U.S. patent application number 11/643481 was filed with the patent office on 2008-01-24 for thin-film thermoelectric cooling and heating devices for dna genomic and proteomic chips, thermo-optical switching circuits, and ir tags.
Invention is credited to Rama Venkatasubramanian.
Application Number | 20080020946 11/643481 |
Document ID | / |
Family ID | 23080431 |
Filed Date | 2008-01-24 |
United States Patent
Application |
20080020946 |
Kind Code |
A1 |
Venkatasubramanian; Rama |
January 24, 2008 |
Thin-film thermoelectric cooling and heating devices for DNA
genomic and proteomic chips, thermo-optical switching circuits, and
IR tags
Abstract
A thermoelectric cooling and heating device including a
substrate, a plurality of thermoelectric elements arranged on one
side of the substrate and configured to perform at least one of
selective heating and cooling such that each thermoelectric element
includes a thermoelectric material, a Peltier contact contacting
the thermoelectric material and forming under electrical current
flow at least one of a heated junction and a cooled junction, and
electrodes configured to provide current through the thermoelectric
material and the Peltier contact. As such, the thermoelectric
cooling and heating device selectively biases the thermoelectric
elements to provide on one side of the thermolectric device a grid
of localized heated or cooled junctions.
Inventors: |
Venkatasubramanian; Rama;
(Cary, NC) |
Correspondence
Address: |
MYERS BIGEL SIBLEY & SAJOVEC
PO BOX 37428
RALEIGH
NC
27627
US
|
Family ID: |
23080431 |
Appl. No.: |
11/643481 |
Filed: |
December 21, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10118236 |
Apr 9, 2002 |
7164077 |
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11643481 |
Dec 21, 2006 |
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60282185 |
Apr 9, 2001 |
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Current U.S.
Class: |
506/40 ; 136/203;
136/204; 205/421; 250/330; 257/E23.082; 455/422.1; 536/25.3 |
Current CPC
Class: |
H01L 2924/01068
20130101; B01L 7/52 20130101; F25B 21/04 20130101; H01L 27/14649
20130101; B01L 7/54 20130101; H01L 23/38 20130101; H01L 2224/95145
20130101; H01L 2224/95147 20130101; H01L 2924/01019 20130101; H01L
2924/01077 20130101; H01L 2924/00 20130101; B01L 3/5085 20130101;
B01L 2400/0448 20130101; H01L 2924/1461 20130101; H01L 35/08
20130101; H05B 3/10 20130101; H01L 2924/1461 20130101 |
Class at
Publication: |
506/040 ;
136/203; 136/204; 205/421; 250/330; 455/422.1; 536/025.3 |
International
Class: |
H01L 35/32 20060101
H01L035/32; C07H 21/04 20060101 C07H021/04; C25B 3/00 20060101
C25B003/00; C40B 50/00 20060101 C40B050/00; H04Q 7/20 20060101
H04Q007/20; C40B 60/14 20060101 C40B060/14; H01L 31/00 20060101
H01L031/00 |
Claims
1. A thermoelectric cooling and heating device comprising: a
substrate; a plurality of thermoelectric elements arranged on one
side of the substrate and configured to perform at least one of
selective heating and cooling, each thermoelectric element
including, a thermoelectric material, a Peltier contact contacting
the thermoelectric material and configured to form under electrical
current flow at least one of a heated junction and a cooled
junction, and electrodes configured to provide current through the
thermoelectric material and the Peltier contact; and a receptacle
thermally contacting the thermoelectric elements and including an
array of patches configured to receive a biological material.
2. The device of claim 1, wherein the patches of the receptacle are
aligned with the thermoelectric elements.
3. (canceled)
4. The device of claim 1, wherein the biological material includes
DNA material for genomics analysis.
5. The device of claim 1, wherein the biological material includes
proteins for proteomics analysis.
6. The device of claim 1, wherein the thermoelectric elements are
configured to at least one of heat and cool the biological
material.
7. The device of claim 6, wherein the patches are configured to
receive as the biological material single stranded DNA and the
thermoelements are configured to control the temperature of the
single stranded DNA for polymorphism conformation.
8. The device of claim 6, wherein the thermoelectric elements are
configured to at least one of heat and cool DNA double-helix
material to form single-stranded DNA material.
9. The device of claim 6, wherein the thermoelectric elements are
configured to provide localized thermo-genetic switches to switch
at least one of DNA chemistry, DNA-RNA chemistry, protein
synthesis, cross conversion dominant genes to recessive genes, and
production of antibodies.
10. The device of claim 6, wherein the patches are configured to
receive as the DNA material single stranded DNA and the
thermoelements are configured to control the temperature of the
single stranded DNA for polymorphism conformation.
11. The device of claim 6, wherein the thermoelectric elements are
configured to have a thermal response time less than 1.0 ms.
12. The device of claim 11, wherein the thermoelectric elements are
configured to heat shock biological material including at least one
of DNA material, proteins, and protein-related DNA.
13-18. (canceled)
19. A thermoelectric cooling and heating device comprising: a
substrate; a plurality of thermoelectric elements arranged on one
side of the substrate and configured to perform at least one of
selective heating and cooling, each thermoelectric element
including, a thermoelectric material, a Peltier contact contacting
the thermoelectric material and configured to form under electrical
current flow at least one of a heated junction and a cooled
junction, and electrodes configured to provide current through the
thermoelectric material and the Peltier contact; and a
microsurgical tool thermally contacting the thermoelectric elements
and configured to control the temperature of bio-tissues in contact
with the microsurgical tool.
20. A thermoelectric cooling and heating device comprising: a
substrate; a plurality of thermoelectric elements arranged on one
side of the substrate and configured to perform at least one of
selective heating and cooling, each thermoelectric element
including, a thermoelectric material, a Peltier contact contacting
the thermoelectric material and configured to form under electrical
current flow at least one of a heated junction and a cooled
junction, and electrodes configured to provide current through the
thermoelectric material and the Peltier contact; and a thermo-optic
phase shifter in thermal contact with the plurality of
thermoelectric elements and configured to vary an index of
refraction of an optical medium via temperature variations.
21. The device of claim 20, wherein the thermoelectric elements are
configured to heat the thermo-optic phase shifter.
22. The device of claim 20, wherein the thermoelectric elements are
configured to cool the thermo-optic phase shifter.
23. (canceled)
24. The device of claim 23, wherein the thermoelectric elements are
configured to have a thermal response time less than 1.0 ms.
25-32. (canceled)
33. A thermoelectric cooling and heating device comprising: a
substrate; a plurality of thermoelectric elements arranged on one
side of the substrate and configured to perform at least one of
selective heating and cooling, each thermoelectric element
including, a thermoelectric material, a Peltier contact contacting
the thermoelectric material and configured to form under electrical
current flow at least one of a heated junction and a cooled
junction, and electrodes configured to provide current through the
thermoelectric material and the Peltier contact; and an integrated
module including at least one electronic component in thermal
contact with the plurality of thermoelectric elements and
configured to control a temperature of the at least one electronic
component of the integrated module.
34. The device of claim 33, wherein the thermoelectric elements are
configured to selectively heat the at least one electronic
component.
35. The device of claim 33, wherein the thermoelectric elements are
configured to selectively cool the at least one electronic
component.
36-38. (canceled)
39. The device of claim 33, wherein the integrated module comprises
an optoelectronics module.
40. The device of claim 39, wherein the optoelectronics module
includes at least one of a bias circuit, a laser driver, a monitor
diode, a VCSEL array, an out-going optical connector, an in-coming
optical connector, a photodetector, a pre-amplification circuit,
and a post-amplification circuit.
41. The device of claim 33, wherein the integrated module comprises
an infrared imaging array.
42. A thermoelectric cooling and heating device comprising: a
substrate; a plurality of thermoelectric elements arranged on one
side of the substrate and configured to perform at least one of
selective heating and cooling, each thermoelectric element
including, a thermoelectric material, a Peltier contact contacting
the thermoelectric material and configured to form under electrical
current flow at least one of a heated junction and a cooled
junction, and electrodes configured to provide current through the
thermoelectric material and the Peltier contact; and a switching
optical network including optical switches in thermal contact with
the plurality of thermoelectric elements and configured to control
a temperature of the optical switches in the switching optical
network.
43. The device of claim 42, wherein the optical switches comprise
electroholographic optical switches.
44. (canceled)
45. The device of claim 42, wherein the optical switches comprise
thermocapillary switches.
46. The device of claim 45, wherein the optical switches comprise
bubblejet switches.
47. A thermoelectric cooling and heating device comprising: a
substrate; a plurality of thermoelectric elements arranged on one
side of the substrate and configured to perform at least one of
selective heating and cooling, each thermoelectric element
including, a thermoelectric material, a Peltier contact contacting
the thermoelectric material and configured to form under electrical
current flow at least one of a heated junction and a cooled
junction, and electrodes configured to provide current through the
thermoelectric material and the Peltier contact; and a cellular
communications network including micro-strip delay lines in thermal
contact with the plurality of thermoelectric elements and
configured to control a temperature of the micro-strip delay lines
in the cellular communications network.
48-55. (canceled)
56. A method for hybridizing DNA, comprising: depositing a first
set of DNA strands across at least a part of a DNA array; cooling
selected sites on the DNA array to attach the first set of DNA
strands onto the selected sites; heating the selected sites to
unravel the attached strands of DNA and to detach strands of DNA
which are not cross-linked to the selected sites; and hybridizing
the attached strands of DNA with a second set of DNA strands.
57. The method of claim 56, further comprising: exposing, between
the steps of heating and cooling, attached DNA strands to UV light
to promote cross-linking to the selected sites.
58. The method of claim 56, wherein the steps of cooling and
heating comprises: controlling a temperature at the selected sites
with a thermoelectric cooler including a plurality of
thermoelectric elements arranged on one side of a substrate and
configured to perform at least one of selected heating and
cooling.
59. The method of claim 58, wherein the step of controlling further
comprises: biasing selectively electrodes of each of the
thermoelectric elements in at least one of a first direction to
form a cooled junction and a second direction to form a heated
junction.
60. The method of claim 56, wherein the step of cooling comprises:
attaching the first set of DNA strands utilizing at least one of
charge-bonding and electrovalent bonding.
61. The method of claim 60, wherein the step of attaching further
comprises: providing, prior to the step of cooling, lysine on the
array, and cross-linking the first set of DNA strands to the lysine
with UV light exposure.
