U.S. patent application number 17/744126 was filed with the patent office on 2022-09-01 for sensor and device for lifetime imaging and detection applications.
This patent application is currently assigned to Tesseract Health, Inc.. The applicant listed for this patent is Tesseract Health, Inc.. Invention is credited to David Boisvert, Keith G. Fife, Jonathan M. Rothberg.
Application Number | 20220273174 17/744126 |
Document ID | / |
Family ID | 1000006333507 |
Filed Date | 2022-09-01 |
United States Patent
Application |
20220273174 |
Kind Code |
A1 |
Rothberg; Jonathan M. ; et
al. |
September 1, 2022 |
SENSOR AND DEVICE FOR LIFETIME IMAGING AND DETECTION
APPLICATIONS
Abstract
A method of luminance lifetime imaging includes receiving
incident photons at an integrated photodetector from luminescent
molecules. The incident photons being received through one or more
optical components of a point-of-care device. The method also
includes detecting arrival times of the incident photons using the
integrated photodetector. A method of analyzing blood glucose
includes detecting luminance lifetime characteristics of tissue
using, at least in part, an integrated circuit that detects arrival
times of incident photons from the tissue. The method also includes
analyzing blood glucose based upon the luminance lifetime
characteristics.
Inventors: |
Rothberg; Jonathan M.;
(Miami Beach, FL) ; Fife; Keith G.; (Palo Alto,
CA) ; Boisvert; David; (San Jose, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Tesseract Health, Inc. |
Guilford |
CT |
US |
|
|
Assignee: |
Tesseract Health, Inc.
Guilford
CT
|
Family ID: |
1000006333507 |
Appl. No.: |
17/744126 |
Filed: |
May 13, 2022 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
16550841 |
Aug 26, 2019 |
11344200 |
|
|
17744126 |
|
|
|
|
62296546 |
Feb 17, 2016 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/0071 20130101;
A61B 5/14552 20130101; A61B 5/14542 20130101; A61B 2562/0233
20130101; G01N 21/6408 20130101; G01N 21/6486 20130101; A61B
5/14532 20130101; A61B 5/444 20130101; A61B 5/1455 20130101 |
International
Class: |
A61B 5/00 20060101
A61B005/00; A61B 5/1455 20060101 A61B005/1455; A61B 5/145 20060101
A61B005/145; G01N 21/64 20060101 G01N021/64 |
Claims
1. An eye imaging and/or measuring device comprising: an integrated
photodetector comprising: a photodetection region configured to, in
response to receiving incident photons from and/or reflected by a
subject's eye, generate charge carriers; a charge carrier storage
region electrically coupled to the photodetection region by a
charge carrier travel region; a first electrode configured to:
receive, from a control circuit, a first signal; establish, in
response to receiving the first signal, in the charge carrier
travel region, an electric potential allowing the charge carriers
to travel, in the charge carrier travel region, from the
photodetection region toward the charge carrier storage region;
receive, from the control circuit, a second signal; and produce, in
response to receiving the second signal, in the charge carrier
travel region, a potential barrier; and a second electrode
configured to: receive, from the control circuit, a third signal;
produce, in response to receiving the third signal, a potential
barrier, wherein the first and second electrodes are positioned
such that, when the first electrode receives the second signal and
the second electrode receives the third signal, the potential
barriers confine at least some of the charge carriers between the
first and second electrodes.
2. The eye imaging and/or measuring device of claim 1, wherein the
charge carrier storage region is positioned such that, when the
potential barrier confines charge carriers between the first and
second electrodes, the charge carriers are stored in the charge
carrier storage region.
3. The eye imaging and/or measuring device of claim 1, wherein the
photodetection region has an electric field established therein to
force the charge carriers toward the charge carrier storage region
via the charge carrier travel region.
4. The eye imaging and/or measuring device of claim 1, wherein the
photodetection region has a spatially graded doping profile.
5. The eye imaging and/or measuring device of claim 1, further
configured to establish a potential gradient from the
photodetection region toward the at least one charge carrier
storage region.
6. The eye imaging and/or measuring device of claim 1, further
comprising an excitation light source configured to illuminate the
subject's eye to cause emission of the incident photons toward the
integrated photodetector, wherein charge carriers are aggregated in
the at least one charge carrier storage region over a course of a
plurality of excitations of the excitation light source.
7. The eye imaging and/or measuring device of claim 2, wherein the
integrated photodetector further comprises: a second charge carrier
storage region electrically coupled to the photodetection region by
a charge carrier travel region; a third electrode configured to:
receive, from a control circuit, a fourth signal; establish, in
response to receiving the fourth signal, in the charge carrier
travel region, an electric potential allowing the charge carriers
to travel, in the charge carrier travel region, from the
photodetection region toward the second charge carrier storage
region; receive, from the control circuit, a fifth signal; and
produce, in response to receiving the fifth signal, in the charge
carrier travel region, a potential barrier; and a fourth electrode
configured to: receive, from the control circuit, a sixth signal;
produce, in response to receiving the sixth signal, a potential
barrier, wherein the third and fourth electrodes are positioned
such that, when the third electrode receives the fifth signal and
the fourth electrode receives the sixth signal, the potential
barriers confine the charge carriers between the third and fourth
electrodes.
8. The eye imaging and/or measuring device of claim 7, wherein the
second charge carrier storage region is positioned such that, when
the potential barrier confines the charge carriers between the
third and fourth electrodes, the charge carriers are stored in the
second charge carrier storage region.
9. An eye imaging and/or measuring device, comprising: an
integrated photodetector, comprising: a photodetection region
configured to, in response to receiving incident photons from
and/or reflected by a subject's eye, generate charge carriers; a
first electrode; a second electrode; and a charge carrier storage
region positioned between the first and second electrodes; and a
processor configured to: provide, to the first electrode, at a
first predetermined incident photon arrival time, a first signal,
the first signal establishing an electric potential that allows the
charge carriers to travel from the photodetection region toward the
charge carrier storage region; provide, to the first and second
electrodes, at a second predetermined incident photon arrival time,
second signals, the second signals producing potential barriers
that confine at least some of the charge carriers between the first
and second electrodes for storing in the charge carrier storage
region.
10. The eye imaging and/or measuring device of claim 9, wherein the
processor is further configured to associate, based on the first
and second predetermined incident photon arrival times, a number of
the charge carriers stored in the charge carrier storage region
with fluorescence lifetime information.
11. The eye imaging and/or measuring device of claim 9, wherein the
photodetection region has an electric field established therein to
force the charge carriers toward the charge carrier storage
region.
12. The eye imaging and/or measuring device of claim 9, wherein the
photodetection region has a spatially graded doping profile.
13. The eye imaging and/or measuring device of claim 9, further
configured to establish a potential gradient from the
photodetection region toward the at least one charge carrier
storage region.
14. The eye imaging and/or measuring device of claim 9, further
comprising an excitation light source configured to illuminate the
subject's eye to cause emission of the incident photons toward the
integrated photodetector, wherein charge carriers are aggregated in
the at least one charge carrier storage region over a course of a
plurality of excitations of the excitation light source.
15. The eye imaging and/or measuring device of claim 10, wherein:
the integrated photodetector further comprises: a third electrode;
a fourth electrode; and a second charge carrier storage region
positioned between the third and fourth electrodes; and the
processor is further configured to: provide, to the third
electrode, at a third predetermined incident photon arrival time, a
third signal, the third signal establishing an electric potential
that allows the charge carriers to travel from the photodetection
region toward the second charge carrier storage region; provide, to
the third and fourth electrodes, at a fourth predetermined incident
photon arrival time, fourth signals, the fourth signals producing
potential barriers that confine at least some of the charge
carriers between the third and fourth electrodes for storing in the
second charge carrier storage region.
16. The eye imaging and/or measuring device of claim 15, wherein
the third and fourth predetermined incident photon times associate
the charge carriers stored in the second charge carrier storage
region with second fluorescence lifetime information.
17. The eye imaging and/or measuring device of claim 9, further
comprising: an excitation light source configured to emit
excitation light; and a plurality of optical components configured
to: illuminate the subject's eye with the excitation light; receive
incident photons from the subject's eye; and provide the incident
photons to the integrated photodetector.
18. The eye imaging and/or measuring device of claim 9, wherein the
plurality of optical components comprises a dichromic mirror
configured to reflect and/or refract one of the excitation light
and the incident photons and transmit the other of the excitation
light and the incident photons.
19. A method of eye imaging and/or measuring, the method
comprising: receiving, at a photodetection region of an integrated
photodetector, incident photons from and/or reflected by a
subject's eye; generating, in the photodetection region in response
to receiving the incident photons, charge carriers; providing, by a
processor to a first electrode, at a first predetermined incident
photon arrival time, to establish an electric potential that allows
the charge carriers to travel from the photodetection region toward
a charge carrier storage region, a first signal; providing, by the
processor to the first electrode and a second electrode, at a
second predetermined incident photon arrival time, to produce
potential barriers that confine the charge carriers between the
first and second electrodes for storing in the charge carrier
storage region, second signals.
20. The method of claim 19, further comprising associating with
fluorescence lifetime information, by the processor, based on the
first and second predetermined incident photon arrival times, a
number of the charge carriers stored in the charge carrier storage
region.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a Continuation claiming the benefit of
U.S. application Ser. No. 16/550,841, filed Aug. 26, 2019, and
entitled "SENSOR AND DEVICE FOR LIFETIME IMAGING AND DETECTION
APPLICATIONS", which is a Continuation claiming the benefit of U.S.
application Ser. No. 15/435,432, filed Feb. 17, 2017, and entitled
"SENSOR AND DEVICE FOR LIFETIME IMAGING AND DETECTION
APPLICATIONS", which claims priority to U.S. Provisional
Application Ser. No. 62/296,546, filed Feb. 17, 2016, and entitled
"SENSOR AND DEVICE FOR LIFETIME IMAGING AND DETECTION
APPLICATIONS," each application of which is hereby incorporated
herein by reference in its entirety.
BACKGROUND
[0002] Photodetectors are used to detect light in a variety of
applications. Integrated photodetectors have been developed that
produce an electrical signal indicative of the intensity of
incident light. Integrated photodetectors for imaging applications
include an array of pixels to detect the intensity of light
received from across a scene. Examples of integrated photodetectors
include charge coupled devices (CCDs) and Complementary Metal Oxide
Semiconductor (CMOS) image sensors.
SUMMARY
[0003] Some embodiments relate to method of luminance lifetime
imaging. The method includes receiving incident photons at an
integrated photodetector from luminescent molecules. The incident
photons are received through one or more optical components of a
point-of-care device. The method also includes detecting arrival
times of the incident photons using the integrated
photodetector.
[0004] The method may further comprise discriminating luminance
lifetime characteristics of the luminescent molecules based on the
arrival times.
[0005] The method may further comprise producing an image using the
luminance lifetime characteristics.
[0006] The image may indicate a presence of diseased tissue based
upon the luminance lifetime characteristics.
[0007] The image may indicate a presence of melanoma, a tumor, a
bacterial infection, or a viral infection
[0008] The incident photons may be received from tissue.
[0009] The tissue may comprise skin.
[0010] The method may further comprise illuminating the tissue to
excite the luminescent molecules.
[0011] Some embodiments relate to a method that includes detecting
luminance lifetime characteristics of tissue using, at least in
part, an integrated circuit that detects arrival times of incident
photons from the tissue. The method also includes analyzing blood
glucose based upon the luminance lifetime characteristics.
[0012] The analyzing may comprise determining a blood glucose
concentration.
[0013] Some embodiments relate to a point-of-care device including
one or more optical components, an integrated photodetector
configured to receive, through the one or more optical components,
incident photons from luminescent molecules, and a processor
configured to detect arrival times of the received incident photons
at the integrated photodetector, to perform luminance lifetime
imaging.
[0014] The processor may be further configured to discriminate
luminance lifetime characteristics of the luminescent molecules
based on the arrival times.
[0015] The processor may be configured to produce an image using
the luminance lifetime characteristics.
[0016] The image may indicate a presence of diseased tissue based
upon the luminance lifetime characteristics.
[0017] The image may indicate a presence of melanoma, a tumor, a
bacterial infection, or a viral infection.
[0018] The incident photons may be received from tissue.
[0019] The tissue may comprise skin.
[0020] The point-of-care device may further comprise an excitation
light source configured to illuminate the tissue to excite the
luminescent molecules.
[0021] Some embodiments relate to a point-of-care device including
one or more optical components, an integrated photodetector
configured to receive, through the one or more optical components,
incident photons from luminescent molecules, and a processor
configured to detect luminance lifetime characteristics of tissue
by, at least in part, detecting arrival times of incident photons
from the tissue. The processor may be further configured to analyze
blood glucose based upon the luminance lifetime
characteristics.
[0022] The processor may be further configured to determine a blood
glucose concentration.
[0023] The foregoing summary is provided by way of illustration and
is not intended to be limiting.
BRIEF DESCRIPTION OF DRAWINGS
[0024] In the drawings, each identical or nearly identical
component that is illustrated in various figures is represented by
a like reference character. For purposes of clarity, not every
component may be labeled in every drawing. The drawings are not
necessarily drawn to scale, with emphasis instead being placed on
illustrating various aspects of the techniques described
herein.
[0025] FIG. 1A plots the probability of a photon being emitted as a
function of time for two molecules with different lifetimes.
[0026] FIG. 1B shows example intensity profiles over time for an
example excitation pulse (dotted line) and example fluorescence
emission (solid line).
[0027] FIG. 2A shows a diagram of a pixel of an integrated
photodetector, according to some embodiments.
[0028] FIG. 2B illustrates capturing a charge carrier at a
different point in time and space than in FIG. 2A.
[0029] FIG. 3A shows a charge carrier confinement region of a
pixel, according to some embodiments.
[0030] FIG. 3B shows the pixel of FIG. 3A with a plurality of
electrodes Vb0-Vbn, b0-bm, st1, st2, and tx0-tx3 overlying the
charge carrier confinement region of FIG. 3A.
[0031] FIG. 3C shows an embodiment in which the photon
absorption/carrier generation region includes a PN junction.
[0032] FIG. 3D shows a top view of a pixel as in FIG. 3C, with the
addition of doping characteristics.
[0033] FIG. 3E shows a top view of a pixel as in FIG. 3C, including
the carrier travel/capture area.
[0034] FIG. 3F shows an array of pixels as in FIG. 3E. FIG. 3F
indicates regions of diffusion, polysilicon, contact and metal
1.
[0035] FIG. 3G shows the pixel array of FIG. 3F and also indicates
regions of diffusion, polysilicon, contact, metal 1, N-implant,
P-implant, and P-epi.
[0036] FIG. 4 shows a circuit diagram of the pixel of FIG. 3B. The
charge carrier confinement area is shown in heavy dark lines.
[0037] FIG. 5A illustrates a potential gradient that may be
established in the charge carrier confinement area in the photon
absorption/carrier generation area and the carrier travel/capture
area along the line A-A' of FIG. 3B.
[0038] FIG. 5B shows that after a period of time a potential
barrier to electrons may be raised at a time t1 by decreasing the
voltage of electrode b0.
[0039] FIG. 5C shows that after another time period, another
potential barrier to electrons may be raised at time t2 by
decreasing the voltage of electrode b2.
[0040] FIG. 5D shows that after another time period, another
potential barrier to electrons may be raised at time t3 by
decreasing the voltage of electrode b4.
[0041] FIG. 5E shows that after another time period, another
potential barrier to electrons may be raised at time t4 by
decreasing the voltage of electrode b6.
[0042] FIG. 5F shows that after another time period, another
potential barrier to electrons may be raised at time t5 by
decreasing the voltage of electrode bm.
[0043] FIG. 6A shows the position of a carrier once it is
photogenerated.
[0044] FIG. 6B shows the position of a carrier shortly thereafter,
as it travels in the downward direction in response to the
established potential gradient.
[0045] FIG. 6C shows the position of the carrier as it reaches the
drain.
[0046] FIG. 6D shows the position of a carrier (e.g., an electron)
once it is photogenerated.
[0047] FIG. 6E shows the position of a carrier shortly thereafter,
as it travels in the downward direction in response to the
potential gradient.
[0048] FIG. 6F shows the position of the carrier as it reaches the
potential barrier after time t1.
[0049] FIG. 6G shows that if an electron arrives between electrodes
b0 and b2 between times t1 and t2, the electron will be captured
between potential barrier 501 and potential barrier 502, as
illustrated in FIG. 6G.
[0050] FIG. 6H shows an example in which an electron arrived
between times t1 and t2, so it remains captured between potential
barrier 501 and potential barrier 502.
[0051] FIG. 6I shows an example in which an electron arrived
between times t1 and t2, so it remains captured between potential
barrier 501 and potential barrier 502.
[0052] FIG. 6J shows an example in which an electron arrived
between times t1 and t2, so it remains captured between potential
barrier 501 and potential barrier 502.
[0053] FIG. 6K shows a voltage timing diagram illustrating the
voltages of electrodes b0-b8, st0 and st1 over time.
[0054] FIG. 7A shows a plot of the potential for a cross section of
the charge carrier confinement area along the line B-B' of FIG.
3B.
[0055] FIG. 7B shows that after time t5 the voltage on electrodes
b1, b3, b5 and b7 optionally may be decreased (not shown in FIG.
