U.S. patent application number 10/981440 was filed with the patent office on 2005-12-22 for temperature control for light-emitting diode stabilization.
This patent application is currently assigned to Applera Corporation. Invention is credited to Mirchandani, Vinod L., Oldham, Mark F..
Application Number | 20050279949 10/981440 |
Document ID | / |
Family ID | 35929963 |
Filed Date | 2005-12-22 |
United States Patent
Application |
20050279949 |
Kind Code |
A1 |
Oldham, Mark F. ; et
al. |
December 22, 2005 |
Temperature control for light-emitting diode stabilization
Abstract
A system is provided that includes a light-emitting diode (LED);
a temperature sensor in thermal contact with the LED and capable of
measuring an operating temperature and generating an operating
temperature signal; and a temperature 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 excitation
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 excitation beams.
Inventors: |
Oldham, Mark F.; (Los Gatos,
CA) ; Mirchandani, Vinod L.; (Oak Park, CA) |
Correspondence
Address: |
KILYK & BOWERSOX, P.L.L.C.
3603 CHAIN BRIDGE ROAD
SUITE E
FAIRFAX
VA
22030
US
|
Assignee: |
Applera Corporation
Foster City
CA
|
Family ID: |
35929963 |
Appl. No.: |
10/981440 |
Filed: |
November 4, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10981440 |
Nov 4, 2004 |
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10440719 |
May 19, 2003 |
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10440719 |
May 19, 2003 |
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10216620 |
Aug 9, 2002 |
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10216620 |
Aug 9, 2002 |
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09700536 |
Nov 29, 2001 |
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6818437 |
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Current U.S.
Class: |
250/458.1 ;
356/244 |
Current CPC
Class: |
G05D 23/20 20130101;
F21K 9/64 20160801; G01N 2201/06113 20130101; G01J 3/10 20130101;
F21V 29/54 20150115; G01J 3/0286 20130101; G01N 21/645 20130101;
G05D 23/1919 20130101; G01N 2201/0638 20130101; F21V 29/677
20150115; G01N 2021/6439 20130101; F21V 29/74 20150115; G01N
2201/1211 20130101; G01N 21/64 20130101; G01N 21/6452 20130101;
F21Y 2115/10 20160801; G01N 2201/062 20130101 |
Class at
Publication: |
250/458.1 ;
356/244 |
International
Class: |
G01N 021/01; F21V
009/16 |
Foreign Application Data
Date |
Code |
Application Number |
May 17, 1999 |
WO |
PCT/US99/11088 |
Claims
What is claimed is:
1. A system comprising: a light-emitting diode (LED); a temperature
sensor in thermal contact with the LED and capable of measuring an
operating temperature of the LED and generating an operating
temperature signal; and a temperature regulating system capable of
receiving the operating temperature signal and regulating the
operating temperature based on the operating temperature signal,
and adapted to control excitation of one or more fluorescent
dyes.
2. The system of claim 1, wherein the temperature sensor and the
temperature regulating system comprise a single unit.
3. The system of claim 1, wherein the temperature regulating system
includes a heat-transfer device and a control unit capable of
controlling the heat-transfer device.
4. The system of claim 3, wherein the heat-transfer device includes
a fan capable of forming an air current in thermal contact with the
LED.
5. The system of claim 3, wherein the heat-transfer device includes
one or more cooling fins in thermal contact with the LED.
6. The system of claim 3, wherein the heat-transfer device includes
a heater in thermal contact with the LED.
7. The system of claim 3, wherein the heat-transfer device includes
a thermoelectric device in thermal contact with the LED.
8. The system of claim 7, wherein the heat-transfer device includes
a reversible power supply capable of supplying power to the
thermoelectric device.
9. The system of claim 1, wherein the temperature regulating system
is capable of increasing the operating temperature of the LED.
10. The system of claim 1, wherein the temperature regulating
system is capable of decreasing the operating temperature of the
LED.
