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Christel et al.  Christel 等人。

(10) Patent No.: US 6,369,893 B1
（10） 专利号：US 6,369,893 B1

(45) Date of Patent:  （45） 专利日期：
Apr. 9, 2002  四月 9， 2002

(54) MULTI-CHANNEL OPTICAL DETECTION SYSTEM
（54） 多通道光学检测系统

(75) Inventors: Lee A. Christel, Palo Alto; M. Allen Northrup, Berkeley; Kurt E. Petersen, San Jose; William A. McMillan, Cupertino; Gregory T. A. Kovacs, Stanford; Steven J. Young, Los Gatos; Ronald Chang, Redwood City; Douglas B. Dority, Mill Valley; Raymond T. Hebert, Los Gatos; Gregory J. Kintz, Mountain View, all of CA (US)
（75） 发明者：Lee A. Christel，帕洛阿尔托; M. Allen Northrup，伯克利; Kurt E. Petersen，圣何塞; William A. McMillan，库比蒂诺; 斯坦福大学的 Gregory T. A. Kovacs; Steven J. Young，洛斯加托斯; Ronald Chang，红木城; Douglas B. Dority，米尔谷; Raymond T. Hebert，洛斯加托斯; Gregory J. Kintz，山景城，加利福尼亚州（美国）
(73) Assignee: Cepheid, Sunnyvale, CA (US)
（73） 任务分配人：Cepheid， Sunnyvale， CA （US）
(*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days.
(*) 注意：根据任何免责声明，本专利的期限根据 35 U.S.C. 154（b） 延长或调整 0 天。
Appl. No.: 09/314,605  申请号： 09/314,605
(22) Filed:  （22） 提交：
May 19, 1999  1999 年 5 月 19 日
(63) Continuation-in-part of application No. 09/081,260, filed on May 19, 1998, now abandoned, and a continuation-in-part of application No. 09/194,374, filed on Jul. 25, 2000.
（63） 1998 年 5 月 19 日提交的第 09/081,260 号申请的部分延续，现已放弃，以及 2000 年 7 月 25 日提交的第 09/194,374 号申请的部分延续。
(51)
Int. Cl. 7 7 ^(7){ }^{7} qquad\qquad G01N 21/64
国际 Cl. 7 7 ^(7){ }^{7} qquad\qquad G01N 21/64
U.S. Cl. 356/417; 250/458.1; 422/82.08; 436/172
美国第 356/417 条; 250/458.1; 422/82.08; 436/172
356/317, 318,
356/417; 250/458.1, 459.1, 461.1, 461.2; 422/82.08, 82.07; 436/172

References Cited  引用的参考文献

U.S. PATENT DOCUMENTS  美国专利文件
A 1/1973 O
4,056,724 A 11/1977 Harte ....................... 250/328
哈特 ....................... 250/328
4,192,429 A 3/1980 Yerman ................... 215/307
耶尔曼 ................... 215/307
4,432,644 A 2/1984 Demers et al. ............ 356/316
Demers 等人 ............ 356/316
4,552,458 A 11/1985 Lowne ..................... 356/446
劳恩 ..................... 356/446
4,580,059 A 4/1986 Wolfbeis et al. ......... 250/458
Wolfbeis 等人 ......... 250/458
A 1/1973 O 4,056,724 A 11/1977 Harte ....................... 250/328 4,192,429 A 3/1980 Yerman ................... 215/307 4,432,644 A 2/1984 Demers et al. ............ 356/316 4,552,458 A 11/1985 Lowne ..................... 356/446 4,580,059 A 4/1986 Wolfbeis et al. ......... 250/458| | A | 1/1973 | O | | :---: | :---: | :---: | :---: | | 4,056,724 | A | 11/1977 | Harte ....................... 250/328 | | 4,192,429 | A | 3/1980 | Yerman ................... 215/307 | | 4,432,644 | A | 2/1984 | Demers et al. ............ 356/316 | | 4,552,458 | A | 11/1985 | Lowne ..................... 356/446 | | 4,580,059 | A | 4/1986 | Wolfbeis et al. ......... 250/458 |
(List continued on next page.)
（列表在下一页继续。

