Methods in Enzymology, 197^. 3 : 9-72 , the disclosure of which is incorporated herein by reference, there is described the formation of chemical bonds between porous glass and silicon-containing organic compounds, to which further organic entities can be bound in turn, the products being useful for affinity chromatography.

In Wolfbeis et al, Mikrochimica Acta [Wien], 1984, I: I52-I58, the disclosure of tfhich is incorporated herein by reference, there is described a_fluorescen0e sensor for oxygen in which a thin layer of porous glass incorporating chemically bound light sensitive material is mounted on 2 x 2 platelets of conventional glass, which is set into a wall of flow-through apparatus. Fiber optical techniques are not described or suggested.

In Zhou et al, Anal. Chem. 1988, 60: 2317-2320, the disclosure of which is incorporated herein by reference, there is described a flow-through humidity detector containing an optical glass fiber of which a section has been made porous and impregnated with CoCl , the absorption characteristics of which 2 are utilized for humidity detection.

It will be appreciated that of the prior art described above, only US 4599901, EP 021^768 and the Anal. Chem. 1988 article describe inorganic optical fiber techniques of any kind for detectors, and that none of the prior art either describes or suggests the advantageous use a fused or integral porous glass tips as disclosed in the commonly assigned patent applications referred to above, and which together with the incorporation of chemically bonded materials constitutes the concept of the present invention.

SUMMARY OF THE INVENTION The present invention provides in one embodiment a sensing device for use in the manufacture of an optic probe apparatus for quantitative determination of the chemical properties of a medium in situ, the device comprising essentially at least one inorganic optical fiber means, each of which has at an open end thereof an integral or fused-on porous glass tip, which is characterized by the fact there is chemically bonded to the internal surface thereof at least one substance selected from fluorescent and other light sensitive substances. The inorganic optical fiber means may include e.g. glass and/or fused silica optical fiber means.

According to a further embodiment of the invention, there is provided an apparatus for quantitative determination of the chemical properties of a medium in situ, characterized by the fact that it comprises as an optic probe a sensing device as described above.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 shows in section a sensing device according to an embodiment of the invention which comprises a single unbranched inorganic optical fiber.

Fig. 2 shows in section a sensing device according to a further embodiment of the invention which comprises a single unbranched inorganic optical fiber.

Fig. 3 shows in section an example of a sensing device according to the invention which comprises two inorganic optical fibers which in one embodiment are attached to a single glass tip and in another embodiment are fused together at one end.

Fig. 4 shows in section another sensing device according to the invention which comprises two inorganic optical fibers which in one embodiment are attached to a single glass tip and in another embodiment are fused together at one end.

Fig. 5 shows in section a sensing device according to an embodiment of the invention which comprises a Y-shaped inorganic optical fiber.

Fig. 6 shows in section a sensing device according to a further embodiment of the invention which comprises a Y-shaped inorganic optical fiber.

Fig. 7 shows in section chemical bonding of active material on the inner surface of a single pore of a porous glass tip.

Fig. 8 shows in section a bundle of optical fibers attached to respective glass tips.

DETAILED DESCRIPTION OF THE INVENTION In more detail, the utilized inorganic optical fiber means may be selected e.g. from categories (a), (b) and (c), namely: (a) glass optical fiber means to each of which is attached by fusion at an open end thereof a discrete glass tip, the glass of the tip being selected from substantially non-porous glasses convertible to porous glasses and wherein the tip has been subjected to an after-treatment to convert it to a porous glass tip; (b) fused silica optical fiber means to each of which is attached by fusion at an open end thereof a discrete glass tip, the glass of the tip being selected from substantially non-porous glasses convertible to porous glasses and wherein the tip has been subjected to an after-treatment to convert it to a porous glass tip; (c) glass optical fiber means fabricated from a substantially non-porous glass convertible to a porous glass, an open end of each of which defines the tip thereof and wherein the tip has been subjected to an af er-treatment to convert it to a porous glass tip.