62. The method of claim 56, further comprising: biasing the
selected elements to the DNA at the selected sites.
63. A method for controlling temperature during electrophoresis of
a biological material onto an array, comprising: depositing
electrophoretically biological material across at least a part of
the array; cooling selected sites on the array during the
electrophoresis to attach a first set of biological material onto
the selected sites; and heating the selected sites to detach
biological material which is not cross-linked to the selected
sites.
64. The method of claim 63, further comprising: exposing, between
the steps of heating and cooling, attached biological material to
UV light to promote cross-linking to the selected sites.
65. The method of claim 63, wherein the steps of cooling and
heating comprises: controlling a temperature at the selected sites
with a thermoelectric cooler including a plurality of
thermoelectric elements arranged on one side of a substrate and
configured to perform at least one of selected heating and
cooling.
66. The method of claim 65, wherein the step of controlling further
comprises: biasing selectively electrodes of each of the
thermoelectric elements in at least one of a first direction to
form a cooled junction and a second direction to form a heated
junction.
67. The method of claim 63, wherein the step of cooling includes
the step of: attaching as the biological material at least a first
set of DNA strands and a first set of proteins.
68. The method of claim 63, wherein the step of cooling comprises:
attaching the biological material utilizing at least one of
charge-bonding and electrovalent bonding.
69. The method of claim 68, wherein the step of attaching further
comprises: providing, prior to the step of cooling, lysine on the
array; and cross-linking the biological material to the lysine with
UV light exposure.
70. The method of claim 63, further comprising: biasing the
selected elements to pool the biological material at the selected
sites.
71-76. (canceled)
77. A method for producing an infrared image, comprising: providing
an array of thermoelectric elements; and controlling a temperature
at selected sites on the array of thermoelectric elements.
78. The method of claim 77, wherein the step of controlling a
temperature comprises: controlling a plurality of said
thermoelectric elements arranged on one side of a substrate and
configured to perform at least one of selected heating and
cooling.
79. The method of claim 78, wherein the step of controlling further
comprises: biasing selectively electrodes of each of the
thermoelectric elements in at least one of a first direction to
form a cooled junction and a second direction to form a heated
junction.
80-82. (canceled)
83. A method for improving cellular communications, comprising:
providing an array of thermoelectric elements thermally connected
to a micro-strip delay line; and controlling a temperature of the
micro-strip delay line in a cellular communications system.
84. The method of claim 83, wherein the step of controlling a
temperature comprises: controlling the temperature with a
thermoelectric cooler including a plurality of thermoelectric
elements arranged on one side of a substrate and configured to
perform at least one of selected heating and cooling.
85. The method of claim 84, wherein the step of controlling further
comprises: biasing selectively electrodes of each of the
thermoelectric elements in at least one of a first direction to
form a cooled junction and a second direction to form a heated
junction.
86-90. (canceled)
91. A system for hybridizing DNA material, comprising: a depositing
device configured to deposit a first set of DNA strands across at
least a part of a DNA array; means for cooling selected sites on
the DNA array to attach the first set of DNA strands onto the
selected sites; means for heating the selected sites to unravel the
attached strands of DNA and to detach strands of DNA which are not
cross-linked to the selected sites; and means for hybridizing the
attached strands of DNA with a second set of DNA strands.
92. The system of claim 91, wherein the means for cooling and the
means for heating comprise: a thermoelectric cooler including a
plurality of thermoelectric elements configured to perform at least
one of selected heating and cooling of the array; and a controlling
device configured to control a temperature at the selected sites
with a thermoelectric cooler.
93-99. (canceled)
100. A system for producing an infrared image, comprising: an array
of thermoelectric elements, and a controlling device configured to
control a temperature at selected sites on the array of
thermoelectric elements.
101. The system of claim 100, wherein the controlling device
comprises: a thermoelectric cooler including a plurality of
thermoelectric elements thermally in contact with the selected
sites and configured to perform at least one of selected heating
and cooling one side of the array.
102-103. (canceled)
104. A system for improving cellular communications, comprising: a
controlling device configured to control a temperature of at least
one micro-strip delay line in a cellular communications system.
105. The system of claim 104, wherein the cellular communication
system is spread spectrum system.
106. The system of claim 104, wherein the controlling device
comprises: a thermoelectric cooler including a plurality of
thermoelectric elements thermally in contact with the at least one
micro-strip delay line and configured to perform at least one of
selected heating and cooling of the at least one micro-strip delay
line.
107-131. (canceled)
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority as a divisional of U.S.
application Ser. No. 10/118,236 entitled "Thin-film Thermoelectric
Cooling And Heating Devices For DNA Genomic And Proteomic Chips,
Thermo-Optical Switching Circuits, And IR Tags," filed Apr. 9,
2002, which claims priority under 35 U.S.C. Sec. 119 to U.S.
Provisional Application No. 60/282,185 entitled "Thin-film
Thermoelectric Cooling and Heating Devices for DNA Genomic and
Protemic Chips, Thermo-optical Switching Circuits, and IR Tags,"
filed Apr. 9, 2001 The disclosures of U.S. application Ser. Nos.
10/118,236 and 60/282,185 are hereby incorporated herein in their
entirety by reference. This application includes subject matter
related to that disclosed in U.S. Pat. No. 6,071,351; and U.S. Ser.
No. 09/381,963, filed Mar. 31, 1997, entitled "Thin-film
Thermoelectric Device and Fabrication Method of Same"; and U.S.
Provisional Application Serial No. 60/190,924, filed March 2000,
entitled "Cascade Thermoelectric Cooler"; and U.S. Ser. No.
60/253,743, filed Nov. 29, 2000, entitled "Spontaneous Emission
Enhanced Heat Transport Method and Structure for Cooling, Sensing,
and Power Generation", the disclosures of which are hereby
incorporated herein in their entirety by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to thin-film thermoelectric
cooling and heating devices for application in a broad range of
applications from DNA genomic and proteomic chips, thermo-optical
switching circuits, and infrared tags, and to the application of
anisotropic heat spreaders to electro-holographic optical
switching, thermocapillary and bubblejet optical switching,
micro-strip delay lines for packet switching in cellular
communication, and temperature control for probes in micro-surgery
and bio-tissue analysis.
[0004] 2. Description of the Background
[0005] Solid-state thermoelectric devices can improve the
performance of electronic components, opto-electronic components
and sensors. Today, thermoelectric devices based on bulk (about 1
mm thick) p-Bi.sub.xSb.sub.2-xTe.sub.3 and
n-Bi.sub.2Te.sub.3-xSe.sub.x alloyed materials are used in cooling
applications. FIG. 1A is a schematic of a bulk device consisting of
two thermoelectric materials 2a, 2b having an appropriate bias
voltage for cooling at a Peltier contact 2c. FIG. 1B shows that the
same device can be used for heating at the Peltier contact with an
appropriate opposite bias voltage. Bulk devices present a cold
surface or a hot surface existing across the entire top surface of
the thermoelectric device. So far, bulk thermoelectric devices have
not been made to selectively heat or cool local regions without
heating or cooling adjacent areas because of their relatively large
size (of each element) as well as lack of microelectronic type
processing. As such, thermoelectric devices have not been employed
in applications requiring selective heating or cooling.
SUMMARY OF THE INVENTION
[0006] One object of this invention is to provide thin-film
thermoelectric devices that can cool or heat with response times of
tens of .mu.sec instead of hundreds of msec for bulk devices, and
another object of the invention is to cool or heat extremely small
areas, tens to hundred .mu.m.sup.2, as compared to the mm.sup.2
areas of bulk thermoelectric devices, are locally heated or
cooled.
[0007] Accordingly, one object of the present invention is to
provide spot-cooling and spot-heating at localized areas defined by
the pattern of thin-film thermoelectric devices and the applied
electrical bias.
[0008] Another object of the present invention is to provide the
spot heating and/or cooling on the same side of a thermoelectric
device.
[0009] Still another object of the present invention is to provide
rapid heating or cooling to selective surface components.
[0010] Another object of the present invention is to provide a
thin-film thermoelectric device which can self-assemble DNA
material for genomic and proteomic applications in a microarray
format.
[0011] Another object of the present invention is to control
reaction chemistry, through temperature control of reaction rates,
between molecules such as between DNA or between DNA and RNA or
between protein molecules or between enzyme and reactants or in
general between any two or more molecules in an array format such
as for example DNA-RNA, RNA-RNA, DNA-RNA, protein-DNA, protein-RNA,
protein-ligand, and enzyme-substrate.
[0012] A further object of the present invention is to provide a
thermoelectric device which can, via thermo-optical components,
control optical switches in optical networks.
[0013] Another object of the present invention is to provide a
thermoelectric device which can control the lasing frequency of a
laser via temperature-derived bandgap changes in the laser
material.
[0014] Still another object of the present invention is to provide
a thermoelectric device which can perform spot cooling/heating to
produce infrared images for identity tags.
[0015] These and other objects of the present invention are
achieved by providing a thermoelectric cooling and heating device
including a substrate, a plurality of thermoelectric elements
arranged on one side of the substrate and configured to perform at
least one of selective heating and cooling such that each
thermoelectric element includes a thermoelectric material, a
Peltier contact contacting the thermoelectric material and forming
under electrical current flow at least one of a heated junction and
a cooled junction, and electrodes configured to provide current
through the thermoelectric material and the Peltier contact. As
such, the thermoelectric cooling and heating device selectively
biases each individual thermoelectric element to provide on one
side of the thermolectric device a grid of localized heated or
cooled junctions.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] The patent or application file contains at least one drawing
executed in color. Copies of this patent or patent application
publication with color drawing(s) will be provided by the U.S.