6K) to raise the position of an electron within the potential well,
to facilitate transferring the electron.
[0056] FIG. 7C shows that at time t6 (FIG. 6K), the voltages on
electrodes st0 and st1 may be raised.
[0057] FIG. 7D shows that at time t7, the voltage on electrode st0
may be dropped, thereby confining the captured carrier (if any) in
the corresponding bin (bin2 in this example).
[0058] FIG. 7E shows a plan view illustrating an electron captured
between potential barriers 503 and 504.
[0059] FIG. 7F shows a plan view illustrating the voltage of
electrode st1 being raised and the carrier being transferred.
[0060] FIG. 7G shows a plan view illustrating the voltage electrode
st1 being lowered and the carrier being captured in bin2.
[0061] FIG. 7H shows the characteristics of the electrodes of a
charge carrier segregation structure, according to some
embodiments.
[0062] FIG. 8A shows a flowchart of a method that includes
performing a plurality of measurements, according to some
embodiments.
[0063] FIG. 8B is a diagram showing an excitation pulse being
generated at time t0, and time bins bin0-bin3.
[0064] FIG. 8C shows a plot of the number of photons/charge
carriers in each time bin for a set of fluorescence lifetime
measurements in which the probability of a molecule decreases
exponentially over time.
[0065] FIG. 8D shows a method of operating the integrated
photodetector according to some embodiments in which light is
received at the integrated photodetector in response to a plurality
of different trigger events.
[0066] FIG. 8E illustrates voltages of the electrodes of the charge
carrier segregation structure when performing the method of FIG.
8D.
[0067] FIG. 9A shows an example of a timing diagram for
sequentially reading out bins bin0-bin3 using correlated double
sampling.
[0068] FIG. 9B shows a readout sequence for performing correlated
double sampling that does not require measuring a reset value for
each signal value, according to some embodiments.
[0069] FIG. 10A illustrates an array of pixels having a plurality
of columns C1 to Cn and a plurality of rows, with a selected row Ri
being shown by way of illustration.
[0070] FIG. 10B shows an embodiment in which a common readout
circuit may be provided for a plurality of columns.
[0071] FIG. 10C shows an embodiment with a plurality of readout
circuits, fewer than the number of columns.
[0072] FIG. 10D shows a circuit diagram illustrating column readout
circuitry which includes sample and hold circuitry, amplifier
circuitry and an analog-to-digital (A/D) converter.
[0073] FIG. 10E illustrates an embodiment of readout circuitry in
which both the amplifier circuitry and the A/D converter are shared
by two columns of the pixel array.
[0074] FIG. 10F shows an embodiment in which n columns of the pixel
array share readout circuitry and/or an A/D converter.
[0075] FIG. 10G shows an example of amplifier circuitry that
includes a plurality of amplifiers.
[0076] FIG. 10H shows a diagram of readout circuitry including
amplifier circuitry having first stage amplifiers for respective
columns and a second stage amplifier that is shared by the two
columns.
[0077] FIG. 10I shows a diagram of readout circuitry including
first-stage amplifiers, a second stage amplifier and a third stage
amplifier.
[0078] FIG. 10J shows readout circuitry shared by two columns
including a differential sample and hold circuit and a differential
amplifier.
[0079] FIG. 10K shows a diagram of the differential sample and hold
circuit and a differential amplifier when the first column is in
the sample phase and the second column is in the hold phase.
[0080] FIG. 10L shows a diagram of the differential sample and hold
circuit and a differential amplifier when the second column is in
the sample phase and the first column is in the hold phase.
[0081] FIG. 10M shows readout circuitry shared by more than two
columns including a differential sample and hold circuit and a
differential amplifier.
[0082] FIG. 11 shows the timing of the time bins may be controlled
adaptively between measurements based on the results of a set of
measurements.
[0083] FIG. 12 shows an example of a pixel that includes four
sub-pixels.
[0084] FIG. 13 shows a diagram of a chip architecture, according to
some embodiments.
[0085] FIG. 14A shows a diagram of an embodiment of a chip having a
64.times.64 array of quad pixels, according to some
embodiments.
[0086] FIG. 14B shows a diagram of an embodiment of a chip that
includes 2.times.2 arrays, with each array having 256.times.64
octal pixels array of quad pixels, according to some
embodiments.
[0087] FIG. 15A shows a perspective view of charge confinement
regions that may be formed in a semiconductor substrate.
[0088] FIG. 15B shows a plan view corresponding to FIG. 15A.
[0089] FIG. 16 shows the formation of electrodes over the
insulating layer by forming a patterned polysilicon layer.
[0090] FIG. 17 shows a split-doped electrode having a p+ region and
an n+ region.
[0091] FIG. 18 shows the formation of a metal layer (e.g., metal 1)
over the patterned polysilicon layer to connect to the vias.
[0092] FIG. 19 shows the metal layer overlaid on the polysilicon
layer and charge confinement regions.
[0093] FIG. 20 shows the formation of vias to contact the metal
layer.
[0094] FIG. 21 shows the second metal layer as well as formation of
via(s) to contact the second metal layer.
[0095] FIG. 22 shows the formation of a third metal layer.
[0096] FIG. 23 shows an example of a drive circuit for driving an
electrode of the charge carrier segregation structure, according to
some embodiments.
[0097] FIG. 24 shows an embodiment in which chip is affixed to a
printed circuit board.
[0098] FIG. 25 illustrates enabling 32 rows in a central region of
the chip and disabling 48 rows at the edges of the chip.
[0099] FIG. 26 is a block diagram of an illustrative computing
device.
[0100] FIG. 27A shows a block diagram illustrating an imaging
device imaging a patient, according to some embodiments.
[0101] FIG. 27B shows an example of a point-of-care device for
non-invasive imaging.
[0102] FIG. 27C shows an example of a point-of care device for
imaging by insertion into the body or tissue.
[0103] FIG. 28 shows an image of a patient produced at least in
part using luminance lifetime imaging.
[0104] FIG. 29 is a flowchart of a method of luminance lifetime
imaging.
[0105] FIG. 30 is a flowchart of a method of analyzing blood
glucose of tissue based on luminance lifetime characteristics
DETAILED DESCRIPTION
[0106] Aspects of the present application relate to techniques for
detecting and/or characterizing a condition of a patient by imaging
a region of the patient with an imaging device to obtain data that
can be used to evaluate and/or diagnose the patient's condition in
a non-invasive manner. By imaging an accessible region of tissue
(e.g., skin) with the imaging device rather than by extracting a
biological sample from a patient (e.g., biopsy), assessments of the
patient may be performed in a manner that reduces the amount of
time involved in obtaining results, reduces the invasiveness of a
procedure, and/or facilitates the ability of clinicians to treat
patients. The imaging device may have a configuration that improves
the ability to perform assessments at the time of the patient's
care and provide more immediate treatment to patients than other
medical testing techniques that involve physically moving the
patient to a remote testing location or sending a sample of a
patient to a testing facility. In this manner, the imaging device
may be considered a point-of-care device. In some embodiments, the
imaging device may be used to monitor a condition of a patient
(e.g., glucose detection for monitoring diabetes).
[0107] Applicants have appreciated that biological molecules
present in a patient may provide an indication of the patient's
condition. By detecting the presence and/or relative concentrations
of certain biological molecules, a patient's condition can be
evaluated. Some biological molecules may provide the ability to
differentiate healthy from diseased or unhealthy tissue of a
patient. For some biological molecules, the oxidation state of the
molecule may provide an indication of the patient's condition. By
detecting the relative amounts an oxidized state and a reduced
state of a biological molecule in the tissue of a patient, the
condition of the patient may be assessed and evaluated. Some
biological molecules (e.g., NADH) may bind to other molecules
(e.g., proteins) in a cell as well as have an unbound or free
solution state. Assessment of a cell or tissue may include
detecting a relative amount of molecules in free versus bound
forms.
[0108] Certain biological molecules may provide an indication of a
variety of diseases and conditions including cancer (e.g.,
melanoma), tumors, bacterial infection, virial infection, and
diabetes. As an example, cancerous cells and tissues may be
identified by detecting certain biological molecules (e.g.,
NAD(P)H, riboflavin, flavin). A cancerous tissue may have a higher
amount of one or more of these biological molecules than a healthy
tissue. By detecting an amount of one or more of these molecules, a
tissue may be diagnosed as cancerous. As another example, diabetes
in individuals may be assessed by detecting biological molecules
indicative of glucose concentration, including hexokinase, glycogen
adduct. As another example, general changes due to aging may be
assessed by detecting collagen and lipofuscin.
[0109] Some biological molecules that provide an indication of a
patient's condition may emit light in response to being illuminated
with excitation energy and may be considered to autofluoresce. Such
biological molecules may act as endogenous fluorophores for a
region of a patient and provide label-free and noninvasive labeling
of the region without requiring the introduction of exogenous
fluorophores. Examples of such fluorescent biological molecules may
include hemoglobin, collagen, nicotinamide adenine dinucleotide
phosphate (NAD(P)H), retinol, riboflavin, cholecalciferol, folic
acid, pyridoxine, tyrosine, dityrosine, glycation adduct,
idolamine, lipofuscin, polyphenol, tryptophan, flavin, and melanin,
by way of example and not limitation.
[0110] Fluorescent biological molecules may vary in the wavelength
of light they emit and their response to excitation energy.
Wavelengths of excitation and fluorescence for some exemplary
fluorescent biological molecules are provided in the following
table:
TABLE-US-00001 Molecule Excitation (nm) Fluorescence (nm) NAD(P)H
340 450 Collagen 270-370 305-450 Retinol -- 500 Riboflavin -- 550
Cholecalciferol -- 380-460 Folic Acid -- 450 Pyridoxine -- 400
Tyrosine 270 305 Dityrosine 325 400 Excimer-like aggregate 270 360
Glycation adduct 370 450 Tryptophan 280 300-350 Falvin 380-490
520-560 Melanin 340-400 360-560
[0111] Aspects of the present application relate to detecting one
or more biological molecules indicative of a condition of a cell or
tissue condition by the light emitted from a region of a patient in
response to illuminating the region with excitation energy. An
imaging device may include one or more light sources (e.g., lasers,
light-emitting diodes) and one or more photodetectors. The imaging
device may include one or more optical components configured such
that when the imaging device is used to image a region of a patient
the light is directed to the region. The imaging device may include
one or more optical components configured to receive light emitted
from the region and direct the light to a photodetector of the
imaging device. Data indicative of the detected light by one or
more photodetectors may be used to form an image of the region.
[0112] Fluorescent biological molecules may vary in the temporal
characteristics of the light they emit (e.g., their emission decay
time periods, or "lifetimes"). Accordingly, biological molecules
may be detected based on these temporal characteristics by a
photodetector of an imaging device. In some embodiments, a temporal
characteristic for a healthy tissue may be different than for an
unhealthy tissue. There may be a shift in value of the temporal
characteristic between a healthy tissue and an unhealthy tissue.
Using data based on the temporal characteristics of emitted light
from a patient's tissue may allow a clinician to detect an earlier
stage of a disease in the patient than other assessment techniques.
For example, some types of skin cancer can be detected at a stage
before they are visible by measuring temporal characteristics of
light emitted by fluorescent biological molecules of a cancerous
tissue region.
[0113] FIG. 27A shows a block diagram illustrating an imaging
device 2710, such as a point-of-care device, for example, that
performs luminance lifetime imaging of a patient, according to some
embodiments. Imaging device 2710 includes an excitation light
source 2701, such as a laser, for example, that emits excitation
light 2704 to a subject, such as a patient 2702. The patient (e.g.,
the patient's tissue) may include luminescent molecules 2703,
examples of which are discussed above. In response to the
excitation light 2704, the luminescent molecules 2703 may enter an
excited state that causes them to emit photons 2705. The time at
which the photons 2705 are emitted by the excited luminescent
molecules 2703 after excitation depends on their luminescent
lifetimes. The photons 2705 emitted by the luminescent molecules
2703 are received and processed by one or more optical components
2706 of the imaging device 2710. In some embodiments, the one or
more optical components 2706 may include one or more lenses,
mirrors, and/or any other types of optical components. After
passing through the one or more optical components 2706, the
photons 2705 are received and detected by an integrated
photodetector 2707 which time-bins the arrival of the photons 2705.
By time-binning the arrival of photons 2705, information regarding
the lifetime of the luminescent molecules 2703 can be determined,
which can allow detecting and/or discriminating the luminescent
molecules 2703. In some embodiments, the number of photons 2705
detected may be indicative of the concentration of the luminescent
molecules 2703. The information detected by the integrated
photodetector 2707 may be provided to a processor 2713 for analysis
and/or to produce an image using the information regarding the time
of arrival of photons 2705. The processor 2713 may send image data
to a display device 2714 for the display device 2714 to display the
image.
[0114] FIG. 27B shows an example of a point-of-care device for
non-invasive imaging. In this example, a sample 2712 (e.g., tissue
of a patient) is illuminated with light from excitation light
source 2701, which may be a laser, for example. The optical
component(s) 2706 includes a mirror 2706a that reflects the light
from the excitation light source 2701 to an imaging system 2709,
which may have additional optical component(s), such as a lens, for
example, to process the excitation light. The excitation light
passes through the imaging system 2709 and illuminates the sample
2712. A mechanical standoff 2711 may separate the sample 2712 from
the imaging system 2709 by a suitable distance (e.g., appropriate
for the focal length of the imaging system 2709). Luminescent
molecules of the sample 2712 may be excited by the excitation light
and emit photons that are received by the imaging system 2709 and
pass through the mirror 2705a to reach the integrated photodetector
2707. The mirror 2705a may be dichromic, such that it reflects
light at the wavelength of the excitation light emitted by the
excitation light source 2701 and allows light of the wavelength
emitted by the luminescent molecules to pass through the mirror
2705a. However, this is merely by way of example, and a
point-of-care device for non-invasive imaging may have any suitable
optical component(s) and arrangement thereof.
[0115] FIG. 27B shows an example of a point-of-care device having a
protrusion (e.g., a needle) that may be inserted into a sample 2712
(e.g., tissue of a patient or the patient's body) to perform
imaging. In some embodiments, such a point-of-care device may be an
endoscope. The point-of-care device may include a waveguide (e.g.,
an optical fiber) that carries excitation light to the sample 2712
and receives photons emitted by luminescent molecules of the sample
to provide them to the optical components 2706 for detection by
integrated photodetector 2707. Detection may be performed in vivo,
without the need to remove a sample from a patient or send the
sample to a lab for analysis.
[0116] FIG. 28 illustrates producing an image 2801 of a patient
using luminance lifetime imaging. A portion 2802 of the image 2801
shows luminance lifetimes indicating a presence of diseased tissue,
such as melanoma, a tumor, a bacterial infection or a viral
infection, for example. The portion 2802 may be overlaid on a
standard optical image of a patient, in some embodiments. The
portion 2802 may indicate the luminance lifetime and/or presence of
diseased tissue in any suitable way, such as using tones, colors,
etc. The tones or colors may vary in intensity, color, or
brightness depending on the detected lifetime, intensity of
received photons, or likelihood of the presence of diseased tissue,
for example. Such an image may facilitate a clinician's evaluation
of a condition.
[0117] Aspects of the present application relate to an imaging
device configured to detect temporal characteristics of light
emitted from a region of a patient. Described herein is an
integrated photodetector that can accurately measure, or
"time-bin," the timing of arrival of incident photons. The imaging
device may include the integrated photodetector to measure the
arrival of photons emitted by the region of tissue. In some
embodiments, the integrated photodetector can measure the arrival
of photons with nanosecond or picosecond resolution. Such a
photodetector may find application in a variety of applications
including fluorescence lifetime imaging and time-of-flight imaging,
as discussed further below.
[0118] An integrated circuit having an integrated photodetector
according to aspects of the present application may be designed
with suitable functions for a variety of imaging applications. As
described in further detail below, such an integrated photodetector
can have the ability to detect light within one or more time
intervals, or "time bins." To collect information regarding the
time of arrival of the light, charge carriers are generated in
response to incident photons and can be segregated into respective
time bins based upon their time of arrival.
[0119] FIG. 29 is a flowchart of a method of luminance lifetime
imaging using such an integrated photodetector. Step 2901 includes
receiving incident photons at an integrated photodetector from
luminescent molecules. As discussed above, the incident photons are
received through one or more optical components of a point-of-care
device. Step 2902 includes detecting arrival times of the incident
photons using the integrated photodetector. For example, the
arrival times may be time-binned.
[0120] Although imaging techniques are described herein, the
techniques described herein are not limited to imaging. In some
embodiments, detection of luminance lifetime characteristics of
tissue may be used to measure the concentration of a molecule in a
patient's tissue. For example, such a technique may be used for
non-invasive blood glucose monitoring.
[0121] FIG. 30 is a flowchart of a method of analyzing blood
glucose of tissue based on luminance lifetime characteristics. Step
3001 includes detecting luminance lifetime characteristics of
tissue using, at least in part, an integrated circuit that detects
arrival times of incident photons from the tissue. Step 3002
includes analyzing blood glucose based upon the luminance lifetime
characteristics.