11. The system of claim 1, wherein the temperature regulating
system is capable of maintaining the operating temperature to be
within an operating temperature range including a minimum
temperature and a maximum temperature separated by about 5.degree.
C.
12. The system of claim 1, wherein the temperature regulating
system is capable of maintaining the operating temperature to be
within an operating temperature range including a minimum
temperature and a maximum temperature separated by about 1.degree.
C.
13. The system of claim 1, further comprising a user input device
in communication with the temperature regulating system and capable
of inputting an operating temperature range including a nominal
temperature and an acceptable deviation value rage.
14. The system of claim 1, wherein the temperature sensor comprises
at least one of a thermistor, a thermocouple, a bandgap
semiconductor resistive temperature detector, a platinum resistive
temperature detector, or a bi-metallic temperature detector.
15. The system of claim 1, wherein the temperature sensor comprises
at least one of a thermistor, or a bandgap semiconductor resistive
temperature detector.
16. The system of claim 1, further comprising an error signaling
device capable of signaling an alarm when at least one condition of
(1) the operating temperature is greater than a maximum
temperature, and (2) the operating temperature is less than a
minimum temperature, is met.
17. The system of claim 1, further comprising a substrate
contacting the LED.
18. The system of claim 17, wherein the substrate has a thermal
conductivity of about 0.1 w/cm.multidot.k or greater.
19. The system of claim 17, wherein the LED comprises a plurality
of LED's.
20. The system of claim 17, wherein the substrate is a multi-layer
laminate and at least one layer of the laminate has a thermal
conductivity of about 0.1 w/cm.multidot.k or greater.
21. The system of claim 17, wherein the substrate includes a
printed-circuit board.
22. The system of claim 1, wherein the LED includes an organic
LED.
23. The system of claim 1, wherein the LED includes a quantum-dot
based light source.
24. The system of claim 1, wherein the LED comprises a plurality of
light-emitting diodes that are capable of emitting emissions of
different respective wavelength ranges.
25. The system of claim 24, wherein the plurality of LEDs comprises
at least one Blue LED and at least one Green LED.
26. The system of claim 1, further comprising a reaction region,
and wherein the LED is capable of generating and directing
excitation beams toward the reaction region.
27. The system of claim 26, wherein the reaction region comprises a
plurality of spaced-apart reaction regions.
28. The system of claim 26, wherein the reaction region comprises a
sample disposed therein, and the sample comprises at least one
nucleic acid sequence.
29. The system of claim 26, further comprising a detector capable
of detecting at least one optical property of the reaction
region.
30. The system of claim 26, wherein the reaction region includes at
least one nucleic acid sequence amplification reaction reagent.
31. The system of claim 1, further comprising at least one
separation region, and wherein the LED is capable of generating and
directing excitation beams toward the at least one separation
region.
32. The system of claim 31, wherein the LED comprises a plurality
of light-emitting diodes that are capable of emitting different
respective wavelength ranges.
33. The system of claim 31, wherein the at least one separation
region comprises an electrophoresis separation medium.
34. The system of claim 1, wherein the reaction region includes at
least one fluorescent reporter dye.
35. A system comprising: a reaction region; a light-emitting diode
(LED) capable of generating and directing excitation beams toward
the reaction region; a temperature sensor in thermal contact with
the LED and capable of measuring an operating temperature of the
LED and generating an operating temperature signal; a detector
adapted to detect emission signals from the reaction region and
capable of generating detection data; and a data adjustment unit
capable of receiving the operating temperature signal and the
detection data, and adapted to adjust the detection data for an
excitation beam characteristic shift related to the operating
temperature, to form shifted detection data.
36. The system of claim 35, wherein the data adjustment unit
comprises a memory adapted to store at least two operating
temperatures and at least one respective excitation beam
characteristic shift for each operating temperature.
37. The system of claim 35, wherein the temperature sensor
comprises at least one of a thermistor, a thermocouple, a bandgap
semiconductor resistive temperature detector, a platinum resistive
temperature detector, or a bi-metallic temperature detector.