Patent and Trademark Office upon request and payment of the
necessary fee. A more complete appreciation of the present
invention and many attendant advantages thereof will be readily
obtained as the same becomes better understood by reference to the
following detailed description when considered in connection with
the accompanying drawings, wherein:
[0017] FIG. 1A is a schematic illustration of a bulk thermoelectric
device with a bias voltage for cooling a Peltier contact;
[0018] FIG. 1B is a schematic illustration of a bulk thermoelectric
device with an opposite bias voltage for heating a Peltier
contact;
[0019] FIG. 2A is an illustration of a spot cooled image in the
form of "ONR" and "DARPA" as shown by the IR image, see temperature
scale for reference;
[0020] FIG. 2B is another illustration of a spot heated image in
the form of "ONR" and "DARPA" as shown by the IR image; see
temperature scale for reference;
[0021] FIG. 3 is a schematic illustration of integrated
spot-coolers for local-area cooling or heating;
[0022] FIG. 4 is an illustration of a combined spot cooling and
spot heating of a surface of a low thermal conductivity material
header;
[0023] FIG. 5 depicts graphs illustrating the time responses of a 5
.mu.m thin-film thermoelement as compared to a bulk (1 mm)
thermoelement;
[0024] FIGS. 6A-6D are schematic illustrations of a single-strand
of DNA produced by selective electro-thermal spot-temperature
control using the thin-film thermoelectric devices of the present
invention;
[0025] FIG. 7A is a schematic illustration of a robotic deposition
process utilized to deposit DNA material;
[0026] FIG. 7B is a schematic illustration of a self-assembly of
DNA fragments or protein molecules obtained by selective
temperature control using an electro-thermal genomic chip or
electro-thermal proteomic chip of the present invention;
[0027] FIG. 8 is an illustration of a spatially-controlled
electro-thermal electrophoretic DNA chip;
[0028] FIG. 9 is a schematic illustration of the attachment and
unziping of double-helical strands and the introduction of new DNA
strand to be hybridized, the strands being attached to an
electro-thermal chip of the present invention illustrating spatial
temperature control utilized for genomics and proteomics study;
[0029] FIG. 10 is a flow chart illustrating multiple feedback
processes between DNA, RNA, and proteins;
[0030] FIG. 11 is a schematic depiction of a thermoelectric probe
of the present invention locally contacting a single cell of a
specimen;
[0031] FIG. 12 is a schematic of a nano-scale thermal transducer of
the present invention employing a cantilever arrangement contacting
a single cell;
[0032] FIG. 13 is a schematic diagram depicting a nano scale
thermal transducer of the present invention employing a cantilever
arrangement contacting specific spots of large molecular structures
such as a hybridized DNA pair;
[0033] FIG. 14 is a schematic depicting an apparatus of the present
invention for detecting the heat released from a small-scale
region;
[0034] FIG. 15 is a schematic depiction of a multiple wavelength
VCSEL array located on the thermoelectric device of the present
invention; and
[0035] FIG. 16 is a schematic depiction of an elecrto-holographic
router switching matrix located on the thermoelectric device of the
present invention.
DESCRIPTION OF THE EMBODIMENTS
[0036] Referring now to the drawings, wherein like reference
numerals designate identical, or corresponding parts throughout the
several views, and more particularly to FIG. 2A thereof, FIG. 2A is
an illustration of a spot cooled image in the form of "ONR" and
"DARPA" as shown by an IR image feature produced by cooling of the
present thermoelectric devices. In such cooling, microelectronic
lithography is employed to pattern micro thermoelements arbitrarily
across the surface of a substrate. The second illustration in FIG.
2B shows an infra-red image generated by spot heating in a
thermoelectronic device of the present invention. The ability to
obtain spot cooling or heating with thin-film thermoelements is
enabled by the very low-resistivity specific contact resistivities
leading to relatively high device (which includes the effect of
contact resistance and that of the material) figure-of-merit
(ZT>0.1 at 300K) which can be obtained with the thin-film
thermoelements. By reversal of the bias voltage to the
thermoelements, the spots can be made to heat as shown by the image
of heated spots in FIG. 2B. Based on the results in FIGS. 2A and
2B, the device modules shown in FIGS. 3 and 4 can both arbitrarily
cool and heat local surface spots.
[0037] FIG. 3 is a schematic of integrated spot-coolers for
local-area cooling or heating. In FIG. 3, several thin-film
thermoelectric elements are placed in parallel and heat or cool a
particular area depending on the direction of current flow in these
elements. As shown in FIG. 3, the thermoelectric cooling and
heating device of the present invention includes a substrate 1 and
a plurality of thermoelectric elements 2 arranged on the substrate
1 with each thermoelectric element 2 having an n-type
thermoelectric material 2a, a p-type thermoelectric material 2b
located adjacent to the n-type thermoelectric material 2a, a
Peltier contact 2c connecting the n-type thermoelectric material 2a
to the p-type thermoelectric material 2b. Electrodes 3 contact both
a side of the n-type thermoelectric material 2a opposite the
Peltier contact 2c and a side of the p-type thermoelectric material
2b opposite the Peltier contact 2c.
[0038] Appropriately biased electrical current flow through
selected ones of the thermoelectric elements 2 makes the Peltier
contact 2c either a heated junction 7 or a cooled junction 8.
Further, the thermoelectric cooling and heating device of the
present invention includes a controller connected to the electrodes
and configured to selectively bias the electrodes of each of the
thermoelectric elements in an appropriate direction to form the
cooled junction or an opposite direction to form the heated
junction. As shown in FIG. 3, the thermoelectric elements 2 are
patterned onto the substrate 1. This pattern can frequently be a
grid pattern, but many other patterns designed to interface the
thermoelectric cooling and heating device of the present invention
to specific applications are possible.
[0039] According to the present invention, a wiring grid can
individually connect to each of the thermoelectric elements
providing the controller access to each thermoelectric element for
application of an appropriate bias for cooling or an opposite bias
for heating. One side of all the thermoelectric elements can,
according to the present invention be connected to a common ground.
Similar grid wiring connections and control are utilized in liquid
crystal display grids as described in U.S. Pat. No. 6,154,266, the
entire contents of which are incorporated herein by reference.
However, the grids may alternatively be connected or segmented in
pre-designated sets (e.g. columns and rows) which are commonly
connected to have the same polarity of voltage simultaneously
applied, enabling the pre-designated sets to be block-addressed by
the controller.
[0040] Contrary to FIG. 3, in one embodiment of the present
invention, only one leg of the thermoelectric element is required
to produce heating or cooling. In this embodiment, a selected type
of thermoelectric material (i.e. n-type or p-type) is utilized with
the Peltier contact 2c. Current flow in a first direction through
an electrode, a thermoelectric material, the Peltier contact 2c,
and a subsequent electrode results in a heated junction at the
Peltier contact 2c. A current flow in a second direction opposite
to the first produces a cooled junction at the Peltier contact 2c.
Indeed, the spot cooled images in FIGS. 2A and 2B were produced
utilizing current flow through an electrode, a thermoelectric
material, a Peltier contact, and a subsequent electrode.
[0041] FIG. 4 is an illustration of a combined spot cooling and
spot heating of a surface header 10 made of a low thermal
conductivity material. Shown in FIG. 4 is an overlay chip 12 which
mates to the surface header. The ability to both spot-cool and
spot-heat on the same side of the thermoelectric device of the
present invention permits flexibility in the application of
thermoelectric thin-film devices to temperature dependent process
control. In some applications, utilization of a thermally
insulating material (e.g. a low-thermal conductivity material like
glass or quartz rather than a high-thermal conductivity material
like AIN) for the heat-source header is not necessary to preserve
the pattern of cooled or heated spots.
[0042] The thin film thermoelectronic devices of the present
invention, according to one embodiment of the present invention,
are thermally coupled to a surface header 10 which is an
anisotropic heat spreader in which the thermal conductivity is
excellent in a direction normal to the surface header (i.e. the
direction of heat flow from a point which needs to be cooled or
heated to the Peltier contact region of the device) while the
lateral thermal conductivity in the plane of the surface header
(i.e. in a direction across the surface header 10) is low. In this
embodiment, the anisotropic heat spreader includes a composite of a
high thermal conductivity material (e.g., oriented crystals in a
polycrystalline matrix or a high thermal conductivity rods (e.g.,
silicon rods or copper rods) in a low-thermal conductivity matrix
(e.g., glass). The composite, according to the present invention,
provides high thermal conductivity perpendicular to a plane of the
surface header 10 and low thermal conductivity parallel to the
plane of the surface header 10, thus preserving the
spot-cooling/heating character of the thin film thermoelectric
devices of the present invention. Furthermore, the anisotropic heat
spreaders, according to the present invention, can utilize other
forms of-heat spreaders such as graphite or metal fibers in an
aerogel matrix to achieve high thermal conductivity perpendicular
to the plane of the header compared to low thermal conductivity in
the plane of the header.
[0043] One advantage of the 1 to 10 .mu.m thin-film thermoelectric
devices of the present invention is that the spot cooling and/or
spot heating is extremely fast. FIG. 5 illustrates the
time-response of a 5 .mu.m thick thermoelectric device and a time
response of a typical state-of-the-art bulk (1 mm-thick) element
after currents which produce cooling are applied to these devices.
As shown in FIG. 5, the thin film thermoelectric device of the
present invention responds within 15 .mu.s while the bulk
thermoelectric device responds within 0.40 s. Thus, the thin-film
thermoelectric devices of the present invention have a time
constant on the order of a few microseconds, while the bulk
thermoelectric devices have a time constant of hundreds of
milliseconds. The time constant difference arise directly from the
fact that the thermal response time (.tau..sub.r) is significantly
smaller in thinner thermoelements. The .tau..sub.r is approximately
given by equation (1): .tau..sub.r=4L.sup.2/.sup.2D (1)
[0044] where L is thickness of the thermoelectric device and D is
the thermal diffusivity. Thus, the thin-film thermoelectric devices
of the present invention have a fast response time allowing for
rapid changes to surface temperatures and hence rapid control of
chemical, physical, mechanical, or optical phenomenon associate
with these surface temperature changes. L for bulk thermoelectronic
devices ranges from 500 to 2000 microns in bulk while D ranges from
0.01 to 0.03 cm.sup.2/sec. In contrast, L for thin-film devices
ranges 1 to 10 microns while D in Bi.sub.2Te.sub.3 superlattice
thin-film materials is from 0.001 to 0.003 cm.sup.2/sec and D in
Si/Ge thin-film materials is from 0.01 to 0.05 cm.sup.2/sec. Higher
speed cooling/heating applications which require higher D and
reasonable ZT is needed to obtain cooling. For small temperature
excursions, a low ZT can be sufficient. Thus, according to the
present invention, higher speed may be achievable with higher D
materials such as for example InSb and their alloys and PbTe and
their alloys.
