公开(公告)号：US20120295278A1

公开(公告)日：2012-11-22

申请号：US13574087

申请日：2011-01-19

申请人： Hironori Hayashi ,  Shigeyuki Nakada

发明人： Hironori Hayashi ,  Shigeyuki Nakada

IPC分类号： G01N21/64 ,  G06F19/00

CPC分类号： G01N21/6408 ,  G01N15/1459 ,  G01N21/645 ,  G01N2021/6419 ,  G01N2021/6441

摘要： Two or more kinds of fluorescent beads containing at least two kinds of basic fluorochromes different in fluorescence intensity, fluorescence wavelength, and fluorescence relaxation time from each other, wherein a content ratio between the at least two kinds of basic fluorochromes and absolute amounts of contents of the basic fluorochromes are set so as to be different between different kinds of fluorescent beads. The fluorescent beads are used in a flow cytometer for fluorescence detection. This makes it possible to identify a greater variety of beads than before with high accuracy in a single measurement.

摘要翻译： 两种或更多种荧光珠，其含有荧光强度，荧光波长和荧光松弛时间彼此不同的至少两种碱性荧光染料，其中所述至少两种碱性荧光染料与含量绝对量的含量比 基本荧光染料被设定为在不同种类的荧光珠之间是不同的。 荧光珠用于流式细胞仪进行荧光检测。 这使得可以在单次测量中以高精度识别比以前更多种类的珠粒。

公开(公告)号：US20120183440A1

公开(公告)日：2012-07-19

申请号：US13498632

申请日：2010-09-13

申请人： Shigeyuki Nakada ,  Hironori Hayashi ,  Kazuteru Hoshishima

发明人： Shigeyuki Nakada ,  Hironori Hayashi ,  Kazuteru Hoshishima

IPC分类号： G01N21/64

CPC分类号： G01N21/6408 ,  G01N15/1429 ,  G01N15/1459 ,  G01N15/147 ,  G01N2015/0038

摘要： Among donor molecules labeling protein in living cells to be measured, the rate of donor molecules binding to an acceptor molecule and occurring FRET is determined. In a plurality of previous measurement samples having different ratios of first molecule concentration to second molecule concentration, a fluorescence lifetime of the first molecule are calculated and the fluorescence lifetime minimum value of the first molecule is calculated. The samples are irradiated with a laser beam having time-modulated intensity and the fluorescence emitted by the laser-irradiated measurement samples are measured. By using the fluorescent signals thus measured, the fluorescence lifetime of the first molecule is calculated. By using the fluorescence lifetime minimum value of the first molecule and the fluorescence lifetime of the first molecule that is calculated above, the rate of the first molecules occurring FRET in the first molecules in the measurement samples is calculated.

摘要翻译： 在要测量的活细胞中标记蛋白质的供体分子中，确定供体分子与受体分子结合的速率和发生的FRET。 在具有不同比例的第一分子浓度与第二分子浓度的多个先前测量样品中，计算第一分子的荧光寿命并计算第一分子的荧光寿命最小值。 用具有时间调制强度的激光束照射样品，并测量由激光照射的测量样品发射的荧光。 通过使用如此测量的荧光信号，计算第一分子的荧光寿命。 通过使用上述计算的第一分子的荧光寿命最小值和第一分子的荧光寿命，计算测量样品中第一分子中发生FRET的第一分子的速率。

