|United States Patent
,   et al.
March 14, 2000
Sensors for detection and spectroscopy
For multicolor fluorescence detection or spectroscopy with low
signal-to-noise ratio and rapid readout, signals from multiple sensors are
combined in analog form so that only one signal per fluorescent response
needs to be read from a sensor array. The contributions of sensors in the
array to a given output signal are programmable, for exclusive selection
of the desired information. As the contributions of sensors to output
signals are electronically programmed, the energy of the light source can
be filtered electronically. Such devices can be programmed in real time
for adaptive measurements.
Carlson; Bradley S. (Northport, NY);
Gouzman; Mikhail (Lake Grove, NY);
Gorfinkel; Vera (Stony Brook, NY);
Luryi; Serge (Old Field, NY)
The Research Foundation of State University of New York (Stony Brook, NY)
July 31, 1998|
|Current U.S. Class:
||356/326; 356/328 |
|Field of Search:
References Cited [Referenced By]
U.S. Patent Documents
|4320971||Mar., 1982||Hashimoto et al.||356/328.
|5822058||Oct., 1998||Adler-Golden et al.||356/303.
|Foreign Patent Documents|
|WO 91/03714||Mar., 1991||WO||356/326.
Primary Examiner: Evans; F. L.
Attorney, Agent or Firm: Baker Botts LLP
1. A detector comprising:
a diffractive element which is configured and disposed for receiving
electromagnetic radiation and for generating a spectrum from the received
a plurality of radiation-sensitive elements wherein each
radiation-sensitive element is disposed and configured to receive a
different portion of the spectrum and to generate a signal depending on
radiation in its portion of the spectrum;
a control means configured for holding a control entry for each of the
radiation-sensitive elements, operationally coupled to the
radiation-sensitive elements such that each of the radiation-sensitive
elements is operationally coupled for outputting its signal depending on
the status of its control entry; and
a multiplexer operationally coupled for multiplexing the output signals
from the radiation sensitive elements.
2. The detector according to claim 1, wherein the diffractive element
comprises a prism.
3. The detector according to claim 1, wherein the diffractive element
comprises a grating.
4. The detector according to claim 1, configured for outputting the signals
from the radiation-sensitive elements individually.
5. The detector according to claim 1, configured for combining the signals
from the radiation-sensitive elements whose signals are being outputted.
6. The detector according to claim 5, wherein combining comprises adding.
7. The detector according to claim 1, configured for combining selected
ones of the signals from the radiation-sensitive elements onto selected
ones of a plurality of outputs.
8. The detector according to claim 7, wherein combining comprises adding.
9. The detector according to claim 7, wherein each of the selected ones of
the signals from the radiation-sensitive elements is combined onto exactly
one of the plurality of outputs.
10. The detector according to claim 9, wherein combining comprises adding.
11. The detector of claim 7, wherein at least some of the selected ones of
the signals from the radiation-sensitive elements are combined onto more
than one of the plurality of outputs.
12. The detector according to claim 11, wherein combining comprises adding.
13. The detector according to claim 1, wherein the control means comprises
a control register.
14. The detector according to claim 13, wherein the control means comprises
a plurality of switching devices, with each switching device being
operationally coupled to an entry in the control register.
15. The detector according to claim 14, wherein each switching device
comprises a CMOS.
FIELD OF THE INVENTION
The invention relates to radiation detection and, more particularly, to
spectral radiation detection.
BACKGROUND OF THE INVENTION
Electromagnetic radiation detectors and spectrometers are being used to
measure the emission of radiation from samples of solids, liquids and
gases. Typically, a sample is excited with suitable first radiation to
stimulate the emission of second radiation, and the latter is analyzed to
identify characteristics of the sample. This general principle is applied
in medical imaging, DNA sequencing and other materials analysis, laser
In a variety of applications it is important to measure the spectral
content of electromagnetic radiation, for which purpose spectrometers and
calorimeters are typically being used. Other applications involve spectral
pattern recognition, wherein specialized signal processing is performed in
addition to spectral measurements. In many applications, such as detection
and identification of fluorescent objects, it is important to be able to
measure selected bands of a received spectrum, and it is often
advantageous to be able to change the selection of the measured bands in
the course of the measurement.