Fluorescent Lifetime Measurements
[0122] One type of temporal characteristic of emitted light from a
fluorescent molecule is a fluorescent lifetime. Fluorescence
lifetime measurements are based on exciting one or more fluorescent
molecules, and measuring the time variation in the emitted
luminescence. The probability of a fluorescent molecule to emit a
photon after the fluorescent molecule reaches an excited state
decreases exponentially over time. The rate at which the
probability decreases may be characteristic of a fluorescent
molecule, and may be different for different fluorescent molecules.
Detecting the temporal characteristics of light emitted by
fluorescent molecules may allow for identifying fluorescent
molecules, discriminating fluorescent molecules with respect to one
another, and/or quantifying the concentrations of fluorescent
molecules.
[0123] After reaching an excited state, a fluorescent molecule may
emit a photon with a certain probability at a given time. The
probability of a photon being emitted from an excited fluorescent
molecule may decrease over time after excitation of the fluorescent
molecule. The decrease in the probability of a photon being emitted
over time may be represented by an exponential decay function
p(t)=e{circumflex over ( )}(-t/.tau.), where p(t) is the
probability of photon emission at a time, t, and .tau. is a
temporal parameter of the fluorescent molecule. The temporal
parameter .tau. indicates a time after excitation when the
probability of the fluorescent molecule emitting a photon is a
certain value. The temporal parameter, .tau., is a property of a
fluorescent molecule and may be influenced by its local chemical
environment, but may be distinct from its absorption and emission
spectral properties. Such a temporal parameter, .tau., is referred
to as the luminance lifetime, the fluorescence lifetime or simply
the "lifetime" of a fluorescent molecule.
[0124] FIG. 1A plots the probability of a photon being emitted as a
function of time for two fluorescent molecules with different
lifetimes. The fluorescent molecule represented by probability
curve B has a probability of emission that decays more quickly than
the probability of emission for the fluorescent molecule
represented by probability curve A. The fluorescent molecule
represented by probability curve B has a shorter temporal
parameter, .tau., or lifetime than the fluorescent molecule
represented by probability curve A. Fluorescent molecules may have
fluorescence lifetimes ranging from 0.1-20 ns, in some
embodiments.
[0125] Detecting lifetimes of fluorescent molecules may allow for
fewer wavelengths of excitation light to be used than when the
fluorescent molecules are differentiated by measurements of
emission spectra. In some embodiments, sensors, filters, and/or
diffractive optics may be reduced in number or eliminated when
using fewer wavelengths of excitation light and/or luminescent
light. In some embodiments, one or more excitation light source(s)
may be used that emits light of a single wavelength or spectrum,
which may reduce the cost of an imaging device. In some embodiments
a quantitative analysis of the types of molecule(s) present and/or
analysis of characteristics of tissue may be performed by
determining a temporal parameter, a spectral parameter, an
intensity parameter, or a combination of the temporal, spectral,
and/or intensity parameters of the emitted luminescence from a
fluorescent molecule.
[0126] A fluorescence lifetime may be determined by measuring the
time profile of emitted fluorescence from a region of tissue. By
illuminating the tissue with excitation energy, the fluorescent
molecules may be excited into an excited state and then emit
photons over time. A photodetector may detect the emitted photons
and aggregate collected charge carriers in one or more time bins of
the photodetector to detect light intensity values as a function of
time. In a tissue, multiple types of fluorescent biological
molecules with different lifetimes may be present. The emitted
fluorescence from the tissue may include photons from the multiple
types of fluorescent biological molecules, and the time profile of
the emitted fluorescence may be representative of the different
lifetimes. In this manner, a signature lifetime value may be
obtained for a tissue that corresponds to the collection of
fluorescent molecules present in the tissue.
[0127] In some embodiments, a time profile representative of a
tissue may be determined by performing one or more measurements
where the tissue is illuminated with excitation energy and then the
time when a photon emits is measured. For each measurement, the
excitation source may generate a pulse of excitation light directed
to the region of tissue, and the time between the excitation pulse
and subsequent photon event from the tissue may be determined.
Since multiple fluorescent molecules may be present in a tissue,
multiple photon events may occur after a single pulse of excitation
light. The photon events may occur at different times after the
pulse of excitation light and provide a time profile representative
of the tissue. Additionally or alternatively, when an excitation
pulse occurs repeatedly and periodically, the time between when a
photon emission event occurs and the subsequent excitation pulse
may be measured, and the measured time may be subtracted from the
time interval between excitation pulses (i.e., the period of the
excitation pulse waveform) to determine the time of the photon
absorption event.
[0128] The number of photon events after one or more pulses of
excitation light may populate a histogram representing the number
of photon emission events that occur within a series of discrete
time intervals or time bins. The number of time bins and/or the
time interval of each bin may be set and/or adjusted to identify a
particular lifetime and/or a particular set of fluorescent
molecules. The number of time bins and/or the time interval of each
bin may depend on the sensor used to detect the photons emitted.
The number of time bins may be 1, 2, 3, 4, 5, 6, 7, 8, or more,
such as 16, 32, 64, or more. A curve fitting algorithm may be used
to fit a curve to the recorded histogram, resulting in a function
representing the probability of a photon to be emitted after
excitation of the fluorescent molecule at a given time. An
exponential decay function, such as p(t)=e{circumflex over (
)}(-t/.tau.), may be used to approximately fit the histogram data.
From such a curve fitting, the temporal parameter or lifetime may
be determined. The determined lifetime may be compared to known
lifetimes of fluorescent molecules to identify the type of
fluorescent molecule present. The determined lifetime may also act
as a signature lifetime value indicative of the combination of one
or more types of fluorescent molecules.
[0129] A lifetime may be calculated from the intensity values at
two time intervals. FIG. 1B shows example intensity profiles over
time for an example excitation pulse (dotted line) and example
fluorescence emission (solid line). In the example shown in FIG.
1B, the photodetector measures the intensity over at least two time
bins. The photons that emit luminescence energy between times t1
and t2 are measured by the photodetector as intensity I1 and
luminescence energy emitted between times t3 and t4 are measured as
I2. Any suitable number of intensity values may be obtained
although only two are shown in FIG. 1B. Such intensity measurements
may then be used to calculate a lifetime. The time binned
luminescence signal may be fit to a single exponential decay. In
some embodiments, the time binned signal may be fit to multiple
exponential decays, such as double or triple exponentials. A
Laguerre decomposition process may be used to represent multiple
exponential decays in the time binned signal. Where multiple
fluorescent molecules contribute to the intensity profiles, an
average fluorescence lifetime may be determined by fitting a single
exponential decay to the luminescence signal.
[0130] A photodetector having a pixel array may provide the ability
to image a region by detecting temporal characteristics of light
received at individual pixels from different areas of the region.
Individual pixels may determine lifetime values corresponding to
different areas of the region. An image of the region may
illustrate variation in lifetime across the region by displaying
contrast in the image based on a lifetime value and/or other
features of the time profile determined for each pixel. The imaging
device may perform imaging of tissue based on the temporal
characteristics of light received from the tissue, which may enable
a physician performing a procedure (e.g., surgery) to identify an
abnormal or diseased region of tissue (e.g., cancerous or
pre-cancerous). In some embodiments, the imaging device may be
incorporated into a medical device, such as a surgical imaging
tool. In some embodiments, time-domain information regarding the
light emitted by tissue in response to a light excitation pulse may
be obtained to image and/or characterize the tissue. For example,
imaging and/or characterization of tissue or other objects may be
performed using fluorescence lifetime imaging.
[0131] In some embodiments, fluorescence lifetimes may be used for
microscopy techniques to provide contrast between different types
or states of samples including tissue regions of a patient.
Fluorescence lifetime imaging microscopy (FLIM) may be performed by
exciting a sample with a light pulse, detecting the fluorescence
signal as it decays to determine a lifetime, and mapping the decay
time in the resulting image. In such microscopy images, the pixel
values in the image may be based on the fluorescence lifetime
determined for each pixel in the photodetector collecting the field
of view.
[0132] In some embodiments, fluorescence lifetime measurements may
be analyzed to identify a condition or state of a sample.
Statistical analysis techniques including clustering may be applied
to lifetime data to differentiate between unhealthy or diseased
tissue and healthy tissue. In some embodiments, lifetime
measurements are performed using more than one excitation energy
and lifetime values obtained for the different excitation energies
may be used as part of statistical analysis techniques. In some
embodiments, statistical analysis is performed on individual time
bin values corresponding to photon detection events for certain
time intervals.
[0133] Fluorescence lifetime measurements of autofluorescence of
endogenous fluorescent biological molecules may be used to detect
physical and metabolic changes in the tissue. As examples, changes
in tissue architecture, morphology, oxygenation, pH, vascularity,
cell structure and/or cell metabolic state may be detected by
measuring autofluorescence from the sample and determining a
lifetime from the measured autofluorescence. Such methods may be
used in clinical applications, such as screening, image-guided
biopsies or surgeries, and/or endoscopy. In some embodiments, an
imaging device of the present application may be incorporated into
a clinical tool, such as a surgical instrument, for example, to
perform fluorescence lifetime imaging. Determining fluorescence
lifetimes based on measured autofluorescence provides clinical
value as a label-free imaging method that allows a clinician to
quickly screen tissue and detect small cancers and/or pre-cancerous
lesions that are not apparent to the naked eye. Fluorescence
lifetime imaging may be used for detection and delineation of
malignant cells or tissue, such as tumors or cancer cells which
emit luminescence having a longer fluorescence lifetime than
healthy tissue. For example, fluorescence lifetime imaging may be
used for detecting cancers on optically accessible tissue, such as
gastrointestinal tract, respiratory tract, bladder, skin, eye, or
tissue surface exposed during surgery.
[0134] In some embodiments, exogenous fluorescent markers may be
incorporated into a region of tissue. The exogenous fluorescent
markers may provide a desired level of fluorescence for detecting a
condition of the tissue by measuring the fluorescence and
determining a lifetime from the measured fluorescence. In some
embodiments, the measured fluorescence may include autofluorescence
from endogenous fluorescent biological molecules and exogenous
fluorescent markers. Examples of exogenous fluorescent markers may
include fluorescent molecules, fluorophores, fluorescent dyes,
fluorescent stains, organic dyes, fluorescent proteins, enzymes,
and/or quantum dots. Such exogenous markers may be conjugated to a
probe or functional group (e.g., molecule, ion, and/or ligand) that
specifically binds to a particular target or component. Attaching
an exogenous tag or reporter to a probe allows identification of
the target through detection of the presence of the exogenous tag
or reporter. Exogenous markers attached to a probe may be provided
to the region, object, or sample in order to detect the presence
and/or location of a particular target component. In some
embodiments, exogenous fluorescent markers that can be easily
applied to a patient (e.g., topical application to skin, ingestion
for gastrointestinal tract imaging) may provide a desired level of
detection from fluorescence measurements. Such markers may reduce
the invasiveness of incorporating an exogenous fluorescent marker
into the tissue.
[0135] Fluorescence lifetime measurements may provide a
quantitative measure of the conditions surrounding the fluorescent
molecule. The quantitative measure of the conditions may be in
addition to detection or contrast. The fluorescence lifetime for a
fluorescent molecule may depend on the surrounding environment for
the fluorescent molecule, such as pH or temperature, and a change
in the value of the fluorescence lifetime may indicate a change in
the environment surrounding the fluorescent molecule. As an
example, fluorescence lifetime imaging may map changes in local
environments of a sample, such as in biological tissue (e.g., a
tissue section or surgical resection).
Time-of-Flight Measurements
[0136] In some embodiments, the imaging device may be configured to
measure a time profile of scattered or reflected light, including
time-of-flight measurements. In such time-of-flight measurements, a
light pulse may be emitted into a region or sample and scattered
light may be detected by a photodetector, such as the integrated
photodetector described above. The scattered or reflected light may
have a distinct time profile that may indicate characteristics of
the region or sample. Backscattered light by the sample may be
detected and resolved by their time of flight in the sample. Such a
time profile may be a temporal point spread function (TPSF). The
TPSF may be considered and impulse response. The time profile may
be acquired by measuring the integrated intensity over multiple
time bins after the light pulse is emitted. Repetitions of light
pulses and accumulating the scattered light may be performed at a
certain rate to ensure that all the previous TPSF is completely
extinguished before generating a subsequent light pulse.
Time-resolved diffuse optical imaging methods may include
spectroscopic diffuse optical tomography where the light pulse may
be infrared light in order to image at a further depth in the
sample. Such time-resolved diffuse optical imaging methods may be
used to detect tumors in an organism or in part of an organism,
such as a person's head.
[0137] The imaging device may be configured for multiple imaging
modes. Imaging modes may include fluorescent lifetime imaging,
time-of-flight imaging, intensity imaging, and spectroscopic
imaging.
Integrated Photodetector for Time Binning Photogenerated Charge
Carriers
[0138] Some embodiments relate to an integrated circuit having a
photodetector that produces charge carriers in response to incident
photons and which is capable of discriminating the timing at which
the charge carriers are generated by the arrival of incident
photons with respect to a reference time (e.g., a trigger event).
In some embodiments, a charge carrier segregation structure
segregates charge carriers generated at different times and directs
the charge carriers into one or more charge carrier storage regions
(termed "bins") that aggregate charge carriers produced within
different time periods. Each bin stores charge carriers produced
within a selected time interval. Reading out the charge stored in
each bin can provide information about the number of photons that
arrived within each time interval. Such an integrated circuit can
be used in any of a variety of applications, such as those
described herein.
[0139] An example of an integrated circuit having a photodetection
region and a charge carrier segregation structure will be
described. In some embodiments, the integrated circuit may include
an array of pixels, and each pixel may include one or more
photodetection regions and one or more charge carrier segregation
structures, as discussed below.
[0140] Overview of Pixel Structure and Operation
[0141] FIG. 2A shows a diagram of a pixel 100, according to some
embodiments. Pixel 100 includes a photon absorption/carrier
generation region 102 (also referred to as a photodetection
region), a carrier travel/capture region 106, a carrier storage
region 108 having one or more charge carrier storage regions, also
referred to herein as "charge carrier storage bins" or simply
"bins," and readout circuitry 110 for reading out signals from the
charge carrier storage bins.
[0142] The photon absorption/carrier generation region 102 may be a
region of semiconductor material (e.g., silicon) that can convert
incident photons into photogenerated charge carriers. The photon
absorption/carrier generation region 102 may be exposed to light,
and may receive incident photons. When a photon is absorbed by the
photon absorption/carrier generation region 102 it may generate
photogenerated charge carriers, such as an electron/hole pair.
Photogenerated charge carriers are also referred to herein simply
as "charge carriers."
[0143] An electric field may be established in the photon
absorption/carrier generation region 102. In some embodiments, the
electric field may be "static," as distinguished from the changing
electric field in the carrier travel/capture region 106. The
electric field in the photon absorption/carrier generation region
102 may include a lateral component, a vertical component, or both
a lateral and a vertical component. The lateral component of the
electric field may be in the downward direction of FIG. 2A, as
indicated by the arrows, which induces a force on photogenerated
charge carriers that drives them toward the carrier travel/capture
region 106. The electric field may be formed in a variety of
ways.
[0144] In some embodiments one or more electrodes may be formed
over the photon absorption/carrier generation region 102. The
electrodes(s) may have voltages applied thereto to establish an
electric field in the photon absorption/carrier generation region
102. Such electrode(s) may be termed "photogate(s)." In some
embodiments, photon absorption/carrier generation region 102 may be
a region of silicon that is fully depleted of charge carriers.
[0145] In some embodiments, the electric field in the photon
absorption/carrier generation region 102 may be established by a
junction, such as a PN junction. The semiconductor material of the
photon absorption/carrier generation region 102 may be doped to
form the PN junction with an orientation and/or shape that produces
an electric field that induces a force on photogenerated charge
carriers that drives them toward the carrier travel/capture region
106. Producing the electric field using a junction may improve the
quantum efficiency with respect to use of electrodes overlying the
photon absorption/carrier generation region 102 which may prevent a
portion of incident photons from reaching the photon
absorption/carrier generation region 102. Using a junction may
reduce dark current with respect to use of photogates. It has been
appreciated that dark current may be generated by imperfections at
the surface of the semiconductor substrate that may produce
carriers. In some embodiments, the P terminal of the PN junction
diode may be connected to a terminal that sets its voltage. Such a
diode may be referred to as a "pinned" photodiode. A pinned
photodiode may promote carrier recombination at the surface, due to
the terminal that sets its voltage and attracts carriers, which can
reduce dark current. Photogenerated charge carriers that are
desired to be captured may pass underneath the recombination area
at the surface. In some embodiments, the lateral electric field may
be established using a graded doping concentration in the
semiconductor material.
[0146] In some embodiments, an absorption/carrier generation region
102 that has a junction to produce an electric field may have one
or more of the following characteristics:
[0147] 1) a depleted n-type region that is tapered away from the
time varying field,
[0148] 2) a p-type implant surrounding the n-type region with a gap
to transition the electric field laterally into the n-type region,
and/or
[0149] 3) a p-type surface implant that buries the n-type region
and serves as a recombination region for parasitic electrons.
[0150] In some embodiments, the electric field may be established
in the photon absorption/carrier generation region 102 by a
combination of a junction and at least one electrode. For example,
a junction and a single electrode, or two or more electrodes, may
be used. In some embodiments, one or more electrodes may be
positioned near carrier travel/capture region 106 to establish the
potential gradient near carrier travel/capture region 106, which
may be positioned relatively far from the junction.
