Chemical apparatus and process disinfecting – deodorizing – preser – Analyzer – structured indicator – or manipulative laboratory... – Calorimeter
Reexamination Certificate
2000-07-07
2001-12-25
Snay, Jeffrey (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Analyzer, structured indicator, or manipulative laboratory...
Calorimeter
C422S082090, C436S165000
Reexamination Certificate
active
06333007
ABSTRACT:
The present invention relates generally to determining the transmission of a liquid sample in a microcuvette by means of a photometer, which has a holder for the microcuvette and measuring means for measuring the transmission of a bundle of rays directed towards the cuvette. The microcuvette has a cavity for a capillary layer of the liquid sample, which has a free liquid surface extended transversely of the principal plane of the cavity. More specifically, the cavity can be such that the free liquid surface of the liquid sample is formed in the actual cavity or in connection therewith. The cavity is initially prepared with a reagent to achieve a reaction, which affects the transmission of the liquid sample and enables determination of its contents of a predetermined substance.
Optical methods, such as absorption or transmission photometry, for quantitative determination of the concentration of a substance in a solution are well known and well documented.
Photometers for carrying out such quantitative determinations are also well known and usually have an optical part, a mechanical part and an electrical part. The optical part comprises a source of light with, for instance, a monochromator or an interference filter for generating a bundle of rays of light with a predetermined wavelength and a light detector, which generates an electric signal corresponding to the luminous energy in the transmitted bundle of rays. The mechanical part comprises a casing, in which the optical part is mounted, and a holder which is also arranged in the casing and intended for a sample which is to be measured in the photometer.
The electrical part, which is also suitably arranged in the casing, comprises the necessary circuits for controlling the source of light and handling the signal from the light detector as well as a unit for presenting measurement results. A microprocessor with instructions can be included as an essential element in the electrical part.
A photometer like the one above is disclosed in EP 0 469 097. This patent discloses a photometer for determining glucose in whole blood. The photometer is based on measurement at two different wavelengths. One of these constitutes the measurement wavelength and the other a compensation wavelength for e.g. increasing the safety in measurements on turbid samples. The design of the photometer is simple and robust.
Disposable microcuvettes are disclosed in, for instance, U.S. Pat. No. 4,088,448. These microcuvettes are intended for sampling of liquid, such as blood, mixing of the liquid sample with a reagent and direct optical analysis of the sample mixed with the reagent. The cuvette comprises a body with two parallel and preferably planar surfaces, which define an optical wavelength and are placed at a predetermined distance from one another to form a planar measuring cavity. The measuring cavity communicates with the surroundings outside the body via an inlet. Moreover, the measuring cavity has a predetermined volume and is designed such that the sample can enter by capillary force. A dry reagent is applied to the inner surface of the cavity.
Microcuvettes based on the invention according to U.S. Pat. No. 4,088,448 have been commercially successful to a considerable extent and are currently used for quantitative determination of, for instance, haemoglobin and glucose in whole blood. An important factor which has contributed to this success is that the time from sampling to response is very short. One reason for this period of time being very short is that the reagent compositions that are used for determination of haemoglobin and glucose are readily soluble in the small amount of blood that is sucked into the capillary cavity of the microcuvette. This results in a mixing with uniform distribution of the reagent components practically immediately. However, it has been found that these prior-art microcuvettes are not suitable for determining components that require reagents, which are not readily soluble and which therefore require a comparatively long period of time for dissolution. Even if, as suggested in U.S. Pat. No. 4,088,448, a mixing of sample and reagent is carried out while vibrating the microcuvette, the mixing is insufficient.
A method, which has been developed specifically for mixing a liquid and a reagent in the thin capillary layers that exist in microcuvettes, has been suggested in U.S. Pat. No. 4,936,687. In this method, use is made of small magnetic particles as means to accomplish the mixing, and the actual mixing operation is carried out by using outer magnets, which are specially designed and arranged and operated in a predetermined fashion. After the mixing procedure, the magnetic particles are separated from that part of the sample which is to be analyzed.
Although this method functions well for certain combinations of liquids and reagents, it is not particularly attractive from an industrial and commercial point of view since special arrangements and designs of magnets are necessary. The use of fine magnetic particles and the separation of these particles after the mixing step also require time and work, which makes this method complicated and comparatively expensive. Moreover, there is a risk of chemical obstruction of both samples and reagents.
Furthermore, EP 75 605 discloses a method for mixing in capillary liquid layers. According to this method, the mixing is carried out in a reaction vessel, which comprises two parallel plates between which the liquid samples which are to be analyzed are applied as a thin layer. The mixing is carried out by relative motion of the plates perpendicularly to their planes. This type of mixing, however, cannot be applied to microcuvettes of the type stated above since the two parallel surfaces thereof which define the measuring cavity are arranged at a predetermined distance from one another.
A simple and effective method for mixing of liquid and reagent in thin capillary layers, which is also suitable for less soluble reagents, would increase the number of determinations that can be carried out in microcuvettes. As a result, the microcuvettes could be attractive also for analyses which up to now could not be performed or for which there has previously been no interest.
According to one aspect of the present invention, a solution has been found to the problem of mixing in the thin liquid layer in a microcuvette by means of a specially designed photometer, which has the distinguishing features stated in appended claim
1
. Preferred embodiments of the photometer are recited in the associated dependent claims.
The inventive photometer carries out a mixing process, which in itself constitutes a second aspect of the invention with the features that are evident from appended claim
7
. Preferred embodiments of this mixing process are evident from the associated dependent claims.
According to a first aspect, the invention thus concerns a photometer for determining the transmission of a liquid sample in a microcuvette which has a cavity for a capillary layer of the liquid sample with a free liquid surface extended transversely of the principal plane of the cavity. Moreover the cavity is initially prepared with a reagent to achieve a reaction, which affects the transmission of the liquid sample for quantification of the contents of the liquid sample of a predetermined substance. The photometer has a holder for the cuvette and measuring means for measuring the transmission through the cuvette. According to the invention, the holder is mounted in bearings for vibration in a direction having a component, which is positioned in the plane of the free liquid surface and is parallel with the principal plane of the cavity. This component is preferably a main component of the vibrating direction, i.e. the vibration occurs essentially in the plane of the free liquid surface and essentially in parallel with the principal plane of the cavity. As a result, a relative quick mixing is achieved, thus accelerating the dissolution and the reaction.
This vibration causes the free liquid surface to perform a wave m
Jansson Lars
Jonsson Bo
Nilsson Bertil
Olsson Per
Svensson Johnny
Burns Doane Swecker & Mathis L.L.P.
Hemocue AB
Snay Jeffrey
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