To measure selected spectral bands, certain known devices scan a dispersed
spectrum, or apply signal processing of a spectral image obtained by
optical dispersion. Both of these techniques suffer from being relatively
slow, so that they are inconvenient where rapidly varying spectral
information needs to be processed, such as, e.g., information obtained in
spectroscopy of modulated radiation.
SUMMARY OF THE INVENTION
For rapid reconfiguration of signals corresponding to different spectral
bands of received electromagnetic radiation, a preferred technique in
accordance with the invention provides for grouping of several selected
spectral bands. Signals from selected sets of pixels of a photo-receiving
array or matrix are combined into one or several registration paths.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a graphic representation of typical fluorescent response of a
solid, liquid or gas sample.
FIG. 2 is a graphic representation of the fluorescent response according to
FIG. 1, further illustrating selected spectral bands of interest.
FIG. 3 is a graphic representation of data acquired by a prior-art
spectrometer based on the fluorescent response according to FIG. 1.
FIG. 4 is a schematic of a fluorescent spectrometer.
FIG. 5 is a graphic representation illustrating selection of spectral bands
to optimize signal acquisition for multiple fluorescent responses.
FIG. 6 is a block diagram of a multicolor detector in accordance with a
preferred first embodiment of the invention.
FIG. 7 is a block diagram of a multicolor detector for detecting responses
from multiple fluorophores in accordance with a preferred second
embodiment of the invention.
FIG. 8 is a block diagram of a programmable spectrometer in accordance with
a preferred third embodiment of the invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
For specificity and exemplification, preferred sensors are described in the
following for optical detection and spectroscopy of fluorescence.
Applications within the scope of the invention further include sensors for
other types of electromagnetic radiation, as well as for non-radiative
quantities such as gas concentrations, for example.
Excitation of a fluorescent sample produces fluorescence. A fluorescent
sample may be excited by an external modulated light source such as a
laser, for example, and generate a modulated fluorescent signal in
response. A fluorescent sample may be naturally fluorescent, or become
fluorescent when fluorescent markers (fluorophores) are added. The
characteristic fluorescence can be used to determine the material
composition, e.g., to detect when fluorophores are added to a solution, to
identify the fluorescent species added, and to quantify the amount of the
added species. A typical fluorescent response of a solid, liquid or gas
sample is shown in FIG. 1. The sample is excited by the laser source and
the fluorescent response is produced by the atomic interaction of the
light and the sample. The fluorescent response can be acquired using an
optical spectrometer. The wavelength of the light source is controlled,
and the response is measured using an optical spectrometer or detector. An
optical spectrometer divides the optical spectrum into discrete spectral
bands and collects photons from each of the bands. The spectrometer
outputs a sequence of electrical signals corresponding to the intensity of
light in each spectral band. Using terminology from electronic imaging,
such a sequence of electrical signals will be referred to as a frame of
data. This sequence of signals can be processed to produce a diagram
similar to that of FIG. 1.
While the inventive technique is described in the following primarily in
the instance of stimulated fluorescence, other forms of stimulated optical
response are not precluded, such as reflection, transmission, Raman and
the like. Furthermore, the inventive technique can be applied
advantageously to measurement of the spectral composition of various types
of radiation, especially radiation whose spectral composition varies in
An optical detector differs functionally as compared to an optical
spectrometer. While the spectrometer's purpose is to faithfully account
for the distribution of light intensities over a spectral region, the
purpose of an optical detector is to measure the total intensity received
in its optical input. The optical input may comprise a narrow spectral
region, a wide spectral region, or a plurality of spectral bands having
different widths. Typically, an optical detector has higher sensitivity in
specialized spectral regions. For many applications it may be advantageous
to combine the spectral resolution of a spectrometer with the sensitivity
of an optical detector. For example, in the case of fluorescent response,
one is often interested in a spectral shape as illustrated in FIG. 2,
comprising the entire fluorescent response except for a region around the
laser line that has caused the fluorescent response.
The output signals of the spectrometer corresponding to the spectral bands
of interest can be accumulated external to the sensor. In known
spectrometers it is necessary to read the entire sequence of signals from
the spectrometer, from which signals of interest are then selected.
Single, discrete optical detectors are not ideal for fluorescence
detection because the wavelength of the laser source often falls within
the spectral sensitivity of the detector. Optical filtering is necessary
to suppress the radiation of the laser. In addition, the spectral response
of discrete optical detectors is difficult to control.