The at least one light sensitive substance preferably comprises a substance such that when incident light of a known exciting (first) wave-length impinges thereon, it will emit light of a particular (second) wave length when present in below a preselected concentration per unit internal surface area and it will commence to emit light in a significant and detectable quantity of a particular (third) wave length when present in at least the preselected concentration per unit internal surface area. The substance having the properties just described is desirably present in at least the preselected concentration per unit internal surface area. By way of example, this substance may contain a pyrene ring system.

The sensing device of the invention may be made, e.g., by a process comprising the step of attaching by fusion a glass tip to an open end of each one of at least one inorganic (e.g. glass or fused silica) optical fiber means, and wherein the glass of the tip is selected from substantially non-porous glasses convertible to porous glasses, or alternatively by a process comprising the step of treating an open end at the tip thereof of each one of at least one glass optical fiber means fabricated from a substantially non-porous glass convertible to a porous glass, thereby to convert the or each tip to a porous glass tip.

It is to be understood that the device of the invention comprises in one embodiment a glass tip either fused to or integral with an open end of inorganic optical fiber means (or a plurality of glass tips fused to or integral with respective open ends of a plurality of inorganic optical fiber means), which when used as the sensor of an optic probe will have been made porous , and will then have chemically bonded to the internal surface thereof at least one light sensitive substance.

A "light sensitive substance" in the present context means a substance which will react to incident light by emitting a light signal. It is presently preferred that this substance is an agent which imparts information exclusively by means of the internally unmodified intensity of the light emitted therefrom. In other words, it is preferred not. to add any substance, such as the absorber of EP 021*1768, which will vary the intensity of the emitted light signal. The intensity of the emitted signal will of course be modified by an external agent, namely, by the particular chemical property of the medium, the determination of which is desired.

The sensitivity of, such substance (which may be a fluorescent substance) to light, e.g. visible or ultraviolet light, will be affected by the chemical properties of the medium in which the sensor is inserted. While it is presently contemplated that the device of the present invention will be applicable to the quantitative determination of the chemical properties of any medium, as e.g. the liquid or gas phase in an industrial process, such as a reaction medium of a chemical industrial process, nevertheless it is believed that it will be especially useful in respect of such determinations made on blood or blood cells, and more particularly for the determination in vivo of chemical properties of blood, such as pH and the partial pressure of oxygen and of carbon dioxide. In other words, the intensity of the light emitted from the substance or substances adsorbed on the internal surface of the sensor, will be a function of such chemical properties.

By the expression "at least one inorganic optical fiber means" it is intended to convey that the invention includes, on the one hand, either one or a plurality of inorganic optical fiber means, and on the other hand that what is termed "inorganic optical fiber means" may assume a number of configurations of inorganic optical fibers. Thus, for example, each inorganic optical fiber means may be constituted in one or other of the following modes, namely, where: (i) the inorganic optical fiber means comprises one unbranched inorganic optical fiber; (ii) the inorganic optical fiber means comprises at least two inorganic optical fibers all of which are attached to, or are fused together to form, a single glass tip; (iii) the inorganic optical fiber means is Y-shaped, and the glass tip (which is porous or is to be made porous) is located at an open end of one of the arms of the Y. In mode (i) , it is evident that both the light directed to the sensor and that emitted therefrom will be channelled along the same optical fiber. In mode (ii), it is intended that the light directed to the sensor will be channelled along one (or more) optical fibers, and the emitted light will be mainly channelled along another one (or more) optical fibers. In mode (iii), it is intended that the light directed to the sensor will be channelled along one arm of the Y to the junction and thereafter to the sensor (i.e. the sensitized tip), while the emitted light will be channelled from the sensor to the junction and thereafter (mainly) along the other arm of the Y. Whatever the manner in which the or each inorganic optical fiber means is constituted, the device of the invention may comprise one or a plurality of such inorganic optical fiber means.

