# US 2013/0157282 A1 · Chemiluminescence compact imaging scanner

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- Number: US 2013/0157282 A1
- Document ID: US20130157282A1
- Status: Published application
- Kind: A1
- Application number: 13/432,410
- Filed: 2012-03-28
- Published: 2013-06-20
- Earliest claimed: 2011-12-16
- Assignees: LI-COR, Inc.
- Inventors: Ahmed Bouzid; Chris Lesiak; Daniel W. Konz; David L. Franzen; William Biggs; Jon P. Anderson
- Web page: https://patentgrep.com/patent/US20130157282A1

## CPC

- C12Q 1/6825: Nucleic acid detection involving sensors
- G01J 1/0403: {Mechanical elements; Supports for optical elements; Scanning arrangements}
- G01N 21/62: Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N 21/6486: {Measuring fluorescence of biological material, e.g. DNA, RNA, cells (G01N21/6428 takes precedence)}
- G01N 21/76: Chemiluminescence; Bioluminescence
- G01N 33/53: Immunoassay; Biospecific binding assay; Materials therefor
- G01N 33/5302: {Apparatus specially adapted for immunological test procedures}
- G01N 33/54373: {involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings}
- H04N 1/1017: {the main-scanning components remaining positionally invariant with respect to one another in the sub-scanning direction}
- H04N 1/191: the array comprising a one-dimensional [1D] array
- H04N 1/1933: {Staggered element arrays, e.g. arrays with elements arranged in a zigzag}
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01J: MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY (light sources F21, H01J, H01K, H05B; investigating properties of materials by optical means G01N)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- H04N: PICTORIAL COMMUNICATION, e.g. TELEVISION

## Abstract

Systems, devices, and methods for accurately imaging chemiluminescence and other luminescence are disclosed. A compact, flat-bed scanner having a light-tight enclosure, one or more detector bars of linear charge-coupled device (CCD) or complementary metal oxide semiconductor (CMOS) imaging chips, and high working numerical aperture (NA) optics scans closely over a sample in one direction and then the opposite direction. Averages or other combinations of intensity readings for each pixel location (x, y) between the two or more passes are averaged together in order to compensate for luminescence that varies over time. On-chip pixel binning and multiple clock frequencies can be used to maximize the signal to noise ratio in a CCD-based scanner.

## Claims

### Claim 1

A luminescence scanner apparatus comprising:
a sample bed configured to hold a luminescent sample medium;
a detector bar comprising one or more image sensor arrays, each image sensor array having a plurality of pixel elements, the pixel elements adapted to detect photons simultaneously with one another, the detector bar configured to move with respect to the sample bed;
a motor configured to move the detector bar with respect to the sample bed in a first direction and move the detector bar with respect to the sample bed in a second direction opposite the first direction;
a circuit operatively coupled with the motor and having instructions to move the detector bar with respect to the sample bed in the first direction in a first pass and store a first pixel reading from a position in the first pass and then to move the detector bar with respect to the sample bed in the second direction in a second pass and take a second pixel reading at the same position during the second pass and combine the pixel readings of the same position from the first and second passes; and
a circuit having instructions to construct an image from the combined pixel readings.

### Claim 2 (depends on 1)

The apparatus of claim 1 wherein combining the pixel readings includes averaging the pixel reading from the position in the first pass with the pixel reading from the same position in the second pass.

### Claim 3 (depends on 1)

The apparatus of claim 1 wherein the at least one of the one or more image sensor arrays comprises a charge-coupled device (CCD) sensor array.

### Claim 4 (depends on 3)

The apparatus of claim 3 wherein the CCD sensor array is integrated within an integrated circuit (IC), the apparatus further comprising:
a circuit having instructions to sum multiple photo-charges from adjacent CCD photodiodes into a readout capacitor of the CCD sensor array,
thereby increasing a signal to noise ratio of the CCD sensor array.

### Claim 5 (depends on 1)

The apparatus of claim 1 wherein the one or more image sensor arrays are not cooled below 0 degrees Celsius.

