as) United States
`a2) Patent Application Publication (10) Pub. No.: US 2005/0279949 Al
`
` Oldham etal. (43) Pub. Date: Dec. 22, 2005
`
`
`US 20050279949A1
`
`(54) TEMPERATURE CONTROL FOR
`LIGHT-EMITTING DIODE STABILIZATION
`
`(30)
`
`Foreign Application Priority Data
`
`(75)
`
`Inventors: Mark F. Oldham, Los Gatos, CA (US);
`Vinod L. Mirchandani, Oak Park, CA
`(US)
`
`Correspondence Address:
`KILYK & BOWERSOX, P.L.L.C.
`3603 CHAIN BRIDGE ROAD
`SUITE E
`
`FAIRFAX, VA 22030 (US)
`
`(73) Assignee: Applera Corporation, Foster City, CA
`
`(21) Appl. No.:
`
`10/981,440
`
`(22)
`
`Filed:
`
`Nov. 4, 2004
`
`Related U.S. Application Data
`
`(63) Continuation-in-part of application No. 10/440,719,
`filed on May 19, 2003, which is a continuation-in-part
`of application No. 10/216,620, filed on Aug. 9, 2002,
`which is a continuation of application No. 09/700,
`536, filed on Nov. 29, 2001, now Pat. No. 6,818,437.
`
`May 17, 1999
`
`(WO) crrscscsssssscteven PCT/US99/11088
`
`Publication Classification
`
`(51) Une C17 caccccccccscesssseee GOIN 21/01; F21V 9/16
`(52) US. Che
`cscssessssessssssstensvnsnen 250/458.1; 356/244
`
`(57)
`
`ABSTRACT
`
`A system is provided that includes a light-emitting diode
`(LED); a temperature sensor in thermal contact with the
`LEDand capable of measuring an operating temperature and
`generating an operating temperature signal; and a tempera-
`ture regulating system capable of receiving the operating
`temperature signal and regulating the operating temperature
`based on the operating temperature signal. A method for
`stabilizing the temperature of an LED is provided. A method
`is provided that includes providing a system comprising an
`LED, a reaction region, and a sample in the reaction region;
`generating excitation beams with the LED; directing exci-
`tation beams to the sample; detecting an optical property of
`the sample to obtain detection data; measuring the operating
`temperature of the light emitting diode; and adjusting the
`detection data of an excitation beam characteristic shift
`
`related to the operating temperature, when the LED is
`operated at the operating temperature to generate the exci-
`tation beams.
`
`114
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`
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`104
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`108|4
`ES
`107
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`1
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`APPLE 1050
`Apple v. Masimo
`IPR2022-01299
`
`APPLE 1050
`Apple v. Masimo
`IPR2022-01299
`
`1
`
`

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`Patent Application Publication Dec. 22,2005 Sheet 1 of 3
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`US 2005/0279949 Al
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`Patent Application Publication Dec. 22,2005 Sheet 2 of 3
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`US 2005/0279949 Al
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`330
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`FIG. 3b
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`3
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`Patent Application Publication Dec. 22,2005 Sheet 3 of 3
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`US 2005/0279949 Al
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`574
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`US 2005/0279949 Al
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`Dec. 22, 2005
`
`TEMPERATURE CONTROL FOR
`LIGHT-EMITTING DIODE STABILIZATION
`
`CROSS-REFERENCE TO RELATED
`APPLICATION
`
`[0006] According to various embodiments, a method for
`illuminating a reaction region with excitation beamsis
`[0001] The present application is a continuation-in-part of
`provided. The method can include providing a system that
`
`co-pending U.S. patent application Ser. No. 10/440,719, includes an LED andareaction region. The method can
`filed May 19, 2003, which in turn is a continuation-in-part
`include generating excitation beamswith the LED; directing
`of co-pending U.S. patent application Ser. No. 10/216,620,
`excitation beamsto the sample; detecting an optical property
`filed Aug. 9, 2002, which in turn is a continuation of
`of the sample to obtain detection data; measuring the oper-
`co-pending U.S. patent application Ser. No. 09/700,536,
`ating temperature of the light emitting diode; and adjusting
`filed Nov. 29, 2001, which claims priority to PCT/US99/
`the detection data based on the operating temperature. The
`11088, filed May 17, 1999, which published as publication
`adjustment can be made, for example, by shifting the
`number WO 99/60381 on Nov. 29, 1999, all of which are
`detection data. The shifting of the detection data can include,
`incorporated herein in their entireties by reference. Cross-
`for example, a shift in intensity, spectra, or both.
