Fluid simulating the rheological properties of biological fluids

0001The present invention relates to a liquid for simulating the rheological behavior of biological fluids, especially blood.

0002To Rheologieforschung, such as the investigation of Flow behavior of a bioliquid, in particular blood, changes in operating Vessels, the wear testing of prosthetic heart valves, Quality Inspection of heart pumps, investigation of circulation models, calibration and Calibration of rheometers, including it is necessary to do this with a liquid perform the same as possible in terms of the rheological behavior Characteristics as the respective biofluid. However, blood is Suspension consisting of a carrier liquid and a proportion of flexible Solids, the one indicating a hematocrit level in the blood. Thus a corresponding Hematocrit level of 42, z. B., 42% solids in whole blood. Outside the human body is human blood only conditionally stable and reacts immediately with Near (coagulation or sedimentation). Consequently, one from Human blood sample taken off by this reaction to the environmental influences only of very brief duration compare blood in the human body. If larger Amounts of human blood for testing is necessary, can not drawn blood to work. The use of blood products is not possible, as these additives, which the viscoelastic Characteristics affect. The human blood of various subjects similar in its rheological behavior, but the measurement scatter very is large. A real human blood sample can not therefore be used to Devices or similar parts for use in the bloodstream, the blood transport or to check the adjustment and calibration of measuring instruments blood.

0003For this reason, a liquid containing glass beads was already tried to provided, which however due to their weight not in limbo can be kept. Given that blood particles, despite their already small size (red blood cells 7 to 8 microns, white blood cells 9 to 12 microns) to by capillary with an even smaller diameter move through and deform it, they are rheologically like a solid treat. On Device that is calibrated with a liquid, reacts in the application with deformable solids bodies ie for example in the body, different so Here difficulties are to be expected.

0004To date, there is no standard that really a bioliquid as For example, blood corresponds, that is a standard that consists of two parts, namely a liquid and (deformable) solid body and Theologically as the real liquid behaves.

0005Partly also blood plasma has been used in practice. However, this has also like other liquids used hitherto no solid body and therefore provides only partial information.

0006There is a huge need for a calibration, for example, to calibrate laboratory devices, thus always reproducible Comparison measurements may be performed. This is particularly important when medication adjustments due to the rheological carried out of the blood and this blood measurements at different Ask, for example, in the clinic and later the doctor be performed. There is then no match the measurements inside and outside the clinic.

0007The present invention is therefore the object of a blood-like to develop suspension user- and device-independent as Standard liquid for biological fluids, particularly blood, is suitable.

0008This object is inventively achieved by a calibration with the Features of claim 1. Further advantageous embodiments are in the dependent claims.

0009The calibration according to the invention consists of a suspension of Micro-plastic particles and a liquid. The micro-plastic particles can be elastic. Their size corresponds substantially to the size of the Blood cells, ie they are in the range of 5 to 10 microns. The micro-plastic particles serve on the one hand, as a particulate fraction that to imitate blood cells and, moreover, a physiological or pathological blood viscosity at least in the Newtonian field (shear rate> 200 s^-1) Set. As micro-plastic particles can do this, for example, used beads made of polyamide with a diameter of 5 to 10 microns will.

0010The fluid as a non particulate content to imitate the plasma consists of Water to which at least one agent in the micro-plastic particles Suspension holds, a viscoelastic liquid to adjust the non-Newtonian viscosity, and a salt to adjust the physiological Electrolyte concentration is attached. As suspension agent are particularly Emulsifiers, preferably lecithin suitable. The concentration of the emulsifier, is dependent on the amount of the micro-plastic particles and increases with this Amount. This means changes course, the non-Newtonian Features of the calibration. are as viscoelastic fluid For example, surfactant, but preferably polyethylene glycols, prefers.

0011As the salt to adjust the physiological or pathophysiological Electrolyte concentrations are sodium chloride and / or other salts added.

0012According to other preferred embodiments is to prevent bacterial and Fungal growth accompanied by a preservative. This has Potassium sorbate proven suitable. Also other equally effective Preservatives are suitable.

0013Since the calibration and their properties with regard to the rheological to maintain shelf life at least for a certain period, has shown that success through the addition of a dispersant, a Bonding the micro-plastic particles can be prevented. In order to it is achieved that the viscosity over a period of about 1 month can be kept constant and not as in the absence of a Disperser already increases during this period. with the above-mentioned Preservatives could only a growth of bacteria or fungi, not, however, agglomeration of the micro-plastic particles can be prevented.

0014The inventively constructed Kalibrierfüssigkeit complies to a long-term stable measurement sample. You can in sufficient quantity and sufficient accuracy be reproducibly prepared. It makes it possible to test equipment and components in vitro according to standards and to consider. However, it is not suitable to be used in vivo, as they do Requirement of a blood substitute to maintain the vital functions of the People are not met.

0015In one embodiment, micro-plastic particles of nylon in were a size of 5 microns in a concentration of about 23% weight / volume used. This was a normal blood viscosity in Newtonian field with a shear rate> 200 s^-1 set. Without insoluble portions were 1.15% Lecithin, 0.25% polyethylene glycol, 0.9% sodium chloride and 0.03% Potassium sorbate used. All concentrations are in weight / volume indicated. These non-particulate fractions are weighed and with the appropriate quantity of distilled water in a blender. The Solution is then to set the appropriate final volume degassed. The nylon particles are weighed and with the appropriate amount the plasma portion mixed with the non-particulate fractions in the mixer. These Solution is then degassed to adjust the final volume.

0016To increase the durability in respect of rheological were 40 to 100 ul attached preferably 50 to 55 .mu.l of a dispersant. This consists of a sodium salt of a low molecular weight polyacrylic acid, and is For example, under the trade name Busperse Buckman Laboratories marketed.

0017This suspension produced is like blood from non-particulate and particulate fractions. In the low shear rate range of 0.05 x 10^-3to 120 s^-1 shows the suspension the typical behavior of a non-Newtonian Suspension, equivalent to human blood. In the higher range of 120 to 300 s^-1showing them the required Newtonian behavior. The test substance is made Particles which are suspended in a liquid. The viscosity and Solids are adjustable.

0018The micro-plastic particles can also vary in diameter , so that microspheres having different diameters in the Calibrating contained.