When the device of the invention comprises a single inorganic optical fiber means, it will be most readily adapted to Ik 88967/2 the determination of a single chemical property. Nevertheless, it is within the scope of the present invention to chemically bond to the internal surface of a single porous tip, more than one light sensitive substance and to measure the light emitted from each such substance present in the porous tip, in order to determine more than one chemical property. In an alternative embodiment of the device of the invention, in which the "at least one inorganic optical fiber means" comprises in fact a plurality of inorganic optical fiber means, each of which has attached thereto or integral therewith a different porous inorganic tip, then at least two of the tips may have adsorbed thereon different light sensitive substances, respectively, thereby facilitating the determination of at least two different chemical properties of the medium.

For the device according to the invention to be usable in an optic probe, it will be necessary for the (at least one) attached or integral tip to be subjected to a process step whereby the substantially non-porous glass of the tip is converted to a porous glass. This step will normally comprise acid treatment, using e.g. hydrochloric acid, the acid treatment being preceded by a heat treatment. The porous tip or tips thus produced may then be reacted so as to chemically bond to the internal surface thereof at least one light sensitive composition, e.g. a fluorescent composition.

It is advantageous, for a number of reasons, for the thus-treated porous discrete glass tip to be overlaid with a porous polymeric film prior to actual use. Such a film would protect the external glass surface thereof from nicks and scratches, and especially if extended somewhat over the adjacent part of the inorganic fiber means which is either integral with it or to which it is attached, would also have a safety function in preventing any light sensitive substance, from contaminating the medium under test. (However, tests have shown that it is extremely unlikely that under conditions of use generally prevailing, any light sensitive substance will become detached from the internal surface of glass to which it has been chemically bonded.) It will be appreciated that in any event the porosity of the polymeric film will necessarily be such as to allow the ingress of the medium or at least the components thereof which are the subject of quantitative determination. A suitable material for the film would appear to be an RTV silicone such as that marketed under the trade name "Dow Silastic Corning 89Ο (or 891)", which incidentally has been approved by the FDA for body implants. It is also possible to overlay the end of the inorganic optical fiber with a preformed polymeric tube (e.g. that marketed under the trade name "Celeguard" ) , the end of which can be closed and (if necessary) adhered to the outer fiber surface by gluing. It may be noted in passing that such gluing does not interfere with the analytical determination as does glue used in the prior art to bond a glass tip to an optical fiber, since it is effected on the outside of the optical fiber and consequently does not obstruct the light path.

As has already been indicated, the invention provides in a further aspect a process for making a sensing device in accordance with the details already described above. In yet another aspect, the invention provides an apparatus for quantitative determination of the chemical properties of a medium in situ, characterized by the fact that it comprises as an optic probe a sensing device in accordance with the details already described above.

The concept of the present invention resides principally in the device comprising inorganic fiber optic means having integral therewith (in the case of a glass fiber optic means) or fused thereto a glass tip convertible to a porous glass tip, rendering this tip porous, and thereafter chemically bonding to the internal surface thereof at least one light sensitive material. It will therefore be appreciated that in the apparatus aspect of the invention, such features as the means for sending the light to the sensor, receiving light emitted therefrom, and calculating the desired properties from the intensity of the emitted light, will in principle be known, and per se form no part of the present inventive concept.

Examples of suitable materials which fluoresce when subjected to ultraviolet light and which may be useful as the light sensitive substances for being chemically bonded to the internal surfaces of the porous glass tips of the sensing device of the invention, when used for in vivo or in vitro determinations in the blood (or in industrial applications) are with reference to the determination of oxygen, for example, polycyclic aromatic compounds e.g. pyrene compounds. 17 N Materials fluorescing in light other than UV are also operable.