[0151] As illustrated in FIG. 2A, a photon may be captured and a
charge carrier 101A (e.g., an electron) may be produced at time t1.
In some embodiments, an electrical potential gradient may be
established along the photon absorption/carrier generation region
102 and the carrier travel/capture region 106 that causes the
charge carrier 101A to travel in the downward direction of FIG. 2A
(as illustrated by the arrows shown in FIG. 2A). In response to the
potential gradient, the charge carrier 101A may move from its
position at time t1 to a second position at time t2, a third
position at time t3, a fourth position at time t4, and a fifth
position at time t5. The charge carrier 101A thus moves into the
carrier travel/capture region 106 in response to the potential
gradient.
[0152] The carrier travel/capture region 106 may be a semiconductor
region. In some embodiments, the carrier travel/capture region 106
may be a semiconductor region of the same material as photon
absorption/carrier generation region 102 (e.g., silicon) with the
exception that carrier travel/capture region 106 may be shielded
from incident light (e.g., by an overlying opaque material, such as
a metal layer).
[0153] In some embodiments, and as discussed further below, a
potential gradient may be established in the photon
absorption/carrier generation region 102 and the carrier
travel/capture region 106 by electrodes positioned above these
regions. An example of the positioning of electrodes will be
discussed with reference to FIG. 3B. However, the techniques
described herein are not limited as to particular positions of
electrodes used for producing an electric potential gradient. Nor
are the techniques described herein limited to establishing an
electric potential gradient using electrodes. In some embodiments,
an electric potential gradient may be established using a spatially
graded doping profile and/or a PN junction. Any suitable technique
may be used for establishing an electric potential gradient that
causes charge carriers to travel along the photon
absorption/carrier generation region 102 and carrier travel/capture
region 106.
[0154] A charge carrier segregation structure may be formed in the
pixel to enable segregating charge carriers produced at different
times. In some embodiments, at least a portion of the charge
carrier segregation structure may be formed over the carrier
travel/capture region 106. As will be described below, the charge
carrier segregation structure may include one or more electrodes
formed over the carrier travel/capture region 106, the voltage of
which may be controlled by control circuitry to change the electric
potential in the carrier travel/capture region 106.
[0155] The electric potential in the carrier travel/capture region
106 may be changed to enable capturing a charge carrier. The
potential gradient may be changed by changing the voltage on one or
more electrodes overlying the carrier travel/capture region 106 to
produce a potential barrier that can confine a carrier within a
predetermined spatial region. For example, the voltage on an
electrode overlying the dashed line in the carrier travel/capture
region 106 of FIG. 2A may be changed at time t5 to raise a
potential barrier along the dashed line in the carrier
travel/capture region 106 of FIG. 2A, thereby capturing charge
carrier 101A. As shown in FIG. 2A, the carrier captured at time t5
may be transferred to a bin "bin0" of carrier storage region 108.
The transfer of the carrier to the charge carrier storage bin may
be performed by changing the potential in the carrier
travel/capture region 106 and/or carrier storage region 108 (e.g.,
by changing the voltage of electrode(s) overlying these regions) to
cause the carrier to travel into the charge carrier storage
bin.
[0156] Changing the potential at a certain point in time within a
predetermined spatial region of the carrier travel/capture region
106 may enable trapping a carrier that was generated by photon
absorption that occurred within a specific time interval. By
trapping photogenerated charge carriers at different times and/or
locations, the times at which the charge carriers were generated by
photon absorption may be discriminated. In this sense, a charge
carrier may be "time binned" by trapping the charge carrier at a
certain point in time and/or space after the occurrence of a
trigger event. The time binning of a charge carrier within a
particular bin provides information about the time at which the
photogenerated charge carrier was generated by absorption of an
incident photon, and thus likewise "time bins," with respect to the
trigger event, the arrival of the incident photon that produced the
photogenerated charge carrier.
[0157] FIG. 2B illustrates capturing a charge carrier at a
different point in time and space. As shown in FIG. 2B, the voltage
on an electrode overlying the dashed line in the carrier
travel/capture region 106 may be changed at time t9 to raise a
potential barrier along the dashed line in the carrier
travel/capture region 106 of FIG. 2B, thereby capturing carrier
101B. As shown in FIG. 2B, the carrier captured at time t9 may be
transferred to a bin "bin1" of carrier storage region 108. Since
charge carrier 101B is trapped at time t9, it represents a photon
absorption event that occurred at a different time (i.e., time t6)
than the photon absorption event (i.e., at t1) for carrier 101A,
which is captured at time t5.
[0158] Performing multiple measurements and aggregating charge
carriers in the charge carrier storage bins of carrier storage
region 108 based on the times at which the charge carriers are
captured can provide information about the times at which photons
are captured in the photon absorption/carrier generation area 102.
Such information can be useful in a variety of applications, as
discussed above.
[0159] Detailed Example of Pixel Structure and Operation
[0160] FIG. 3A shows a charge carrier confinement region 103 of a
pixel 100A, according to some embodiments. As illustrated in FIG.
3A, pixel 100A may include a photon absorption/carrier generation
area 102A (also referred to as a photodetection region), a carrier
travel/capture area 106A, a drain 104, a plurality of charge
carrier storage bins bin0, bin1, bin2, and bin3 of a carrier
storage region 108A, and a readout region 110A.
[0161] Charge carrier confinement region 103 is a region in which
photogenerated charge carriers move in response to the electric
potential gradient produced by a charge carrier segregation
structure. Charge carriers may be generated in photon
absorption/carrier generation area 102A within charge carrier
confinement region 103.
[0162] Charge carrier confinement region 103 may be formed of any
suitable material, such as a semiconductor material (e.g.,
silicon). However, the techniques described herein are not limited
in this respect, as any suitable material may form charge carrier
confinement region 103. In some embodiments, charge carrier
confinement region 103 may be surrounded by an insulator (e.g.,
silicon oxide) to confine charge carriers within charge carrier
confinement region 103.
[0163] The portion of charge carrier confinement region 103 in
photon absorption/carrier generation area 102A may have any
suitable shape. As shown in FIG. 3A, in some embodiments the
portion of charge carrier confinement region 103 in photon
absorption/carrier generation area 102A may have a tapered shape,
such that its width gradually decreases near carrier travel/capture
area 106A. Such a shape may improve the efficiency of charge
handling, which may be useful particularly in cases where few
photons are expected to arrive. In some embodiments the portion of
charge carrier confinement region 103 in photon absorption/carrier
generation area 102A may be less tapered, or may not be tapered,
which can increase the dynamic range. However, the techniques
described herein are not limited as to the shape of charge carrier
confinement region 103 in photon absorption/carrier generation area
102A.
[0164] As shown in FIG. 3A, a first portion of charge carrier
confinement region 103 in carrier travel/capture area 106A may
extend from the photon absorption/carrier generation area 102A to a
drain 104. Extensions of the charge carrier confinement region 103
extend to the respective charge storage bins, allowing charge
carriers to be directed into the charge carrier storage bins by a
charge carrier segregation structure such as that described with
respect to FIG. 3B. In some embodiments, the number of extensions
of the charge carrier confinement region 103 that are present may
be the same as the number of charge carrier storage bins, with each
extension extending to a respective charge carrier storage bin.
[0165] Readout region 110A may include a floating diffusion node fd
for read out of the charge storage bins. Floating diffusion node fd
may be formed by a diffusion of n-type dopants into a p-type
material (e.g., a p-type substrate), for example. However, the
techniques described herein are not limited as to particular dopant
types or doping techniques.
[0166] FIG. 3B shows the pixel 100A of FIG. 3A with a plurality of
electrodes Vb0-Vbn, b0-bm, st1, st2, and tx0-tx3 overlying the
charge carrier confinement region 103 of FIG. 3A. The electrodes
shown in FIG. 3B form at least a portion of a charge carrier
segregation structure that can time-bin photogenerated
carriers.
[0167] The electrodes shown in FIG. 3B establish an electric
potential within the charge carrier confinement region 103. In some
embodiments, the electrodes Vb0-Vbn, b0-bm may have a voltage
applied thereto to establish a potential gradient within regions
102A and 106A such that charge carriers, e.g., electrons, travel in
the downward direction of FIG. 3B toward the drain 104. Electrodes
Vb0-Vbn may establish a potential gradient in the charge
confinement region 103 of photon absorption/carrier generation area
102A. In some embodiments, respective electrodes Vb0-Vbn may be at
constant voltages. Electrodes b0-bm may establish a potential
gradient in the charge confinement region 103 of carrier
travel/capture area 106A. In some embodiments, electrodes b0-bm may
have their voltages set to different levels to enable trapping
charge carriers and/or transferring charge carriers to one or more
charge storage bins.
[0168] Electrodes st0 and st1 may have voltages that change to
transfer carriers to the charge storage bins of charge carrier
storage region 108A. Transfer gates tx0, tx1, tx2 and tx3 enable
transfer of charge from the charge storage bins to the floating
diffusion node fd. Readout circuitry 110 including reset transistor
rt, amplification transistor sf and selection transistor rs is also
shown.
[0169] In some embodiments, the potentials of floating diffusion
node fd and each of the transfer gates tx0-tx3 may allow for
overflow of charge carriers into the floating diffusion rather than
into the carrier travel/capture area 106A. When charge carriers are
transferred into a bin within the carrier storage region 108, the
potentials of the floating diffusion node fd and the transfer gates
tx0-tx3 may be sufficiently high to allow any overflow charge
carriers in the bin to flow to the floating diffusion. Such a
"barrier overflow protection" technique may reduce carriers
overflowing and diffusing into the carrier travel/capture area 106A
and/or other areas of the pixel. In some embodiments, a barrier
overflow protection technique may be used to remove any overflow
charge carriers generated by an excitation pulse. By allowing
overflow charge carriers to flow to the floating diffusion, these
charge carriers are not captured in one or more time bins, thereby
reducing the impact of the excitation pulse on the time bin signals
during readout.
[0170] In some embodiments in which electrodes Vb0-Vbn and b0-bm
are disposed over the photon absorption/carrier generation region
102 and/or the carrier travel/capture region 106, the electrodes
Vb0-Vbn and b0-bm may be set to voltages that increase for
positions progressing from the top to the bottom of FIG. 3B,
thereby establishing the potential gradient that causes charge
carriers to travel in the downward direction of FIG. 3B toward the
drain 104. In some embodiments, the potential gradient may vary
monotonically in the photon absorption/carrier generation region
102 and/or the carrier travel/capture region 106, which may enable
charge carriers to travel along the potential gradient into the
carrier travel/capture region 106. In some embodiments, the
potential gradient may change linearly with respect to position
along the line A-A'. A linear potential gradient may be established
by setting electrodes to voltages that vary linearly across the
vertical dimension of FIG. 3B. However, the techniques described
herein are not limited to a linear potential gradient, as any
suitable potential gradient may be used. In some embodiments, the
electric field in the carrier travel/capture region 106 may be high
enough so charge carriers move fast enough in the carrier
travel/capture region 106 such that the transit time is small
compared to the time over which photons may arrive. For example, in
the fluorescence lifetime measurement context, the transit time of
charge carriers may be made small compared to the lifetime of a
fluorescent molecule or marker being measured. The transit time can
be decreased by producing a sufficiently graded electric field in
the carrier travel/capture region 106.
[0171] FIG. 3C shows an embodiment in which the photon
absorption/carrier generation region 102 includes a PN junction.
FIG. 3C shows an outer electrode 302, which may be at a relatively
low potential, thereby "pinning" the surface potential at a
relatively low potential. An electrode 304 may be included to
assist in producing the potential gradient for a static electric
field that drives carriers toward carrier travel/capture area 106
(the lower portion of carrier travel/capture area 106 is not
shown). FIG. 3C indicates regions of diffusion, polysilicon,
contact and metal 1.
[0172] FIG. 3D shows a top view of a pixel as in FIG. 3C, with the
addition of doping characteristics. FIG. 3D also shows the electric
field sweeping carriers down to region 106 along the potential
gradient established by the PN junction and the electrode 304. FIG.
3D indicates regions of diffusion, polysilicon, contact, metal 1,
N-implant, P-implant, and P-epi.
[0173] FIG. 3E shows a top view of a pixel as in FIG. 3C, including
the carrier travel/capture area 106.
[0174] FIG. 3F shows an array of pixels as in FIG. 3E. FIG. 3F
indicates regions of diffusion, polysilicon, contact and metal
1.
[0175] FIG. 3G shows the pixel array of FIG. 3F and also indicates
regions of diffusion, polysilicon, contact, metal 1, N-implant,
P-implant, and P-epi.
[0176] FIG. 4 shows a circuit diagram of the pixel 100A of FIG. 3B.
The charge carrier confinement area 103 is shown in heavy dark
lines. Also shown are the electrodes, charge carrier storage area
108 and readout circuitry 110. In this embodiment, the charge
storage bins bin0, bin1, bin2, and bin3 of carrier storage region
108 are within the carrier confinement area 103 under electrode
st1. As discussed above, in some embodiments a junction may be used
to produce a static field in region 102 instead of or in addition
to the electrodes.
[0177] Light is received from a light source 120 at photon
absorption/carrier generation area 102. Light source 120 may be any
type of light source, including a region or scene to be imaged, by
way of example and not limitation. A light shield 121 prevents
light from reaching carrier travel/capture area 106. Light shield
121 may be formed of any suitable material, such a metal layer of
the integrated circuit, by way of example and not limitation.
[0178] FIG. 5A illustrates a potential gradient that may be
established in the charge carrier confinement area 103 in photon
absorption/carrier generation area 102 and carrier travel/capture
area 106 along the line A-A' of FIG. 3B. As illustrated in FIG. 5A,
a charge carrier (e.g., an electron) may be generated by absorption
of a photon within the photon absorption/carrier generation area
102. Electrodes Vb0-Vbn and b0-bm are set to voltages that increase
to the right of FIG. 5A to establish the potential gradient the
causes electrons to flow to the right in FIG. 5A (the downward
direction of FIG. 3B). Additionally or alternatively, a PN junction
may be present to establish or assist in establishing the field. In
such an embodiment, carriers may flow below the surface, and FIG.
5A (and related figures) shows the potential in the region where
the carriers flow. Initially, carriers may be allowed to flow
through the carrier travel/capture area 106 into the drain 104, as
shown in FIGS. 6A, 6B and 6C. FIG. 6A shows the position of a
carrier 101 once it is photogenerated. FIG. 6B shows the position
of a carrier 101 shortly thereafter, as it travels in the downward
direction in response to the established potential gradient. FIG.
6C shows the position of the carrier 101 as it reaches the drain
104.
[0179] FIG. 5B shows that after a period of time a potential
barrier 501 to electrons may be raised at a time t1 by decreasing
the voltage of electrode b0. The potential barrier 501 may stop an
electron from traveling to the right in FIG. 5B, as shown in FIGS.
6D, 6E and 6F. FIG. 6D shows the position of a carrier 101 (e.g.,
an electron) once it is photogenerated. FIG. 6E shows the position
of a carrier 101 shortly thereafter, as it travels in the downward
direction in response to the potential gradient. FIG. 6F shows the
position of the carrier 101 as it reaches the potential barrier 501
after time t1.
[0180] FIG. 5C shows that after another time period, another
potential barrier 502 to electrons may be raised at time t2 by
decreasing the voltage of electrode b2. If an electron arrives
between electrodes b0 and b2 between times t1 and t2, the electron
will be captured between potential barrier 501 and potential
barrier 502, as illustrated in FIG. 5C and FIG. 6G.
[0181] FIG. 5D shows that after another time period, another
potential barrier 503 to electrons may be raised at time t3 by
decreasing the voltage of electrode b4. If an electron arrives
between electrodes b2 and b4 between times t2 and t3, the electron
will be trapped in a location between potential barrier 502 and
potential barrier 503. In the example of FIGS. 5D and 6H, an
electron arrived between times t1 and t2, so it remains captured
between potential barrier 501 and potential barrier 502.
[0182] FIG. 5E shows that after another time period, another
potential barrier 504 to electrons may be raised at time t4 by
decreasing the voltage of electrode b6. If an electron arrives
between electrodes b4 and b6 between times t3 and t4, the electron
will be trapped in a location between potential barrier 503 and
potential barrier 504. In the example of FIGS. 5E and 6I, an
electron arrived between times t1 and t2, so it remains captured
between potential barrier 501 and potential barrier 502.
[0183] FIG. 5F shows that after another time period, another
potential barrier 505 to electrons may be raised at time t5 by
decreasing the voltage of electrode bm. If an electron arrives
between electrodes b6 and bm between times t4 and t5, the electron
will be trapped in a location between potential barrier 504 and
potential barrier 505. In the example of FIGS. 5F and 6J, an
electron arrived between times t1 and t2, so it remains captured
between potential barrier 501 and potential barrier 502.
[0184] FIG. 6K shows a voltage timing diagram illustrating the
voltages of electrodes b0-b8, st0 and st1 over time. A charge
carrier moving through the carrier travel/capture area 106 during
the sequence of raising potential barriers 501-505 will be captured
at a location within the carrier travel/capture area 106 that
depends on the time at which it arrives at the carrier
travel/capture area 106, which in turn depends upon the time at
which the charge carrier was generated by photon absorption in
photon absorption/carrier generation area 102. The timing with
which potential barriers 501-505 are raised sets the timing of the
charge storage bins bin0-bin3. As shown in FIG. 6K, a carrier that
arrives between times t1 and t2 will be trapped within a time
interval for bin0, a carrier that arrives between times t2 and t3
will be trapped within a time interval for bin1, a carrier that
arrives between times t3 and t4 will be trapped within a time
interval for bin2, and a carrier that arrives between times t4 and
t5 will be trapped within a time interval for bin3.
