WO1992011801A1

WO1992011801A1 - Method and sensor for detecting specific parameters of circulating blood inside a living organism

Info

Publication number: WO1992011801A1
Application number: PCT/SE1991/000535
Authority: WO
Inventors: Åke ÖBERG; Lars-Göran LINDBERG; Robert Axelsson; Jan Svenson
Original assignee: Oeberg Aake; Lindberg Lars Goeran; Robert Axelsson; Jan Svenson
Priority date: 1990-12-28
Filing date: 1991-08-13
Publication date: 1992-07-23
Also published as: SE9100008D0; AU8616791A

Abstract

The invention relates to method and sensor for detecting specific parameters of a blood flow in a blood vessel in a living organism by detecting optical properties of the flowing blood, depending on said specific parameter, by using at least one optical plastic or glass fibre. The detection is effected according to the invention in a peripheral layer of blood plasma closest to the wall of the blood vessel the optical fiber being disposed adjacent said wall at the outside or inside surface thereof. The sensor comprises means (10) for applying one or more optical plastic or glass fibres (14, 15) to the outside surface of the wall of the blood vessel (11).

Description

METHOD AND SENSOR FOR DETECTING SPECIFIC PARAMETERS OF CIRCULATING BLOOD INSIDE A LIVING ORGANISM The invention relates to a method and a sensor for detecting specific parameters of a blood flow in a blood vessel in a living organism by detecting optical properties of the flowing blood, depending on said specific parameter, by using at least one optical plastic or glass fibre.

It is desirable to be able to perform continuous detection or quantitative monitoring of specific parameters of circulating blood in order to be able to control in dependance of the continuously obtained readings, for example the supply of drugs, to measure the drug concentration in the blood, or to establish a required dosage for the intake of a drug at predetermined intervals (multiple-dose system) via e.g. a pump or the like located in or outside the body. It may, for example, be a matter of establishing the glucose content of a diabetic in order to control by guidance thereof the intravascular, subcutaneous or intraperitoneal supply of insulin or to adjust the required insulin dosage. High standards are required of the sensors used at such detection above all with respect to the safety of the patient as well as the reliability in the detection obtained, but also with respect to miniaturization, biocompatability, replaceability, simple handling, specificity, long-term stability, low cost, and producibility. During the last 30 years a great number of sensor principles have been suggested for this purpose, which function according to different physical principles, but none of these is satisfactory in every respect. The object of the invention is to provide a method and a sensor of the above mentioned type satisfying the above mentioned requirements as far as possible, and this is achieved by the method according to the invention having obtained the characterizing features of claim 1, and the proposed sensor according to the invention for working this method having obtained the characterizing features of claim 5.

In order to explain the invention in more detail reference is made to the accompanying drawings, in which FIG 1 is a cross sectional view of a blood vessel with a blood flow passing through it,

FIG 2 is a perspective view of a blood vessel with a sensor thereto connected which is disposed on the outside of the vessel,

FIG 3 is a view corresponding to FIG 2 but with the sensor attachment fixedly rooted on to the blood vessel,

FIG 4 is a perspective view which shows a blood vessel with the sensor disposed on the outside of the vessel, FIG 5 is a perspective view like FIG 4 but with a sensor of another type than that in FIG 4, FIG 6 is a cross sectional view which shows a principle for detection in a blood vessel, and FIG 7 is a graph which shows the relative change of reflected light as per cent at different wavelengths when measuring glucose. When there is a flow of blood in a blood vessel the concentration of red blood cells varies with the radial position as is schematically illustrated in FIG 1. Inside the blood vessel, represented by 10, adjacent to the vascular wall there is a thin layer DI of plasma which contains few or no red blood cells at all. By radial movement towards the center of the blood vessel the concentration of red blood cells increases successively in the layer D2 to reach a maximum in the center D3 of the blood vessel. When the blood flow is increased, the cell-free layer DI will be thicker and the concentration of blood cells in the center of the blood vessel will increase. Simultaneously with this accumulation of red blood cells towards the center, the blood cells will also orient themselves in different ways in the blood vessel when the flow varies. At a low blood flow the blood cells are more or less randomnly oriented. When the flow is increasing, the blood cells will orient themselves with their plane surfaces parallel to the direction of flow. The reason for this accumulation and reorientation is supposed to be due to both physical interaction between the blood cells proper, and the torque to which the blood cells are exposed when in motion. Close to the wall of the blood vessel the concentration of red blood cells is low when the blood is in motion and then mainly plasma is to be found here.