A general method for attaching organic molecules to' porous glass is described, for example, in Weetall and Filbert (loc cit). This general method, which may be applied to chemically bonding light sensitive substances to porous glass tips for the purpose of the present invention, consists of first activating the porous glass e.g. by boiling with nitric acid, then silanizing by reacting the porous glass with an organic molecule containing silylalkoxy group (which reacts with the glass surface) at one end and a functional group (which is available for further reaction) at the other end. Silanization may be effected in organic or in aqueous solution. A typical silanization reagent is (EtO) Si(CH ) NH , but the process is 3 2 3 2 evidently not to be construed as restricted to this particular reagent. Where this reagent (or an analogous reagent containing a primary amino group) is utilized, the residual primary amino group attached through a chain to the glass may be derivatized, e.g. by acylation. Thus for present purposes, pyrene which contains an alkanoic side-chain (such as e.g. pyrenebutyric acid) could be reacted with such residual primary amino groups, as indeed was done by Wolfbeis et al (loc cit) . Other fluorescing or otherwise light sensitive residues, besides pyrene, are of course within the scope of the method of Weetall and Filbert and are also within the scope of the present invention, for the > purpose of creating chemical bonds between the light sensitive molecules and the internal surfaces of the porous glass tips. !8 V DETAILED DESCRIPTION OF THE DRAWINGS It will be appreciated that the drawings are generally schematic and while enlarged compared with the actual size, are not drawn to scale. The same numerals in different drawings depict corresponding features of the illustrated device.

Fig. 1 shows a single unbranched inorganic optical fiber 2, to which is attached at the end 4 thereof, in one embodiment, by fusion, substantially non-porous (but convertible to porous) glass tip 6. In another embodiment, 2 is a single unbranched inorganic optical fiber fabricated from substantially non-porous glass convertible to porous glass, which at the end denoted 4 may potentially be treated as described herein to render the tip porous, e.g. in region denoted 6, up to the broken line. In Fig. 2, tip 6 of the device of Fig. 1 (either embodiment) has been made porous in the manner described herein, and thus now incorporates pores such as those denoted by reference numeral 8. Following adsorption of active substance on the inner surfaces of pores 8, tip 6 as well as at least part of the adjacent portion 4 of glass optical fiber 2 may optionally be coated with porous polymeric film 10.

In Fig. 3i two inorganic optical fibers 12 and 14 are fused together in the vicinity of one end, at region 16; in one embodiment, this end of the fused-together pair of fibers is attached by fusion in region 18' to a single substantially non-porous glass tip l8, whereas in another embodiment, when the fibers are fabricated from substantially non-porous glass convertible to porous glass, the structure already contains a non-porous tip 18 , convertible to a porous tip. In Fig. 4 , tip l8 of the device of Fig. 3 (either embodiment) has been made porous in the manner described herein, and thus now incorporates pores such as those denoted by reference numeral 8. Following adsorption of active substance on the inner surfaces of pores 8, tip 18 , and at least part of the adjacent portion 18 ' , of the inorganic optical fiber, may optionally be coated with porous polymeric film 20.

In Fig. 5. a inorganic fiber continuum including Y-shaped junction A from which extends respective arms 24 and 26 , is, in one embodiment, attached at end 28 to a substantially non-porous glass tip 32 at fusion region 30 ; in another embodiment, in which the inorganic fiber continuum is fabricated from substantially non-porous glass convertible to porous glass, 32 represents a region (bounded e.g. by broken line 30) which may potentially be made porous. In Fig. 6 , tip 32 of the device of Fig. 5 (either embodiment) has been made porous in the manner described herein, and thus now incorporates pores such as those denoted by reference numeral 8. Following adsorption of active substance on the inner surfaces of pores 8 , tip 3 as well as part of the adjacent portion 28 (inclusive of region 30) of the inorganic optical fiber may optionally be coated with porous polymeric film 12. As a variation of the embodiments of Figs. 5 and 6 , arm 28 may be replaced by a plurality of separate arms attached (e.g. by fusion) to the apex of the V formed by arms 24 and 26 ; these separate arms, with respective sensitized tips which are as described either attached thereto or integral 20 \ therewith, may be used as separate sensors, or as a bundle as described below with reference to Fig.8.