`reference is made to co-pending U-S. patent application Ser.
`No. 10/440,920 entitled “Optical InstrumentIncluding Exci-
`tation Source” to Boegeet al. (Attorney Docket No. 5010-
`027-01), co-pending U.S. patent application Ser. No.
`10/440,852 entitled “Apparatus And Method For Differen-
`tiating Multiple Fluorescence Signals By Excitation Wave-
`length” to King et al. (Attorney Docket No. 5010-047-01),
`both filed on May 19, 2003, and to U.S. patent application
`Ser. No. 10/735,339, filed Dec. 12, 2003, all of which are
`incorporated herein in their entireties by reference.
`
`operating temperature by transferring heat away from and/or
`into the LED, based on the measured operating temperature.
`The reaction region can include a sample retained therein.
`
`features and advantages of various
`[0007] Additional
`embodiments will be set forth in part in the description that
`follows, and in part will be apparent from the description,or
`can be learned by practice of various embodiments. Other
`advantages of the various embodiments will be realized and
`attained by meansof the elements and combinations exem-
`plified in the application.
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`[0008] Various embodiments of the present teachings are
`exemplified in the accompanying drawings. The teachings
`are notlimited to the embodiments depicted in the drawings,
`and include equivalent structures and methodsas set forth in
`the following description and as would be knownto those of
`ordinary skill in the art in view of the present teachings. In
`the drawings:
`
`[0009] FIG.1 is a side view in partial cross-section of a
`system including a heater providing temperature stabiliza-
`tion for an LED array according to various embodiments;
`
`[0010] FIG.2 is a view in partial side cross-section of a
`system including a thermoelectric device providing tem-
`perature stabilization for an LED array according to various
`embodiments;
`
`(0011] FIG. 3a is a side view in partial side cross-section
`of a system including a fan and cooling fins providing
`temperature stabilization for an LED array according to
`various embodiments;
`
`[0012] FIG. 35 is a top plan view of a capillary sample
`holder according to various embodiments;
`
`[0013] FIG.4 is a top view in partial cross-section of a
`system including a fan and heating element providing tem-
`perature stabilization for an LED according to various
`embodiments; and
`
`[0014] FIG.5 is a side view in a partial cross-section of
`a system providing a strong thermal conductive path accord-
`ing to various embodiments.
`
`FIELD
`
`[0002] The present teachings relate to an optical instru-
`ment using excitation beams generated by a light-emitting
`diode.
`
`BACKGROUND
`
`[0003] Light-Emitting Diodes (LEDs) can be used as an
`excitation source for optical detection,
`for example,
`in
`fluorescent measurement. There is a need for providing an
`LED excitation beam source that does not exhibit beam
`
`intensity changes and/or spectral shift. A device compatible
`with nucleotide amplification reactions, detecting such reac-
`tions, and capable of processing a relatively large number of
`amplification reactions is desirable.
`
`SUMMARY
`
`[0004] According to various embodiments, a system is
`provided that includes one or more light-emitting diode
`(LED), a temperature sensor, and a temperature regulator.
`The temperature sensor can be in thermal contact with the
`LED, can be capable of measuring an operating temperature,
`and can be capable of generating an operating temperature
`signal. The temperature regulator can be capable of receiv-
`ing an operating temperature signal of the LED and regu-
`lating the operating temperature based on the operating
`temperature signal. Herein, it is to be understood that by
`LED what is meantis at least one LED, and that a group or
`array of LED’s can be included in an “LED”as described
`herein.
`
`is to be understood that both the foregoing
`It
`[0015]
`general description and the following detailed description
`[0005] According to various embodiments, a method for
`are exemplary and explanatory only and are intended to
`provide a further explanation of the various embodiments of
`illuminating a reaction region with excitation beams is
`provided. The method can include providing a system that
`the present teachings.
`includes an LED andareaction region. The method can
`DESCRIPTION OF VARIOUS EMBODIMENTS
`include generating excitation beams with the LED; directing
`the excitation beams toward the reaction region; measuring
`an operating temperature of the LED; and regulating the
`
`[0016] According to various embodiments, a system is
`provided that includes one or more light-emitting diode
`
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`US 2005/0279949 Al
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`Dec. 22, 2005
`
`system can include a detector capable of detecting an optical
`property of the reaction region.