[0045] Further, the performance of any thermoelectric device is
dependent on the figure-of-merit (ZT) of the thermoelectric
materials used to fabricate the device. The cooling or heating of
the present invention can utilize high-performance high-ZT
Bi.sub.2Te.sub.3-based superlattice structured thin-film materials
to obtain enhanced performance levels, as described in U.S. patent
application Ser. No. 09/381,963, the contents of which have been
incorporated herein by reference. Alternatively, non-superlattice
structured thermoelectric materials can be used in the present
invention. In general, the present invention is not limited to any
particular design, material, or fabrication process of a bulk or
thin film thermoelectric device.
[0046] Specific applications which can take advantage of the above
described developments in small area/fast response time thin-film
thermoelectric devices include but are not limited to applications
in DNA array fabrication, DNA electrophoresis for genome
sequencing, DNA functional genomics, and DNA proteomics. Genomincs
and protemics research have been described in Proteomics in
Genomeland, in Science, vol. 291, No. 5507, pp. 1221-1224, the
entire contents of which are incorporated herein by reference. In
addition, the thermoelectric devices of the present invention can
be used for electro-thermal optical switching for high-speed
optical communications and other selective-cooled optoelectronic
applications. Further, the thermoelectric cooling devices of the
present invention can be used as identification tags for military
personnel, military systems, and even commercial systems.
Identification tags utilizing the spot cooling or heating of the
present invention can be scanned by IR-imaging devices.
[0047] Fabrication of conventional DNA chips (or microarrays) for
electrophoresis or genomics or proteomics begins with glass silicon
substrates. Onto these substrates are fixed or assembled thousands
of patches of single-stranded DNA, referred to as probes. Each
patch measures just tens of .mu.m in lateral dimension.
Microelectronic photolithographic techniques offer the best
technique for obtaining the highest density of probes. Conventional
production scale microarrays can have 400,000 probes in 20-micron
size patches. Conventional procedures are described in Making
Chips, in IEEE Spectrum, March 2001, pp. 54-60, the entire contents
of which are incorporated herein by reference.
[0048] A first step in DNA analysis on a microarray fabrication is
the separation of twisted strands of the DNA by unzipping the DNA
along the rungs of the ladder, using temperature or biochemical
methods. DNA consists of nucleotides stacked atop each other in two
strands forming a twisted ladder. The twisted ladder has the
sugar-phosphate support backbone. The rungs of the ladder are the
bases. Adenine pairings occur with thymine, and guanine pairings
occur with cytosine.
[0049] According to the present invention, the formation of single
unzipped strands of DNA molecules occurs using a
spot-cooling/heating electro-thermal chip as shown in FIG. 6A. In
the spot-cooling/heating electro-thermal chip of the present
invention, patches are patterned lithographically in a receptacle
array to have dimensions ranging from 1 to 500 m. FIGS. 6A-D show
schematically the steps of forming a single-strand of DNA by
selective electro-thermal spot-temperature control. A template 11
is attached to the surface header 10 where the DNA array is to be
located. The DNA double helix will typically unzip at the "hot"
points. However, certain DNA molecules, depending on their
chemistry, may selectively unzip at "cold" points. The
spot-cooling/heating of the electro-thermal chip of the present
invention will heat or cool the DNA to predetermined temperatures
to unzip the DNA strands, as shown in FIG. 6B. Once the DNA strands
are unzipped at the respective "hot" or "cold" locations, the
electro-thermal chip of the present invention can by charge control
(using the fact that DNA molecules themselves carry charge) adhere
DNA to predetermined areas on the surfaces of the electro-thermal
chip. Alternatively, selective cooling can be utilized to enhance
adsorption of a single strand of DNA to a specific site. Thus, the
electro-thermal chip of the present invention produces
single-strand generation and selective adsorption at predetermined
locations. These steps, according to the present invention, can be
followed by attachment and single-strand generation of another DNA
molecule at adjacent locations, as shown in FIG. 6C. In FIG. 6D,
the process of selective adsorption of various DNA molecules at the
all desired sites is complete. Thus, once self-assembled, the DNA
array is available for analytical characterizations such as for
example mass spectroscopic analysis, NMR studies, x-ray analysis,
etc.
[0050] DNA microarrays numbering 100,000 to a million, with
20-micron size patches, can typically be deposited on glass or
silicon substrates by robotic deposition as shown in FIG. 7A.
However, robotic deposition is time consuming and costly.
Conventional robotic deposition techniques have been described in
U.S. Pat. No. 5,865,975, the entire contents of which are
incorporated herein by reference. Instead, according to the present
invention, by using a electro-thermal cooling/heating chip as shown
in FIG. 7B, spot temperature control will self-assemble selective
DNA or proteins. FIG. 7B is a schematic of a self-assembly of DNA
fragments or protein molecules obtained by selective temperature
control using an electro-thermal chip of the present invention.
Thus, rapid fabrication of pre-determined DNA arrays for genomics
or protein arrays for proteomic studies is realized by the
self-assembling character of the biological material when deposited
on the electro-thermal genomic or proteomic chips of the present
invention.
[0051] Further, the spatially-controlled-temperature of the
thin-film thermoelectric devices of the present invention can be
utilized with existing DNA array fabrication methods. Today, DNA
arrays are made either by inkjet printing or by in-situ
fabrication. The inkjet printing process has been described in U.S.
Pat. No. 6,180,351, the entire contents of which are incorporated
herein by reference. In the inkjet printing process, droplets
containing many copies of a sequence of DNA are deposited on a
substrate. The thin-film thermoelectric device of the present
invention permits spatial temperature control combined with rapid
cooling/heating to promote adhesion or adsorption of the DNA
strands. Furthermore, the in-situ fabrication of DNA sequences by
the photolithography process, as described in U.S. Pat. No.
5,874,219, the entire contents of which are incorporated herein by
reference, can be replaced by the selective adhesion of the DNA at
the spot-temperature controlled areas on the thin-film
thermoelectric device of the present invention. For example, the
traditional in-situ fabrication of DNA sequence by deposition of
one nucleotide at a time(shown in FIG. 7a.) can be replaced by
thermal activation or cooling-enhanced adsorption on a
spatially-controlled-temperature grid. Thus, the self-assembly
method of the present invention avoids exposure of the DNA to UV
light required in the traditional photolithographic process. UV
exposure can cause unintentional chemical modification of the DNA.
Further, replacing spot photo-chemistry with spot thermochemistry
of the present invention has other advantages in that the DNA is
preserved in tact without chemical modification, as can occur when
the capping chemicals used in the traditional photolithographic DNA
array process are applied.
[0052] In addition to spot temperature control, in another
embodiment of the present invention, spot temperature control can
be combined spot electric fields. For example, arrays of
electrically active (-1.3 to 22.0 Volts) pads can, according to the
present invention, control the pooling of DNA onto particular
sites. Pooling of DNA onto electrically charged sites speeds the
hybridization reaction of the DNA by a factor of as much as 1000.
Hybridization represent the pairing of individual genetic species
which belong to genetically different species. For example,
complementary RNA and DNA strands can be paired to make a RNA-DNA
hybrid which forms a "new" double-strand from genetically different
sources. FIG. 9A is a schematic illustration of DNA strands each
containing a double helix, separation of the strands, and the
introduction of new DNA strand to be hybridized. FIG. 9B is a
schematic illustration of an electro-thermal chip of the present
invention which depicts spatial temperature control utilized for
genomics and proteomics study. Formation of new pairs can be
assisted in the present invention by cooling weakly hybridized
pairs to inhibit the strands from prematurely breaking apart before
hybridization. Furthermore, excessive temperatures can result in a
hybridized pair dehybridizing, defeating the engineering
process.
[0053] Thus, the process of selective adsorption, single-strand
generation, and hybridization as directed by the thin-film
thermoelectric devices of the present invention is accomplished by
decreasing the temperature at selected sites to facilitate
charge-bonding or electrovalent bonding of a first set of DNA
strands to lysine which pre-existed on a template of the selected
sites, exposing the charge-bonded or the electrovalent-bonded DNA
strands to UV light to cross-link the lysine and the DNA strands,
heating the selected sites to unravel the first set of DNA strands
whereby one strand is no longer attached, introducing a second set
of DNA strands, and hybridizing the second set of DNA strands to
the attached single stranded DNA of the first set.
[0054] Further, the present invention provides a tool by which
chemical kinetic processes of DNA cell systems can be studied to
observe reaction rates affected not only by temperature but also by
other physical and chemical parameters. Currently, genomic data is
static: sequence and structure. Dynamic information in the form of
enzymology experiments, which measure reaction kinetics in DNA
microchips and arrays, would yield valuable information. The
reaction kinetics studied in conventional DNA microarrays suggest
that study of faster chemical reaction times through spatial
temperature control can lead to a better understanding and could
eventually permit manipulation and control of DNA reaction
kinetics. Genomic engineers need to reduce the experimental
iterations to better understand the DNA structure and need faster
analysis when introducing deliberate changes to the functional
genomics. Control of the DNA structure will profoundly influence
the speed and ability to safely engineer new crops, medicines, and
genetic treatments. According to the present invention, the
thermoelectric elements can act as localized thermo-genetic
switches to switch (i.e. temperature activate) DNA chemistry,
DNA-RNA chemistry, protein synthesis, enzyme-aiding conversion of
dominant genes to recessive genes and vice-versa, and production of
medical antibodies.
[0055] Furthermore, interpreting data from DNA micro-arrays has
emerged as a major difficulty. An array is a technology that
provides massively parallel molecular genetic information.
Biostatistics and bioinformatics which truncate the data defeat the
whole purpose of array sampling. Usually, the data in such arrays
are interpreted by finding a logical link between the expression of
a gene and its function. Since biological and chemical processes
are controlled by temperature, temperature control in micro-arrays
as enabled by the present invention will act as a control lever.
Raising the temperature will accelerate reactions; lowering the
temperature will retard reactions. Statistically Manageable A real
Rapid Temperature-control DNA arrays or SMART DNA arrays can be
developed using the thermoelectronic devices of the present
invention to aid in data interpretation, particularly the finding
of functional links.
[0056] Advantages of the spot-cooling/heating method of the present
invention include (1) high-speed inkjet printing of DNA
micro-arrays using spatial temperature-controlled thin-film
thermoelectric devices to assist self-assembly, (2) replacement or
augmentation of photolith-based DNA micro-arrays with
thermochemistry using the spatial temperature-controlled to form
the array of DNA, (3) rapid thermal cycling for DNA sequencing, and
(4) DNA sequencing for high throughput process for determining the
ordered base pairs in DNA strands.