38. The system of claim 35, wherein the LED comprises a plurality
of light-emitting diodes that are capable of emitting different
respective wavelength ranges.
39. The system of claim 38, wherein the data adjustment unit
comprises a memory adapted to store at least two operating
temperatures, and at least one respective excitation beam
characteristic shift for each operating temperature, and wherein
the at least one respective excitation beam characteristic shift
comprises at least one respective excitation beam characteristic
shift for each different wavelength range.
40. The system of claim 38, wherein the plurality of LEDs comprises
at least one blue LED and at least one green LED.
41. The system of claim 35, further comprising at least one
separation region, and wherein the LED is capable of generating and
directing excitation beams toward the at least one separation
region.
42. The system of claim 35, wherein the LED comprises a plurality
of LEDs disposed adjacent one another and each LED has a respective
operating temperature and a respective excitation beam
characteristic shift.
43. The system of claim 35, wherein the LED comprises a plurality
of LEDs stacked along a path for directing excitation beams towards
the reaction region, and each LED has a respective operating
temperature and a respective excitation beam characteristic
shift.
44. The system of claim 35, further comprising a temperature
regulating system capable of receiving the operating temperature
signal and regulating the operating temperature based on the
operating temperature signal.
45. The system of 35, wherein the excitation beam characteristic
comprises a spectrum of the generated excitation beams.
46. The system of 35, wherein the excitation beam characteristic
comprises an intensity of the generated excitation beams.
47. A method for illuminating a reaction region with excitation
beams, the method comprising: providing a system comprising an LED,
a reaction region, and a sample in the reaction region; generating
excitation beams with the LED; directing excitation beams at the
sample; measuring an operating temperature of the LED; and
regulating the operating temperature by at least one of
transferring heat from the LED and transferring heat to the LED,
based on the operating temperature.
48. The method of claim 47, wherein said regulating the operating
temperature includes maintaining the operating temperature to be
within an operating temperature range including a minimum
temperature and a maximum temperature separated by about 5.degree.
C.
49. The method of claim 47, wherein said regulating the operating
temperature includes maintaining the operating temperature to be
within an operating temperature range including a minimum
temperature and a maximum temperature separated by about 1.degree.
C.
50. The method of claim 47, wherein said regulating the operating
temperature occurs prior in time to said generating the excitation
beams.
51. The method of claim 47, wherein said regulating the operating
temperature comprises setting the operating temperature to be
greater than an ambient environment temperature.
52. The method of claim 47, wherein the sample includes reagents
necessary to perform a nucleic acid sequence amplification
reaction.
53. The method of claim 47, wherein the LED comprises a plurality
of light-emitting diodes that are capable of emitting different
respective wavelength ranges.
54. A method for illuminating a reaction region with excitation
beams, the method comprising: providing a system comprising an LED,
a reaction region, and a sample in the reaction region; generating
excitation beams with the LED; directing excitation beams to the
sample; detecting an optical property of the sample to obtain
detection data; measuring the operating temperature of the light
emitting diode to determine a measured temperature; and adjusting
the detection data of an excitation beam characteristic shift
related to the measured temperature.
55. The method of 54, wherein the excitation beam characteristic
comprises a spectrum of the generated excitation beams.
56. The method of 54, wherein the excitation beam characteristic
comprises an intensity of the generated excitation beams.
57. The method of claim 54, wherein the sample includes reagents
necessary to perform a nucleic acid sequence amplification
reaction.
58. The method of claim 54, wherein the LED comprises a plurality
of light-emitting diodes that are capable of emitting different
respective wavelength ranges.
59. The method of claim 58, adjusting the detection data comprises
picking the excitation beam characteristic shift based on the
position of an activated LED from the plurality of LEDs.
60. The method of claim 54, wherein the LED comprise a plurality of
LEDs disposed adjacent to one another and each LED has a respective
operating temperature and a respective excitation beam
characteristic shift.