Known modular spectrometers utilizing charge-coupled device (CCD) sensors
include optics that spatially distributes the light by wavelength over a
linear CCD sensor, with each pixel in the line sensor collecting photons
in a given spectral band. To measure the fluorescence of a sample, the
entire CCD array is read out and signal processing is performed on a
digital computer. FIG. 3 shows the response of this type of spectrometer
to the fluorescence in FIG. 1.
Although many of the pixels of the sensor collect photons from background
noise only, and are not useful for the measurement desired, the nature of
the CCD requires that all pixels be read. Also, the spatial resolution of
the CCD is fixed, so that many pixels collect photons from the same
fluorescent response and must be accumulated outside the spectrometer.
Furthermore, digital processing is required to separate the energy of the
laser source from the energy of the fluorescence.
In recent years the use of CMOS (complementary metal oxide semiconductor)
technology has received attention for the implementation of image sensors,
e.g. for general purpose imagers and vision systems. CMOS imaging systems
have several advantages which include lower cost and higher frame rate,
which is important for imaging rapidly moving pictures and for handling
temporally modulated radiation. Another technical advantage of CMOS
imagers is the absence of interference between nearby pixels which is due
to electric charge spreading inherent in many CCD designs.
A particular further advantage of CMOS imagers is that they permit rapid
reconfiguration of the sensor, as well as flexible control and signal
processing. As a result, CMOS imagers have proven useful in vision
systems, where it is important to adapt to wide and rapid variations in
The fluorescent spectrometer of FIG. 4 is shown with a source 41 of
radiation for stimulating fluorescence in a sample 49, an optical fiber 42
for receiving fluorescent radiation, a prism 43, and a detector array 44
for producing an electrical signal output. Known spectrometers, e.g. Ocean
Optics, Model 2000, utilize a CCD detector array. The spectral resolution
is fixed by the characteristics of the dispersive element exemplified by
the prism 43, and can be changed only by manually retrofitting the device
with a new dispersive element.
Preferred detectors and spectrometers in accordance with the invention are
advantageous over known CCD-based spectrometers in that the width of the
spectral bands is programmable, and only those signals which are useful
for a desired measurement are read out of the spectrometer. The photons
from any set of spectral bands can be collected and read out as one
signal. The width of the spectral bands selected need not be uniform
across the array. Thus, photons from multiple fluorescent responses can be
collected simultaneously, and the spectral bands can be selected to
optimize signal-to-noise ratio.
In accordance with an aspect of the invention, a sensor can be programmed
such that any number of signals corresponding to selected spectral bands
are read out of the spectrometer, e.g. so that only one electrical signal
per fluorescent response is read out per frame. For example, as
illustrated by FIG. 5, the spectrometer can be programmed such that a
frame of data contains only two signals, one for each of two fluorescent
responses. Furthermore, each signal contains information from multiple
sensors so the signal-to-noise ratio can be optimized and the energy of
the laser source can be filtered electronically. The acquisition time
compared to a CCD sensor is improved by several orders of magnitude,
because only the signals of interest need to be read from the sensor
array. The device can be programmed automatically from the information of
one entire frame of data. During an experiment, such as DNA sequencing by
electrophoresis, the device can be re-programmed in real time to adapt to
changing experimental conditions such as drift of fluorescent wavelengths
(e.g., due to temperature variations) and instabilities of the light
source excitation spectrum, such as temperature instabilities known to
occur in semiconductor lasers.
The invention is particularly advantageous when the excitation source is
modulated. The sensor and read-out circuitry can be designed to operate in
continuous-time mode, permitting straightforward demodulation of the
collected radiation signal. This advantage may be appreciated especially
vis-a-vis CCD-based devices which are inherently discrete-time due to
their method of photo-electric conversion which makes demodulation of
collected radiation difficult. To obtain functionality similar to that of
the invention, a CCD-based spectrometer would have to be coupled to a
digital computer with custom software for signal processing, amounting to
orders of magnitude more resources. In accordance with an aspect of the
invention, optical band selection requires minimal hardware for real-time
readout of selected information only, without readout of extraneous
information. The selection can be changed simply by writing new control
information into the control register, in real time.
For sensing electromagnetic radiation, sensor devices are not restricted as
to type or spectral sensitivity. For example, sensors with continuous-time
mode of photoelectric conversion such as photo diodes can be used, and
sensitivity may lie outside the visible and near-infrared wavelength range
of a CCD-based system.