`
`(LED), a temperature sensor in thermal contact with the
`LED, and a temperature regulator. The temperature sensor
`can be capable of measuring an operating temperature and
`[0023] According to various embodiments, the tempera-
`generating a signal. The signal can include an operating
`ture sensor can include a thermister, a thermocouple, a
`temperature signal. The signal can be a digital signal. The
`resistance temperature detector (RTD), a bandgap semicon-
`digital signal can be indicative of whether the temperature
`ductor temperature sensor, a non-contact temperature sensor,
`being sensed is above or belowaset point. The temperature
`a bandgap semiconductor resistive temperature detector, a
`sensor can generate a signal without thermal contact with the
`platinum resistive temperature detector, a bi-metallic tem-
`LED. The temperature sensor does not have to directly
`perature detector, a combination thereof, or the like.
`generate an operating temperature signal but rather can
`simply indicate whether a temperature is above or below a
`set point. The temperature regulator can be capable of
`receiving the operating temperature signal and regulating the
`operating temperature based on the operating temperature
`signal.
`
`[0017] According to various embodiments, the system can
`include a heat-transfer device and a control unit capable of
`controlling the heat-transfer device. The heat-transfer device
`can include a fan capable of forming an air current
`in
`thermal contact with the LED. The heat-transfer device can
`
`include a cooling fin in thermal contact with the LED. The
`heat-transfer device can include a heater in thermal contact
`with the LED. The heat-transfer device can include a ther-
`moelectric device in thermal contact with the LED. The
`thermoelectric device can be connected to a reversible-DC-
`
`power supply. According to various embodiments, the tem-
`perature regulator can include a temperature system that can
`be capable of increasing and/or decreasing the operating
`temperature of the LED.
`
`[0018] According to various embodiments, the tempera-
`ture regulator can comprise a system adapted to control
`excitation of one or more fluorescent dyes. The temperature
`regulator can be adapted such that it is capable of maintain-
`ing the operating temperature within an operating tempera-
`ture range including a minimum temperature and a maxi-
`mum temperature separated by, for example, about 15° C.,
`about 5° C., about 1° C., or about 0.5° C. The operating
`temperature range can also be specified as a nominal tem-
`perature and an acceptable deviation value range.
`
`[0019] According to various embodiments, the tempera-
`ture regulator can be a temperature regulating system that
`can include a user input device that is capable of being
`programmed to maintain an operating temperature range
`including a minimum temperature and a maximum tempera-
`ture. The system can includea display capable of displaying
`the operating temperature signal.
`
`[0020] According to various embodiments, the system can
`include an error signaling device capable of signaling an
`alarm when the operating temperature is greater than a
`maximum temperature. The error signaling device can sig-
`nal an alarm when the operating temperature is less than a
`minimum temperature.
`
`[0021] According to various embodiments, the system can
`include a substrate in contact with the LED. The substrate
`can include, for example, a Printed-Circuit Board (PCB).
`According to various embodiments,the reaction region can
`include a sample retained therein.
`
`[0022] The sample can include one or more nucleotide.