In the embodiments illustrated in Fig. 2, both the light directed to the sensitized tip 6 and that emitted therefrom will be channelled along the same optical fiber 2. In the embodiments illustrated in Fig. 4 , it is intended that the light directed to sensitized tip 6 will be channelled along one of optical fibers 12 and l4 , and that the emitted light will be mainly channelled along the other of these optical fibers. In the embodiments illustrated in Fig. 6 , it is intended that the light directed to the sensor will be channelled along one arm (24 or 26 ) of the Y to the junction A and thereafter to the sensitized tip 32 , and that the emitted light will, be channelled therefrom to junction A and thereafter (mainly) along the other of arms 24 and 26.

Fig. 7 depicts the adsorption of active substance at a number of sites 22 on the inner surface of a typical pore 8.

Fig. 8 shows a bundle of individual inorganic optical fibers 40, 42, 44 and 46. According to one embodiment, to the respective ends of these fibers there are attached by fusion in respective regions 60 , 62 , 64 and 66 , individual tips 50 , 52 , 4 and 6 ; according to another embodiment in which the fibers are fabricated from substantially non-porous glass convertible to porous glass, regions 50 , , 54 and 56 , bounded respectively by (e.g.) lines 60 , 62 , 64 and 66 , may be made porous and thereafter sensitized as described herein. The bundle of fibers may in either embodiment be held together by insertion in a flexible sleeve (not shown) . In the first mentioned embodiment, the fusion is effected individually with non-porous glass tips convertible to porous glass tips, and the steps of making the tips porous, adsorption of sensitive material and (if desired) coating with a porous polymeric material, are effected as described herein. The optional coating step may of course also be carried out in the case of the second mentioned embodiment. It will be appreciated that in this bundle of fibers, each tip which has been made porous may be sensitized by adsorption of a different substance, thereby making possible the simultaneous analysis of different properties of the medium in which the sensor is inserted. While a bundle of four sensors is shown in Fig. 8, alternatively a bundle of two, three or of more than four sensors, may of course also be utilized.

The invention will now be illustrated by the following non-limiting examples.

EXAMPLE 1 Preparation of parent glass and optical fibers having porous glass tips. (i) Milled sand (67^ g. ) , boric acid (^ 7 g- ) and sodium carbonate (119 g- ) were melted in a 1 1. alumina crucible at o I5OO-I52O C in a gas furnace for 1.5 hours. The glass (approximately 1 kg.) was cast, broken into pieces and remelted o at I52O C in an electrical furnace for 2 hours. It was then cast into a steel mold, pressed into a plate about 15 mm. thick and ea ng. s p a e was cu to rods "15 x 15 x 40 mm. The resultant parent glass had the composition (wt. %) : SiO 67.4; B 0 25 - 7 ; Na 0 6.9. 2 2 3 2 (ii) Graded index 100-140 plastic coated glass optical fibers made by Israel Product Research Co. Ltd., Herzlia, Israel were used in 2.5 m. lengths. Approximately 100 cm. length of the plastic coating was removed at one end of each fiber, using 1 , 2-dichloroethane; the exposed parts were cleaned well in an ultrasonic bath using successively 1 , 2-dichloroethane (followed by shaking off excess solvent and air drying), water and ethanol, and finally hot air drying to obtain a product at this stage which was free of grease and moisture.

The parent glass from part (i) (approx. 50 g.) was o remelted at 950 C in an electrical furnace. At this temperature the glass was sufficiently fluid to draw fibers. The end of a parent glass fiber was fused in a flame to the end of a commercial glass optical fiber (prepared as described in the preceding paragraph), removing almost all the parent glass, leaving only a small fused glass tip. Alternatively, the ends of commercial glass optical fibers were dipped into molten parent glass, and the fibers were then pulled out with their tips coated with parent glass. In the product, the parent glass tip had a diameter in the range 100 - 500 pm. (iii) The parent glass tip of the product of part (ii) (produced by either alternative) was. heated in an electrical o o furnace for 2 hours at 610 C, then for 75 hours at 530 C, the heating rate being 3~5 C per minute. The heat-treated tip was then subjected to concentrated aqueous sodium hydroxide for 0.5 hour to remove the surface layer, and leached with 3N aqueous HCl o for 25 hours at ~50 C. The specific area of the resultant porous glass tip was 120-140 m2/g.