Programmable Multiwavelength Detector
The systems described in the following generally use an optical system of
the type depicted in FIG. 4. The light source is interfaced to the system
by fiber optical or other means, and the light is distributed in the
optical spectrum using a prism or a diffractive element and focused onto a
detector or sensor array. Novel sensor arrays in accordance with the
invention significantly improve the performance and flexibility of such
systems for multiwavelength detection and spectroscopy. The new sensor
architecture can be used with any array of sensors, which can be
integrated with sensor read-out electronics on the same crystal of silicon
in the case of visible-light silicon p-n junction or silicon photogate
sensors. The sensor array can also be separate from the read-out
electronics and interfaced to it using known bonding and assembly
techniques. Suitable read-out electronics are included depending on the
sensor type, e.g., for visible or non-visible electromagnetic radiation
sensors, chemical sensors, magnetic sensors, acoustic sensors, and the
like. In the specific embodiments described below, sensor arrays are
linear, but different arrangements are not precluded, such as two
dimensional arrays, for example.
As shown in FIG. 6, each pixel 61 contains a photosensitive element 62 and
a switch 63 that is controlled by the content of a binary memory element
in the control register 64. A set of pixels, not necessarily contiguous,
or spectral bands are selected by writing a bit pattern to the control
register. The photocurrents of the selected pixels are summed at the input
of the amplifier 65. Antiblooming techniques can be used so that
electron-hole pairs excited by the absorption of photons in unselected
pixels recombine without affecting neighboring pixels. The elements 62 can
be operated in integrating mode or continuous mode, and the amplifier can
be integrated on-chip with the sensors or connected external to the chip.
The control circuitry can be implemented in CMOS technology, and the
photosensitive elements can be implemented in CMOS also, in forming a
monolithic device, or in any other suitable sensor technology, in forming
a hybrid device.
Information from several fluorescent responses can be encoded in a single
electrical signal and decoded electronically. E.g., the light sources for
each fluorescent response can be modulated at different frequencies. The
spectral bands corresponding to each fluorescent response can be selected
for read-out, and the electrical signals are encoded according to the
modulation frequencies of the light sources. The separate signals can be
decoded from the read-out signal with the knowledge of the modulation
For simultaneous and independent readout of several spectral bands, 1 to n,
FIG. 7 shows each pixel 71 having a photosensitive element 72 and n
switches 731 to 73n. The switches are under the control of bits in a bit
pattern in the control register 74. Separate amplifiers 751 to 75n are
associated with the pixels. A single pixel can be selected to contribute
to any number of outputs, and the number of outputs is limited only by the
pin-out of the packaging technology. This is on the order of hundreds for
current packaging technologies. Photosensitive elements can be in CMOS or
in a more sensitive technology, for example. The photosensors 72 can be
continuous-time photodetectors, and the output amplifiers 751 to 75ncan be
on or off chip.
FIG. 8 illustrates a programmable spectrometer which can be programmed to
control spectral resolution and read-out. The spectrometer includes a row
of photosensitive elements 82 for pixels 81, and control circuitry
including switches 83, a control register 84 as described above for FIGS.
6 and 7, amplifiers 85, a multiplexer 86, and a sequencer 87. For a
two-dimensional array of pixels, the control register bit can be included
within the pixel. The photosensors operate in an integrating mode or a
continuous mode. A bit pattern is written to the control register 84 to
select the spatial resolution. If the switch between two pixels is closed,
the signals induced by the photons incident on both sensors contribute to
the same output signal. Spectral bands of arbitrary width can be selected,
but only adjacent pixels can be selected to contribute to an output
signal. For a sensor with 100 pixels, and with light spread over an
optical band 100 nm wide, the optical spatial resolution of the sensor is
1 nm per pixel. If the switches between k adjacent pixels are closed, then
the acquired signal corresponds to the accumulation of photons in an
optical band k.times.1 nm wide. The sequencer 87 controls signal read-out
of the pixel array using virtual addressing. It is initialized with a
count and a set of addresses corresponding to the sets of pixels to be
read. One frame of read-out consists only of those pixels whose addresses
are stored in the sequencer. To read the signal from a group of pixels,
any one of the pixels in the group can be selected by the sequencer.
* * * * *