`The reaction region can include reagents necessary to per-
`form a nucleic acid sequence amplification reaction. The
`sample can include fluorescent dyes, labels, or markers. The
`
`[0024] FIG.1 is side cross-sectional view of a system 100,
`according to various embodiments, including an LED array
`110 that includes a plurality of LEDs 111. The system can
`also include a focal lens 106. The focal lens 106 can focus
`
`excitation beams emitted by the LED array 110. The LED
`array 110 can be in physical and/or thermal contact with a
`substrate 112. The LED array 110 can include one or more
`rowsor patterns of individual LEDs. The substrate 112 can
`be a PCB. A heating device 116, for example, a resistive
`heating element, can be provided in thermal contact with the
`LED array 110. The heating device 116 can be included in,
`on, or in and on the substrate 112. The system 100 can
`include a temperature sensor 118 in thermal contact the LED
`array 110. The temperature sensor can be centrally located
`with respect to the LED array 110. The temperature sensor
`118 can be included on the substrate 112. A temperature
`regulator or temperature regulating system 122 can be
`provided that
`is capable of receiving a signal from the
`temperature sensor 118. The temperature sensor 118 and
`temperature regulating system 122 can be integrated and/or
`can be of a unitary construction. The temperature regulating
`system 122 can control the heating device 116. The tem-
`perature regulating system 122 can control a fan 114. The
`temperature regulating system 122 can control the fan 114
`and the heating device 116. For example, the temperature
`regulating system 122 can be used to control the heating
`device 116 to reach or maintain a nominal operating tem-
`perature while the fan 114 prevents the operating tempera-
`ture from getting too high. This optimization can be used, for
`example, if the LED array 111 is not continuously on. The
`fan 114 can direct an air current over one or more cooling
`fins 104. The cooling fins 104 can be in thermal contact with
`the LED array 110, with the substrate 112, or with both. The
`temperature regulating system 122 can send signals to
`and/or receive signals from the temperature sensor 118, the
`heating device 116, and/or the fan 114. The temperature
`regulating system 122 can send and receive signals using
`wires 120. Excitation beams can be emitted from LED array
`110 and directed to one or more reaction region 108. The
`reaction region 108 can include a sample 107. The reaction
`region can be a microtiter tray.
`
`[0025] FIG.2 is a side cross-sectional view of a system
`200, according to various embodiments,
`that
`includes a
`temperature stabilization device for an LED array 210, for
`example, by including a plurality of LEDs 111. A focal lens
`206 can be included to focus excitation beams emitted from
`each of the individual LEDs 211. The LED array 210 can be
`in physical and/or thermal contact with a substrate 212. The
`system 200 can include a temperature sensor 218 in thermal
`contact with the LED array 210, the substrate 212, or both.
`The temperature sensor 218 can be included in or on the
`substrate 212. A temperature regulating system 222 can
`receive a signal from the temperature sensor 218. The
`temperature regulating system 222 can control a thermo-
`
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`
`electric device 214, for example, a Peltier device. The
`thermoelectric device 214 can be in thermal contact with the
`
`LED array 210, with substrate 212, or with both. The
`thermoelectric device 214 can transfer thermal energy from
`an ambient environment to the LED array 210. The ther-
`moelectric device 214 can transfer thermal energy to an
`ambient environment from the LED array 210. The thermo-
`electric device 214 can include a temperature sensor. A
`plurality of cooling fins 204 can be in thermal contact with
`the LED array 210 and/or with the thermoelectric device
`214. The temperature regulating system 222 can send signals
`to and/or receive signal from the temperature sensor 218,
`and/or the thermoelectric device 214, for example, through
`wires 220. Excitation beams can be emitted from LED array
`210 and can be directed to a plurality of reaction regions
`208, for example, held in a thermal cycling block 230. The
`thermoelectric device 214 can be used to maintain a lower
`
`temperature than could be otherwise achieved under oper-
`ating conditions. This can permit the LED array 210 to
`operate moreefficiently, with a highertotal flux output. The
`thermoelectric device 214 can be used in a heating mode, for
`example, to reach or maintain a temperature when the LED
`array 210 is not on. The thermoelectric device 214 can be
`used in a cooling mode whenthe duty cycle of the LED array
`210 is high enough to require cooling.
`
`FIG.3ais a side cross-sectional view of a system
`[0026]
`300 according to various embodiments and capable of
`providing temperature stabilization for an LED array 310
`including a plurality of individual LEDs 311. A focal or
`collimating lens 306 can be included to focus excitation
`beams emitted from each of the individual LEDs 311. The
`collimating lens can be a Fresnel lens. A beam splitter 307
`can be included to separate excitation beams from emission
`beams. The beam splitter 307 can be replaced bya filter or
`beam splitter as described, for example,
`in U.S. patent
`application Ser. No. 10/735,339, filed Dec. 12, 2003, which
`is incorporated herein in its entirety by reference. The LED
`array 310 can be in contact with a substrate 312. The system
`300 can include a temperature sensor 318 in thermal contact
`with the LED array 310. The temperature sensor 318 can be
`included in, on,or in and on the substrate 312. A temperature
`regulating system 322 can receive a signal from the tem-
`perature sensor 318. The temperature regulating system 322
`can control a fan 314. The fan 314 can direct an air current
`
`overa plurality of cooling fins 304. The cooling fins 304 can
`be in physical and/or thermal contact with the LED array
`310. The temperature regulating system 322 can communi-
`cate with the temperature sensor 318, and/or the fan, through
`wires 320. Excitation beams can be emitted from LED array
`310 and directed to a reaction region 308 formedor disposed
`in, on, or in and on a substrate 309. The reaction regions can
`include capillaries 330 of a capillary array. The capillaries
`330 can each have a portion that passes through a detection
`zone 356.