FOREIGN PATENT DOCUMENTS  国外专利文献

0318255 5 / 1989 5 / 1989 5//19895 / 1989
1045038 10 / 2000 10 / 2000 10//200010 / 2000
WO 97/41421  WO 97/41421 号 11 / 1997 11 / 1997 11//199711 / 1997
WO 98/38487 9 / 1998 9 / 1998 9//19989 / 1998
0318255 5//1989 1045038 10//2000 WO 97/41421 11//1997 WO 98/38487 9//1998| 0318255 | $5 / 1989$ | | ---: | ---: | | 1045038 | $10 / 2000$ | | WO 97/41421 | $11 / 1997$ | | WO 98/38487 | $9 / 1998$ |

OTHER PUBLICATIONS  其他出版物

Wittwer, C.T. et al. The Light Cycler TM TM ^(TM){ }^{\mathrm{TM}} : A Microvolume Multisample Fluorimeter with Rapid Temperature Control, BioTechniques 22:176-181; Jan. 1997.
Wittwer， C.T. 等人。 光循环仪 TM TM ^(TM){ }^{\mathrm{TM}} ：具有快速温度控制的微量多样品荧光计，BioTechniques 22：176-181; 1997 年 1 月。
Primary Examiner-F. L. Evans
主要审查员-F. L. 埃文斯
(74) Attorney, Agent, or Firm-Heller Ehrman White & McAuliffe LLP
（74） 律师、代理人或公司-Heller Ehrman White & McAuliffe LLP

ABSTRACT  抽象

An apparatus for thermally controlling and optically interrogating a reaction mixture includes a vessel [2] having a chamber [10] for holding the mixture. The apparatus also includes a heat-exchanging module [37] having a pair of opposing thermal plates [34A, 34B] for receiving the vessel [2] between them and for heating/and or cooling the mixture contained in the vessel. The module [37] also includes optical excitation and detection assemblies [ 46 , 48 ] [ 46 , 48 ] [46,48][46,48] positioned to optically interrogate the mixture. The excitation assembly [46] includes multiple light sources [100] and a set of filters for sequentially illuminating labeled analytes in the mixture with excitation beams in multiple excitation wavelength ranges. The detection assembly [48] includes multiple detectors [102] and a second set of filters for detecting light emitted from the chamber [10] in multiple emission wavelength ranges. The optics assemblies [ 4 6 , 4 8 ] [ 4 6 , 4 8 ] [46,48][\mathbf{4 6 , 4 8}] thus provide a multi-channel system for detecting a plurality of different target analytes in the mixture.
用于热控制和光学询问反应混合物的装置包括一个容器 [2]，该容器具有用于盛放混合物的腔室 [10]。 该设备还包括一个热交换模块[37]，该模块具有一对相对的热板[34A，34B]，用于接收它们之间的容器[2]以及用于加热/和/或冷却混合物 包含在容器中。 该模块 [37] 还包括光学激发和检测组件 [ 46 , 48 ] [ 46 , 48 ] [46,48][46,48] 定位以光学方式询问混合物。 激发组件 [46] 包括多个光源 [100] 和一组滤光片，用于用多个激发光束顺序照亮混合物中标记的分析物 激发波长范围。 检测组件 [48] 包括多个检测器 [102] 和第二组滤光片，用于检测从腔室 [10] 在多个发射波长范围内发射的光。 [ 4 6 , 4 8 ] [ 4 6 , 4 8 ] [46,48][\mathbf{4 6 , 4 8}] 因此，光学组件提供了一个多通道系统，用于检测混合物中的多种不同目标分析物。