EXAMPLE 2 Chemical bonding of light sensitive material to porous glass tips.

Several single optical fibers 100 cm. in length and having porous glass tips, prepared as described above, were tied around a 50 cm. glass bar with a band of Teflon (Registered Trade Mark) . The edge of the bar with the adjacent porous tips was introduced into a 150 ml. flask and tightened around one its necks with Teflon bands. Activation of the porous tips was effected by reflux ng with 10% nitric acid for 18 hours, they were then washed with acetone, rinsed with distilled water and dried in vacuum. The bar with attached fibers was immersed in a solution of 3 ml. (EtO) Si(CH ) NH (Aldrich) in 7 ml. toluene 3 2 3 2 (Merck) containing 0.1 ml. distilled water. Silanization was effected by refluxing for 18 hours, after which the bar with attached fibers was left immersed in distilled water to dissolve residues of polymeric byproducts. After 2k hours, the porous tips were washed with acetone and dried at room temperature for several hours under vacuum.

The glass bar with attached fibers was placed in a tube containing 15 mg. pyrenebutyric acid (PBA) (Aldrich) and 250 mg. dicyclohexylcarbodiimide (Merck) in 10 ml. dry toluene (Merck), 2k secured to the neck of the tube with a Teflon band, allowed to stand for 48 hours, rinsed with toluene and acetone, and left for successive periods of 24 hours in toluene, acetone and dimethylacetamide , separately, in order to remove impurities, in particular unbound PBA.

The sensitivity of the material bonded to the porous glass tip towards oxygen was checked by measuring the fluorescent signal in an Applied Photophysics SP 70/80 spectrofluorometer . The other end of the glass fiber was connected to one end of a Litton Polyscientific beam splitter equipped with a Newport fiber optic positioner. The other two ends of the beam splitter were centered in front of the photomultiplier slit entrance of the spectrofluorometer and at the centre of the slit of the exciting light which was focussed with a quartz lens (focal length = 5 cm.)- A strong fluorescent signal was observed by exciting the porous glass tip with light at 3^8 nm. The maximum of the emission spectrum was recorded at 460 nm which indicates that excimers were formed (as compared with 370~400 nm in absence of excimers). No signs of monomers were detected in the emission band. The fluorescence signal was quenched by pure oxygen at atmospheric pressure by a factor of at least 25.

EXAMPLE 3 Coating the sensors with a porous polymeric film.

A solution of 1 g. RTV silicone marketed under the trade name "Dow Corning Silastic 890 (or 891 ) " in 150 ml. toluene was prepared (c.f. Wolfbeis et al, Anal. Chem., 1 85 57 :2556) . The product of the preceding example was dipped therein and curing was effected at room temperature over a 48 hour period. The porous polymeric film extended over the sensitized porous tip and about 10 cm. along the adjacent fiber. The device was now ready for determination of the partial pressure of oxygen. In an alternative procedure, the uncoated sensitized fiber is protected with a sheath of Celeguard plastic tube which is adhered to the outside of the fiber with any suitable glue, by way of example EPO-TEK 301 (manufactured by Epoxy Technology Inc., Billerica, Massachusetts, U.S.A.), which is also used to close the end of the overlay tube.

EXAMPLE 4 Correlation of light emission with oxygen content of a test gas.

The product of Example 3 was set up with the sensitized tip in a chamber and in such manner that incident light was led through the fiber to the sensor and emitted light wa_ conducted through the fiber from the sensor to a photomultiplier and means for recording the intensity of the emitted light. 100% nitrogen was led through the chamber at a rate of about 300 c.c./min. and the intensity of the light emitted from the sensor was noted. At approximately 10 second intervals, the composition of the feed gas was changed so as to increase its oxygen content initially from 0 to about 6.67% by volume and thereafter in steps of about 6.67% by volume, so that after 2.5 minutes the gas contained 100% oxygen. The intensity of the light emitted from the sensor was noted at each step of increasing the oxygen content. It was found that over the greater part of the composition range there was a substantially linear correlation between the amount of reduction of the intensity of the emitted light, corresponding with an increase in the oxygen content of the feed gas. A similar result is obtained when the sensor is immersed in an aqueous medium, through which the feed gas is bubbled.