`
`[0027] According to various embodiments, the tempera-
`ture control system can include a heater. The system can
`include a cooler. The system can include both a heater and
`a cooler. Cooling and heating rates can be augmented by
`using a plurality of heaters and/or coolers as desired. If a
`heater is provided, it can comprise a plurality of different
`types of heating devices. If a cooler is provided,
`it can
`comprise a plurality of different types of cooling devices.
`
`[0028] FIG.3b is a top plan partial view of the array of
`capillaries 330 shown in FIG. 3a, and the detection zone
`356. The capillaries can traverse the detection zone 356,
`where excitation beams from the LED array 310 (FIG.3a)
`can be directed. For example, the excitation beams can be
`used for fluorescence detection of analytes in capillaries of
`a capillary electrophoresis device. Such can be the case in
`DNAsequencing and fragment length analysis applications.
`
`[0029] An LED illumination system can provide consis-
`tent illumination, can be light in weight, and can require
`minimal cooling and/or heating. The LED can be a standard
`semi-conductor device, an organic LED, or an inorganic
`LED. Examples of organic LEDs are QDOT-based LEDs
`and a nanotube-based LEDs. The LED can bea stack of
`LED’s such as a stack of organic LEDsora stack of organic
`LED layers.
`
`[0030] According to various embodiments, LEDs produc-
`ing several different excitation wavelengths can be used,
`either simultaneously or sequentially. The use of a plurality
`of different excitation wavelengths can improvethe calibra-
`tion matrix necessary to distinguish fluorescence emissions
`of various dyes.
`
`[0031] According to various embodiments, a system can
`comprise LEDs, photodiodes, operational amplifiers, and
`LED-current control circuits. The components of the system
`can change properties with operating temperature variations.
`A temperature regulating system can maintain these com-
`ponents at a constant temperature. The constant temperature
`can be elevated from an ambient temperature. The constant
`temperature can be lower than an ambient temperature. For
`example, the system components can be held at a constant
`temperature above an ambient temperature using a resistive
`heating element as a heat source under the control of the
`temperature regulating system. A strong or high thermal
`conductivity pathway can be used between the system
`components, for example, to the temperature sensor from a
`heat source and/or a heat sink.
`
`[0032] The temperature sensor can be used to measure
`directly, indirectly, or by calculation, the temperature of the
`system components. The temperature sensor can measure an
`operating temperature for various components of the system.
`The temperature sensor can provide feedback to a tempera-
`ture regulating system. The temperature regulating system
`can monitor the amount of heating or cooling provided by a
`heat source or a heat sink to maintain the system components
`at a nominal temperature within an acceptable deviation
`value range.
`
`[0033] The temperature control characteristics of a tem-
`perature regulating system can be improved by enclosing the
`system componentsin a thermally isolated environment. For
`example, the system components and the temperature sen-
`sor, and/or the temperature regulating system, can be placed
`in an enclosure or housing. The enclosure can have openings
`for allowing illumination from the LEDs to illuminate a
`detection zone. Heat exchange pathways can be disposed in
`the enclosure to allow for thermal
`transfer between the
`
`system and an ambient environment. The heat exchange
`pathway can be a vent in the enclosure. A cooling fan can
`cool the thermally isolated environment provided by the
`enclosure. The heat exchange pathway can include, for
`example, a high conductivity thermal surface included in the
`enclosure and in thermal contact with a thermoelectric
`
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`device. The system components can be separated from the
`enclosure using a thermal insulator to lower a heat exchange
`rate between the enclosure and the temperature control
`components. The temperature sensor can be in thermal
`contact with, in heat-transfer communication with, or oth-
`erwise thermally coupled to, the substrate. Known methods
`of heat transfer include, but are not limited to conduction,
`convection, and thermal radiation.