公开(公告)号：US20120085933A1

公开(公告)日：2012-04-12

申请号：US13377698

申请日：2010-05-27

申请人： Kyouji Doi ,  Hironori Hayashi ,  Kazuteru Hoshishima ,  Yumi Asano

发明人： Kyouji Doi ,  Hironori Hayashi ,  Kazuteru Hoshishima ,  Yumi Asano

IPC分类号： G01N21/64

CPC分类号： G01N21/645 ,  G01N15/1429

摘要： A fluorescence emitted by a measurement object at a measurement point is measured. When the fluorescence is measured, a measurement object is irradiated with laser light whose intensity is time-modulated by using a modulation signal at a predetermined frequency. Then, the fluorescence emitted by the measurement object is formed to a flux of the fluorescence having uniform distribution of light intensity, and a plurality of partial fluorescent signals are generated by receiving a plurality of divided portions of the flux of the fluorescence. At least some of the partial fluorescent signals are added altogether to generate a single fluorescent signal. Finally, a fluorescence relaxation time of the fluorescence emitted by the measurement object is calculated from the generated fluorescent signal by using the modulation signal. When fluorescence intensity of the fluorescence calculated from the fluorescent signal exceeds a predetermined threshold, the partial fluorescent signals to be added are limited in number. Thereby, an output power of the light-receiving unit can not be prevented from saturation.

摘要翻译： 测量由测量对象发射的荧光。 当测量荧光时，通过使用预定频率的调制信号对其强度进行时间调制的激光照射测量对象。 然后，由测量对象发射的荧光形成为具有均匀光强分布的荧光的通量，并且通过接收荧光通量的多个分割部分来产生多个部分荧光信号。 总共添加至少一些部分荧光信号以产生单个荧光信号。 最后，通过使用调制信号，从产生的荧光信号计算由测量对象发射的荧光的荧光弛豫时间。 当从荧光信号计算的荧光的荧光强度超过预定阈值时，要添加的部分荧光信号的数量受到限制。 因此，不能防止光接收单元的输出功率饱和。

公开(公告)号：US20110313725A1

公开(公告)日：2011-12-22

申请号：US13148388

申请日：2010-01-25

申请人： Hironori Hayashi

发明人： Hironori Hayashi

IPC分类号： G06F15/00

CPC分类号： G01N15/147 ,  G01N15/1429 ,  G01N21/6408 ,  G01N2015/0038

摘要： Disclosed herein is a fluorescence detecting device intended to improve the measurement accuracy of a fluorescence relaxation time. The fluorescence detecting device includes a laser light source unit that irradiates a measurement object with laser light, a light-receiving unit that outputs a fluorescent signal of fluorescence emitted by the measurement object irradiated with the laser light, a light source control unit that generates a modulation signal for time-modulating an intensity of the laser light emitted from the laser light source unit by at least two frequency components, and a processing unit that determines a fluorescence relaxation time of the fluorescence emitted by the measurement object by using the fluorescent signal outputted by the light-receiving unit and the modulation signal, wherein the processing unit determines phase delays of the fluorescent signal with respect to the modulation signal at the at least two frequency components, and determines a fluorescence relaxation time at each of the frequency components by using the phase delay, and determines an average fluorescence relaxation time by weighted averaging of the fluorescence relaxation times.

摘要翻译： 本文公开了旨在提高荧光弛豫时间的测量精度的荧光检测装置。 荧光检测装置包括用激光照射测量对象的激光光源单元，输出被激光照射的测量对象发出的荧光的荧光信号的光接收单元，产生 调制信号，用于通过至少两个频率分量对从激光光源单元发射的激光的强度进行时间调制;以及处理单元，其通过使用输出的荧光信号确定测量对象发射的荧光的荧光弛豫时间 由所述光接收单元和所述调制信号，其中所述处理单元确定所述荧光信号相对于所述至少两个频率分量处的所述调制信号的相位延迟，并且通过使用所述频率分量来确定每个频率分量处的荧光弛豫时间 相位延迟，并确定平均荧光弛豫时间b y加权平均荧光弛豫时间。

公开(公告)号：US08450702B2

公开(公告)日：2013-05-28

申请号：US12867448

申请日：2009-02-18

申请人： Kazuteru Hoshishima ,  Hironori Hayashi ,  Shigeyuki Nakada

发明人： Kazuteru Hoshishima ,  Hironori Hayashi ,  Shigeyuki Nakada

IPC分类号： G01N21/64

CPC分类号： G01N21/6408 ,  G01N15/1427 ,  G01N2015/1438

摘要： A fluorescence detecting method includes the steps of collecting a first fluorescence signal of the fluorescence received by a light receiving unit when the analyte passes a position irradiated with a laser beam, collecting a second fluorescence signal of the fluorescence received by the light receiving unit in the absence of the analyte at the position irradiated with the laser beam, and adjusting a first phase difference information on the first fluorescence signal with respect to the modulation signal by using a second phase difference information on the second fluorescence signal with respect to the modulation signal to obtain a third phase difference information on the fluorescence signal of the fluorescence, and obtaining a fluorescence relaxation time constant of the fluorescence based on the third phase difference information thus obtained.