[0185] After the sequence shown in FIG. 5A-5F, a captured charge
carrier may then be transferred to the appropriate charge carrier
storage bin based on the location at which the charge carrier is
captured within the carrier travel/capture area 106. In this
embodiment, if an electron is captured under electrode b1, it is
transferred to bin0. If an electron is captured under electrode b3,
it is transferred to bin1. If an electron is captured under
electrode b5, it is transferred to bin2. If an electron is captured
under electrode b7, it is transferred to bin3. In some embodiments,
transfer of any captured carrier(s) within the carrier
travel/capture area 106 to their corresponding bin(s) may be
performed in parallel (e.g., simultaneously). However, the
techniques described herein are not limited as to transferring
captured carriers to charge storage bins in parallel.
[0186] As shown in FIG. 6K, after the sequence shown in FIG. 5A-5F
the voltages on electrodes st0 and st1 may be changed to transfer
any captured charge carriers to the corresponding charge carrier
storage bin(s). An example sequence for transferring captured
charge carrier(s) will be discussed with respect to FIG. 6K and
FIGS. 7A-7G.
[0187] FIG. 7A shows a plot of the potential for a cross section of
the charge carrier confinement area 103 along the line B-B' of FIG.
3B. FIG. 7A shows the potential at time t5 (FIG. 6K) in an example
where an electron is captured between potential barriers 503 and
504. A plan view showing an electron captured between potential
barriers 503 and 504 is shown in FIG. 7E.
[0188] FIG. 7B shows that after time t5 the voltage on electrodes
b1, b3, b5 and b7 optionally may be decreased (not shown in FIG.
6K) to raise the position of an electron within the potential well,
to facilitate transferring the electron.
[0189] FIG. 7C shows that at time t6 (FIG. 6K), the voltages on
electrodes st0 and st1 may be raised. Changing the voltages of the
electrodes in this manner may provide a potential gradient that
causes a transfer a charge carrier captured in carrier
travel/capture area 106 to a corresponding charge storage bin under
electrode st1. A plan view showing the voltage of electrode st1
being raised and the carrier 101 being transferred is shown in FIG.
7F.
[0190] FIG. 7D shows that at time t7, the voltage on electrode st0
may be dropped, thereby confining the captured carrier (if any) in
the corresponding bin (bin2 in this example). The voltage on
electrode b6 may be raised at time t8 to reestablish the potential
gradient in the carrier travel/capture area 106. A plan view
showing the voltage electrode st1 being lowered and the carrier 101
being captured in bin2 is shown in FIG. 7G.
[0191] FIG. 7H shows the characteristics of the electrodes of a
charge carrier segregation structure, according to some
embodiments. FIG. 7H specifies, for each electrode, the voltage
during the gradient phase, the voltage during the binning phase,
the voltage during the transfer phase, the voltage during the
readout phase the high, and type of voltage change. However, this
is merely an example, and the techniques described herein are not
limited as to the implementation details illustrated in FIG.
7H.
[0192] Example Sequence of Measurements
[0193] Repeating the process of photon absorption/carrier
generation and time binning of photogenerated charge carriers may
enable gathering statistical information about the times at which
photons arrive at the photodetector, as discussed below.
[0194] In some embodiments, a "measurement" may include receiving a
photon, capturing a charge carrier at a particular time and/or
location and transferring the captured carrier to a charge storage
node corresponding to a particular time period or bin. A
measurement may be repeated a plurality of times to gather
statistical information about the times at which photons arrive at
the photodetector.
[0195] FIG. 8A shows a flowchart of a method 700 that includes
performing a plurality of measurements 720, according to some
embodiments. Such a method may be performed at least partially by
an integrated device as described herein.
[0196] In step 702 a measurement 720 may be initiated by a trigger
event. A trigger event may be an event that serves as a time
reference for time binning arrival of a photon. The trigger event
could be an optical pulse or an electrical pulse, for example, and
could be a singular event or a repeating, periodic event. In the
context of fluorescence lifetime measurement, the trigger event may
be the generation of a light excitation pulse to excite a
fluorophore. In the context of time-of-flight imaging, the trigger
event may be a pulse of light (e.g., from a flash) emitted by an
imaging device comprising the integrated photodetector. The trigger
event can be any event used as a reference for timing the arrival
of photons or carriers.
[0197] The generation of the light excitation pulse may produce a
significant number of photons, some of which may reach the pixel
100 and may produce charge carriers in the photon
absorption/carrier generation area 102. Since photogenerated
carriers from the light excitation pulse are not desired to be
measured, they may be allowed to flow down the electric potential
to the drain 104 without being captured. Allowing photogenerated
carriers produced by a light excitation pulse to flow to the drain
104 without being captured may reduce the amount of unwanted signal
that otherwise may need to be prevented from arriving by complex
optical components, such as a shutter or filter, which may add
additional design complexity and/or cost. The timing of the raising
of one or more potential barriers within the carrier travel/capture
area 106 may be timed such that photogenerated carriers caused by
any unwanted optical signal flow to the drain 104. Moreover, this
technique may be used with any number of time bins, including
embodiments with only a single time bin. For example, a pixel may
include a single time bin and a drain where the timing of the
potential barriers reduces signal associated with the excitation
pulse while capturing the desired optical signal within the carrier
travel/capture area 106.
[0198] The measurement 720 may then commence at step 704, in which
photon(s) desired to be detected may be absorbed and a charge
carrier may be generated in region 102. In the context of
fluorescence lifetime measurement or time-of-flight imaging, step
704 may commence after the light excitation pulse is completed.
[0199] In step 706 charge carrier(s) moving through the carrier
travel/capture area 106 may be captured at predetermined locations
at selected times with respect to trigger event 702. In some
embodiments, charge carrier(s) may be captured in one or more
regions of the carrier travel/capture area 106 by raising one or
more potential barriers to trap a carrier in a location that
depends upon the time at which it was generated by photon
absorption, as discussed above.
[0200] In step 708 captured charge carrier(s), if present, may be
transferred from the location at which captured charge carrier(s)
were captured to a corresponding charge storage bin, thereby
"time-binning" the charge carrier.
[0201] Following step 708 the measurement 720 may be repeated n-1
times to obtain statistical information regarding the time periods
at which photons tend to arrive after a trigger event 702.
Time-binned charge carriers may be aggregated in the corresponding
charge storage bins as the measurement 720 is repeated. Repeating
the measurement 720 may enable aggregating a sufficient number of
charge carriers in the charge carrier storage bins to provide
statistically meaningful results. For example, in the context of
fluorescence lifetime measurement, it may be expected that a photon
absorption event in response to a photon received from a
fluorophore may occur relatively rarely. For example, such an event
may be expected to occur once in about 1,000 measurements.
Accordingly, a large number of measurements 720 may need to be
performed to aggregate a sufficient number of charge carriers in
the charge carrier storage bins such that the results are
statistically meaningful. In some embodiments, the number of
measurements n of a fluorophore that may be performed for
fluorescence lifetime measurement may be 500,000 or more, or
1,000,000 or more, to enable capturing and binning a sufficient
number of charge carriers in each bin (i.e., tens or hundreds, or
more, in some embodiments).
[0202] Once the allotted number of measurements n has been
performed, the method 700 may proceed to step 710 of reading out
the time bins. Reading out the time bins may include converting the
amount of charge aggregated in each of the charge storage bins into
corresponding voltages, as will be discussed below.
[0203] FIG. 8B is a diagram showing an excitation pulse being
generated at time t0, and time bins bin0-bin3. Note that in this
example the time bins for measuring photons do not begin until t1,
a period of time after t0, which lets the excitation light end
prior to measuring signal photons.
[0204] FIG. 8C shows a plot of the number of photons/charge
carriers in each time bin for a set of fluorescence lifetime
measurements in which the probability of a marker or die
fluorescing decreases exponentially over time. By repeating the
sequence of excitation, charge capture, and transfer into
respective bins many times, and reading out the quantity of charge
carriers transferred into each bin, a histogram of the number of
photons registered in different bins may be produced that allows
determining or approximating the lifetime of a fluorophore.
[0205] Method 700 may be performed over any suitable time period in
which photons are desired to be captured. In the context of
fluorescence lifetime measurement, a suitable period for performing
method 700 may be 10 milliseconds, for example. In some
embodiments, steps 702 to 708 may be repeated at a frequency that
is the MHz range. In some embodiments, the time bins may have a
resolution on the scale of picoseconds or nanoseconds.
[0206] Temporal Multiplexing of Detection in Response to Different
Trigger Events
[0207] In some embodiments, measurements may be performed using a
plurality of different types of trigger events. The trigger events
may be multiplexed in time such that a pixel receives light in
response to different types trigger events in different time
periods. For example, in the context of luminance lifetime
measurements, the trigger events may be excitation light pulses
(e.g., laser pulses) of different wavelengths .lamda.1 and
.lamda.2, which can excite different luminescent molecules (e.g.,
fluorophores). In some embodiments, fluorophores may be identified
and/or discriminated from one another based on their response to
different wavelengths .lamda.1 and .lamda.2 of excitation light.
Exciting a sample with light excitation pulses of wavelengths
.lamda.1 and .lamda.2 at different times, and analyzing the
fluorescence emitted by the sample in response, can enable
detecting and/or identifying fluorescent molecules based on whether
fluorescence is detected in a first time period in response to
excitation light of wavelength .lamda.1, or in a second time period
in response to excitation light of wavelength .lamda.2. In addition
to, or as an alternative to such temporal multiplexing, fluorescent
molecules may be identified and/or discriminated based upon
measuring their fluorescence lifetimes.
[0208] In some embodiments, the integrated photodetector may
temporally multiplex detection of photons produced by a sample in
response to light excitation pulses of different wavelengths. For
example, in a first time period, light produced by a sample in
response to excitation light of wavelength .lamda.1 may be
detected. Subsequently, in a second time period, light produced by
a sample in response to excitation light of wavelength .lamda.2 may
be detected. To do so, a pixel having a plurality of time bins may
use a first subset of time bins to detect arrival of photons in the
first time period and a second subset of time bins to detect
arrival of photons in the second time period. By examining whether
light arrives at a pixel during the first time period or the second
time period, it can be determined whether a fluorophore is
fluorescing in response to light of wavelength .lamda.1 or light of
wavelength .lamda.2.
[0209] In some embodiments, information regarding the arrival times
of photons in response to a light excitation pulse can be used to
determine and/or discriminate fluorescence lifetime. The
fluorescence lifetime may be used to determine a condition of a
tissue. Multiple fluorescent molecules may contribute to a
fluorescent lifetime which may act as a signature of a tissue.
Since the type and/or amount of fluorescent molecules may vary
depending on a tissue's condition, a fluorescence lifetime
signature of a tissue may be indicative of the tissue's condition.
In some embodiments, an excitation pulse of light may be emitted,
then a subset of the time bins of a pixel may be used to time-bin
the arrival of incident photons in a time interval. One or more
fluorescent lifetimes may be identified from the distribution of
photons collected by the subset of time bins. The one or more
fluorescent lifetimes may act as a signature of a sample irradiated
by the excitation pulse of light.
[0210] In some embodiments, a first excitation pulse of a first
wavelength may be emitted, then a first subset of the time bins of
a pixel may be used to time-bin the arrival of incident photons in
a first time interval. Then, a second excitation pulse of a second
wavelength may be emitted, and a second subset of time bins of the
pixel may be used to time-bin the arrival of incident photons in a
second time interval. Accordingly, if photons are received in the
first time interval and/or the second time interval, information
about the lifetime of the fluorescent molecule that produced the
photons can be obtained. Repeating the process of temporal
multiplexing of light excitation pulses along with measuring
information regarding fluorescence lifetimes can provide sufficient
information to enable identification tissue conditions and/or
characteristics.
[0211] FIG. 8D shows a method of operating the integrated
photodetector according to some embodiments in which light is
received at the integrated photodetector in response to a plurality
of different trigger events. FIG. 8E illustrates voltages of the
electrodes of the charge carrier segregation structure when
performing the method of FIG. 8D.
[0212] In step 802, a measurement 820 may be initiated by a trigger
event A. Trigger event A may be an event that serves as a time
reference for time binning arrival of a photon. The trigger event
may be an optical pulse or an electrical pulse, for example, and
could be a singular event or a repeating, periodic event. In the
context of fluorescence lifetime measurement, the trigger event A
may be the generation of a light excitation pulse at a first
wavelength to excite a first type of fluorophore.
[0213] The generation of the light excitation pulse may produce a
significant number of photons, some of which may reach the pixel
100 and may produce charge carriers in the photon
absorption/carrier generation area 102. Since photogenerated
carriers from the light excitation pulse are not desired to be
measured, they may be allowed to flow down the electric potential
to the drain 104 without being captured, as discussed above. The
raising of one or more potential barriers within the carrier
travel/capture area 106 may be timed such that photogenerated
carriers caused by any unwanted optical signal flow to the drain
104.
[0214] The measurement 820 may then proceed at step 804, in which
photon(s) desired to be detected may be absorbed and a charge
carrier may be generated in region 102. In the context of
fluorescence lifetime measurement, step 804 may commence after the
light excitation pulse is completed.
[0215] In step 806, charge carrier(s) moving through the carrier
travel/capture area 106 may be captured at predetermined locations
at selected times with respect to trigger event 802. In some
embodiments, charge carrier(s) may be captured in one or more
regions of the carrier travel/capture area 106 by raising one or
more potential barriers to trap a carrier in a location that
depends upon the time at which it was generated by photon
absorption, as discussed above. In some embodiments, step 806 may
include raising potential barriers 501, 503 and 503 in succession,
thereby capturing charge (if present) corresponding to time bins
bin0 and/or bin1.
[0216] In step 808, captured charge carrier(s), if present, may be
transferred from the location at which they were captured to a
corresponding charge storage bin, thereby "time-binning" the charge
carrier. For example, any charge captured corresponding to time
bins bin0 and/or bin1 may be transferred to bins bin0 and/or bin1
in step 808 using a technique shown in FIGS. 7A-7D, for
example.
[0217] In step 810, a second measurement 821 may be initiated by a
trigger event B. Trigger event B may be an event that serves as a
time reference for time binning arrival of a photon. The trigger
event may be an optical pulse or an electrical pulse, for example,
and could be a singular event or a repeating, periodic event. In
the context of fluorescence lifetime measurement, the trigger event
B may be the generation of a light excitation pulse at a second
wavelength to excite a second type of fluorophore.
[0218] The generation of the light excitation pulse may produce a
significant number of photons, some of which may reach the pixel
100 and may produce charge carriers in the photon
absorption/carrier generation area 102. Since photogenerated
carriers from the light excitation pulse are not desired to be
measured, they may be allowed to flow down the electric potential
to the drain 104 without being captured, as discussed above. The
raising of one or more potential barriers within the carrier
travel/capture area 106 may be timed such that photogenerated
carriers caused by any unwanted optical signal flow to the drain
104.
[0219] The second measurement 821 may then proceed at step 812, in
which photon(s) desired to be detected may be absorbed and a charge
carrier may be generated in region 102. In the context of
fluorescence lifetime measurement, step 812 may commence after the
second light excitation pulse is completed.
[0220] In step 814, charge carrier(s) moving through the carrier
travel/capture area 106 may be captured at predetermined locations
at selected times with respect to trigger event 810. In some
embodiments, charge carrier(s) may be captured in one or more
regions of the carrier travel/capture area 106 by raising one or
more potential barriers to trap a carrier in a location that
depends upon the time at which it was generated by photon
absorption, as discussed above. In some embodiments, step 814 may
include raising potential barriers 503, 504 and 505 in succession,
thereby capturing charge (if present) corresponding to time bins
bin2 and/or bin3.
[0221] In step 816, captured charge carrier(s), if present, may be
transferred from the location at which they were captured to a
corresponding charge storage bin, thereby "time-binning" the charge
carrier. For example, any charge captured corresponding to time
bins bin2 and/or bin3 may be transferred to bins bin2 and/or bin3
in step 816 using a technique shown in FIGS. 7A-7D, for
example.
[0222] Although an example has been described in which a pixel has
four time bins, and two bins are allocated to measuring arrival
times of light produced in response to each of the respective light
excitation pulses, the techniques described herein are not limited
in this respect. For example, the pixel may have a larger or
smaller number of bins, which may be allocated in any suitable way
to measuring light in response to different excitation pulses.
Further, the techniques described herein are not limited to light
excitation pulses of two different wavelengths, as light excitation
pulses of any number of wavelengths may be used, and multiplexed
accordingly.
[0223] Following step 816, the measurements 820 and 821 may be
repeated n-1 times to obtain statistical information regarding the
time periods at which photons tend to arrive after a trigger event.
Time-binned charge carriers may be aggregated in the corresponding
charge storage bins as the measurements are repeated.
[0224] Once the allotted number of measurements n has been
performed, the method 800 may proceed to step 710 of reading out
the time bins. Reading out the time bins may include converting the
amount of charge aggregated in each of the charge storage bins into
corresponding voltages, as will be discussed below.