[0057] Another embodiment of the present invention, a
spatially-controlled-temperature electro-thermal electrophoretic
chip, as shown in FIG. 8. For clarity, only a few cooling and
heating spots are shown in FIG. 8. Yet, a large number of
electrophoretic array spots exist in the electrophoretic chip. Spot
sizes of the present invention ranging from 5 .mu.m*5 .mu.m to 1000
.mu.m*1000 .mu.m, resulting in spot densities ranging from 100 to a
million or more spots per cm.sup.2. The electro-thermal
electrophoretic chip of the present invention cools hot spots
generated during electrophoresis of DNA. For example, the heat
generated during electrophoresis can approach 30 to 100 W/cm.sup.2.
Removal of such high heat fluxes can be easily achieved with
microelectronically processed thin-film thermoelectric devices (see
for example U.S. patent application Ser. No. 09/381,963). Further,
in electrophoresis, the ability to individually cool or heat in a
controlled 20 .mu.m*20 .mu.m patch or other similar geometries
provides a tool to understand, modify, and control DNA
electrophoresis. In addition, charge control can be augmented to
provide selective adsorption at precharged sites.
[0058] The method of choice for DNA sequencing to determining a
size of a DNA strands is a four-color electrophoresis utilizing
fluorescent labeling specific to the bases in the DNA. There are
several sources of noise in such analysis such as surplus DNA
without attached fluorescent labels, single-stranded DNA folding on
itself, etc. These noise sources are reduced using purification of
samples before loading, engineering of gel and buffer chemistries
and optimization of temperature, all leading to better resolution.
The spatially-controlled-temperature electro-thermal
electrophoretic chip can potentially solve several of these
problems leading to faster and reliable DNA sequencing. For
example, it is known that if the temperature is sub-optimal, the
folding of the single strand of DNA can change the
electropherogram. Thus, by using the
spatially-controlled-temperature electro-thermal electrophoretic
chip of the present invention, in one process step, the optimal
temperature range can be obtained leading to faster DNA
sequencing.
[0059] Another embodiment of the present invention is a
spatially-controlled-temperature electro-thermal chip for
self-assembly of biological material. Today, DNA microarrays or
biological chips are made as follows. Using polymerase chain
reaction or biochemical synthesis, strands of DNA are separated.
Photolithography techniques are used to convert glass, plastic, or
silicon substrates into a receptacle array for DNA strands.
Electrophoretic bonding or robotic deposition or tiny droplet
sprayers are used to adhere the genetic material to the substrate.
With the present invention, the receptacle array is thermally
coupled to a spot-cooling/heating thin-film thermoelectric module
to realize the electro-thermal chip of the present invention. DNA
strands can be self-assembled by the spot-temperature control
process illustrated in FIGS. 6 and 7. The spot-cooling/heating
thin-film thermoelectric module in the electro-thermal chip is
reusable from receptacle to receptacle. Thus, the electrothermal
chip of the present invention permits rapid self-assembly of DNA
arrays and reduces the cost of fabrication of DNA chips by avoiding
robotic or photolithographic DNA transfer techniques. The
electro-thermal chip of the present invention cools or heats very
small areas, such as 20 .mu.m*20 .mu.m spots as in the DNA patches
of a modem microarray. Thus, each of the 20 .mu.m*20 .mu.m patches
or other similar geometries, if individually cooled or heated in a
controlled manner, provides a tool to understand, modify, and
control DNA genomics.
[0060] Proteins are chains of amino acids assembled in an order
specified by the sequence of DNA bases located in the chromosomes
in the cell nucleus. RNA molecules move messages from the nucleus
to ribosomes that assemble proteins by matching three-base sets
(codons) in message-RNA with complementary codons on transfer RNA
attached to individual amino acids. This orderly sequence relates
the "expression" of gene to "activity" of protein in the cell.
However, this relation is very complicated with multiple feedback
loops as shown in FIG. 10.
[0061] As a result of the modifications from regulations and
feedback, some complex human genes can produce hundreds of
different proteins. Tools are needed to do a high-throughput study
of the non-genome (feedbacks) interactions shown in FIG. 10. Unlike
genomics, there is no microarray for measuring the concentration of
many proteins simultaneously. Today, the only way is to separate
different proteins is by mass, since different amino acids
sequences correspond to different masses. The present invention
utilizes 2-D gel electrophoresis which is similar to the
electrophoresis used in DNA sequencing such that disclosed in Fitch
and Sokhansanj, Proc. of IEEE, December 2000, the entire contents
of which are incorporated herein by reference. An electric field is
applied along one axis to get a 2-D spot representing the
concentration of a particular protein in the sample. Spot-cooling
or spot-heating in a two-dimensional array, utilizing the
electro-thermal chip of the present invention, offers a new
approach to the study of proteomic chips. Further, electric field
variations can be combined with temperature variations to
manipulate the protein formation in simulation of real
conditions.
[0062] For example, the temperature variations in the
electro-thermal chips can be used as a genetic switch to control or
regulate the pathway of genes in how they synthesize proteins. The
fast response time/small area control in a electro-thermal chip
will provide a control system to produce useful proteins in an
orderly fashion. Thus the fast response time/small area control, in
combination with the electric field control, afforded by the
electro-thermal chip of the present invention can lead to the
implementation of stable regulatory pathways for protein synthesis
from gene expressions. Further, synthesis, characterization, and
manipulation of heat shock proteins (and the related DNA) in a
micro-array utilizing the electro-thermal chip of the present
invention, is enabled by the ability to rapidly change the
temperature. There are about 23 genes, out of a total of about 1367
typically concerned with human toxicology, that are classified as
specific to heat shock proteins.
[0063] Temperature selection using spatially-temperature-controlled
electro-thermal chips can be used to control either the production
of mRNA, the transport of mRNA and the translation of mRNA to
protein, all leading to new applications in new crops, medicines,
and genetic treatments. For example, the reaction rate constants
that control the binding of RNA polymerase with DNA can be
controlled with temperature so that the effects of repressors can
be overcome and so new proteins (enzymes) can be generated.
Similarly, temperature can be controlled to provide a sharp burst
of mRNA to generate proteins.
[0064] Thus, a further embodiment of the present invention is a
spatially-controlled-temperature electro-thermal chip for proteomic
studies. As previously noted, the electro-thermal chip of the
present invention cools or heats very small areas, such as 20
.mu.m*20 .mu.m spots as in the DNA protein patches of a modern
microarray. Thus, each of these 20 .mu.m*20 .mu.m patches and other
similar geometries, if individually cooled or heated in a
controlled manner, will provide a tool to understand, modify, and
control proteomics.
[0065] The effect of temperature control on DNA analysis, DNA
amplification, protein synthesis, and DNA chemistry has been
unstudied in DNA microarrays mainly because of the lack of suitable
chip technologies. There are some studies that indicate that
temperature may have significant importance in DNA analysis, DNA
amplification, and general DNA and protein chemistry. For example,
in the DNA study of Yersinia pestis, the virulence mechanism of
Yersinia pestis become active at 37 C. J. P. Fitch and B.
Sokhansanj, in Proc. of IEEE, Vol. 88, No. 12, pp. 1949-1971,
(2000), the entire contents of which are incorporated herein by
reference, have shown that some Yersinia pestis genes are expressed
more at 37 C than 25 C while others are expressed more at 25 C than
at 37 C. Temperature control studies can be accomplished in one
step using a spatially-temperature-controlled electro-thermal chip
of the present invention. Rapid heating of small volumes using IR
radiation has been utilized in DNA amplification in polymerase
chain reaction (PCR), see for example IR-Mediated PCR,
http://faculty.virginia.edu/landers/project.htm, the entire
contents of which are incorporated herein by reference. IR-mediated
heating has also been studied in enzyme assays.
[0066] Thus, in another embodiment of the present invention, an
electro-thermal PCR chip of the present invention is utilized to
locally heat or cool DNA sample. The electro-thermal PCR chip can
control the temperature more locally than techniques which rely on
volumetric heating techniques, e.g. IR radiant heating. In one
embodiment of the present invention, the electro-thermal PCR chip
replaces photochemistry with localized thermochemistry.
[0067] As previously noted, some Yersinia pestis genes were
expressed more at 37.degree. C. than 25.degree. C. while other
genes expressed more at 25.degree. C. than at 37.degree. C. A gene
is expressed when the gene acts as a site to make a distinctive
protein, leading to a biological activity like virulence. DNA
microarrays have been powerful templates for understanding patterns
of gene expressions. Similarly, the strength of a gene's expression
depends on how much of the distinctive proteins are made. Thus,
weak genes may be transformed into strong genes, by local
thermochemistry control. Temperature control for gene expression
studies can be easily accomplished in one step using the
spatially-temperature-controlled electro-thermal genomic hip of the
present invention.
[0068] Along the same lines, it may be possible to convert with
temperature control native genes of an individual that would
normally not be able to fight certain bacterial infections to genes
which can be chemically alert, thus resistant to bacterial
infections. Once the converted gene has been expressed, the
subsequent antibodies, i.e. the byproducts of the electro-thermal
chip, can be "safely" transferred to the individual.
[0069] While conventional DNA microarrays are relatively easy to
fabricate, a significant problem with many DNA array experiments is
that the hybridization is not perfect. This in turn necessitates
redundancy and thus reduces speed. Spatial temperature control
utilizing electro-thermal genomic chip represents an expedient way
to find optimal temperatures to achieve improved hybridization.
According to the present invention, electro-thermal heating/cooling
can be integrated with microchips to perform PCR on substrates such
as glass which normally inhibit hybridization reactions. The fast
response times associated with the present thin-film thermoelectric
devices are advantageous for rapid and effective thermocycling of
PCR mixtures.
[0070] The electro-thermal electrophoretic chip, electro-thermal
PCR chip, and the electro-thermal chip of the present invention are
compatible with the low-thermal conductivity silica, glass sides or
nylon membranes. As electrical insulators, these materials
integrate spot temperature control and electrical charge
control.
[0071] Also, the production of high-quality protein crystals
necessary for detailed characterization has been difficult.