It is known that different wavelengths of light penetrate to different depths in blood. A short wavelength of light is extensively absorbed by the blood cells while a long wavelength of light will not be absorbed to the same degree but will be scattered in the blood with great penetration depth as a consequence thereof. A short wavelength of light (up to 560 nm) thus will be absorbed by the blood in the sections D2 and D3, FIG 1, but some of the light in the plasma of the layer DI will be reflected back towards the wall or scattered in the plasma DI and eventualy will reach the other side of the blood vessel. Now the concentration of, for example, glucose varies in the plasma, also the reflected or scattered light will vary.

According to the invention it is essential that the detection takes place in situ inside the blood vessel adjacent to the wall of the vessel by the use of fibre optic, the fibre optic comprising a sensor (photodetector) which can be disposed either at least partly inside a blood vessel or outside the blood vessel or even on the skin over one or several blood vessels in case of the detection being peformed on a superficially located blood vessel.

In FIG 2 a through passage 11 of titanium or another biocompatible material is applied on the blood vessel 10. The through passage at a flange 12 having holes 12A of a minimum diameter of 40 μm is sewn to the wall of the vessel on the outside thereof, which can be achieved by applying conventional microsurgery, and is then fixedly rooted to the blood vessel as shown in FIG 3. Two optical glass or plastic fibres 14 and 15 are drawn through a catheter 13, the fibres being enclosed in a sheath 16 and having their ends disposed against the wall of the blood vessel for detection through the same or, alternatively, being inserted through the wall of the vessel in order to be placed at the ends thereof adjacent the inside of the wall of the vessel. The optical fibres suitably have a thickness of 100-250 μm. The through passage 11 can be of the design described in the Swedish patent application 9003719-3, whereby the optical fibres may be inserted through the central through channel of the through passage in order to have the ends thereof inside the blood vessel. Alternatively, the ends can also be located inside a transparent lens or disc aranged in the inner end of the through passage, separating the channel in the through passage from the interior of the vessel. One of the fibres has to be connected to a light source which emits light of a suitable wavelength such as white, green, red, or infrared light, whereas the other fibre has to be connected to a detector element. The ends of the fibres inside the blood vessel can be arranged as shown in FIG 6. As is evident therefrom, the ends of the fibres are located adjacent to the vascular wall in order to be placed in the layer DI, FIG 1, and they are mutually spaced in the peripheral direction. Glucose molecules present in the blood will be enriched in the plasma. The concentration of glucose molecules in the blood can be detected by the optical properties (light conductivity, reflection, scattering) of the blood being influenced by the presence of glucose molecules by, for example, the light transmission being reduced at increasing concentration of glucose molecules (transmission measurement). With the fibre ends arranged as shown in FIG 6, the optical properties thus will be sensed, the light from the fibre 14 being perceived by the fibre 15 to a varying degree in dependence of the glucose concentration.

When sensing the optical properties of the blood passing through the blood vessel, the fibre ends can be placed inside the blood vessel mutually spaced in the peripheral direction, as have been shown, but a positioning with an axial distance between the fibre ends is also possible.

Said variation of the reflected or scattered light can also be detected by a sensor which is placed outside the blood vessel.

According to FIG 4, an element 17 is applied to the outside of the blood vessel 10, which partly surrounds the blood vessel and suitably consists of titanium or another biocompatible material. An optical glass or plastic fibre 18 is drawn through the element, said fibre extending along the blood vessel closely adjacent the outside of the wall of the vessel. A light source is connected to one end of the fibre 18 and a detector to the other end. Dependent on the concentration of glucose in the blood, more or less of the light supplied will leak out from the fibre and, accordingly, by comparing the received light intensity with the supplied light intensity it is possible to determine the amount of leaked light and thus the amount of glucose in the blood.