U.S. PATENT DOCUMENTS  美国专利文件

4,810,653 A  安培 4,810,653 3/1989 Hefler et al. ............ 435/285.1
Hefler 等人 ............ 435/285.1
4,900,934 A  安培 4,900,934 2/1990 Peeters et al. .......... 250/461.2
Peeters 等人 .......... 250/461.2
4,902,624 A  安培 4,902,624 2/1990 Columbus et al. ....... 435/285.1
5,038,852 A  安培 5,038,852 8/1991 Johnson et al. .............. 165/12
Johnson 等人 .............. 165/12
5,333,675 A  安培 5,333,675 8/1994 Mullis et al. ................ 165/12
Mullis 等人 ................ 165/12
5,376,313 A  安培 5,376,313 12/1994 Kanewske, III et al. ..... 264/1.1
Kanewske， III 等人 ..... 264/1.1
5,422,726 A  安培 5,422,726 6/1995 Tyler ......................... 356/417
泰勒。。。。。。。。。。。。。。。。。。。。。。。。。 356/417
5,439,647 A  安培 5,439,647 8/1995 Saini ...................... 422/82.11
赛尼...................... 422/82.11
5,460,780 A  安培 5,460,780 10/1995 Devaney, Jr. et al. ........ 422/99
Devaney， Jr. 等人 ........ 422/99
5,475,610 A  安培 5,475,610 12/1995 Atwood et al. . ........... 364/500
Atwood 等人。 ........... 364/500
5,543,026 A  安培 5,543,026 8/1996 Hoff et al. ................ 204/612
Hoff 等人 ................ 204/612
5,580,794 A  安培 5,580,794 12/1996 Ljungmann ................ 156/363
5,589,136 A  安培 5,589,136 12/1996 Northrup et al. .......... 422/102
Northrup 等人 .......... 422/102
5,596,414 A  安培 5,596,414 1/1997 Tyler ....................... 356/417
泰勒。。。。。。。。。。。。。。。。。。。。。。。 356/417
5,656,493 A  安培 5,656,493 8/1997 Mullis et al. ........... 435/286.1
Mullis 等人........... 435/286.1
4,810,653 A 3/1989 Hefler et al. ............ 435/285.1 4,900,934 A 2/1990 Peeters et al. .......... 250/461.2 4,902,624 A 2/1990 Columbus et al. ....... 435/285.1 5,038,852 A 8/1991 Johnson et al. .............. 165/12 5,333,675 A 8/1994 Mullis et al. ................ 165/12 5,376,313 A 12/1994 Kanewske, III et al. ..... 264/1.1 5,422,726 A 6/1995 Tyler ......................... 356/417 5,439,647 A 8/1995 Saini ...................... 422/82.11 5,460,780 A 10/1995 Devaney, Jr. et al. ........ 422/99 5,475,610 A 12/1995 Atwood et al. . ........... 364/500 5,543,026 A 8/1996 Hoff et al. ................ 204/612 5,580,794 A 12/1996 Ljungmann ................ 156/363 5,589,136 A 12/1996 Northrup et al. .......... 422/102 5,596,414 A 1/1997 Tyler ....................... 356/417 5,656,493 A 8/1997 Mullis et al. ........... 435/286.1| 4,810,653 A | 3/1989 | Hefler et al. ............ 435/285.1 | | :---: | :---: | :---: | | 4,900,934 A | 2/1990 | Peeters et al. .......... 250/461.2 | | 4,902,624 A | 2/1990 | Columbus et al. ....... 435/285.1 | | 5,038,852 A | 8/1991 | Johnson et al. .............. 165/12 | | 5,333,675 A | 8/1994 | Mullis et al. ................ 165/12 | | 5,376,313 A | 12/1994 | Kanewske, III et al. ..... 264/1.1 | | 5,422,726 A | 6/1995 | Tyler ......................... 356/417 | | 5,439,647 A | 8/1995 | Saini ...................... 422/82.11 | | 5,460,780 A | 10/1995 | Devaney, Jr. et al. ........ 422/99 | | 5,475,610 A | 12/1995 | Atwood et al. . ........... 364/500 | | 5,543,026 A | 8/1996 | Hoff et al. ................ 204/612 | | 5,580,794 A | 12/1996 | Ljungmann ................ 156/363 | | 5,589,136 A | 12/1996 | Northrup et al. .......... 422/102 | | 5,596,414 A | 1/1997 | Tyler ....................... 356/417 | | 5,656,493 A | 8/1997 | Mullis et al. ........... 435/286.1 |