EXAMPLE Preparation of parent glass optical fibers and such fibers having integral porous glass tips. (i) Parent glass (approx. 50 g.) prepared according to the o details given in Example 1 part (i) was remelted at 950. C in an electrical furnace. At this temperature the glass was sufficiently fluid to draw fibers. (ii) A selection was made from fibers formed according to part (i), for use as optical fibers. The tips were heat-treated o in an electrical furnace for 25 hours at 610.C, then for 75 hours. o o at 530 C, the heating rate being 3~5 C per minute. After cooling, the tips of the optical fibers were immersed in 3N o aqueous HC1 for 25 hours at ~50 C. The specific area of the resultant porous tips of the glass fibers was 120-140 m2/g.

The integral porous tips of the product were reactivated and reacted according to the details given in Example 2 , above, with similar results. The resulting sensors were coated with a porous polymeric film as described in Example 3 · Correlation of light emission with oxygen content of a test gas was carried out as detailed in Example 4, with similar results.

While embodiments of the invention have been particularly described, it will be appreciated by those skilled in the art that many variations and modifications are possible. For example, although the utilization pf glass optical fibers has been described above, it will be evident that other compatible inorganic optical fibers may be substituted for these glass optical fibers at least in the embodiment of the invention wherein the glass optical fibers are fused to glass tips which (as described herein) may be converted to porous tips which are subsequently reacted with light sensitive materials and that the obtained sensors employing such other compatible inorganic optical fibers may be regarded as the chemical and/or mechanical equivalents of those which are particularly described herein. Examples of such are compatible fibers are the fused silica optical fibers obtainable from such suppliers as Fiberguide Industries, Polymicro Technologies and Ensign-Bickford Optics Company (U.S.A.). Preliminary experiments by the present inventors have shown that the substitution of such fused silica optical fibers for the glass optical fibers give products which appear to give less background noise and therefore possess potentially even more sensitivity than the glass fiber products. The invention is therefore not to be construed as limited by the embodiments particularly described herein, but the principles thereof may be practised within the spirit of the invention as will be apparent to those skilled in the art.

Q7591CLA.IMS 1-1102 January 10, 1989.

Claims (23)

1. A sensing device for use in the manufacture of an optic probe . apparatus for quantitative determination of the chemical properties of a medium in situ, said device comprising essentially at least one inorganic optical fiber means, each of which has at an open end thereof an integral or fused-on porous glass tip, said tip being characterized by the fact there is chemically bonded to the internal surface thereof at least one substance selected from the group consisting of fluorescent and 'other light sensitive substances.

2. Device according to claim 1, wherein said at least one inorganic optical fiber means is selected from the group consisting of glass and fused silica optical fiber means.

3. Device according to claim 2, wherein said at least one optical fiber means is selected from the group consisting of categories (a), (b) and (c) , namely: (a) glass optical fiber means to each of which is attached by fusion at an open end thereof a discrete glass tip, the glass of said tip being selected from the group consisting of substantially non-porous glasses convertible to porous glasses and wherein said tip has been subjected to an after-treatment to convert it to a porous glass tip; (b) fused silica optical fiber means to each of which is attached by fusion at an open end thereof a discrete glass tip, the glass of said tip being selected from the group consisting of substantially non-porous glasses convertible to porous glasses and wherein said tip has been subjected to an after-treatment to convert it to a porous glass tip; (c) glass optical fiber means fabricated from a substantially non-porous glass convertible to a porous glass, an open end of each of which defines the tip thereof and. wherein said tip has been subjected to an after-treatment to convert it to a porous glass tip.