In the embodiment according to FIG 5 an element 19 containing mirrors or prisms is applied to the blood vessel 10. This element can be placed on the outside of the blood vessel and be sewn to the outside wall of the vessel at a flange on the element, but it can also, as has been assumed in FIG 5, be disposed partly inside the vessel, the flange indicated here by dot and dash lines 20, being fixedly rooted to the wall of the vessel. An optical plastic or glass fibre 21 which guides light from a light source, is connected to the element 19, the mirrors or prisms of the element 19 directing the light towards the interior of the blood vessel. Also connected to the element 19 is another plastic or glass fibre 22 which is connected to a detector for sensing the light reflected from the blood in the blood vessel, the strength of light representing a measure of the existing glucose content in the blood (the reflection method ATR) . Superficial reflection measurement can also be achieved by placing the light-emitting optical fibre and the detecting optical fibre outside the blood vessel in the longitudinal direction thereof, the detecting fibre being located laterally of and alongside the light emitting fibre or at a specific angle to the same, for example an angle of the magnitude of 15°.

If several sensors are placed at several places around the blood vessel, each sensor comprising a fibre with a small diameter, the sensitivity for changes in the reflected and scattered light will increase. As mentioned, the sensing can take place by measuring the light reflection or the light conductivity but it is also possible to achieve sensing by determining existing optical rotation using polarized light or by measuring the refractive index of the blood passing through the blood vessel.

The inventors have found that green or yellowish- green light is sensitive for changes in glucose concentration and drug concentration because this light mirrors the optical changes in the plasma adjacent the wall of the blood vessel in the first place. For detection of glucose a wavelength of the light of about 600 nm is recommended. Other possible wavelengths within the range 300-10000 nm may be considered when applying the method according to the invention. The graph in FIG 7 shows how the reflection of light, calculated as a percentage, changes with the wavelength when measuring glucose.

The term "specific parameter" here refers not only to a specific substance in the blood such as glucose but also to, for example, blood flow, oxygen content, or drug concentration in the blood.

Claims

1. Method for detecting specific parameters of a blood flow in a blood vessel in a living organism by detecting optical properties of the flowing blood, depending on said specific parameter, by using at least one optical plastic or glass fibre, c h a r a c t e r i z e d in that the detection is effected in a peripheral layer of blood plasma closest to the wall of the blood vessel the optical fiber being disposed adjacent to said wall at the outside or inside surface thereof.

2. Method as in claim 1, c h a r a c t e r i z e d in that optical fibres for light transmission to and from the place of measurement are arranged beside each other along the blood vessel on the outside of the wall of the vessel.

3. Method as in claim 1, c h a r a c t e r i z e d in that a single optical fibre for light transmission to and from the place of measurement is arranged along the blood vessel on the outside of the wall of the vessel.

4. Method as in claim 1, c h a r a c t e r i z e d in that two or more optical fibres, at least one for light transmission to the place of measurement and at least one for light transmission from the place of measurement, are inserted through the wall of the blood vessel and are placed with the ends thereof mutually spaced adjacent to the inside of the wall of the vessel.

5. Sensor for detecting specific parameters of a blood flow in a blood vessel in a living organism comprising one or more optical plastic or glass fibres for light transmission to and from the blood vessel and detection of optical properties in the blood, depending on said specific parameter, c h a r a c t e r i z e d in that the sensor comprises means for applying the sensor to the outside of the wall of the blood vessel for detection of a layer of blood flow closest to the inside of the wall of the blood vessel.

6. Sensor as in claim 1, c h a r a c t e r i z e d in that said means comprises a holder to be applied to the outside of the blood vessel for mounting one or more optical glass or plastic fibres mainly in the longitudinal direction of the blood vessel.