[0225] Example Readout Circuitry and Sequences
[0226] As illustrated in FIGS. 2A and 2B, pixel 100 may include
readout circuitry 110 that allows reading out the charge stored in
the charge storage bin(s) of the charge carrier storage region 108.
Pixel 100 may be an active pixel, such that readout circuitry 110
includes a readout amplifier, or a passive pixel in which readout
circuitry 110 does not include a readout amplifier. Any suitable
type of active pixel or passive pixel readout circuitry may be
used.
[0227] If readout circuitry 110 includes a readout amplifier, any
suitable type of amplifier may be used. Examples of suitable
amplifiers include amplifiers abased on a common source
configuration and amplifiers abased on a source-follower
configuration. However, the techniques described herein are not
limited as to any particular amplifier configuration.
[0228] If readout circuitry 110 includes a readout amplifier, the
readout amplifier may take the charge accumulated in a charge
storage bin (e.g., bin0, bin1, bin2 or bin3) as an input and
produce a voltage representative of the charge in the charge
storage bin as an output.
[0229] One example of readout circuitry 110 based on a
source-follower configuration is illustrated in FIG. 4. The example
of readout circuitry 110 shown in FIG. 4 is a "4T" configuration
having four transistors: rt, sf, rs, and one of the transfer gates
tx0-tx3. Since the three transistors rt, sf, and rs are shared
among each charge storage bin, the example circuitry shown in FIG.
4 for all four bins is a "1.75 T" configuration, (4 transfer
gates+3 transistors)/4 bins. However, the techniques described
herein are not limited to using readout circuitry 110 having a 1.75
T configuration, as any other suitable type of readout
configuration may be used.
[0230] Further, any suitable readout techniques may be used,
including noise reduction techniques. In some embodiments, readout
circuitry 110 may read out the charge carrier storage bins using
correlated double sampling. Correlated double sampling is technique
in which a first sample may be taken of a node at a reset voltage
level which includes an undetermined amount of noise, and a second
sample may be taken of a signal level at the node including the
same undetermined noise. The noise can be subtracted out by
subtracting the sampled reset level from the sampled signal
level.
[0231] Readout circuitry 110 may perform readout of the charge
storage bins sequentially or in parallel. An example of a timing
diagram for sequentially reading out bins bin0-bin3 with readout
circuitry 110 shown in FIG. 4 using correlated double sampling is
shown in FIG. 9A. As shown in FIG. 9A, initially reset transistor
rt may be turned on to set the floating diffusion node fd to a
reset voltage ct. During the time period in which the voltage of
the floating diffusion node is reset the transfer gates tx0-tx3 are
turned off to keep the charge carriers stored in their respective
bins. After the floating diffusion node fd is reset the reset
voltage may be sampled by turning off transistor rt and turning on
transistor rs to produce an output voltage cb. The reset voltage
represented by output voltage cb may be stored in an analog format
(e.g., on a capacitor) or in a digital format (e.g., by A/D
conversion and storage). Then, transfer gate tx0 may be turned on
to allow the charge from bin0 to flow to the floating diffusion fd.
The signal voltage may be sampled by turning on transistor rs to
produce an output voltage cb based on the charge stored in bin0.
The signal voltage represented by output voltage cb may be stored
in an analog format (e.g., on a capacitor) or in a digital format
(e.g., by A/D conversion and storage).
[0232] Then, transistor rt may be turned on to set the floating
diffusion fd to a reset voltage ct. During the time period in which
the voltage of the floating diffusion node fd is reset the transfer
gates tx0-tx3 are turned off to keep the charge carriers stored in
their respective bins. After the floating diffusion node fd is
reset the reset voltage may be sampled by turning off transistor rt
and turning on transistor rs to produce an output voltage cb.
Again, the reset voltage represented by output voltage cb may be
stored in an analog format (e.g., on a capacitor) or in a digital
format (e.g., by A/D conversion and storage). Then, transfer gate
tx1 may be turned on to allow the charge from bin1 to flow to the
floating diffusion. The signal voltage may be sampled by turning on
transistor rs to produce an output voltage cb based on the charge
stored in bin1. Again, the signal voltage represented by output
voltage cb may be stored in an analog format (e.g., on a capacitor)
or in a digital format (e.g., by A/D conversion and storage).
[0233] The same process may then be performed for bin2 and bin3 by
performing a reset, sampling the reset voltage, transferring the
charge from a bin to the floating diffusion node fd, and sampling
the signal. Accordingly, in the readout sequence illustrated in
FIG. 9A, eight samples may be taken representing the reset value
and signal values for the four bins. The stored reset value for
each bin may be subtracted from the stored signal value to obtain a
result indicative of the charge stored in each bin, thus completing
the correlated double sampling process.
[0234] Optionally, as discussed above, the sampled reset voltage
level for a bin may be stored on a first capacitor and the sampled
signal for the bin may be stored on a second capacitor. Optionally,
before sampling the reset level and signal level onto the
capacitors the capacitors may be cleared by setting them to the
same voltage.
[0235] FIG. 9B shows a readout sequence for performing correlated
double sampling that does not require measuring a reset value for
each signal value, according to some embodiments. In the example of
FIG. 9B, a single reset value is measured for all the bins of the
pixel. To obtain the signal for the first bin, a reset value may be
subtracted from the measured signal value, as discussed above.
Instead of resetting the floating diffusion at this point, charge
may be transferred to the floating diffusion from the second bin,
thereby aggregating the charge for the first and second bins. The
signal for the second bin can be obtained by subtracting the signal
for the first bin from the aggregated signal for the first and
second bins. Since both the signal for the first bin and the
aggregated signal for the first and second bins include the same
reset noise, the result is that the reset noise is subtracted out.
The process may continue for the remaining bins, with the
aggregated signal for the previous bin being subtracted from the
aggregated signal for the next bin. Aggregating the stored charge
for the bins in this manner can allow reading our larger signals
than would be the case if each bin were read out individually, and
can reduce noise, as the sampled signals will be higher above the
noise floor than would be the case if each bin were read out
individually. In the example with four time bins, five samples may
be taken--one reset value and four samples representing the
cumulative charge stored in the charge storage bins. This process
will be described in greater detail with reference to FIG. 9B.
[0236] As shown in FIG. 9B, initially reset transistor rt may be
turned on to set the floating diffusion node fd to a reset voltage
ct. During the time period in which the voltage of the floating
diffusion node is reset the transfer gates tx0-tx3 are turned off
to keep the charge carriers stored in their respective bins. After
the floating diffusion node fd is reset the reset voltage may be
sampled by turning off transistor rt and turning on transistor rs
to produce an output voltage cb. The reset voltage represented by
output voltage cb may be stored in an analog format (e.g., on a
capacitor) or in a digital format (e.g., by A/D conversion and
storage). Then, transfer gate tx0 may be turned on to allow the
charge from bin0 to flow to the floating diffusion. The signal
voltage for bin0 may be sampled by turning on transistor rs to
produce an output voltage cb based on the charge stored in
bin0.
[0237] Then, transfer gate tx1 may be turned on to allow the charge
from bin1 to flow to the floating diffusion. The signal voltage for
bin1+bin0 may be sampled by turning on transistor rs to produce an
output voltage cb based on the charge stored in bin1 plus the
charge stored on bin0. The output signal value for bin0 may be
subtracted from the output signal value for bin0+bin1 to produce a
signal indicative of the charge stored on bin1.
[0238] A similar process may then be performed for bin2 and bin3 by
subtracting the measured signal level for bin n from the measured
signal level for bin n+1. Accordingly, using such a technique the
number of samples that may need to be taken may be reduced.
[0239] The following formulas show how to calculate the "corrected"
(using correlated double sampling) signal for each bin using only a
single measured reset value.
corrected signal bin0=measured signal bin0-reset level
corrected signal bin1=measured signal for (bin0+bin1)-measured
signal bin0
corrected signal bin2=measured signal for (bin0+bin1+bin2)-measured
signal for (bin 0+bin1)
corrected signal bin3=measured signal for (bin
0+bin1+bin2+bin3)-measured signal for (bin 0+bin1+bin2)
[0240] In some embodiments, oversampling of the readout from a
pixel may be performed. Oversampling involves reading the same
signal from the pixel a plurality of times. Each time a signal is
read from the pixel, there may be slight variations in the signal
that is read due to noise. Oversampling of the readout of a signal
and averaging the samples can reduce the noise (e.g., white noise)
in measurements. In some embodiments, multiple samples may be taken
(e.g., 4-8 samples) to read a single nominal signal value from the
pixel (e.g., a single reset level or signal level). In some
embodiments, each of the samples of a signal may be read out
through the readout signal change and converted into digital values
(e.g., digital words). The average of the samples may then be
calculated, and the average used as the measured signal from the
pixel. For example, if oversampling by 8.times. is used, eight
samples may be taken for each reset and signal value, for a total
of 64 samples in the case of measuring 4 time bins and 4 reset
levels, or 40 samples in the case of measuring 1 reset level and 4
aggregated signal levels.
[0241] Pixel Array Readout Circuitry
[0242] Readout in Parallel, Sequential Readout, and Readout with a
Combination of Parallel and Sequential Readout
[0243] As discussed above, the pixel array may include a plurality
of pixels arranged in rows and columns. In some embodiments,
readout may be performed row by row. In some embodiments, a row of
the pixel array may be selected, and a readout process may be
performed for the selected row of pixels. The readout circuitry for
a column of pixels may be common to the pixels in the column, such
that readout may be performed by the readout circuitry for
respective pixels in the column as different rows are selected.
Readout for a selected row may be performed in parallel (termed
"column parallel"), sequentially, or a combination of parallel and
sequentially (termed "semi-column parallel").
[0244] To perform readout of the pixels of a selected row in column
parallel, individual readout circuitry may be provided for each
column so that the pixels of each column in the selected row can be
read out at the same time, as illustrated in FIG. 10A. FIG. 10A
illustrates an array of pixels having a plurality of columns C1 to
Cn and a plurality of rows, with a selected row Ri being shown by
way of illustration. In the embodiment of FIG. 10A, each column of
pixels has an associated readout circuit 905. Since each column of
pixels has an associated readout circuit 905, the signals from each
pixel in row Ri can be read out at the same time.
[0245] To perform readout of the pixels of a selected row in
sequence, individual readout circuitry need not be provided for
each column. For example, in some embodiments a common readout
circuit may be provided, and each pixel of the selected row may be
read out sequentially. FIG. 10B shows an embodiment in which a
common readout circuit 905 may be provided for a plurality of
columns. The common readout circuit may be selectively connected to
a column by a switch network 906 under the control of suitable
control circuitry. For example, in some embodiments, switch network
906 may sequentially connect individual columns of pixels to the
readout circuit 905.
[0246] To perform readout of the pixels in semi-column parallel, a
plurality of readout circuits 905 may be provided, fewer than the
number of columns, as illustrated in FIG. 10C. In such a
semi-column parallel architecture, each readout circuit 905 may be
shared by a subset of the columns. Each readout circuit 905 may
sequentially read out a subset of columns in the array. As shown in
FIG. 10C, readout circuit 905A may be selectively connected to its
respective columns by a switch network 906A. Readout circuit 905B
may be selectively connected to its respective columns by a switch
network 906B.
[0247] In some embodiments, a readout circuit 905 may include one
or more amplifier(s) to amplify a signal from a pixel and an analog
to digital converter to convert the amplified signal into a digital
value. Examples of configurations of readout circuits 905 according
to various embodiments are described below.
[0248] Sample and Hold Circuit
[0249] In some embodiments, the readout circuitry for a column may
include one or more sample and hold circuits. FIG. 10D shows a
circuit diagram illustrating column readout circuitry 905C, which
includes sample and hold circuitry 907, amplifier circuitry 901,
and an analog-to-digital (A/D) converter 902. The sample and hold
circuit 907 may sample the output voltage from a pixel (e.g., at
node cb) onto a capacitive element (e.g., a capacitor), and then
hold the voltage on the capacitor while it is read out by an
amplifier. As discussed above, the output voltage from the pixel
may represent the number of charge carriers captured during one or
more time intervals.
[0250] The sample and hold circuit may operate in a plurality of
phases, termed a "sample" phase and a "hold" phase. In the "sample"
phase, the voltage value from the pixel may be sampled onto a
capacitive element. The voltage to be read out is thus stored on
the capacitive element. Following the "sample" phase, the voltage
of the capacitor is read in the "hold" phase. During the "hold"
phase, the voltage of the capacitor may be read out from the
capacitive element and processed by one or more amplifiers and then
converted into digital form by an analog to digital (A/D)
converter. As illustrated in FIG. 10D, during the sample phase
(.phi.1), switch s1 is turned on (set in its conductive state) and
switch s2 is turned off (set in its non-conductive state), thereby
sampling the voltage from readout terminal cb of a pixel onto a
capacitive element, e.g., capacitor C1. The hold phase (.phi.2)
follows the sample phase. During the hold phase the switch s1 is
turned off and the switch s2 is turned on, thereby connecting the
capacitor C1 to the amplifier circuitry 901. By turning off switch
S 1, the voltage of the capacitor may be held substantially
constant while the voltage is read, as the amplifier circuitry 901
may have a high input impedance. The amplified signal from the
amplifier circuitry 901 may be provided to an A/D converter 902 to
convert the amplified voltage into a digital value.
[0251] In some embodiments, power consumption and/or cost can be
reduced by reducing or minimizing the number of circuits (e.g.,
amplifiers, analog to digital converters) used. In some
embodiments, to reduce or minimize the number of circuits in the
readout chain one or more circuits of the readout chain may be
shared by more than one column of the pixel array.
[0252] Multiplexing Readout Circuitry Component(s)
[0253] In some embodiments, one or more components of the readout
circuitry may be shared by two or more columns of the pixel array.
For example, as shown in FIG. 10E, all or a portion of amplifier
circuitry 901, the A/D converter 902, or both, may be shared by two
or more columns of the pixel array. FIG. 10E illustrates an
embodiment of readout circuitry 905D in which both the amplifier
circuitry 901 and the A/D converter 902 are shared by two columns
of the pixel array. In the embodiment of FIG. 10E, respective
column lines are connected to respective pixel nodes cb1 and cb2.
Each column line is connected to a respective sample and hold
circuit 907A, 907B. Amplifier circuitry 901 and A/D converter 902
may be shared by both columns. The input to the amplifier circuitry
901 may be multiplexed between the sample and hold circuits 907A
and 907B such that their outputs are connected to the amplifier
circuitry 901 at different times (e.g., sequentially). By using
shared readout circuit components such as amplifier circuitry 901
and/or A/D converter 902, the number of components in the readout
circuitry can be reduced, which can reduce the cost and/or power
consumption of the readout circuitry.
[0254] In some embodiments, the sample and hold phases for the
columns sharing the amplifier circuitry 901 may be alternated, such
that when a the column is in the sampling phase and not connected
to the amplifier circuitry 901, the other column is in the hold
phase and its sample and hold circuit is connected to amplifier
circuitry 901 to amplify the voltage it previously sampled. In the
embodiment of FIG. 10F, the sample and read phases are alternated
between the two columns, with the upper column being in the sample
phase during phase 1 and in the hold phase during phase 2, and the
lower column being in the sample phase during phase 2 and the hold
phase during phase 1. During phase 1 (.phi.1), the signal from node
cb1 is sampled onto capacitor C1 by turning on switch s1, and
switch s2 is turned off, switch s3 is turned off, and capacitor C2
is connected to the amplifier 901 via switch s4, which is turned
on. During phase 2 (.phi.2), the signal from node cb2 is sampled
onto capacitor C2 by turning on switch s3, switch s4 is turned off,
switch s1 is turned off, and capacitor C1 is connected to the
amplifier 901 via switch s2, which is turned on. Sharing the
amplifier circuitry 901 by more than one column may reduce the
downtime of amplifier circuitry 901, as it does not need to sit
idle during a sampling phase for a column.
[0255] In some embodiments, more than two columns of the pixel
array may share readout circuitry 901 and/or A/D converter 902.
FIG. 10F shows an embodiment in which n columns of the pixel array
share readout circuitry 901 and/or A/D converter 902. Capacitors
C1-Cn may be sequentially connected to the readout circuitry 901 to
read out their voltage values. Capacitors C1-Cn may be connected to
the readout circuitry 901 in any suitable order. The sampling phase
of the respective sample and hold circuits for each column may be
timed to occur during a period in which the sample and hold circuit
is not being read out by the amplifier circuitry 901. In some
embodiments, and as discussed above, the sampling phases may be
timed to occur during a time interval in which the amplifier
circuitry 901 is reading out a different row, to limit the amount
of time the amplifier circuitry 901 sits idle. For example, as
discussed above, the voltage from node cb1 may be sampled on
capacitor C1 during phase 1. During phase 2, the voltage of
capacitor C1 may be read out by amplifier circuitry 901 and the
voltage from node cb2 may be sampled on capacitor C2. During phase
3, the voltage of capacitor C2 may be read out by amplifier
circuitry 901 and the voltage from a third node cb3 may be sampled
on a third capacitor C3, etc. The process may then begin again with
phase 1 starting during the time the last column (row n) is read
out by amplifier circuitry 901, or after the last column is read
out by amplifier circuitry 901. Any suitable number of columns may
share amplifier circuitry 901, such as 2, 4, 8, 16, 32, 64, 128,
etc., or any other suitable number (which need not be a power of
2).