`
`[0034] According to various embodiments, a heat conduc-
`tive adhesive or compliant pad can be used to attain good
`thermal conductivity between a heat sink or heat source, and
`other system components, for example,
`to maintain tem-
`perature stability in the system. A heat exchange pathway
`can be established for system components such as photo-
`diodes and LEDs using a ground path to the same metal or
`layer plate, for example, in a PCB. The plate can be a metal,
`for example, aluminum, copper, or other electrically con-
`ductive metals. The system can thus maintain temperature
`stability and keep various system components at substan-
`tially the same temperature. The heat exchange pathway can
`exchange heat with the ground plate. Other temperature
`interface materials, for example, adhesive backedresistive
`elements, can be used to achieve good contact with the
`system components.A resistive heater can be disposed in or
`on a common substrate shared with other electrical circuits
`
`included in the system.
`
`[0035] FIG. 4 is a top plan cross-sectional view of a
`system 400. A housing 401, also known as a cave, an oven,
`or an enclosure, can include openings such as 403 and 407
`as shown. LEDs 413, 415 can irradiate through respective
`openings (403) to illuminate one or more reaction regions
`(not shown). The opening 407 can allow transmission or
`passing of emission beams from a reaction region to a
`detector 440. One or more temperature sensor 418 can be
`disposed in or on a housing substrate 412. The substrate 412
`can include a heating device 416. The temperature sensor
`418 can be disposed on or in the housing substrate 412.
`LEDs 413 and 415, and detector 440, can be disposed on or
`in the housing substrate 412. A temperature regulator or
`temperature regulating system 422, capable of receiving a
`signal from the temperature sensor 418, can be included,for
`example, in the housing 412. The temperature regulating
`system 422 can control the heating device 416 and/or a
`cooling fan 414, as desired, for example, to maintain the
`system 400 within a desired or pre-set temperature range.
`The housing 401 can provide a relatively small, thermally
`isolated, volume to be temperature-regulated by the tem-
`perature regulating system 422. Control circuits (not shown)
`necessary to utilize the LEDs 413, 415 and the detector 440
`can be housed within the housing 401. Excitation beams can
`be emitted from the LEDs 413, 415 and directed toward one
`or more reaction regions. LED 413 can produce excitation
`beamsof a different wavelength range than LED 415, for
`example, LED 413 can produce blue light and LED 415 can
`produce green light. LED 413 can be operated simulta-
`neously or sequentially with LED 415.
`
`FIG.5 is a side cross-sectional view of a system
`[0036]
`500 according to various embodiments. The system 500 can
`include photodiode detectors 550, 552, and 554 disposed on
`a substrate 574. The substrate 574 can have control circuits
`
`560, 562, 564, and 566 disposed ona first surface or back
`side 575 thereof. The system 500 can include an LED 513
`mounted on a plate 568 having a thermal conductivity of
`
`about 0.1 w/cm-k or higher, for example, about 0.3 w/em-k
`or higher or about 0.5 w/cm-k or higher. For example, the
`plate 568 can comprise,
`for example, aluminum,steel,
`stainless steel, another metal oralloy, a printed circuit board,
`or a combination thereof. An elastomer pad 570 having a
`high thermal conductivity can be disposed between the
`substrate 574 and the plate 568. The substrate can be a
`multi-layer structure including a layer having a thermal
`conductivity of about 0.1 w/em-k or higher. The elastomer
`pad 570 can electrically isolate an electric resistive heater
`518 from the substrate 574. The photodiode detectors 550,
`552, and 554 can be adhered or bondedto the substrate 574
`using, for example, an adhesive 572. A temperature sensor
`519 can be disposed in thermal contact with the system 500,
`for example, the temperature sensor 519 can be disposed in
`contact with the plate 568. Thermal insulation 576 can be
`disposed adjacent the second surface or backside 575 of the
`substrate 574 to thermally isolate the system 500 from an
`ambient environment. The system can maintain the control
`circuits 560, 562, 564, 566, the photodiode detectors 550,
`552, 554, and the LEDs 511, 513, at the same temperature.
`Accordingly, a constant and uniform temperature can be
`maintained across the system 500.
