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：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：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：US08415627B2

公开(公告)日：2013-04-09

申请号：US13119696

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： G01J1/42 ,  G01J1/58 ,  G21K5/00

CPC分类号： G01N21/6408 ,  G01N15/1429 ,  G01N15/1459 ,  G01N21/6428

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

摘要翻译： 在场地仪表中使用的荧光检测装置发射通过调制信号强度调制的激光，并获取从通过激光测量点的测量对象发出的荧光的荧光信号。 该装置与调制信号分开产生参考信号，该参考信号具有与调制信号的频率不同的频率并且具有与调制的相位同步的相位。 该装置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：US20120282649A1

公开(公告)日：2012-11-08

申请号：US13520830

申请日：2011-01-05

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

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

IPC分类号： G01N21/64

CPC分类号： G01N21/6408 ,  G01N15/1429

摘要： Disclosed herein is a fluorescence detecting apparatus. The fluorescence detecting apparatus includes a light-receiving element that receives fluorescence emitted from an object to be measured irradiated with laser light modulated at a predetermined frequency and outputs a fluorescence signal at an adjusted output level; a signal processing unit that mixes the outputted fluorescence signal and a modulation signal with the frequency to generate fluorescence data including information about phase and intensity; and an analyzing device that calculates a first phase shift of the fluorescence emitted from the object to be measured with respect to the modulation signal, calculates a second phase shift by correcting the calculated first phase shift depending on conditions for adjusting the output level, and calculates a fluorescence relaxation time of the fluorescence emitted from the object to be measured using the calculated second phase shift.

摘要翻译： 本文公开了荧光检测装置。 荧光检测装置包括：受光元件，其接收由以预定频率调制的激光照射的被测定物体发出的荧光，并以调整的输出电平输出荧光信号; 信号处理单元，其将输出的荧光信号和具有频率的调制信号混合以产生包括关于相位和强度的信息的荧光数据; 以及分析装置，其计算相对于调制信号从被测量对象发射的荧光的第一相移，根据调整输出电平的条件，通过校正计算出的第一相移来计算第二相移，并计算 使用所计算的第二相移从待测物体发射的荧光的荧光弛豫时间。

公开(公告)号：US20110168916A1

公开(公告)日：2011-07-14

申请号：US13119696

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

CPC分类号： G01N21/6408 ,  G01N15/1429 ,  G01N15/1459 ,  G01N21/6428

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

摘要翻译： 在场地仪表中使用的荧光检测装置发射通过调制信号强度调制的激光，并获取从通过激光测量点的测量对象发出的荧光的荧光信号。 该装置与调制信号分开产生参考信号，该参考信号具有与调制信号的频率不同的频率并且具有与调制的相位同步的相位。 该装置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：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：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：US20100320398A1

公开(公告)日：2010-12-23

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： Provided are a fluorescence detecting method and a fluorescence detecting device for calculating the fluorescence relaxation time constant more accurately than in the prior art when fluorescence emitted from an analyte is detected by applying laser beam. When the analyte passes the position irradiated with laser beam modulated in intensity by a modulation signal of a predetermined frequency, a first fluorescence signal of fluorescence received by a light-receiving means is collected. A second fluorescence signal of the fluorescence received by the light-receiving means is collected in a state in which the analyte is not in the position irradiated with the laser beam after the analyte has passed the position irradiated with the laser beam. Phase difference information of a fluorescence signal of the fluorescence emitted from the analyte with respect to the modulation signal of the laser beam is obtained by using the collected first fluorescence signal and second fluorescence signal, and the fluorescence relaxation time constant of the fluorescence emitted from the analyte is obtained from the obtained phase difference information of the fluorescence signal of the fluorescence emitted from the analyte.

摘要翻译： 提供了一种荧光检测方法和荧光检测装置，用于当通过施加激光束检测从分析物发射的荧光时，比现有技术更准确地计算荧光弛豫时间常数。 当分析物通过以预定频率的调制信号强度调制的激光束照射的位置时，收集由光接收装置接收的荧光的第一荧光信号。 在分析物通过激光束照射的位置之后，由受光装置接收的荧光的第二荧光信号被收集在分析物不处于被激光束照射的位置的状态。 通过使用所收集的第一荧光信号和第二荧光信号以及从第二荧光信号发射的荧光的荧光弛豫时间常数，获得从分析物发射的荧光相对于激光束的调制信号的荧光信号的相位差信息 从获得的从分析物发出的荧光的荧光信号的相位差信息中获得分析物。

公开(公告)号：US07822558B2

公开(公告)日：2010-10-26

申请号：US11816244

申请日：2006-02-15

申请人： Noriaki Kimura ,  Kyoji Doi ,  Takayoshi Yumii ,  Takashi Yoshida ,  Shigeyuki Nakada ,  Hironori Hayashi ,  Kazuteru Hoshishima

发明人： Noriaki Kimura ,  Kyoji Doi ,  Takayoshi Yumii ,  Takashi Yoshida ,  Shigeyuki Nakada ,  Hironori Hayashi ,  Kazuteru Hoshishima

IPC分类号： G06F19/00

CPC分类号： G01N21/274 ,  G01N15/1459 ,  G01N21/6408 ,  G01N21/6428 ,  G01N21/645 ,  G01N2021/6419 ,  G01N2021/6421 ,  G01N2021/6439 ,  G01N2021/6482

摘要： A fluorescence detecting device irradiates an object to be measured with a laser beam, receives fluorescence generated from the object and processes a fluorescence signal generated when receiving the fluorescence. The device includes a laser light source section outputting the laser beam for irradiating the object, a light receiving section outputting the fluorescence signal of the fluorescence generated by the irradiated object, a light source control section generates a modulation signal having a frequency in order to time-modulate an intensity of the laser beam, and a processing section that calculates a fluorescence relaxation time of the fluorescence of the object based on the fluorescence signal output from the light receiving section. From the detection values acquired by the device including the phase information on the fluorescence, the intensity of the fluorescence is calculated.

摘要翻译： 荧光检测装置用激光束照射待测物体，接收从物体产生的荧光，并处理在接收荧光时产生的荧光信号。 该装置包括输出用于照射物体的激光束的激光光源部分，输出被照射物体产生的荧光的荧光信号的光接收部分，光源控制部分产生具有频率的调制信号以便时间 - 调制激光束的强度，以及处理部，其基于从光接收部输出的荧光信号，计算对象的荧光的荧光弛豫时间。 根据由包括荧光的相位信息的装置获取的检测值，计算荧光强度。