[0256] FIG. 10G shows a diagram of readout circuitry including
amplifier circuitry 901. In the embodiment of FIG. 10G, amplifier
circuitry 901 includes a plurality of amplifiers 910 and 911. Using
a plurality of cascaded amplifiers 910 and 911 can reduce power
consumption, as achieving the desired signal gain may be achieved
with less power dissipation when a plurality of amplifiers 910 and
911 are used as opposed to using a single amplifier to achieve the
same gain.
[0257] FIG. 10H shows a diagram of readout circuitry including
amplifier circuitry 901 having first stage amplifiers 910A and 910B
for respective columns and a second stage amplifier 911 that is
shared by the two columns. A multiplexer 912 connects first stage
amplifiers 910A and 910B to the second stage amplifier 911 at
different times. In some embodiments, the amplifiers 910A, 910B and
911 may be differential amplifiers.
[0258] FIG. 10I shows a diagram of readout circuitry including
first-stage amplifiers 910A and 910B, a second stage amplifier 911
and a third stage amplifier 912. As discussed above, using an
additional amplifier stage to achieve a desired gain value may
reduce power consumption with respect to using fewer amplifier
stages to achieve the desired gain value. In some embodiments, the
amplifiers 910A, 910B, 911 and 912 may be differential
amplifiers.
[0259] In some embodiments, gain may be applied in the signal chain
in a plurality of stages. In some embodiments, the first-stage
amplifier (e.g., 910A, 910B) may have a gain of 2 or more, the
second stage amplifier (e.g., 911) may have a gain of 1-8, or more,
and the third stage amplifier (e.g., 912) may have a gain of 1-2,
or more, for an overall gain of the three stages of 2-32, or
more.
[0260] In some embodiments, the amplifiers may have a digitally
programmable gain. The gain of one or more stages may be changed
depending on the characteristics of the light being received. For
example, if more than one wavelength of light excitation pulse
(e.g., laser pulse) is used that produce different responses in the
pixel, the gain of one or more amplifiers in the readout chain may
be changed depending on which wavelength of light is currently
being detected. If one wavelength results in smaller number of
charge carriers being produced, the gain may be increased to
accommodate the reduced signal level. If another wavelength results
in a larger number of charge carriers being produced, the gain may
be decreased. In some embodiments, the gains of the readout chain
for different wavelengths may be normalized to one another to
produce the same output levels in response to different
wavelengths.
[0261] Readout Circuitry Design Considerations
[0262] Since in some embodiments, the number of charge carriers
captured for each time bin may be relatively small, e.g., on the
order of hundreds of charge carriers, the signal to be detected
from each pixel may be relatively small. Accordingly, in some
embodiments the signal chain running from a pixel to (and
including) an analog to digital converter may include low-noise
readout circuitry. Techniques and circuits for limiting the noise
in the readout chain will be discussed below.
[0263] In some embodiments, differential processing of signals may
reduce or minimize noise in the readout chain. Differential
processing of signals can reject common-mode noise that may be
injected into the readout chain. The readout circuitry may include
one or more differential components, such as a differential sample
and hold circuit, differential amplifier(s) and/or a differential
A/D converter. In some embodiments, differential signal processing
may be used as early as possible in the readout chain (e.g., as
close as possible to the pixel output), to avoid injecting
common-mode noise into the readout chain. In some embodiments, the
entire readout chain from a pixel output to a digital word may be
performed by differential circuit components. However, the
techniques described herein are not limited in this respect, as in
some embodiments one or more single-ended readout circuitry
components may be used.
[0264] FIG. 10J shows readout circuitry shared by two columns
including a differential sample and hold circuit 908 and a
differential amplifier 909. The differential sample and hold
circuit 908 includes capacitors Cin1 for a first column of the
pixel array and capacitors Cin2 for a second column of the pixel
array. The differential amplifier 909 includes capacitors Cf1 for a
first column of the pixel array and capacitors Cf2 for a second
column of the pixel array.
[0265] FIG. 10K shows a diagram of the differential sample and hold
circuit 908 and a differential amplifier 909 when the first column
is in the sample phase and the second column is in the hold phase,
with capacitors Cin2 being connected to the input of the
differential amplifier 909. FIG. 10L shows a diagram of the
differential sample and hold circuit 908 and a differential
amplifier 909 when the second column is in the sample phase and the
first column is in the hold phase, with capacitors Cin1 being
connected to the input of the differential amplifier 909.
[0266] FIG. 10M shows readout circuitry shared by more than two
columns including a differential sample and hold circuit 908 and a
differential amplifier 909. FIG. 10M is similar to FIG. 10F in that
a differential amplifier 901 is shared by more than two columns,
with the use of a differential sample and hold circuit 908 and a
differential amplifier 909.
[0267] Dark Current Sampling
[0268] As understood by those of ordinary skill in the art, "dark
current" is current that is produced in a photodetector when no
light is being detected by the photodetector. Designing a
photodetector to correct for the effect of dark current can improve
the quality of photodetection.
[0269] In some embodiments of the integrated device described
herein, one or more of the charge storage bins may be used to
sample the dark current. For example, a charge storage bin may
sample dark current by aggregating carriers that arrive during a
time period in which no light or a very low level of light is
received by the photodetector. In some embodiments, such as those
relating to fluorescence lifetime measurements, the last bin (e.g.,
bin3) may be used to sample the dark current if the timing is such
that it occurs once the probability of light emission drops to a
negligible value. Sampling the dark current may allow subtracting
the dark current from samples in other bins, thereby correcting for
the effect of dark current.
[0270] Number and Timing of Time Bins
[0271] Any suitable number of time bins may be used. In FIGS. 3A
and 3B, an example of a pixel with four time bins has been
illustrated. FIG. 8C shows a plot in which eight bins are used.
However, a pixel having any suitable number of time bins may be
produced based on the desired temporal resolution and other
factors. Increasing the number of bins may increase the area taken
up by each pixel, and may be achieved by reducing the overall
number of pixels or by using a fabrication process having a smaller
feature size. Using a small number of bins may allow increasing the
number of pixels that can fit on a chip. In some embodiments, a
single bin may be used to determine the number of photons arriving
within a particular time period. The number of bins may be
increased or decreased at least in part by increasing or decreasing
the number extensions of the charge carrier confinement region
fabricated on the chip extending from the carrier travel/capture
region 106. The number of electrodes b0-bm-1, transfer electrodes,
etc., may be increased or decreased accordingly based on the number
of bins desired to be included in a pixel.
[0272] The timing of the time bins may be chosen in any suitable
way. In some embodiments, the timing may be selected by setting
start and end times for the time bin(s), as illustrated in FIG. 6K.
For example, the timing for bin0 may be set by selecting the times
at which t1 and t2 occur, and the timing of the remaining bins may
be set similarly.
[0273] In some embodiments, the timing for the time bins may be a
fixed such that the timing is the same in each measurement period.
The timing may be set based upon a global timing signal. For
example, a timing signal may establish the start of a measurement
period, and time bins may be controlled to start and end based upon
a predetermined amount of time having elapsed from the timing
signal. In the fluorescence lifetime measurement context, the
timing for the time bins may be set with respect to the timing of
an excitation pulse based upon the possible range of fluorescence
lifetimes that are expected to be detected. In the time-of-flight
imaging context, the timing of the time bins may be set based on an
expected distance range for the scene to be imaged. However, in
some embodiments the timing of the time bins may be variable or
programmable.
[0274] In some embodiments, the timing for the time bins may be set
based upon the timing of a trigger event 702 that initiates a
measurement period for a measurement 720. In the fluorescence
lifetime measurement context, the timing for the time bins may be
set in response to detecting the timing of an excitation pulse that
excites a fluorophore. For example, when a light excitation pulse
reaches the pixel 100, a surge of carriers may travel from the
photon absorption/carrier generation region 102 to the drain 104.
The accumulation of photogenerated carriers at the drain 104 in
response to the excitation pulse may cause a change in voltage of
the drain 104. Accordingly, in some embodiments the excitation
pulse may be detected by detecting the voltage of the drain 104.
For example, a comparator may compare the voltage of the drain 104
to a threshold, and may produce a pulse when the voltage of the
drain 104 exceeds the threshold. The timing of the pulse may be
indicate the timing of the trigger event 702, and the timing of the
time bins (e.g., t1, t2, etc.) may be set based upon this timing.
However, the techniques described herein are not limited in this
respect, as any suitable technique may be used to detect the start
of a measurement 720.
[0275] In some embodiments, the integrated device may be
programmable to enable changing the timing of the time bins. In
some embodiments, the timing of the time bins may be programmed for
a particular set of measurements to be performed. For example, if
the integrated device is used for a first type of test to measure
lifetimes within a first range, the time bins may be programmed to
suitable values for discriminating lifetimes within that range.
However, if the integrated device is used for another type of test
to measure lifetimes in a different range, the time bins may be
changed by programming them to correspond to different time
intervals suitable for the second type of test.
[0276] In some embodiments, the timing of the time bins may be
controlled adaptively between measurements based on the results of
a set of measurements. For example, as illustrated in FIG. 11, a
first set of measurements (Measurement Set A) may be performed
using a first set of time bins that span a relatively large time
interval. The quantity of photons that arrived for each bin may be
analyzed to determine whether a change should be made to the timing
selected for the time bins to improve or optimize the temporal
information obtained. In some embodiments, the quantity of photons
that arrive for each bin may be analyzed to determine a narrower
time interval of interest. For example, after performing a set of
measurements with time bins as shown in Measurement Set A of FIG.
11, it may be determined that a significant number of photons
arrived in the time period corresponding to bin2 and no photons
arrived in the time periods corresponding to other bins. A second
set of time bins may then be selected for a second set of
measurements (Measurement Set B) that focuses on the narrower time
period corresponding to bin2 of Measurement Set A. As illustrated
in FIG. 11, Measurement Set B has four time bins within the time
period corresponding to bin2 of Measurement Set A. By performing
measurements with time bins according to Measurement Set B, further
detail about the timing of arrival of photons may be obtained. For
example, as illustrated in FIG. 11, higher temporal resolution
about the timing of arrival of incident photons may be obtained
within a selected time interval. Such an adaptive time bin
determination process may allow obtaining a level of time
resolution using a relatively small number of bins (e.g., 4 bins)
that otherwise may necessitate a large number of bins (e.g., 16
bins).
[0277] In some embodiments, the timing for the time bins may be the
same in all pixels of the array. In some embodiments, the timing
may be different in different pixels such that different pixels
capture carriers in different time bins. For example, a first set
of pixels may capture carriers in a first set of time bins, and a
second set of pixels may capture carriers in a second set of time
bins that are at least partially different from the first set of
time bins. For example, one row of pixels may have the time timing
for their time bins and another row of pixels may have a different
timing for their time bins. In some embodiments, a first set of
rows of pixels (e.g., four rows) may have the same timing for their
time bins, and another set of rows of pixels (e.g., another four
rows) may have a different timing for their time bins. Pixels may
be set and/or programmed individually and/or as a group.
[0278] Pixels with Sub-Pixels
[0279] Wavelength Discrimination
[0280] In some embodiments, a pixel of a pixel array may include a
plurality of sub-pixels that are each capable of performing
different types of measurements. Any number of sub-pixels may be
included in a pixel.
[0281] FIG. 12 shows an example of a pixel 1100 that includes four
sub-pixels 100A. In some embodiments, each sub-pixel 100A in pixel
1100 may be configured to receive light of a different wavelength.
For example, filters may be formed above sub-pixels 100A that allow
photons of different wavelengths to be transmitted to sub-pixels
100A. For example, a first wavelength may be transmitted to a first
sub-pixel 100A, a second wavelength may be transmitted to a second
sub-pixel 100A, a third wavelength may be transmitted to a third
sub-pixel 100A, and a fourth wavelength may be transmitted to a
fourth sub-pixel 100A. A pixel 1100 having sub-pixels configured to
receive light of different wavelengths may allow both temporal and
spectral discrimination of incident light. In the fluorescence
lifetime measurement context, providing the capability of both
temporal and spectral discrimination may allow discriminating
different types of fluorescent molecules and/or markers having
different lifetimes, different spectral characteristics, or both
different lifetimes and different spectral characteristics.
[0282] Temporal Discrimination
[0283] In some embodiments, different sub-pixels 100A may be
controlled to sample time bins for different time intervals. For
example, a first sub-pixel 100A may be configured to sample a first
set of time bins and a second sub-pixel may be configured to sample
a second set of time bins. Similar structures in different
sub-pixels 100A may sample time bins for different time intervals
by controlling the timing of the charge carrier segregation
structure to be different in different sub-pixels.
[0284] Pixel Array/Chip Architecture
[0285] FIG. 13 shows a diagram of the chip architecture, according
to some embodiments. As shown in FIG. 13, an integrated circuit or
chip 1300 may include a pixel array 1302 including a plurality of
pixels 100, a control circuit 1304 that includes a timing circuit
1306, voltage/current bias generation circuits 1305 and an
interface 1308.
[0286] Pixel array 1302 includes an array of pixels 101 laid out in
any suitable pattern, such as a rectangular pattern, for example.
The pixel array 1302 may have any suitable number of pixels. In
some embodiments, the pixel array may have a 64.times.64 array of
4096 pixels 101, each including four sub-pixels 101A. However, the
techniques described herein are not limited as to the number or
arrangement of pixels and sub-pixels included in the pixel array
1302. The pixel array may have row and/or column conductors for
reading out rows or columns of the pixel array 1302. Pixels may be
read out in parallel, in series, or a combination thereof. For
example, in some embodiments a row of pixels may be read out in
parallel, and each row of the pixel array may be read out
sequentially. However, the techniques described herein are not
limited in this respect, as the pixels may be read out in any
suitable manner.
[0287] The pixel array 1302 is controlled by a control circuit
1304. Control circuit 1304 may be any suitable type of control
circuit for controlling operations on the chip 1300, including
operations of the pixel array 1302. In some embodiments, control
circuit 1304 may include a microprocessor programmed to control
operations of the pixel array 1302 and any other operations on the
chip 1300. The control circuit may include a computer readable
medium (e.g., memory) storing computer readable instructions (e.g.,
code) for causing the microprocessor performing such operations.
For example, the control circuit 1304 may control producing
voltages to be applied to electrodes of the charge carrier
segregation structure(s) in each pixel. The control circuit 1304
may change the voltages of one or more electrodes, as discussed
above, to capture carriers, transfer carriers, and to perform
readout of pixels and the array. The control circuit may set the
timing of operations of the charge carrier segregation structure
based on a stored timing scheme. The stored timing scheme may be
fixed, programmable and/or adaptive, as discussed above.
[0288] The control circuit 1304 may include a timing circuit 1306
for timing operations of the charge carrier segregation
structure(s) of the pixels or other operations of the chip. In some
embodiments, timing circuit 1306 may enable producing signals to
precisely control the timing of voltage changes in the charge
carrier segregation structure(s) to accurately time bin charge
carriers. In some embodiments the timing circuit 1306 may include
an external reference clock and/or a delay-locked loop (DLL) for
precisely setting the timing of the signals provided to the charge
carrier segregation structure(s). In some embodiments, two
single-ended delay lines may be used, each with half the number of
stages aligned 180-degrees out of phase. However, any suitable
technique may be used for controlling the timing of signals on the
chip.
[0289] The chip 1300 may include an interface 1308 for sending
signals from the chip 1300, receiving signals at the chip 1300, or
both. The interface 1308 may enable reading out the signals sensed
by the pixel array 1302. Readout from the chip 1300 may be
performed using an analog interface and/or a digital interface. If
readout from the chip 1300 is performed using a digital interface,
the chip 1300 may have one or more analog to digital converters for
converting signals read out from the pixel array 1302 into digital
signals. In some embodiments, the readout circuit may include a
Programmable Gain Amplifier. One or more control signals may be
provided to the chip 1300 from an external source via interface
1308. For example, such control signals may control the type of
measurements to be performed, which may include setting the timing
of the time bins.
[0290] Analysis of signals read out from the pixel array 1302 may
be performed by circuitry on-chip or off-chip. For example, in the
context of fluorescence lifetime measurement, analysis of the
timing of photon arrival may include approximating one or more
fluorescence lifetimes from a distribution of photons across the
time bins. Any suitable type of analysis may be performed. If
analysis of signals read out from the pixel array 1302 is performed
on-chip, chip 1300 may have any suitable processing circuitry for
performing the analysis. For example, chip 1300 may have a
microprocessor for performing analysis that is part of or separate
from control circuit 1304. If analysis is performed on-chip, in
some embodiments the result of the analysis may be sent to an
external device or otherwise provided off-chip through interface
1308. In some embodiments all or a portion of the analysis may be
performed off-chip. If analysis is performed off-chip, the signals
read out from the pixel array 1302 and/or the result of any
analysis performed by the chip 1300, may be provided to an external
device through interface 1308.
[0291] In some embodiments, the chip 1300 may include one or more
of the following:
[0292] 1) on-chip, digitally controlled, pixel bias generators
(DACs).
[0293] 2) on-chip, digitally programmable gain amplifiers that
convert the single-ended pixel output voltage signal to a
differential signal and applies gain to the signal
[0294] 3) digitally-controlled amplifier bias generators that allow
scaling the power dissipation with the output rate.
