Chemical apparatus and process disinfecting – deodorizing – preser – Analyzer – structured indicator – or manipulative laboratory... – Sample mechanical transport means in or for automated...
Reexamination Certificate
1999-09-28
2001-12-25
Warden, Jill (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Analyzer, structured indicator, or manipulative laboratory...
Sample mechanical transport means in or for automated...
C436S049000, C436S047000, C436S048000, C436S174000, C436S177000, C436S180000, C422S068100, C422S063000, C422S052000, C422S105000, C422S105000, C422S091000, C422S105000, C422S091000
Reexamination Certificate
active
06333008
ABSTRACT:
The invention relates to a measuring system for performing luminometric series analyses on reaction components to be investigated and the liquid samples containing the magnetizable carrier particles binding said components, with a sample chamber that receives the liquid sample and can be transported to a measuring station on a conveyor, with a permanent magnet that acts on the sample chamber with its magnetic field during transport, as well as a separating station preferably equipped with a suction and rinsing device to remove the surplus reaction components separated from the carrier particles that accumulate on a wall area of the sample chamber under the influence of the magnetic field.
The invention also relates to a method for luminometric series analyses in which a sample chamber, filled with a liquid sample containing reaction components to be investigated and the carrier particles that are magnetizable and bind the latter, is transported on a conveyor to a luminescence measuring station with the carrier particles being accumulated during the course of transport in a collecting area of the sample chamber wall during a separating phase under the influence of a magnetic field and with surplus reaction components being removed from the sample chamber in a washing process that follows the separating phase.
Measuring techniques of this kind serve primarily in medical diagnosis, food-chemistry analysis, biotechnology, and environmental technology for specific and quantitative determination of very small amounts of biomolecules and toxins, with a large number of samples frequently having to be processed. For measurement, the target substances contained in a sample liquid are labeled in an immunochemical reaction with a specific antibody bearing a marker (luminogen) capable of luminescence. For concentration with chemical and physical agents, the target structure thus obtained is additionally coupled with a magnetic particle coated with specific antibodies and separated as quantitatively as possible from the liquid component under the influence of a magnetic field. This component can then be removed by suction or decanting. The measuring process itself takes place following the addition of a starting reagent that excites the luminogen and causes it to glow. The fluorescence photons then emitted are collected by a photodetector designed as a photomultiplier which “looks at” the sample volume in a darkened measuring station and produces a recording in the form of counting pulses. On the basis of the total photon yield determined in the form of integrated counting pulses, the concentration of the target substance is finally determined by a calibration relationship.
A device of the species recited at the outset is known (DE 39 26 462 A1) in which a large number of samples is fed in individual test tubes on a conveyor to a separating station. During transport, permanent magnets are introduced cyclically into the conveyor and carried along with the associated test tubes through a section of the conveyor. All of the permanent magnets in this conveyor section are aligned in the same way and cause the solid magnetic particles to accumulate at a specific point on the inside wall of each test tube. Although it is possible to use this device to permit the separating and washing procedures as well as the subsequent measurement process to take place fully automatically, the entire structure of this system is mechanically complex and requires a high operating cost due to the handling of a large number of individual tubes. In particular, however, it has been found that when the magnetic particles accumulate on the walls of the test tubes, they have a tendency to clump and to trap free luminogens because of their coating that bears the antibodies. During luminescence measurement, these luminogens then generate a certain amount of background noise from which the light signals from the target substances can no longer be distinguished below a resultant limiting concentration for detection.
Therefore the goal of the invention is to improve a measuring system and a method of the species recited at the outset as well as the associated multiple cuvette in such fashion that the measurement results are quickly available at a lower detection limit with reduced handling expense.
To achieve this goal, the combinations of features included in Claims 1, 20, and 26 are proposed. Advantageous embodiments and improvements on the invention are contained in the dependent claims.
The solution according to the invention is based on the idea of connecting several sample chambers with one another as units that can be handled in common and adjusting these in conjunction with the magnetic field configuration in an optimum fashion to match the special nature of both the magnetic separating process and the optical measuring process. For this purpose, according to the invention it is proposed that a plurality of cuvette units each forming a sample chamber be connected together to form a multiple cuvette and that at least two permanent magnets be mounted along the conveyor with a distance between them, with the permanent magnets penetrating the cuvette units transported past them sequentially with their magnetic fields from wall areas that are opposite one another. The action of the magnets placed in stationary positions on both sides of the conveyor ensures in simple fashion that the magnetizable carrier particles that are attracted during cuvette transport will accumulate alternately, first on one side and then on the other, of the sample chambers, with the free luminogens that adhere to the carrier particles as they pass through the sample liquid redistributing themselves in the sample liquid.
According to one preferred embodiment of the invention, each permanent magnet is a double magnet that consists of two bar magnets that are preferably cylindrical, arranged parallel to one another with opposite polarity, with the double magnets being rotatable by means of a rotary drive around an axis of rotation that extends centrally and axially parallel, preferably horizontally, and transversely with respect to the conveyor. As a result, a magnetic field is generated that penetrates the cuvette units in the form of a lobe, under whose influence the carrier particles move along long spiral paths and can accumulate pointwise as pellets on the cuvette walls. The pellets can then be picked up in the peak area of the elliptical field line with sufficient attractive force by a double magnet located downstream with a mirror-symmetric action, without carrier particles settling in dead spaces in the individual cuvettes that are poor in field lines.
To generate a magnetic field that is as strong as possible, with a low distribution of the scattered field, the two bar magnets are preferably made of a metal alloy of the rare earths, and coupled magnetically by a yoke at their opposite poles that face away from the conveyor. A strong, highly bundled magnetic field permits rapid and efficient concentration of the magnetic particles and thus a high sample throughput.
In order to limit the action of the field primarily to the cuvette unit being carried past at any given moment, the two bar magnets of each double magnet are rigidly connected together at a distance that approximately corresponds to the cross section of the cuvette units.
A pulsed action of permanent magnetic fields on the individual cuvette units moving past can be achieved by mounting the double magnets along a section of the conveyor at intervals that correspond to those between adjacent cuvette units.
For preconcentration, at the beginning of this section of the conveyor, a nonrotatable double magnet is arranged horizontally, with bar magnets mounted approximately at intervals equal to those of adjacent cuvette units. With its extensive magnetic field, this double magnet penetrates the entire volume of the sample chamber, thus collecting carrier particles even from areas that could not be affected by double magnets downstream, with their more tightly bundled magnetic fields.
A
Leistner Hermann
Schiessl Hans
Sines Brian
Stratec Eletronik GnbH
Warden Jill
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