Chemistry: analytical and immunological testing – Optical result – With fluorescence or luminescence
Reexamination Certificate
2002-04-22
2003-12-16
Snay, Jeffrey (Department: 1743)
Chemistry: analytical and immunological testing
Optical result
With fluorescence or luminescence
C436S174000, C436S180000
Reexamination Certificate
active
06664113
ABSTRACT:
The present invention relates to a fluorescent detection system, which detects a fluorescent signal from a specific substance included in a sample and determines the quantity of the specific substance based on a volume of the detected fluorescent signal, in particular a fluorescence detection system, which is effective to carry out real-time monitoring (tracing changes in the volume of the fluorescent signal with time) on many samples in the field of clinical diagnosis wherein incubation at a certain temperature is required for, e.g., enzymatic reaction.
For example, in the case of carrying out real-time monitoring on the progress in generation of a fluorescent reaction product caused by enzymatic reaction, it is necessary to carry out fluorescence detection while incubating a sample (reaction liquid) at a certain temperature. In addition, many samples need to be simultaneously and rapidly dealt with in some cases as in the field of clinical diagnosis.
As systems proposed to solve the problems, there are scanning type fluorescence detection systems disclosed in JP-A-2000-088752, JP-A-2000-214090 and JP-A-2001-091463.
The scanning type fluorescence detection system disclosed in JP-A-2000-088752 is configured to have sample containers provided so as to spread along an arc, have the ring portion of a ring type optical guide provided so as to confront the sample containers in the vicinity of the sample containers with a partition plate being provided between the ring portion and the sample containers, and have the partition plate fixedly provided with an optical unit for excitation light and an optical unit for fluorescent light as shown in
FIGS. 5A and 5B
, whereby the partition plate, the optical unit for excitation light and the optical unit for fluorescent light are integrally rotated to individually pick up fluorescent signals and transmit the fluorescent signals to an optical sensor through the ring type optical guide.
The scanning type fluorescence detection system disclosed in JP-A-2000-214090 is configured to have sample containers provided so as to spread along a plurality of arcs, have the ring portion of a ring type optical guide provided so as to confront the sample containers with a partition plate being provided between the ring portion and the sample containers, and have the partition plate fixedly provided with an optical unit for excitation light and an optical unit for fluorescent light including at least one optical guide as shown in
FIG. 6
, whereby the partition plate, the optical unit for excitation light and the optical unit for fluorescent light are integrally rotated to individually pick up fluorescent signals and transmit the fluorescent signals to an optical sensor through the ring type optical guide.
The scanning type fluorescence detection system disclosed in JP-A-2001-091463 is configured to have sample containers provided so as to spread along an arc as shown in
FIGS. 7A and 7B
, have a partition plate fixedly provided with a small-sized excitation light source, an optical unit for excitation light and an optical unit for fluorescent light in integrally rotatable fashion, and have the fluorescent light outgoing end of an optical guide of the optical unit for fluorescent light provided on the rotational center axis so as to confront an optical sensor, whereby fluorescent light from the respective sample containers is individually picked up for detection.
When the conventional fluorescence detection systems are utilized to carry out real-time monitoring on changes in fluorescent signals from a specific substance included in samples with time while incubating the samples at a certain temperature, the following problems have been raised.
When an excitation light source having a small size and a low output is utilized to make the entire system further smaller in each of the scanning type fluorescent detection systems of JP-A-2000-088752 and JP-A-2000-214090, the fluorescent signals become too feeble to provide sufficient sensitivity even in a supersensitive sensor, such as a photo-multiplier. The reason is that the entrance of the ring type optical guide for transmission of fluorescent signals is normally as narrow as hundreds micrometer, causing the efficiency of fluorescent signals to lower. In particular, the scanning type fluorescence detection system of the JP-A-2000-214090 is likely to have insufficient sensitivity to extremely feeble fluorescent light since additional optical guides, which rotate, are provided in series with the stationary ring type optical guide to mediate the transmission of signals between the entrance and the ring type optical guide. Although the use of an excitation light source having a high output, such as an argon ion laser, can solve the insufficiency in sensitivity, a combination with a control source requires a large space, which is a bar to reduction in the physical size of the system.
Although the scanning type fluorescent detection system of JP-A-2001-091463 can solve the problem of reduction in the size, another problem is created when the number of samples to be simultaneously detected is large. The problem is caused by the followings: A reagent is added to many prepared samples one after another, and the samples with the reagent added thereto, and the samples are set in a conventional fluorescent detection system. In order to prevent external light from entering, the conventional fluorescent detection systems can not be operated until a shade cover is closed after the final sample has been set.
In particular, when the progress in incubation is rapid, a serious problem is raised. Specifically speaking, when the progress in incubation of samples is rapid, and when the number of samples to be simultaneously detected is large, it is become impossible to carry out real-time monitoring on the incubation since the incubation of a sample set at an early stage has been completed when the fluorescence detection system is operated. For this reason, even when the number of samples to be set in a single fluorescent detection system is determined as, e.g., n in design, there has been created a problem in that only far less than n number of samples can be used in practice.
This problem can be solved by eliminating the shade cover, which is provided in many fluorescence detection systems to cover the entire systems or all samples to be measured at one time for preventing external light from entering the fluorescence detection systems, or by enabling fluorescent measurement in an open state. Hereinbelow, the fluorescence measurement wherein the measurement is carried out without a shade cover for covering the entire system or all samples to be measured at one time is called “open fluorescence measurement” for convenience of explanation. A method for open fluorescence measurement is to provide shading caps for shading respective sample containers in a number equal to the number of the sample containers. However, when shading caps are provided to shade respective sample containers in a fluorescence detection system for measuring many samples, another problem, such as an increase in size and a cost rise, is created.
As explained, the fluorescence detection system for carrying our real-time monitoring on a fluorescent signal, in particular, carrying our real-time monitoring while incubating samples at a certain temperature needs to meet the requirements of, e.g., (a) temperature control with high accuracy, (b) rapid treatment of many samples, (c) high sensitivity, (d) high reliability (a reduce in mechanical trouble typified by disconnection or malfunction in movable parts, improvement in reproducibility of fluorescence detection, and a reduction in possibility of carry-over), (e) cost reduction (simplification in the structure of the system, and disuse of expensive parts for data treatment), and (f) a reduction in the physical size of the system, and further to realize (g) the open fluorescence detection to solve the problem deriving from a decrease in the incubation time.
It is an object of the present invention to provide a flu
Hayashi Toshinori
Ishiguro Takahiko
Kurihara Yoshifumi
Saitoh Juichi
Snay Jeffrey
Tosoh Corporation
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