61. The method of claim 60, wherein the LED's comprise inner LEDs
and outer LEDs, and the method comprises making a greater
adjustment of excitation beam characteristic shift for one or more
of the inner LEDs compared to the adjustment for one or more of the
outer LED's.
62. The method of claim 60, wherein adjusting the detection data
comprises retrieving from a memory source a respective excitation
beam characteristic shift.
63. The method of claim 54, wherein the LED comprises a plurality
of LEDs stacked in along a path for directing excitation beams
towards the reaction region and each LED has a respective operating
temperature and a respective excitation beam characteristic
shift.
64. The method of claim 54, further comprising profiling the
plurality of LEDs to obtain a calculated operating temperature
based on a position of each LED in the plurality of LEDs.
65. A method for maintaining emission intensity and spectral
stability of an LED, the method comprising: providing a system
comprising an LED; generating excitation beams with the LED;
measuring an operating temperature of the LED; and regulating the
operating temperature by at least one of transferring heat from the
LED and transferring heat to the LED, based on the operating
temperature, to maintain emssion intensity and spectral stability
of the LED.
66. The method of claim 65, wherein the regulating the operating
temperature comprises retrieving from a memory source adjustment
data corresponding to a desired operating temperature or
temperature range at which emission intensity and spectral
stability of the LED are maintained.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] The present application is a continuation-in-part of
co-pending U.S. patent application Ser. No. 10/440,719, filed May
19, 2003, which in turn is a continuation-in-part of co-pending
U.S. patent application Ser. No. 10/216,620, filed Aug. 9, 2002,
which in turn is a continuation of co-pending U.S. patent
application Ser. No. 09/700,536, filed Nov. 29, 2001, which claims
priority to PCT/US99/11088, filed May 17, 1999, which published as
publication number WO 99/60381 on Nov. 29, 1999, all of which are
incorporated herein in their entireties by reference.
Cross-reference is made to co-pending U.S. patent application Ser.
No. 10/440,920 entitled "Optical Instrument Including Excitation
Source" to Boege et al. (Attorney Docket No. 5010-027-01),
co-pending U.S. patent application Ser. No. 10/440,852 entitled
"Apparatus And Method For Differentiating Multiple Fluorescence
Signals By Excitation Wavelength" 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.
FIELD
[0002] The present teachings relate to an optical instrument 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 reactions, 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 receiving an operating temperature signal of the LED and
regulating the operating temperature based on the operating
temperature signal. Herein, it is to be understood that by LED what
is meant is at least one LED, and that a group or array of LED's
can be included in an "LED" as described herein.
[0005] According to various embodiments, a method for illuminating
a reaction region with excitation beams is provided. The method can
include providing a system that includes an LED and a reaction
region. The method can 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
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.
[0006] According to various embodiments, a method for illuminating
a reaction region with excitation beams is provided. The method can
include providing a system that includes an LED and a reaction
region. The method can include generating excitation beams with the
LED; directing excitation 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 based on the operating temperature. The
adjustment can be made, for example, by shifting the detection
data. The shifting of the detection data can include, for example,
a shift in intensity, spectra, or both.
[0007] Additional features and advantages of various 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 means of the elements
and combinations exemplified in the application.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] Various embodiments of the present teachings are exemplified
in the accompanying drawings. The teachings are not limited to the
embodiments depicted in the drawings, and include equivalent
structures and methods as set forth in the following description
and as would be known to 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 stabilization 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 temperature
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. 3b 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 temperature
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 according to various
embodiments.
[0015] It is to be understood that both the foregoing general
description and the following detailed description are exemplary
and explanatory only and are intended to provide a further
explanation of the various embodiments of the present
teachings.