Spatially-temperature-controlled electro-thermal proteomic chips of
the present invention can be used to crystallize protein crystals
by optimizing the temperature. A single chemistry process sequence,
with spatially varying temperatures, can produce a whole range of
crystals which in turn can be characterized. Structural genomics is
an effort to do high-throughput identification of the 3-D protein
structures corresponding to every gene in the genome. There are two
experimental methods for determining 3-D protein structure: NMR and
X-ray diffraction. NMR measures the coupling of atoms across
chemical bonds and short distances through space under the
influence of a magnetic field. A variable temperature NMR analysis,
of the same protein, located at various points of a
spatially-resolved electro-thermal chip of the present invention
can offer new insights into structural identification. Similarly,
variable temperature X-ray crystallography of the same protein can
be done to understand structures of various protein crystals.
[0072] In a further embodiment of the present invention, the
thermoelectric devices of the present invention are utilized in
electrophoresis applications in an array format for single-stranded
conformation polymorphism (SSCP) detection. Mass spectroscopy
studies of DNA sequence polymorphisms as well as PCR processes have
been described in U.S. Pat. No. 5,869,242, the entire contents of
which are incorporated herein by reference. Additionally, it has
been found that temperature control is particularly crucial in
applications such as SSCP where precise temperature selection allow
detection of mutations which are apparent only at specific
temperatures. Typically these temperatures can range from near 0 to
80 C, with 1 C control. By thermally coupling the thermoelectric
devices of the present invention to the SSCP array, precise
temperature control is achieved.
[0073] In another embodiment of the present invention, the
thermoelectric devices of the present invention are utilized for
precise temperature control in probes and prosthetics used for
micro-surgery and bio-tissues. Rapid and spot temperature control,
both in heating or cooling mode, is particularly useful in medical
applications such as in micro-surgery involving bio-tissues as in
brain tissues. Spot temperature control, especially in the cooling
mode without a lot of heat dissipation, using the high-performance
thermoelectric devices of the present invention would control the
temperatures of bio-tissues on a chronic basis for providing relief
against variety of ailments such as for example, epilepsy seizures
from certain regions of the brain. According to the present
invention, high-performance thermoelectric devices based on
high-performance materials, such as superlattices, leads to longer
battery life in such chronic applications and reduced parasitic
heat dissipation in nearby tissues.
[0074] Besides biological applications, in another embodiment of
the present invention, the fast response time/small area thin-film
thermoelectric devices can be used for electro-thermal optical
switching for high-speed, high-density optical communication
networks as well as for a variety of selective (individual
component controlled) cooling or heating in integrated
optoelectronic transmitters/receivers.
[0075] For example, space-division optical switches are utilized in
optical to make fiber-to-fiber interconnections. For large-scale
optical networks, a planar technology for switching is preferred.
Mechanical switches, employing mechanical moving elements such as
micro-electro-mechanical-system (MEMS) mirrors or magnets, are not
scaleable to large-scale M*N switches. In addition, repeatability,
wear-and-tear and reproducibility of moving elements in MEMS
mirrors as well as the requirement of high voltages (about 50
Volts) for operation are undesirable features.
[0076] Waveguide space-division switches can realize large-scale
N*N switches. Typically, the switching function is achieved by
controlling the refractive indices of the waveguide elements. The
physical mechanism used to control the refractive indices of these
waveguides depend on the waveguide material. Silica planar
waveguide type switches typically employ an electrode that changes
the temperature of a waveguide by a thermo-optic effect.
Thermo-optic devices are described in U.S. Pat. No. 6,084,050, the
entire contents of which are incorporated by reference. Other
waveguide switches include semiconductor waveguide switches
controlled by current injection, and ferroelectric crystal
(LiNbO.sub.3)-based switches, controlled by an applied electric
field. Although semiconductor-based switches and LiNbO.sub.3-based
switches can achieve high switching speeds (switching time about
10.sup.-9 sec), it is difficult to realize polarization independent
switches with these technologies.
[0077] Silica planar waveguide switches employ a Mach-Zender type
interferometer as basic switching elements. For example, a
thermo-optic phase-shifter in an interferometer changes the
propagation delay in the interferometer. Although the response time
of conventional thermo-optic switches is of the order of a ms,
thermo-optic switches offer many advantages such as polarization
independence and stability against environmental changes. By
combining thermo-optic switches into a 2*2 array, a large scale
matrix optical switch can be realized, as long as the switch
elements are loss-free and 100% of the input power is transferred
to desired output ports. However, in real switching elements,
several problems arise including loss imbalance among the output
ports and cross-talk. Typically, dummy switches are employed for
overcoming such effects.
[0078] According to the present invention, Mach-Zender
interferometer switches can utilize the fast response time/small
area thin-film thermoelectric devices of the present invention to
change propagation delays. Thermoelectrically heated/cooled
thin-film thermoelements are attached, according to the present
invention, to silica waveguides to obtain the necessary switching
function. The waveguide switches can be cross-connected waveguides.
Each section of the waveguide can be heated or cooled so as to
change the refractive index, affecting the optical pathlength, and
thus determining whether constructive or destructive interference
occurs. The thin-film thermoelectric elements of the present
invention can switch in tens of .mu.s (see FIG. 5) or even smaller.
Two to three orders of improvement in speed with electro-thermal
Mach-Zender optical switches coupled to the thermoelectric coolers
of the present invention are expected as compared to conventional
thermo-optical switches. For example, the reversibility of
temperature (with reversal of current) with thin-film
thermoelectric devices of the present invention can be used
advantageously in a "quenching" mode to further increase the speed
of a waveguide switching element of the present invention.
[0079] Furthermore, simultaneous heating (in one interferometer
leg) and cooling (in the other interferometer leg) will, according
to the present invention, enhance the differential gain in the
switching efficiency. These dual-temperature electro-thermal
Mach-Zender optical switches will considerably reduce the number of
dummy switches typically employed. This reduction leads to reduced
losses and therefore a reduced need for periodic fiber
amplification.
[0080] The thin-film fast response time/small area thermoelectric
cooling/heating devices of the present invention can be combined
with polymeric optical waveguide switches as well. Fluorinated
polymers have large thermo-optic coefficients. The combination of
such large coefficients with the ability to obtain both heating and
cooling with thin-film thermoelectric devices can, according to the
present invention, produce low-loss, large, planar switching
networks. Thin-film thermoelectrically controlled thermo-optical
switches can be operated as electro-thermal optical switching
networks, offering advantages such as low insertion loss,
polarization insensitive operation, long-term solid-state
reliability, and suitability for large-scale integration.
[0081] Large scale switches require large refractive index changes
at the switching element. This requirement means that temperature
excursions beyond the average room temperature excursions must be
realized before a switching phenomena can be distinguished from
noise due to room temperature variations. Heating, as in
conventional thermo-optic switches, is not an attractive way to
implement such large temperature excursions since large heating
temperatures are not desirable for other components in the
integrated optical system. However, a combination of cooling and
heating, simultaneously, can achieve larger temperature
differentials. For example, with a thermo-optic coefficient of
dn/dT of about 1e-4 K.sup.-1, as in the polymeric waveguides,
approximately 75 C of heating (implying about 100 C hot point if
room temperature is 25 C) is necessary to obtain 0.75% refractive
index difference waveguides (i.e. 0.75%-D waveguide). This 0.75%-D
waveguides can be used for a 8*8 switching matrix. For about the
same reliability and performance-loss, a 16*16 matrix with a 1.5%-D
waveguides is necessary. This would imply, for a dn/dT of about
1e-4 K.sup.-1, a hot point of 175 C with a reference point of 25 C.
However, if simultaneous heating and cooling were used to create a
large temperature differentials, a lower "hot" points would be
realized. For example, for a 0.75%-D waveguide with a 50 C hot
point and -25 C cold point could be employed using the anywhere
anytime thermoelectric cooling/heating devices of the present
invention. Similarly, for a 1.5%-D waveguide, a 100 C hot point and
-50 C cold point could be employed using the anywhere anytime
thermoelectric cooling/heating devices of the present invention. A
greater than 1.5%-D waveguides can be realize utilizing a
combination cooling/heating thermoelectric device to create at
least a 16*16 switching matrix. The use of "lower" absolute hot
temperatures, for the same induced refractive index change, avoids
high-temperature deterioration of polymeric materials, thus opening
up the range of electro-optic materials which can be used in this
application.
[0082] In another embodiment the fast response time/small area
thermoelectric cooling/heating thin-film technology of the present
invention is applied to optoelectronic circuitry. One technology
enabler for all-optical networking is a component known as a
multi-wavelength substrate. Otherwise, extensive
wavelength-selective routing and add/drop capabilities are needed
to provide rigid capabilities and thus costly implementations.
[0083] The ability to design and deploy an optical network layer
hierarchy has been limited by the conventional process in which all
lasers on a wafer have the same emission wavelength and lasing
characteristics. One approach is to manufacture on a single wafer
diode lasers (e.g. distributed feedback DFB lasers) with different
emission wavelengths within a gain bandwidth of 1530 nm to 1560 nm
of the erbium doped fiber amplifier, and to control the grating
pitch to increments of less than 0.01 nm. The control of the
grating pitch can be enormously relaxed, leading to greater device
yields, if temperature variations (using electro-thermal spot
cooling/heating control) is combined with grating control.
Temperature variations change the bandgap of the lasing
semiconductor material in the active region of the laser, which in
turn controls the lasing wavelength. For example, 30K heating or
cooling from ambient can change the wavelength by about 15 nm.
Thus, a change from 30K cooling to 30K heating, will produce a 30
nm wavelength shift. Thus, a multi-wavelength hybrid
electro-thermal-spot-temperature-controlled DFB lasers for
multi-wavelengths laser applications is realized by the present
invention and permits active wavelength shifting.
[0084] Vertical-cavity surface-emitting lasers (VCSELs) are well
suited for optoelectronic applications due to the fact that the
well-confirmed circular surface emission is compatible with
easy/efficient coupling to optical fibers as well as that the
devices can be pre-tested at the wafer level before packaging.
VCSEL and VCSEL-based devices are described in U.S. Pat. No.
6,154,479, the entire contents of which are incorporated herein by
reference. VCSELs are compatible with wafer-scale manufacturing.
Here again, electro-thermal spot cooling/heating control can be
employed to thereby control the bandgap of the active lasing
material, to produce multiple wavelengths. Thus, multiple
wavelength electro-thermal spot-temperature-controlled lasers are
realized by the multi-wavelength
electro-thermal-spot-temperature-controlled VCSELs of the present
invention. Large-area VECSEL devices are about 0.01 to 0.02
cm.sup.2. Spot cooling of such devices can be accommodated by the
thermoelectronic devices of the present invention.