`
`[0037] Various embodiments depicting configurations of
`LED’s, reaction regions, and intervening devices that can be
`used to direct excitation beams from light sources, for
`example, LEDs, toward reaction regions, can be found, for
`example, in U.S. patent application Ser. No. 10/440,920,
`filed May 19, 2003, entitled “Optical Instrument Including
`Excitation Source” to Boege et al., U.S. patent application
`Ser. No. 10/440,719, filed May 19, 2003, entitled “Optical
`Instrument Including Excitation Source” to Boege et al.,
`US. patent application Ser. No. 10/440,852, filed May 19,
`2003, entitled “Apparatus And Method For Differentiating
`Multiple Fluorescence Signals By Excitation Wavelength”
`to King et al., U.S. patent application Ser. No. 10/735,339,
`filed Dec. 12, 2003, and International Publication No. PCT/
`US01/35079. All Patents, Patent Applications, and publica-
`tions mentioned herein are incorporated herein in their
`entireties by reference.
`
`[0038] The LED or the LED array can include a plurality
`of LEDs mounted on a substrate. The LED can thermally
`contact a temperature regulating system. The temperature
`regulating system can control a heat-transfer device and/or
`a temperature sensor. The temperature regulating system can
`maintain the operating temperature of the LED suchthat the
`operating temperature does not change appreciably, by not
`more than 0.5° C., that is, does not fluctuate by more than
`10° C. during operation, for example, by not more than 5°
`C., by not more than 1° C., by not more than 0.5° C., or by
`not more than 0.1° C. or less. The temperature regulating
`system can maintain the operating temperature of the LED
`such that the operating temperature does not exceed the
`bounds of a programmed temperature range. According to
`various embodiments, a temperature regulating system and
`a temperature sensor can be includedin a single-unit or can
`be included in an integrated device, for example, a Maxim
`DS1620 device available from Maxim Integrated Products,
`Inc. of Sunnyvale, Calif.
`
`[0039] The temperature sensor and the LED do not nec-
`essarily have to be in physical contact. The temperature
`regulating system can adjust a monitored temperature of the
`LED to compensate for any thermal masses intervening
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`US 2005/0279949 Al
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`Dec. 22, 2005
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`between the LED and the temperature sensor and to thus
`derive, calculate, or estimate an operating temperature.
`
`[0040] According to various embodiments, the LED can
`be cooled to maintain life and illumination uniformity
`requirements of a system. According to various embodi-
`ments, a forced air cooling system or a thermoelectric
`device, for example, a Peltier device, can be used to cool the
`LED and to keep the LED from exceeding a maximum
`operating temperature.
`
`[0041] According to various embodiments, the tempera-
`ture of the LED can be monitored, for example, with a
`temperature sensor, and thermal characteristics of a system
`and spectral characteristics of any LEDs embedded within
`the system, can be recorded. With understanding and repro-
`ducibility of the spectral coefficients of the LED as a
`function of an operating temperature, the effects of a spectral
`shift can be mitigated upon detection of optical properties of
`a sample. According to various embodiments, a dye matrix
`or detection data can be altered in accordance with the
`
`conditions under which the dye matrix or detection data was
`gathered or detected. Thermal effects on excitation beams
`emitted by LEDs,
`including spectral shifts and intensity
`changes, can thus be minimized or effectively eliminated.
`According to various embodiments, the temperature of an
`LEDcan be monitored and a computing apparatus can adjust
`the detection data to compensate for the spectral shifts
`and/or intensity changes of excitation beams emitted from
`the LED. The compensation for the shifting can be varied
`across wavelength ranges, for example, different compen-
`sations can be provided for different wavelengths of LEDs.
`Asystem can be provided that can include a data adjustment
`unit comprising a memory adapted to store at least two
`operating temperatures and at least one respective excitation
`beam characteristic shift for each operating temperature. A
`plurality of respective excitation beam characteristic shifts
`can be stored in the memory. The adjustment data can be in
`the form of a plurality of respective coefficients. Each
`coefficient can correspond to a respective LED of an LED
`array. An exemplary range of coefficients can be from about
`0.4 nm/° C.
`to about 4.0 nm/° C., for example, based on
`deviation from a set or average operating temperature. The
`coefficients can include two or more nominal temperature
`coefficients corresponding to two or more LEDs. The coef-
`ficients can be determined or designated based on the
`position of a respective LED in an LED array.
`
`[0042] According to various embodiments, optical detec-
`tion instruments utilizing LEDs can obtain very stable
`intensity or spectral characteristics by stabilizing an oper-
`ating temperature of an LED. [lumination stability can be
`important to minimize the signal noise in the system. Illu-
`mination stability can improve the sensitivity of the instru-
`mentto detec