DESCRIPTION OF VARIOUS EMBODIMENTS
[0016] According to various embodiments, a system is provided that
includes one or more light-emitting diode (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 generating a signal. The signal can
include an operating temperature signal. The signal can be a
digital signal. The digital signal can be indicative of whether the
temperature being sensed is above or below a set point. The
temperature sensor can generate a signal without thermal contact
with the LED. The temperature sensor does not have to directly
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 thermoelectric device in thermal contact with the LED.
The thermoelectric device can be connected to a reversible-DC-power
supply. According to various embodiments, the temperature 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 temperature 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 maintaining the operating temperature within
an operating temperature range including a minimum temperature and
a maximum temperature separated by, for example, about 15.degree.
C., about 5.degree. C., about 1.degree. C., or about 0.5.degree. C.
The operating temperature range can also be specified as a nominal
temperature and an acceptable deviation value range.
[0019] According to various embodiments, the temperature 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 temperature. The system can include a 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 signal 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 perform a nucleic acid
sequence amplification reaction. The sample can include fluorescent
dyes, labels, or markers. The system can include a detector capable
of detecting an optical property of the reaction region.
[0023] According to various embodiments, the temperature sensor can
include a thermister, a thermocouple, a resistance temperature
detector (RTD), a bandgap semiconductor temperature sensor, a
non-contact temperature sensor, a bandgap semiconductor resistive
temperature detector, a platinum resistive temperature detector, a
bi-metallic temperature detector, a combination thereof, or the
like.
[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 rows or 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 temperature 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 temperature while the fan 114 prevents the operating
temperature 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 thermoelectric 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
thermoelectric device 214 can transfer thermal energy to an ambient
environment from the LED array 210. The thermoelectric 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 operating conditions. This can permit
the LED array 210 to operate more efficiently, with a higher total
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 when the duty cycle of the LED array 210 is high
enough to require cooling.
[0026] FIG. 3a is a side cross-sectional view of a system 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 by a 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 temperature sensor 318. The temperature regulating
system 322 can control a fan 314. The fan 314 can direct an air
current over a 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 communicate 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 formed or 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 temperature 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 DNA sequencing and fragment length
analysis applications.
[0029] An LED illumination system can provide consistent
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 be
a stack of LED's such as a stack of organic LEDs or a stack of
organic LED layers.
[0030] According to various embodiments, LEDs producing several
different excitation wavelengths can be used, either simultaneously
or sequentially. The use of a plurality of different excitation
wavelengths can improve the calibration 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 components 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 temperature 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 temperature
regulating system can be improved by enclosing the system
components in a thermally isolated environment. For example, the
system components and the temperature sensor, 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 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
otherwise 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 conductive 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 temperature stability in the system. A
heat exchange pathway can be established for system components such
as photodiodes 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 conductive metals.
The system can thus maintain temperature stability and keep various
system components at substantially the same temperature. The heat
exchange pathway can exchange heat with the ground plate. Other
temperature interface materials, for example, adhesive backed
resistive 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 temperature 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
beams of 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 simultaneously or sequentially with LED
415.
[0036] FIG. 5 is a side cross-sectional view of a system 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 on a 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.multidot.k or higher, for example,
about 0.3 w/cm.multidot.k or higher or about 0.5 w/cm.multidot.k or
higher. For example, the plate 568 can comprise, for example,
aluminum, steel, stainless steel, another metal or alloy, 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/cm.multidot.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 bonded to 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., U.S. 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 publications 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
such that the operating temperature does not change appreciably, by
not more than 0.5.degree. C., that is, does not fluctuate by more
than 10.degree. C. during operation, for example, by not more than
5.degree. C., by not more than 1.degree. C., by not more than
0.5.degree. C., or by not more than 0.1.degree. 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 included in 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 necessarily 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 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 embodiments, 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 temperature 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 reproducibility 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 LED can 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
compensations can be provided for different wavelengths of LEDs. A
system 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/.degree. C. to about 4.0 nm/.degree. 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
coefficients can be determined or designated based on the position
of a respective LED in an LED array.