4. . Device according to any of the preceding claims, wherein said at least one inorganic optical fiber means is constituted in one of the following modes, namely: it comprises a single inorganic optical fiber means; or it comprises a plurality of inorganic optical fiber means, each of which in the case of categories (a) and (b) has attached thereto a different discrete porous glass tip; or it comprises one unbranehed inorganic optical fiber; or it comprises at least two inorganic optical fibers all of which are attached to or are integral with a single porous glass tip; it is Y-shaped.

5. · Device- according to any of claims 1 to 3. wherein said at least one inorganic optical fiber means is constituted by a single unbranehed inorganic optical fiber.

6. Device according to any of the preceding claims, wherein said at least one substance is at least one fluorescent substance which is sensitive to ultraviolet light.

7. Device according to claim 1, wherein said at least one optical fiber means comprises a plurality of optical fiber means each of which has attached thereto or integral therewith a different porous glass tip each of which has chemically bonded to the internal surface thereof a ^substance selected from the group consisting of fluorescent and' other light sensitive substances, such that at least two porous glass tips have chemically bonded different said substances, respectively, whereby the device is' adapted for the determination of at least two different chemical properties of said medium.

8. Device according to any of the preceding claims, wherein the or each porous glass tip has an overlay of a porous polymeric film, which optionally extends to a portion of the optical fiber means adjacent to the or each porous tip.

9. . Device according to any of the preceding claims , wherein said at least one substance is an agent which imparts information exclusively by means of the internally unmodified intensity of the light emitted therefrom.

10. Device according to any of the preceding claims, wherein said at least one substance comprises a substance such that when incident light of a known exciting (first) wave-length impinges thereon, it will emit light of a particular (second) wave length when present in below a preselected concentration per unit internal surface area and it will commence to emit light in a significant and detectable quantity of a particular (third) wave length when present in at least said preselected concentration per unit internal surface area.

11. . Device according to claim 10 , wherein said substance having the properties defined in claim is present in at least said preselected concentration per unit internal surface area.

12. Device according to either claim 10 or claim 11 , wherein said substance having the properties defined in claim 10 contains a pyrene ring system.

13. Device according to any of the preceding claims, wherein said chemical bonding is effected in two stages, the first stage comprising silanization of the internal surface of the- porous glass by reacting the latter with an organosilicon compound containing a reactive first functional group and the second stage comprising reacting said first functional group with a preselected light sensitive compound containing a second functional group which is reactive with said first functional group .

14. . Device according to claim 13 , wherein said first functional group is a primary amino group and said second functional group is a carboxylic group or a reactive derivative thereof.

15. Device according to claim 13 or claim 14, wherein said porous glass is subjected to an activation treatment prior to said silanization.

16. Device according to claim 15 , wherein said activation treatment comprises treatment with nitric acid. 88967/2

17. · Sensing device according to claim 1 and substantially as hereinbefore described.

18. Sensing device for use in the manufacture of an optic probe apparatus for quantitative determination of the chemical properties of a medium in situ, substantially as described with reference to any of the accompanying drawings.

19. Apparatus for quantitative determination of the chemical properties of a medium in situ, which comprises as an optic probe a sensing device as defined in any of the preceding claims .

20. Apparatus according to claim 19, which is adapted for quantitative determination of the chemical properties of a medium in situ, which medium is selected from the group consisting of blood and blood cells either in vitro or in vivo.

21. Apparatus according to claim 20, wherein said chemical properties are selected from the group consisting of pH, the partial pressure of oxygen and the partial pressure of carbon dioxide .

22. Apparatus according to claim 19, which is adapted for quantitative determination of the chemical properties of a medium in situ, which medium is selected from the group consisting of the gas and liquid phases in industrial processes.

23. Apparatus according to claim 19 and substantially as hereinbefore described. 2k. Apparatus according to claim .13 and substantially as hereinbefore described with reference to any of the accompanying drawings . For the Applicants, C: Θ7591 1-1102