[0085] Another technology enabler for all-optical networking is the
ability to wavelength translate for payload transparency demanded
by carriers on optical networks. The multi-wavelength hybrid
electro-thermal-spot-temperature-controlled DFB lasers and the
multi-wavelength electro-thermal-spot-temperature-controlled VCSELs
of the present invention will, along with the electro-thermal spot
heating/cooling of Mach-Zender optical switches, attenuators, and
filters enable flexibility in wavelength operation and wavelength
shifting operations. The integration of optical components
including DFB lasers into optical switching networks have been
described in U.S. Pat. No. 6,072,925, the entire contents of which
are incorporated herein by reference.
[0086] In another embodiment of the present invention, the
thermoelectric devices of the present invention are thermally in
contact with thermocapillary optical switches enabling operation of
high-speed thermocapillary switches. Thermocapillary switches seal
fluid with a bubble in a slit. Thermocapillary and bubble switches
have been described in U.S. Pat. No. 6,062,681, the entire contents
of which are incorporated herein by reference. Typically heaters at
either end of the slit shift the bubble in the fluid from side to
side away from the heat source to manipulate the optical path, thus
achieving an optical gate. By replacing the passive micro-heaters
with the active thermoelectric devices of the present invention
(which can be reversibly cooled by switching the current
direction), the switching speed is enhanced. The augmentation of
such a slit with spot cooling and the fast response thermoelectric
devices of the present invention enhances the switching efficiency,
leading to lower optical loss. Thus, high speed thermocapillary
switches can utilize a higher number of ports than what is
available today with the same optical loss. With reduced optical
loss, the high-speed thermocapillary switches of the present
invention are applicable to be used other than just as protection
switches which route traffic around network disruptions.
[0087] In another embodiment of the present invention, the
thermoelectric devices of the present invention are thermally in
contact with bubblejet optical switches, thus enabling operation of
high-speed bubblejet switches. Bubblejet switches involve a small
hole at each intersection of a waveguide, filled with a fluid that
has an index of refraction identical to that of the waveguide.
Consequently, light traverses each intersection as though no trench
was there. However, by micro-heating the fluid, a small bubble
forms in the intersection and diverts optical signals down another
path. By replacing the passive micro-heaters with the active
thermoelectric devices of the present invention (which can be
reversibly cooled by switching the current direction), the
switching speed is enhanced. The augmentation of such a waveguide
suitably with spot cooling and heating can enhance the switching
efficiency, leading to less optical loss.
[0088] In a further embodiment, a 3-substrate sandwich which
monolithically integrates a "middle-wafer" VCSEL chip with
electro-thermal spot cooling/heating thin-film thermoelectric chip
on one side for wavelength selection/control and another
electro-thermal spot cooling/heating thin-film thermoelectric chip
on the other side for directional coupling/switching/attenuation
functions can be realized by the present invention.
[0089] In still another embodiment, the electro-thermal spot
cooling/heating thermoelectric technology of the present invention
can, according to the present invention be integrated with
optoelectronic modules. For example, a typical VCSEL-based
transceiver module has a bias circuit, laser driver, monitor
diodes, VCSEL arrays, out-going optical connectors, in-coming
optical connectors, photodetectors, pre-amplification circuits, and
post-amplification circuits. Using electro-thermal spot
cooling/heating chip of the present invention, it is possible to
individually optimize the performance of many of these components
on a chip.
[0090] In another embodiment of the present invention, high-speed
spot temperature control of the thermoelectric devices of the
present invention is thermally coupled to an electroholographic
optical switch. The electroholographic optical switch, according to
the present invention, can include Potassium Lithium Tantalate
Niobate (KLTN) crystals in packet-switching optical networks.
Typically, KLTN crystals have dimensions of about 2 mm*2 mm*1.5 mm.
Conventional bulk thermoelectric technology is not well suited to
achieve cooling in such small crystals. R. Hofineister et. al.,
Physical Review Letters, vol. 69, pp. 1459-1462, (1992), the entire
contents of which are herein incorporated by reference, have shown
that KLTN crystals can be cooled to temperatures around -23 C to
enhance the quadratic electro-optic effect, the basis for
electroholographic optical switching. The quadratic electro-optic
effect dramatically increases as a ferroelectric-paraelectric
transition temperature of -23 C is approached. Cooling of KLTN
crystals to achieve higher diffraction efficiency or electro-optic
efficiency in electroholographic optical switches can reduce the
need for large voltages in switching networks. For example, in KLTN
crystals, for the same quadratic electro-optic effect leading to a
diffraction efficiency of 5%, an electric field of nearly 1500 V/cm
is required at 21 C whereas an electric field of only 250 V/cm at
-15 C. Thus, for a given crystal of thickness 1.5 mm, the DC
voltage needed to provide the electric field would drop from around
225 V to approximately 38V. According to the present invention,
spot-cooling KLTN crystals, with areas such as for example of a 0.1
mm*0.1 mm size, allows smaller voltages to be used for producing
the requisite electric field. Smaller voltages are attractive from
a system implementation point-of-view.
[0091] Furthermore, thermal expansion effects complicate the
storage of volume holograms, stored as spatial distributions of
space charge. Temperature stabilization of KLTN crystals in
electroholographic optical switches the thermoelectric cooling
technology of the present invention enables high-resolution (i.e.,
the smallest) spacing of the various wavelengths that are switched
by the KLTN crystals. The higher the resolution of this spacing,
the larger the number of wavelengths that can be precisely switched
in dense wavelength division multiplexing (DWDM) networks.
Similarly, according to the present invention, temperature control
is utilized to vary a spatial distribution of space charge, thereby
tuning the holographic grating to a particular wavelength. Thus,
the same physical grating, with variable temperature control
offered by the thermoelectric cooling technology of the present
invention, allows wavelength translation needed for payload
transparency in DWDM optical networks. FIG. 15 is a schematic
depiction of a multiple wavelength VCSEL array 1502 located on a
thermoelectric device 1504 of the present invention. FIG. 16 is a
schematic depiction of an elecrto-holographic router switching
matrix 1602 located on the thermoelectric device 1604 of the
present invention.
[0092] In yet a further embodiment of the present invention, the
small area/fast response time of the thermoelectric devices of the
present invention are utilized to control other electro-optic
crystals operating in the paraelectric regime.
[0093] In another embodiment of the present invention, the small
area/fast response time of the thermoelectric devices of the
present invention are utilized in an electronics module to
selectively cool or control the temperature of discrete module
components, such as for example diodes, capacitors, inductors,
filter networks, memory chips, or CPU chips on the electronic
module.
[0094] In still a further embodiment, the fast response time/small
area thin-film thermoelectric cooling devices of the present
invention can be used as identification tags for military
personnel, military systems, and even commercial systems that are
scanned by IR-imaging devices. The fast response time/small area
cooling devices can be arranged in a particular order (as shown in
FIG. 2) to produce fast response time IR-tags. These IR-tags can be
made to be powered only when a signal is received. These tags,
which are based on localized hot or cold spots (as shown in FIG. 2)
are, according to the present invention, amenable for digitizing,
encryption, and safe electronic transmission.
[0095] In another embodiment of the present invention, the
fast-response thermoelectric devices of the present invention are
utilized in applications for cell and molecular engineering. As
such, the thermoelectric devices of the present invention provide
precise temperature control in probes and prosthetics used for
microsurgery and bio-tissues probes. Specific designs to implement
spot cooling or heating towards cell and molecular levels, with
respect to their dimensions and control, are shown for exemplary
purposes below. In addition, specific application examples of the
present invention are illustrated.
[0096] FIG. 11 is a schematic depiction of a thermoelectric probe
1102 of the present invention locally contacting a single cell 1104
of a specimen 1106. Shown in FIG. 11 is an example of a cell about
50 .mu.m in size. The ability to obtain spot cooling or heating, at
flux levels in a preferred range of 0.1 to 2000 W/cm.sup.2 enabled
by the present invention, can be used to keep certain regions such
for example the nucleus of the cell "cool" or "hot", while
engineering of other cell areas. Similarly, the other parts of the
cell can be kept cool or hot when the chemistry of the nucleus is
manipulated with a hypodermic needle.
[0097] A thermoelectric module 1200 of the present invention
thermally contacts specific spots of the cell nucleus using for
example a spring coil as a cantilever, and the cooling/heating
module cools or heats those specific spots of the cell. FIG. 12 is
a schematic of a nano-scale thermal transducer 1202 of the present
invention employing a cantilever 1204 contacting a single cell
1104. With the cantilever set up, a tip 1206 approaching very small
dimensions in the range of nanometers is a highly flexible stylus
exerting a lower downward force on delicate cell parts, resulting
in less distortion and cell damage. A tube 1208 can provide
constituents to the cell 1106 to induce chemical or biological
reactions with the specimen 1106.
[0098] The cantilever of the present invention is similar to
arrangements known in the art for atomic force microscopy (AFM).
The cantilevers of the present invention have spring constants of
about 0.1 N/m, lower than a spring constant of 1 N/m. The
integration of a thermoelectric cooling/heating device or module
with a cantilever, especially the cantilevers similar to those used
in AFM, provides according to the present invention for
"nanometer-size temperature control" of bio-tissues, cells, and
perhaps other atomic-scale structures in nano technology such as
for example nano-self-assembly.
[0099] The resonant frequency of a spring is given by: 1 F r e q u
e n c y=12 K M,
[0100] where K is the spring constant and M is the mass of the
spring.
[0101] Thus in contrast to AFM images, where low mass is also
required (in addition to low spring constant) to keep the resonant
frequency high for high speed imaging, in nano-thermal transducers
(or probes) of the present invention, a higher mass spring may be
tolerable,- if not used in a scanning mode.
[0102] In addition to spot cooling or heating of certain intra-cell
features, the nano-thermal transducers of the present invention can
be utilized for manipulation of individual DNA strains and other
molecules, such as large molecular strands of sugar, proteins, etc.
These nano-thermal transducers can control reaction chemistries and
hence biological processes of both large scale and small scale
molecular structures such as for example controlling the reactions
of sugar and proteins by controlling the reaction chemistry of
reaction mediators (such as for example ribo-nucleic acid RNA),
thereby leading to alternate approaches to genetic engineering.