[0042] According to various embodiments, optical detection
instruments utilizing LEDs can obtain very stable intensity or
spectral characteristics by stabilizing an operating temperature of
an LED. Illumination stability can be important to minimize the
signal noise in the system. Illumination stability can improve the
sensitivity of the instrument to detect low concentration dyes.
Spectral stability can be used to maintain values for the
deconvolution matrix associated with a set of dyes to prevent
quantification errors. Similarly, variations in intensity resulting
from temperature changes can be different for different wavelengths
of LEDs, resulting in apparent spectral instability.
[0043] According to various embodiments, illumination stability can
be improved by allowing the illumination source to warm-up.
According to various embodiments, shutters can block excitation
beams from reaching a sample to prevent bleach out. According to
various embodiments, shutters can block excitation beams from
reaching a sample to prevent bleach out during illumination source
warm-up. The illumination source can be brought to a desired
operating temperature range prior to enabling or turning on the
illumination source, using a heater and/or a cooler. Regulating the
temperature of the illumination source prior to enabling the
illumination source can prevent the need for a shutter and/or can
reduce the warm-up time period. According to various embodiments,
samples can be subjected to a reaction or a series of reactions,
for example, temperature cycled in a nucleic acid sequence
amplification or in a sequencing process. According to various
embodiments, the shutter can be unblocked in co-ordination with the
reaction or the series of reactions, to detect and collect data at
an appropriate time, for example, during a fluorescence detection
reading of the sample.
[0044] According to various embodiments, sensitivity of the
instrument to detect low concentration dyes can be used. An LED can
shift, for example, 5% over a 15.degree. C. ambient temperature
range maintained by some optical instrumentation. According to
various embodiments, a spectral shift of an LED can vary depending
on a center wavelength of the LED, for example, blue LEDs can shift
less than red LEDs. The spectral shift can be from about 0.04
nm/.degree. C. to about 0.4 nm/.degree. C. The spectral shift can
be different for different temperatures. The spectral shift can be
calculated. The spectral shift can be obtained from a look-up
table. The table can be sorted by temperature, for example. The
table can be provided in a long-term storage of a computer system,
for example. According to various embodiments, some optical
instrumentation can be sensitive to a dye shift of about 1 nm or
less. According to various embodiments, laboratory instrumentation
utilizing a relatively more robust dye matrix can be less
susceptible to the spectral shift of an LED than a system with a
relatively less robust dye matrix. The AB 7500 system available
from Applied Biosystems of Foster City, Calif., can have a very
good dye matrix and can have little susceptibility to spectral
shift for at least most dyes.
[0045] According to various embodiments, the LED radiation source
can contain one Light Emitting Diode (LED) or an array of
individual LEDs. According to various embodiments, each LED can be
a high power LED that can emit greater than or equal to about 1 mW
of excitation energy. In various embodiments, a high power LED can
be used that can emit at least about 5 mW of excitation energy. In
various embodiments wherein the LED or array of LEDs can emit, for
example, at least about 50 mW of excitation energy, a cooling
device such as, but not limited to, a heat sink or fan can be used
with the LED. An array of high-powered LEDs can be used that draws,
for example, about 10 watts of energy or less, about five watts of
energy or less, or about 3 watts of energy or less. Exemplary LED
array sources are available, for example, from Stocker Yale (Salem,
N.H.) under the trade name LED AREALIGHTS, and from Lumileds
Lighting, LLC (San Jose, Calif.) under the trade name Luxeon Star.
According to various embodiments, LED light sources can use about 1
microwatt (.mu.W) of power or more, for example, about 5 mW, about
25 mW, about 50 mW, about 1 W, about 5 W, about 50 W, or about 100
W or more, each individually or collectively when used in an
array.