### Claim 6 (depends on 1)

The apparatus of claim 1 wherein the detector bar comprises a plurality of linear image sensor array integrated circuits (ICs) staggered with respect to each other along the detector bar.

### Claim 7 (depends on 6)

The apparatus of claim 6 wherein the linear image sensor array ICs overlap one another longitudinally on the detector bar.

### Claim 8 (depends on 1)

The apparatus of claim 1 further comprising:
a second detector bar comprising one or more image sensor arrays, the second detector bar configured to move with respect to the sample bed,
wherein the detector bars are configured to scan over different, non-overlapping areas of the sample bed; and
a circuit having instructions to construct the image from pixel readings from both of the detector bars.

### Claim 9 (depends on 8)

The apparatus of claim 8 wherein the detector bars are further configured to scan over a common, overlapping portion of the sample bed in addition to their respective non-overlapping areas.

### Claim 10 (depends on 1)

The apparatus of claim 1 wherein the detector bar is configured to be moved and the sample bed is configured to be physically stationary.

### Claim 11

(canceled)

### Claim 12 (depends on 1)

The apparatus of claim 1 wherein the luminescent sample medium is selected from a nylon membrane, a nitrocellulose membrane, and a well plate.

### Claim 13 (depends on 1)

The apparatus of claim 1 further comprising:
a gradient index (GRIN) lens array disposed between the sample bed and the one or more image sensor arrays, the GRIN lens array having a working numerical aperture (NA) of greater-than-or-equal-to 0.10.

### Claim 14 (depends on 13)

The apparatus of claim 13 wherein the GRIN lens array is disposed between 1 and 100 millimeters of the sample bed.

### Claim 15 (depends on 1)

The apparatus of claim 1 further comprising:
a light tight enclosure configured to enclose the sample bed.

### Claim at position 16

16-31. (canceled)

### Claim 32 (depends on 1)

The apparatus of claim 1 wherein the first pass occurs over an amount of time and the second pass occurs over an equal amount of time.

### Claim 33 (depends on 3)

The apparatus of claim 3 wherein the CCD sensor array is integrated within an integrated circuit (IC), the apparatus further comprising:
a circuit having instructions to:
apply a first CCD clock frequency to the CCD sensor array; and then
apply a fixed preset voltage to a readout capacitor of the CCD sensor array;
sample a value of the preset voltage on one or more output pins on the CCD sensor array; and then
apply a second CCD clock frequency to the CCD sensor array; and then
clock multiple photon-induced charges from adjacent CCD pixel elements into the readout capacitor of the CCD sensor array.

### Claim 34

A luminescence scanner apparatus comprising:
a sample bed configured to hold a luminescent sample medium;
a moveable detector bar comprising one or more image sensor arrays;
a circuit having instructions to:
move the detector bar in a first pass and take a first pixel reading at a position in the first pass;
move the detector bar in an opposite direction in a second pass and take a second pixel reading at the same position during the second pass; and
combine the pixel readings of the same position from the first and second passes; and
a circuit having instructions to construct an image from the combined pixel readings.

### Claim 35 (depends on 34)

The apparatus of claim 34 wherein combining the pixel readings includes averaging the pixel reading from the position in the first pass with the pixel reading from the same position in the second pass.

### Claim 36 (depends on 34)

The apparatus of claim 34 wherein at least one of the one or more image sensor arrays comprises a charge-coupled device (CCD) sensor array.

### Claim 37

A luminescence scanner apparatus comprising:
a sample bed with a light tight enclosure, the sample bed configured to hold a luminescent sample medium;
a moveable detector bar comprising one or more uncooled charge-coupled device (CCD) image sensor arrays;
a circuit having instructions to:
move the detector bar in a first pass and take about 0.5 second exposure pixel readings during first pass;
move the detector bar in an opposite direction in a second pass and take about 0.5 second exposure pixel readings during the second pass; and
combine the pixel readings from the first and second passes; and
a circuit having instructions to construct an image from the combined pixel readings.

### Claim 38 (depends on 37)

The apparatus of claim 37 wherein one of the circuits has instructions to combine pixel readings from three or more passes of the detector bar.