摘要翻译： 荧光检测方法包括以下步骤：当分析物通过激光束照射的位置时，收集由光接收单元接收的荧光的第一荧光信号，收集由光接收单元接收的荧光的第二荧光信号 在激光束照射的位置不存在分析物，并且通过使用关于调制信号的第二荧光信号的第二相位差信息来调整关于调制信号的第一荧光信号的第一相位差信息， 获得关于荧光的荧光信号的第三相位差信息，并且基于由此获得的第三相位差信息获得荧光的荧光弛豫时间常数。

公开(公告)号：US08049185B2

公开(公告)日：2011-11-01

申请号：US12866265

申请日：2009-02-04

申请人： Hironori Hayashi ,  Shigeyuki Nakada

发明人： Hironori Hayashi ,  Shigeyuki Nakada

IPC分类号： G01N21/64

CPC分类号： G01N21/645 ,  G01N15/1459 ,  G01N21/51 ,  G01N2015/149 ,  G01N2021/4707 ,  G01N2021/6482

摘要： In a fluorescence detection device and a fluorescence detection method, forward-scattered light which is scattered from a measurement object irradiated with a laser beam is received and detection signals for informing the measurement object passing through the measurement point and for identifying a focus position of the forward-scattered light are produced. While, fluorescence emitted by the measurement object is received through a collecting lens and a light-reception signal of the fluorescence is outputted. The fluorescence intensity level is outputted based on the outputted light-reception signal and the produced detection signals. A focus position of the forward-scattered light is identified from the produced detection signals and the light reception-signal is corrected using a correction coefficient corresponding to the identified focus position.

摘要翻译： 在荧光检测装置和荧光检测方法中，接收从照射激光的被测物体散射的前向散射光和用于通知测量对象的检测信号，通过测量点， 产生前向散射光。 同时，通过收集透镜接收由测量对象发出的荧光，并且输出荧光的光接收信号。 荧光强度电平根据输出的光接收信号和产生的检测信号输出。 根据产生的检测信号来识别前向散射光的聚焦位置，并且使用与所识别的焦点位置对应的校正系数校正光接收信号。

公开(公告)号：US5128469A

公开(公告)日：1992-07-07

申请号：US722497

申请日：1991-06-26

申请人： Shigeru Nishimoto ,  Akio Nakao ,  Yasuji Ikeda ,  Hiroyuki Nate ,  Hironori Hayashi ,  Tamotsu Okuno ,  Masashi Kitano ,  Sadao Maeda

发明人： Shigeru Nishimoto ,  Akio Nakao ,  Yasuji Ikeda ,  Hiroyuki Nate ,  Hironori Hayashi ,  Tamotsu Okuno ,  Masashi Kitano ,  Sadao Maeda

IPC分类号： C07D281/10

CPC分类号： C07D281/10

摘要： This disclosure describes a process for the preparation of 1,5-benzothiazepinone derivatives. The process involves the use of sulfonic acids as catalysts to effect ring closure to form the 1,5-benzothiazepinone ring. The resulting compounds have well known pharmaceutical properties.