[0046] According to various embodiments, the light source can
include a combination of two, three, or more LEDs, laser diodes,
and the like, such as, for example, an LED that can emit radiation
at about 475 nm, an LED that can emit radiation at about 539 nm,
and an LED that can emit radiation at about 593 nm. The LED can be,
for example, an Organic Light Emitting Diode (OLED) an inorganic
Light Emitted Diode, that can be polymer-based or
small-molecule-based (organic or inorganic), an edge emitting diode
(ELED), a Thin Film Electroluminescent Device (TFELD), or a Quantum
dot based inorganic "organic LED." The LED can include a
phosphorescent OLED (PHOLED). Super bright LEDs can be used and can
be arranged in a light array. According to various embodiments,
separate LEDs or a packaged set of LEDs can be used in an array.
Spectral emissions of the light sources can be effected by an
operating temperature of the light source. Other suitable light
sources will be apparent to practitioners in the art given the
teachings herein. OLEDs can be used as an array while being
designed as a single part. As used herein, the terms "excitation
source," "irradiation source," and "light source" are used
interchangeably.
[0047] According to various embodiments, excitation beams emitted
from the light source can diverge from the light source at an angle
of divergence. The angle of divergence can be, for example, from
about 5.degree. to about 75.degree. or more. The angle of
divergence can be substantially wide, for example, greater than
45.degree., yet can be efficiently focused by use of a lens, such
as the focusing lens 106 (FIG. 1), 206 (FIG. 2), and 306 (FIG. 3).
The lens can be a collimating lens, for example, a Fresnel
lens.
[0048] According to various embodiments, a quantum dot can be used
as a source for luminescence and as a fluorescent marker. Quantum
dots can be used for both. The quantum dot based LED can be tuned
to emit light in a tighter emission bandpass, for example, an
emission bandpass including a full-width of half-max of about 10 nm
or less, about 20 nm or less, or about 50 nm or less. The quantum
dot based LED can increase the efficiency of the fluorescent
system. The efficiency of a quantum dot based LED can theoretically
be higher than that of conventional LEDs, potentially over 90% when
sandwiched directly between two conductive films with each film
directly touching each quantum dot as opposed to the present 20%
efficiency for standard LEDs. Quantum dot based LEDs can be made
utilizing a slurry of quantum dots, where current flows through an
average of several quantum dots before being emitted as a photon.
This conduction through several quantum dots can cause resistive
losses in efficiency. Quantum dots can provide many more colors
than conventional LEDs.
[0049] A Quantum dot based LED can emit light in an emission band
that is narrower than an emission band of a normal LED, for
example, about 50% narrower or about 25% narrower. The emission
band of the quantum dots can be a function of the size distribution
of the quantum dots, and thus can theoretically be extremely
narrow. The Quantum dot based LED can also emit light at an
electrical energy conversion efficiency of about, 90% or more, for
example, approaching 100%. OLED films, including Quantum dot based
LEDs, can be applied to a thermal block, used for heating and
cooling samples, in a fluorescence system without interfering with
the operation of the thermal block.
[0050] According to various embodiments, an OLED can be used and/or
produced on a flexible substrate, on an optically clear substrate,
on a substrate of an unusual shape, or on a combination thereof.
Multiple OLEDs can be combined on a substrate, wherein the multiple
OLEDs can emit light at different wavelengths. Multiple OLEDs on a
single substrate or multiple adjacent substrates can form an
interlaced or a non-interlaced pattern of light of various
wavelengths. The pattern can correspond to, for example, a sample
reservoir arrangement or array. One or more OLEDs can form a shape
surrounding, for example, a sample reservoir, a series of sample
reservoirs, an array of a plurality of sample reservoirs, or a
sample flow path. The sample flow path can be, for example, a
channel, a capillary, or a micro-capillary. One or more OLEDs can
be formed to follow the sample flow path. One or more OLEDs can be
formed in the shape of a substrate or a portion of a substrate. For
example, the OLED can be curved, circular, oval, rectangular,
square, triangular, annular, or any other geometrically regular
shape. The OLED can be formed as an irregular geometric shape. The
OLED can illuminate one or more sample reservoirs, for example, an
OLED can illuminate one, two, three, four, or more sample
reservoirs simultaneously, or in sequence. The OLED can be
designed, for example, to illuminate all the wells of a
corresponding multi-well array.