[0103] The present invention also permits the study of molecular
level calorimetry. In this embodiment of the present invention, the
heat of the reaction is transmitted through a nano-thermal
transducer, in an adiabatic system, and applied as a thermal load
onto a thermoelectric (TE) device. For a fixed current through the
TE device, the extra thermal load reduces the differential
temperature (.DELTA.T) that exists across the TE device by a
certain quantity. A reduction in the differential temperature
(.DELTA.T) translates into a reduction in the Peltier component
voltage across the device.
[0104] The molecular reaction proceeds over a certain time period.
The faster the voltage of the TE device can be measured, the more
sensitive the TE device will be. This requires smaller
thermoelectric element areas because, for a fixed heat flux from
the reaction, more .DELTA.T will be generated with a smaller-size
thermoelement, allowing as shown below for sensitivities
approaching the heat liberated by a single molecular reaction.
[0105] FIG. 13 is a schematic diagram depicting a nano scale
thermal transducer of the present invention employing a nano-scale
cantilever 1302 contacting specific spots of large molecular
structures such as a hybridized DNA pair 1304. Materials needed for
the nano-thermal transducer (i.e. the cantilever) include materials
with high thermal conductivity and a low thermal emissivity;
perhaps diamond-like materials can be considered as well. For
example, thermal conductivities in the range of 0.75 to 20 W/cm-K,
and emissivities<0.3 are preferred in the nano scale thermal
transducers.
[0106] The spring constant is a function of frequency response
required. For example, for molecular calorimetry with high spatial
resolution as well a scanning mode calorimeter, low spring constant
materials in addition to low density materials are utilized. For
example, low density materials (i.e. less than 3.0 gm/cm.sup.3)
like diamond (e.g., 2.25 g/cm.sup.3) or aluminum (e.g., 2.7
g/cm.sup.3) are preferred for the present invention.
[0107] An example of nano-scale thermal control, in the attachment
of a molecular fragment, at the tip of the hybridized DNA pair is
shown schematically in FIG. 14 below. FIG. 14 is a schematic
depicting an apparatus of the present invention for detecting the
heat released from a small-scale region. The apparatus is similar
to the apparatus in FIG. 13, but includes a constant current power
supply configured to deliver a constant current to the
thermoelectric module 1200. The sample or specimen depicted in FIG.
14 is an organic, biological sample. However, the present invention
is applicable to calorimetric determination of heat released from
inorganic samples as well as other devices that locally generate or
dissipate heat.
[0108] The ability to control temperature at a nanoscale or
molecular level using a combination of high-power density (or high
power flux) thin-film thermoelectric devices (as a heat pump) and
AFM tip-like nanothermal transducers enables, according to the
present invention, the measurement of heat of reactions at the
nanoscale or molecular level or small geometries (volume).
[0109] A total voltage VT across the thermoelectric device of FIG.
14 is given by: [0110] V.sub.T is approximately equal to
V.sub.R+V.sub.O,
[0111] where V.sub.T is the total voltage measured, V.sub.R is the
ohmic component and V.sub.O is the Peltier component. [0112] Also,
V.sub.T is approximately equal to IR+.alpha..sub.eff.DELTA.T,
[0113] where R is the "Ohmic" resistance of the thermoelectric
module, I is a constant current supplied through the thermoelectric
device, .alpha..sub.eff is the effective Seebeck coefficient of the
thermoelectric module. For example, a module including m `p`
elements and including m `n` elements, each with an .alpha..sub.p
and an .alpha..sub.n respectively, will have:
.alpha..sub.eff.apprxeq.m(.alpha..sub.p+.alpha..sub.n). [0114]
Combining these equations,
(V.sub.T.about.IR)=.alpha..sub.eff.DELTA.T=V.sub.O
[0115] Thus, from the above equation, by measuring V.sub.T, knowing
I, knowing R, and knowing .alpha..sub.eff, .DELTA.T is derived. R
and .alpha..sub.eff of the thermoelectric module can be measured
independently by standard techniques to compensate for temperature
variations in the known values. Thus,
.DELTA.T=(V.sub.T.about.IR)/.alpha..sub.eff. (5)
[0116] From energy balance considerations, the heat flow Q is given
by: Q=.pi.I-1/2I.sup.2R-K.DELTA.T, (6)
[0117] where .pi. is the Peltier coefficient of the module and K is
the thermal conductance of the module, given by k (a/l).sub.eff
with k being the thermal conductivity and (a/l).sub.eff being the
effective aspect ratio of the width a to the length 1 of the
thermoelectric device. From equations (5) and (6), knowing k and by
measuring .DELTA.T (and hence V.sub.T), Q can also be derived.
[0118] Thus, Q can be the heat released per unit time from the
reaction zone as shown in FIG. 14. Note that there are always heat
losses. Furthermore, according to the present invention,
differential calorimetry can be used to derive Q.
[0119] Assume a first steady state condition, with a detectable
heat load on the cantilever probe from a background Q.sub.1 heat
flux: .DELTA.T.sub.1=(V.sub.T1--IR)/.alpha..sub.eff
Q.sub.1=.pi.I-1/2I.sup.2R-K.DELTA.T.sub.1
[0120] Assume a steady state heat load plus heat of reaction per
unit time: .DELTA.T.sub.2=(V.sub.T.sub.2-IR)/.alpha..sub.eff.
Q.sub.2=.pi.I-1/2I.sup.2R-K.DELTA.T.sub.2
[0121] By measuring V.sub.T1 and V.sub.T2, for a specific current I
and assuming .pi., k, .alpha..sub.eff, R do not change
significantly with small temperature changes, the heat of reaction
is derived as follows:
[0122] Assuming the reaction is exothermic, and adiabatic
condition, all the heat will be released at the nano-thermal
transducer. Thus, for a constant current I through the
thermoelectric module, AT across the module should decrease with an
external heat load. Thus,
.DELTA.T1-.DELTA.T2.apprxeq.{(V.sub.T1-IR)/.DELTA..sub.eff]}-{(V.sub.T2-I-
R)/.alpha..sub.eff}=(V.sub.T1--V.sub.T2)/.alpha..sub.eff
[0123] Q2-Q, defined as the heat of reaction `Q.sub.0` is:
.apprxeq.K.DELTA.T.sub.2+K.DELTA.T.sub.1 .apprxeq.K
(.DELTA.T.sub.1-K.DELTA.T.sub.2) .apprxeq.K
(V.sub.T1-V.sub.T2)/.alpha..sub.eff
[0124] Therefore, Q.sub.0, the heat of an exothermic reactor
produced at A, measured by a differential voltage at the
thermoelectric module measured in Watts or Joule/sec is K
(V.sub.T1-V.sub.T2)/.alpha..sub.eff.
[0125] A smaller K, a larger .alpha..sub.eff, and a smaller
V.sub.T1-V.sub.T2 allows the measured Q.sub.0 to be smaller; i.e.,
the smaller K, the larger the .alpha..sub.eff, and the smaller the
[V.sub.T1--V.sub.T2] the more precisely Q.sub.0 can be
measured.
[0126] For example, to measure the standard "heat of reaction" in
Joules or calories, one must integrate as a function of time.
J.sub.o=Energy released in the reaction=the integral from t=0 to
t=.varies.of Qodt
[0127] Typically, a reaction persisting over three to five times
constants (t.sub.R) can produce a change of V.sub.T during that
period.
Thus, J.sub.o the integral from t=0 to t=5tr of Qodt
[0128] The fast time response of the thin-film thermoelectric
device of the present invention allows an accurate determination of
Jo, the total heat of reaction. Also a fast time response of the
thin-film module allows the thermoelectric device of the present
invention to study a time dependent response of reactions.
[0129] If k is the thermal conductivity, and is, for example, 10
mW/cm-K: a/1=2*10.sup.-3,
[0130] assuming 5 .mu.m thick film and area of device as 10
.mu.m*10 .mu.m
[0131] .alpha..sub.eff=500 .mu.V/K for 1 p and 1 n element,
[0132] assuming an accuracy of .DELTA.V.sub.T=1 .mu.V; the accuracy
of Q.sub.0 is 4*10.sup.-8W. For 3t.sub.R.apprxeq.50 .mu.sec, then
an estimate of J.sub.o is 100*10.sup.-4 Joules or about 1 pJ. Note
that more p and n elements can increase the .alpha..sub.eff and
therefore increase the sensitivity of the measured Q.sub.o.
[0133] For a 1 .mu.m*1 .mu.m thermoelectric element, an accuracy of
.DELTA.V.sub.T of 1 nV, and advanced noise-reduction techniques,
and digital-signal processing, according to the present invention,
an estimate a lower limit of a measurable Jo is 1*10.sup.-17 Joules
or 1/100.sup.th of a femtojoule.
[0134] In comparison to the heat released by each molecule during a
reaction: Assume a heat of reaction=150 Kcal/mole. =150*1000* 4.18
Joules/mole J.sub.molecule.apprxeq.1*10.sup.-18 Joules/molecule
[0135] Thus, one anticipates a lower limit of the measured heat of
reaction constitutes a reaction of only about 10 molecules from the
fact that Jo is 1*10.sup.-17 Joules.
[0136] Further, a 0.5 .mu.m*0.5 .mu.m thermoelement able to measure
0.1 nV can reduce 3t.sub.R to about 30 .mu.sec. Consequently,
Jo.sub.easuale.apprxeq.1*10.sup.-17* [(1 .mu.m*1 .mu.m)/(0.5
.mu.m*0.5 .mu.m)].sup.-1*(0.1nV/1nV)*(30 .mu.sec/50
.mu.sec).apprxeq.1.5*10.sup.-19 Joules
[0137] Thus, with such a small scale thermolement, the sensitivity
would easily allow for the measuring the heat flux generated by the
reaction of approximately 1 molecule, assuming a 150 kcal/mole
reaction or perhaps as low as 22.5 Kcal/mole. Even lower heat of
reactions of each molecule are perhaps measurable with larger
.alpha..sub.eff and/or larger number of thermoelectric elements
and/or better sensitive set-up.
[0138] Numerous modifications and variations of the present
invention are possible in light of the above teachings. It is
therefore to be understood that within the scope of the appended
claims, the invention may be practiced otherwise than as
specifically described herein.
* * * * *
References