摘要翻译： 本公开描述了制备1,5-苯并硫氮杂酮衍生物的方法。 该方法包括使用磺酸作为催化剂进行闭环以形成1,5-苯并硫氮杂环。 所得化合物具有众所周知的药物性质。

公开(公告)号：US08330124B2

公开(公告)日：2012-12-11

申请号：US13119702

申请日：2009-09-16

申请人： Kyouji Doi ,  Shigeyuki Nakada ,  Hironori Hayashi ,  Kazuteru Hoshishima

发明人： Kyouji Doi ,  Shigeyuki Nakada ,  Hironori Hayashi ,  Kazuteru Hoshishima

IPC分类号： G01N21/64 ,  G01J1/58

CPC分类号： G01N21/6408 ,  G01N15/1429 ,  G01N15/1459

摘要： A fluorescence detection device for a flow site meter emits laser light intensity-modulated in accordance with a modulation signal and acquires a fluorescent signal of fluorescence emitted from a measurement object that passes through a measurement point of the laser light. The fluorescence detection device generates, separately from the modulation signal, a reference signal having a frequency different from a frequency of the modulation signal and a phase in synchronization with a phase of the modulation signal. The fluorescence detection device determines a fluorescent relaxation time of the measurement object from the fluorescent signal by using the reference signal.

摘要翻译： 流场现场仪的荧光检测装置根据调制信号发射激光强度调制，并获取从通过激光测量点的测量对象发射的荧光的荧光信号。 荧光检测装置与调制信号分离地产生具有与调制信号的频率不同的频率的参考信号和与调制信号的相位同步的相位。 荧光检测装置通过使用参考信号从荧光信号确定测量对象的荧光弛豫时间。

公开(公告)号：US20110168917A1

公开(公告)日：2011-07-14

申请号：US13119702

申请日：2009-09-16

申请人： Kyouji Doi ,  Shigeyuki Nnakada ,  Hironori Hayashi ,  Kazuteru Hoshishima

发明人： Kyouji Doi ,  Shigeyuki Nnakada ,  Hironori Hayashi ,  Kazuteru Hoshishima

IPC分类号： G01J1/58

CPC分类号： G01N21/6408 ,  G01N15/1429 ,  G01N15/1459

摘要： A fluorescence detection device for a flow site meter emits laser light intensity-modulated in accordance with a modulation signal and acquires a fluorescent signal of fluorescence emitted from a measurement object that passes through a measurement point of the laser light. The fluorescence detection device generates, separately from the modulation signal, a reference signal having a frequency different from a frequency of the modulation signal and a phase in synchronization with a phase of the modulation signal. The fluorescence detection device determines a fluorescent relaxation time of the measurement object from the fluorescent signal by using the reference signal.

摘要翻译： 流场现场仪的荧光检测装置根据调制信号发射激光强度调制，并获取从通过激光测量点的测量对象发射的荧光的荧光信号。 荧光检测装置与调制信号分离地产生具有与调制信号的频率不同的频率的参考信号和与调制信号的相位同步的相位。 荧光检测装置通过使用参考信号从荧光信号确定测量对象的荧光弛豫时间。

公开(公告)号：US20100327184A1

公开(公告)日：2010-12-30

申请号：US12866130

申请日：2009-02-04

申请人： Hironori Hayashi

发明人： Hironori Hayashi

IPC分类号： G01J1/58

CPC分类号： G01N21/05 ,  G01N15/1436 ,  G01N15/1459 ,  G01N15/147 ,  G01N21/0303 ,  G01N21/645 ,  G01N2015/1006

摘要： A fluorescence detection device includes a flow cell body including a flow channel through which a measurement object flows, a laser light source unit that irradiates, with a laser beam, the measurement object passing through a measurement point in the flow channel, a light-receiving unit that receives fluorescence emitted from the measurement object irradiated with the laser beam and outputs a light-reception signal, and a processing unit that outputs an output value of fluorescence intensity based on the light-reception signal outputted by the light-receiving unit. The flow cell body has a lens provided on a surface thereof so as to traverse an optical path of the laser beam.

摘要翻译： 荧光检测装置包括：流动池主体，包括测量对象流过的流路;激光束单元，其用激光束照射通过流路中的测量点的测量对象;受光部 接受从激光束照射的测量对象发出的荧光并输出光接收信号的单元，以及基于由光接收单元输出的光接收信号输出荧光强度的输出值的处理单元。 流动池主体具有设置在其表面上的透镜，以便穿过激光束的光路。