[0051] According to various embodiments, an OLED can be used and
can be formed from one or more stable, organic materials. The OLED
can include one or more carbon-based thin films and the OLED can be
capable of emitting light of various colors when a voltage is
applied across the one or more carbon-based thin films. Various
LEDs can use different films, for example, quantum dot based LEDs
can use Indium tin oxide.
[0052] According to various embodiments, an operating temperature
of an LED can be controlled with a Peltier-effect thermoelectric
device, a heat pump, an electrical resistance heating element
(Joule heater), fluid-flow through channels in a metal block,
reservoirs of fluid at different temperatures, tempered air
impingement, a combination thereof, or the like. According to
various embodiments, the thermal device can include a fan to direct
air-flow over cooling fins, or a cold bar to assist in a heat
transfer between an LED and another thermal mass, such as air.
According to various embodiments, the thermal conductivity of the
LED and/or a platform supporting the LED can be greater than that
of a surrounding ambient environment, for example, the surrounding
air.
[0053] According to various embodiments, a thermoelectric device
can be used as a heat-transfer device, for example, an XLT module
available from Marlow Industries, Inc. of Dallas, Tex. Controls for
the thermoelectric device can include an adjustable-bipolar DC
output current power supply. The power supply can provide
programmable PID control/ramp to set point control, deviation
alarms, and automatic and manual operating modes. In reactions, for
example, real-time monitoring of Polymerase Chain Reaction (PCR)
reactions, thermoelectric devices can both heat and cool, as
desired, the LED by using a bi-directional power supply under
programmable and/or logic control. The programmable and logic
control can be provided by using a general purpose computer, or
custom built hardware, for example, a field programmable gate array
(FPGA). Thermoelectric devices can be specifically designed to
withstand the continuous temperature excursions required in PCR
use.
[0054] According to various embodiments, a heat-transfer device can
include a vapor-cycle device, for example, a Freon-based vapor
compression or absorption refrigerator. In such units, thermal
energy can be extracted from a region, thereby reducing its
temperature, then rejected to a "heat sink" region of higher
temperature. Vapor-cycle devices can include moving mechanical
parts and can include a working fluid, while thermoelectric
elements can be totally solid state.
[0055] According to various embodiments, a thermal interface
material (TIM) can provide a good thermal contact between two
surfaces, for example, between an LED support and a substrate,
and/or between an LED housing and a thermoelectric device. The TIM
can include silicone-based greases, elastomeric pads, thermally
conductive tapes, thermally conductive adhesives, or a combination
thereof. Zinc-oxide silicone can be used as a TIM. According to
various embodiments, Gap-Pad products, for example, GAP PAD VO
ULTRA SOFT materials or SIL-PAD, materials available from Berquist
Company of Chanhassen, Minn., can be used as thermal interface
materials. A TIM is described in U.S. Pat. No. 5,679,457 to
Bergerson, which is incorporated herein in its entirety. According
to various embodiments, a TIM can be disposed between a
heat-transfer device and an LED.
[0056] According to various embodiments, a method can be provided
for maintaining emssion intensity and spectral stability of an LED.
The method can comprise: providing a system comprising an LED;
generating excitation beams with the LED; measuring an operating
temperature of the LED; and regulating the operating temperature by
at least one of transferring heat from the LED and transferring
heat to the LED, based on the operating temperature, to maintain
emssion intensity and spectral stability of the LED. The regulating
can comprise retrieving from a memory source adjustment data
corresponding to a desired operating temperature or temperature
range at which emission intensity and spectral stability of the LED
are maintained.
[0057] Other embodiments will be apparent to those skilled in the
art from consideration of the present specification and practice of
various embodiments disclosed herein. It is intended that the
present specification and examples be considered as exemplary
only.
* * * * *