5,675,155 A  安培 5,675,155 A 10/1997 Pentoney, Jr. et al. ... 250/458.1
Pentoney， Jr. 等人 ... 250/458.1
5,721,136 A  安培 5,721,136 A 2/1998 Finney et al. ........... 435/287.2
Finney 等人 ........... 435/287.2
5,783,148 A 7/1998 Cottingham ................ 422/56
科廷汉姆 ................ 422/56
5,784,157 A 7/1998 Gorfinkel et al. .......... 356/417
Gorfinkel 等人 .......... 356/417
5,786,182 A  安培 5,786,182 A 7/1998 Catanzariti et al. ........ 435/91.1
Catanzariti 等人 ........ 435/91.1
5,811,296 A 9/1998 Chemelli et al. ....... 435/287.2
Chemelli 等人 ....... 435/287.2
5,863,790 A 1/1999 Bolea .................... 435/287.4
5,928,907 A 7/1999 Woudenberg et al. ..... 435/91.2
5,958,349 A 9/1999 Petersen et al. ........... 422/198
Petersen 等人 ........... 422/198
6,015,667 A 1/2000 Sharaf ........................ 435/6
沙拉夫 ........................ 435/6
6,015,674 A  安培 6,015,674 A 1/2000 Woudenberg et al. ......... 435/6
Woudenberg 等人 ......... 435/6
6,043,880 A  安培 6,043,880 A 3/2000 Andrews et al. ........... 356/311
Andrews 等人 ........... 356/311
6,140,054 A  安培 6,140,054 A 10/2000 Wittwer et al. ............... 435/6
Wittwer 等人 ............... 435/6
6,144,448 A  安培 6,144,448 A 11/2000 Mitoma ................... 356/317
三苫 ................... 356/317
5,675,155 A A 10/1997 Pentoney, Jr. et al. ... 250/458.1 5,721,136 A A 2/1998 Finney et al. ........... 435/287.2 5,783,148 A 7/1998 Cottingham ................ 422/56 5,784,157 A 7/1998 Gorfinkel et al. .......... 356/417 5,786,182 A A 7/1998 Catanzariti et al. ........ 435/91.1 5,811,296 A 9/1998 Chemelli et al. ....... 435/287.2 5,863,790 A 1/1999 Bolea .................... 435/287.4 5,928,907 A 7/1999 Woudenberg et al. ..... 435/91.2 5,958,349 A 9/1999 Petersen et al. ........... 422/198 6,015,667 A 1/2000 Sharaf ........................ 435/6 6,015,674 A A 1/2000 Woudenberg et al. ......... 435/6 6,043,880 A A 3/2000 Andrews et al. ........... 356/311 6,140,054 A A 10/2000 Wittwer et al. ............... 435/6 6,144,448 A A 11/2000 Mitoma ................... 356/317| 5,675,155 A | A | 10/1997 | Pentoney, Jr. et al. ... 250/458.1 | | :---: | :---: | :---: | :---: | | 5,721,136 A | A | 2/1998 | Finney et al. ........... 435/287.2 | | 5,783,148 | A | 7/1998 | Cottingham ................ 422/56 | | 5,784,157 | A | 7/1998 | Gorfinkel et al. .......... 356/417 | | 5,786,182 A | A | 7/1998 | Catanzariti et al. ........ 435/91.1 | | 5,811,296 | A | 9/1998 | Chemelli et al. ....... 435/287.2 | | 5,863,790 | A | 1/1999 | Bolea .................... 435/287.4 | | 5,928,907 | A | 7/1999 | Woudenberg et al. ..... 435/91.2 | | 5,958,349 | A | 9/1999 | Petersen et al. ........... 422/198 | | 6,015,667 | A | 1/2000 | Sharaf ........................ 435/6 | | 6,015,674 A | A | 1/2000 | Woudenberg et al. ......... 435/6 | | 6,043,880 A | A | 3/2000 | Andrews et al. ........... 356/311 | | 6,140,054 A | A | 10/2000 | Wittwer et al. ............... 435/6 | | 6,144,448 A | A | 11/2000 | Mitoma ................... 356/317 |
FIG. 1  图 1