[0295] FIG. 14A shows a diagram of an embodiment of a chip 1300A,
which is an example of chip 1300 having a 64.times.64 array of quad
pixels, according to some embodiments. In the embodiment of FIG.
14A, half of the pixel output signals are provided via the top side
of the chip and the other half of the pixel output signals are
provided via the bottom side of the chip. Bias circuits are
included for setting the voltage of the electrodes of the charge
carrier segregation structures.
[0296] FIG. 14B shows a diagram of an embodiment of a chip 1300B,
which is an example of chip 1300 includes 2.times.2 arrays, with
each array having 256.times.64 octal pixels array of quad pixels,
according to some embodiments. Bandgap and bias circuits are
included. Digital to analog converts (DACs), including Vhigh DACs
and Vlow DACs are included for setting the high and low voltages of
the electrodes of the pixel array. FIG. 14B also shows light
monitoring sensors 1320. Each light monitoring sensor may include a
photodetector, such as a photodiode. In some embodiments, each
light monitoring sensor may include a quad array of photodetectors
(e.g., photodiodes) for aligning the chip 1300B with a light
source. In an embodiment in which the chip 1300B is configured for
detection of molecules, the light monitoring sensors may enable
alignment of the chip 1300B with a waveguide that receives light
from one or more locations in which the molecules are positioned.
Diode readout circuits and a diode select register is also shown in
FIG. 14B.
[0297] Examples of array sizes, dimensions, numbers of bins, and
feature sizes are described above and shown in the figures merely
by way of illustration, as any suitable of array sizes, dimensions,
numbers of bins, and feature sizes may be used.
[0298] Example Integrated Circuit Realization and Method of Forming
the Integrated Photodetector
[0299] In some embodiments, the chip 1300 may be formed in a
silicon substrate using a standard CMOS (Complementary Metal Oxide
Semiconductor) process. However, the techniques described herein
are not limited in this respect, as any suitable substrate or
fabrication process may be used.
[0300] FIGS. 15-22 illustrate a process of forming a chip 1300,
according to some embodiments.
[0301] FIG. 15A shows a perspective view of charge confinement
regions 103 that may be formed in a semiconductor substrate. FIG.
15B shows a plan view corresponding to FIG. 15A. In some
embodiments, charge confinement regions 103 may be formed in a bulk
semiconductor substrate 1500. However, the techniques described
herein are not limited to use of a bulk semiconductor substrate, as
any suitable type of semiconductor substrate may be used. In some
embodiments, the substrate 1500 and charge confinement regions 103
may be formed of monocrystalline silicon. However, the techniques
described herein are not limited in this respect, as any suitable
type of semiconductor material may be used. In some embodiments,
using a silicon substrate may enable using a cost-effective
industry standard CMOS process. However, any suitable fabrication
process may be used. In some embodiments, a bulk silicon substrate
having a p-type doping type may be used. However, any suitable
doping type may be used, including n-type doping or p-type
doping.
[0302] As shown in FIG. 15A, the charge confinement regions 103 may
be a raised portion of substrate 1500. Charge confinement regions
103 may be formed by etching away regions of the substrate 1500 in
the pattern shown in FIGS. 15A and 15B, thereby leaving raised
charge confinement regions 103 extending above the substrate. An
insulating layer may then be formed over and to the side of the
charge confinement regions 103. For example, in some embodiments an
insulating layer of silicon oxide may be formed on charge
confinement regions 103 by thermal growth. However, any suitable
technique may be used to form the insulating layer, and the
insulating layer may include any suitable insulating material.
[0303] As shown in FIG. 16, electrodes as illustrated in FIG. 3B
may be formed over the insulating layer by forming a patterned
polysilicon layer 1601. The electrodes may be spaced apart from one
another to allow different electrodes to be at different voltages.
The electrodes may be formed of any suitable conductive material.
In some embodiments, the electrodes may be formed of doped
polysilicon. However, the techniques described herein are not
limited to forming the electrodes of polysilicon, as any suitable
conductive material may be used to form the electrodes (e.g., a
metal). Conductive vias 1701 may be formed over the patterned
polysilicon layer 1601 to contact the polysilicon layer 1601
through an insulating layer (not shown) overlying the patterned
polysilicon layer 1601. The conductive vias 1701 may be formed of
any suitable conductor.
[0304] In some embodiments, one or more electrodes (e.g., of
polysilicon layer 1601) may be split-doped electrodes having both
p- and n- type dopants. A split-doped electrode may enable forming
a potential well to capture a carrier, as illustrated in FIG. 17.
FIG. 17 shows a split-doped electrode 2302 having a p+ region and
an n+ region. The n+ region and the p+ region produce different
potential levels in the underlying semiconductor. As shown in FIG.
17, the n+ region of split-doped electrode 2302 may produce a
potential well under the n+ region that can confine charge carriers
(e.g., electrons). FIG. 17 illustrates that keeping the voltage of
the split-doped electrode 2302 high may produce a potential
gradient as shown in dashed lines, which may confine charge
carriers (e.g., electrons) in a potential well 2304. Lowering the
voltage of split-doped electrode 2302 may raise the electric
potential under the split-doped electrode 2302 to enable
transferring charge trapped in the potential well 2304 to a charge
storage bin, for example.
[0305] Dopants may be formed in the semiconductor material to
enable forming transistors of the readout circuitry 110. In some
embodiments, a mask may be disposed over the charge confinement
region 103 to prevent the doping of charge confinement region 103
during the formation of the transistors of readout circuitry 110,
as doping charge confinement region 103 may form undesired
potential wells in the charge confinement regions 103.
[0306] FIG. 18 shows the formation of a metal layer 1801 (e.g.,
metal 1) over the patterned polysilicon layer 1601 to connect to
the vias 1701. FIG. 19 shows the metal layer 1801 overlaid on the
polysilicon layer 1601 and charge confinement regions 103.
[0307] FIG. 20 shows the formation of vias 1901 to contact the
metal layer 1801. Conductive vias 1901 may be formed over the metal
layer 1801 to contact the metal layer 1801 through an insulating
layer (not shown) overlying the metal layer 1801. FIG. 20 also
shows the formation of a second metal layer 2001 (e.g., metal 2)
over the metal layer 1801 and vias 1901.
[0308] FIG. 21 shows the second metal layer 2001 as well as
formation of via(s) 2101 over the metal layer 2001 to contact the
metal layer 2001 through an insulating layer (not shown) overlying
the metal layer 2001.
[0309] FIG. 22 shows the formation of a third metal layer 2201
(e.g., metal 3) over the metal layer 2001 and the via(s) 2101 to
contact the vias 2101.
[0310] The foregoing process is described by way of illustration,
as the techniques described here are not limited to any particular
fabrication process. Further, the techniques described herein are
not limited as to the particular layout shown.
[0311] Drive Circuitry for the Charge Carrier Segregation
Structure
[0312] The electrodes of the charge carrier segregation structure
that overlie the substrate may have a substantial parasitic
capacitance. Changing the voltages on the electrodes necessitates
charging or discharging the parasitic capacitance. The speed with
which current can be provided to charge or discharge the parasitic
capacitance limits the speed at which the voltage of an electrode
can be changed. As discussed above, in some embodiments charge
carriers may be captured and transferred into time bins with
nanosecond or picosecond resolution. The inventors have recognized
and appreciated that the timing with which charge carriers may be
captured may have a higher precision if the voltage of electrodes
b0-bm-1 change more quickly, thereby raising the potential barriers
at precise moments in time. However, rate of change of the voltage
on electrodes b0-bm-1 is limited due to the parasitic inductance
and equivalent series resistance (ESR) of the connection between
the voltage supply and the electrodes b0-bm-1.
[0313] Further, charging and discharging the parasitic capacitances
of the electrodes may consume significant power. The power
dissipated by charging and discharging an electrode is
P.sub.diss=(1/2)fCV.sup.2, where C is the capacitance between the
electrode and the substrate, V is the voltage difference between
the electrode and the substrate, and f is the frequency with which
the voltage is switched.
[0314] FIG. 23 shows an example of a drive circuit 2300 for driving
an electrode 2301 of the charge carrier segregation structure,
according to some embodiments. Electrode 2301 is illustrated as a
capacitor in FIG. 23. As discussed above, the electrode 2301 may be
driven to a relatively low voltage V.sub.low and a relatively high
voltage V.sub.high at selected times. The drive circuit 2300
includes a VdacH generator 2302 that produces the high voltage
V.sub.high and a VdacL generator 2304 that produces the low voltage
V.sub.low. In some embodiments, the difference between V.sub.low
and V.sub.high, may be made as small as possible for the electrode
to influence charge carriers in the manner designed, thereby
reducing or minimizing power dissipation. In some embodiments,
VdacH generator 2302 and/or VdacL generator 2304 may be
programmable voltage generators that can produce desired voltages
V.sub.low and/or V.sub.high, and can allow changing V.sub.low
and/or V.sub.high.
[0315] The drive circuit 2300 also includes Bclk generator 2306,
which can produce a timing signal for timing voltage transitions of
the electrode 2301. The Bclk generator 2306 may be programmable,
and may allow digitally selecting the times at which the edges of
the timing signal occur, based on an input digital word. In some
embodiments, the Bclk generator 2306 may be implemented using a
delay locked loop (DLL), as discussed above. The timing signal from
the Bclk generator 2306 is provided to the input of the Bclk driver
2312 which drives the electrode 2301.
[0316] The drive circuit 2300 also includes a VdacH amplifier 2308
and a VdacL amplifier 2310. The VdacH amplifier 2308 receives a
signal from the VdacH generator and controls transistor 2314 using
feedback to provide the voltage VdacH to the high power supply
terminal of the Bclk driver 2312. The VdacH amplifier 2308 also
charges capacitor 1312A to the voltage VdacH. The VdacL amplifier
2310 receives a signal from the VdacL generator and controls
transistor 2316 using feedback to provide the voltage VdacL to the
low power supply terminal of the Bclk driver 2312. The VdacL
amplifier 2310 also charges capacitor 1312B to the voltage
VdacL.
[0317] As discussed above, the electrode 2301 may have substantial
capacitance. To supply enough current to charge the electrode 2301
with high speed, decoupling capacitors 1312A and 1312B may be
provided to supply current to the to the low power supply terminal
of the Bclk driver 2312 or the high power supply terminal of the
Bclk driver 2312 during transitions.
[0318] The decoupling capacitor(s) may be positioned in close
proximity to the electrode to limit the parasitic inductance and
equivalent series resistance (ESR) between the electrode and the
decoupling capacitor. When the voltage of an electrode is changed
to a new voltage, the electrode is connected to the decoupling
capacitor at the new voltage to supply current to the electrode
through a current path having low parasitic inductance and/or
equivalent series resistance (ESR), so that the voltage of the
electrode can be changed quickly. In some embodiments, the
decoupling capacitor may be positioned close enough to the
electrode such that the parasitic inductance between the decoupling
capacitor and the electrode is less than 3 nH, less than 2 nH, or
less than 1 nH. In some embodiments, the equivalent series
resistance (ESR) of the current path between the decoupling
capacitor and the electrode is less than 70 ohms, less than 35
ohms, or less than 5 ohms. However, these values are provided
merely by way of example, as the techniques described herein are
not limited to specific values of inductance or resistance.
[0319] In some embodiments, electrodes b0-bm-1 may be connectable
to one or more decoupling capacitors. In some embodiments, each
electrode b0-bm-1 may have its own decoupling capacitors(s). For
example, in some embodiments an electrode may have a single
decoupling capacitor coupled between the high and low voltage
supplies of the electrode, or two decoupling capacitors
respectively coupled to the high voltage supply and the low voltage
supply. However, the techniques described herein are not limited in
this respect. Any or all of the electrodes of the charge carrier
segregation structure may be connected to decoupling
capacitors.
[0320] The decoupling capacitors may have any suitable capacitance
value. In some embodiments, the capacitance value of a decoupling
capacitor is ten to one hundred times the capacitance of the
electrode to which it is to be connected. In some embodiments, the
capacitance of a decoupling capacitor may be at least 150 pF, at
least 300 pF, or at least 3 nF or higher. However, these values are
provided merely by way of example, as the techniques described
herein are not limited to specific values of capacitance.
[0321] A decoupling capacitor may be on-chip or off-chip. FIG. 24
shows an embodiment in which chip 1300 is affixed to a printed
circuit board 1310, which may be termed a "chip-on-board" or
"die-on-board" implementation. Wire bonds may connect the chip 1300
to one or more decoupling capacitors 1312 on the printed circuit
board 1310, thereby providing current path having low parasitic
inductance and/or equivalent series resistance (ESR) between an
electrode of the chip 1300 and a decoupling capacitor 1312. In some
embodiments, off-chip decoupling capacitors may be positioned
within 1 cm, or within 5 mm of the chip 1300 or less. However the
techniques described herein are not limited in this respect. As
mentioned above, decoupling capacitor(s) may be formed on the chip
1300.
[0322] As discussed above, charging and discharging the electrodes
of the charge carrier segregation structure may dissipate
significant power. In some embodiments, the one or more rows of
pixels of the chip 1300 and their corresponding electrodes may be
disabled, which may limit the power consumption of the chip 1300.
The chip 1300 may be programmable in this respect, and may allow
selecting which rows will be enabled or disabled. The rows that are
enabled and disabled may be changed over time.
[0323] FIG. 25 illustrates enabling 32 rows in a central region of
the chip and disabling 48 rows at the edges of the chip. Disabling
one or more rows of the chip may allow reducing power consumption
in situations or applications where not all the rows of the chip
are needed.
ADDITIONAL ASPECTS
[0324] In some embodiments, techniques described herein may be
carried out using one or more computing devices. Embodiments are
not limited to operating with any particular type of computing
device.
[0325] FIG. 26 is a block diagram of an illustrative computing
device 1000 that may be used to implement a control circuit for
controlling the pixel array or for performing analysis of the data
from the pixels. Computing device 1000 may include one or more
processors 1001 and one or more tangible, non-transitory
computer-readable storage media (e.g., memory 1003). Memory 1003
may store, in a tangible non-transitory computer-recordable medium,
computer program instructions that, when executed, implement any of
the above-described functionality. Processor(s) 1001 may be coupled
to memory 1003 and may execute such computer program instructions
to cause the functionality to be realized and performed.
[0326] Computing device 1000 may also include a network
input/output (I/O) interface 1005 via which the computing device
may communicate with other computing devices (e.g., over a
network), and may also include one or more user I/O interfaces
1007, via which the computing device may provide output to and
receive input from a user. The user I/O interfaces may include
devices such as a keyboard, a mouse, a microphone, a display device
(e.g., a monitor or touch screen), speakers, a camera, and/or
various other types of I/O devices.
[0327] The above-described embodiments can be implemented in any of
numerous ways. For example, the embodiments may be implemented
using hardware, software or a combination thereof. When implemented
in software, the software code can be executed on any suitable
processor (e.g., a microprocessor) or collection of processors,
whether provided in a single computing device or distributed among
multiple computing devices. It should be appreciated that any
component or collection of components that perform the functions
described above can be generically considered as one or more
controllers that control the above-discussed functions. The one or
more controllers can be implemented in numerous ways, such as with
dedicated hardware, or with general purpose hardware (e.g., one or
more processors) that is programmed using microcode or software to
perform the functions recited above.
[0328] In this respect, it should be appreciated that one
implementation of the embodiments described herein comprises at
least one computer-readable storage medium (e.g., RAM, ROM, EEPROM,
flash memory or other memory technology, CD-ROM, digital versatile
disks (DVD) or other optical disk storage, magnetic cassettes,
magnetic tape, magnetic disk storage or other magnetic storage
devices, or other tangible, non-transitory computer-readable
storage medium) encoded with a computer program (i.e., a plurality
of executable instructions) that, when executed on one or more
processors, performs the above-discussed functions of one or more
embodiments. The computer-readable medium may be transportable such
that the program stored thereon can be loaded onto any computing
device to implement aspects of the techniques discussed herein. In
addition, it should be appreciated that the reference to a computer
program which, when executed, performs any of the above-discussed
functions, is not limited to an application program running on a
host computer. Rather, the terms computer program and software are
used herein in a generic sense to reference any type of computer
code (e.g., application software, firmware, microcode, or any other
form of computer instruction) that can be employed to program one
or more processors to implement aspects of the techniques discussed
herein.
[0329] Various aspects of the present invention may be used alone,
in combination, or in a variety of arrangements not specifically
discussed in the embodiments described in the foregoing and is
therefore not limited in its application to the details and
arrangement of components set forth in the foregoing description or
illustrated in the drawings. For example, aspects described in one
embodiment may be combined in any manner with aspects described in
other embodiments.
[0330] Use of ordinal terms such as "first," "second," "third,"
etc., in the claims to modify a claim element does not by itself
connote any priority, precedence, or order of one claim element
over another or the temporal order in which acts of a method are
performed, but are used merely as labels to distinguish one claim
element having a certain name from another element having a same
name (but for use of the ordinal term) to distinguish the claim
elements.
[0331] Also, the phraseology and terminology used herein is for the
purpose of description and should not be regarded as limiting. The
use of "including," "comprising," or "having," "containing,"
"involving," and variations thereof herein, is meant to encompass
the items listed thereafter and equivalents thereof as well as
additional items.
* * * * *