DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/16/2025 has been entered.
Response to Amendment
The amendment filed on 11/14/2025 has been entered. Claims 1, 12 and 20 have been amended. Claims 7-8 and 17-18 have been cancelled. Claims 1, 4-6, 9-12, 15-16 and 19-22 remain pending.
Applicant argues on Pages 11-14 of the Remarks that references Duma and Takamizawa fail to disclose the claimed limitations listed in Pages 10-11. This argument is moot in view of the new grounds of rejection which relies on the combination of Norita et al (US 6292263 B1; hereafter Norita), Fujinuma et al (US 20150028193 A1; hereafter Fujinuma) and Duma, to disclose these limitations in the claims.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 4-6, 9-12, 15-16 and 19-22 are rejected under 35 U.S.C. 103 as being unpatentable over Norita et al (US 6292263 B1; hereafter Norita), in view of Fujinuma et al (US 20150028193 A1; hereafter Fujinuma), and further in view of Duma et al (Applied Mathematical Modelling 67 (2019) 456-476; hereafter Duma).
With regard to Claim 1, Norita discloses a laser scanning imaging method (Norita, Fig. 1 (cited below) shows a 3D measuring apparatus that discloses a scanning imaging method. Column 5, Lines 41-42, discloses the method using laser as light source: “The projection system 10 includes a semiconductor laser (LD) 11 making up a light source …”), comprising:
determining parameter information related to an effective area (Norita, Column 6, Lines 45-52; “… the position data Xg, Yg in X and Y directions, respectively, of each sampling period sp for address designation of the frame memory 60. As a result, instead of writing the detection data Yp simply in the order of generation, the pixel arrangement on the virtual screen providing an address space of the frame memory 60 coincides with the pixel arrangement of the virtual surface VS.”. For the disclosed “virtual surface VS”, position of evert pixel is pre-determined, as (Xg, Yg). Fig. 2 shows the matrix of the pixels), wherein the effective area comprises an imaging area satisfying a preset condition (Norita, Column 6, Lines 33-39; “In the case where the output of the photo-electric conversion device 25 is periodically sampled during the scanning period, the depth of the object Q (the position in the direction at right angles to the virtual surface VS) can be measured for each sampling period (basically, a spot) sp constituting one of the subdivisions of the virtual surface VS in X and Y directions.”. As demonstrated in cited Fig. 1, the disclosed “virtual surface VS” corresponds to the “imaging area” of Application);
receiving a galvanometer scanning synchronization signal (Specification, Para 0005, specifies “galvanometer scanning synchronization signal” to be “a square wave representing a change in the direction of the motion of the galvanometer”. The claimed “signal” corresponds to the “sampling clock SPCLK” disclosed in Norita, Column 5, Lines 47-49: “The electromagnetic mechanism is supplied with a drive voltage representing the count of the clock SPCLK …”. Norita, Fig. 4 shows an example of SPCLK as a square wave) generated by a driving unit (Norita, Fig. 6, frequency divider 541 as a component of controller 52, which outputs sampling clock SPCLK);
generating, based on the galvanometer scanning synchronization signal and the parameter information related to the effective area, a clock signal (Norita, Column 7, Lines 37-46; “The number of horizontal pixels of the image is 128. … In controlling the main scanning, the sampling clock SPCLK is counted thereby to generate a drive signal.”; Lines 49-53; “The number of vertical pixels is 96. … In the subsidiary scanning, like in the main scanning, the sampling clock SPCLK is counted thereby to generate a drive signal.”; Column 8, Lines 44-45; “The X counter 511 and the Y counter 512 are supplied with a sampling clock SPCLK from a frequency divider 541.” These disclosures disclose “drive signal” along 2 directions are implemented as “X counter 511 and Y counter 512” (also see Fig. 6), and correspond to the “clock signal” of Application); and
sampling, according to the clock signal, a signal received through galvanometer scanning (Norita, Column 6, Lines 42-45; “… the detection data Yp which is a quantized output of the photo-electric conversion device 25 is written in the frame memory 60 as a specific data DD.” Here the disclosed “detection data Yp” corresponds to the sampled signal (by the block “A/D” in the cited Fig. 1)), and obtaining fluorescence image information of the effective area (Norita, Column 6, Lines 60-61; “The detection data Yp written in the frame memory 60 is read for displaying the distance image …”);
wherein the parameter information comprises area range information of the effective area (Norita, Fig. 1 (cited below) shows an example of the disclosed virtual surface VS with definite area range, which is also termed as “scanning range”);
wherein the generating, based on the galvanometer scanning synchronization signal and the parameter information related to the effective area, a clock signal comprises:
determining galvanometer motion parameter information corresponding to each pixel point in the effective area (Norita, Column 5, Lines 50-53; “The look-up table has stored therein conversion data for changing the rotational speed of the mirror, for example, in such a manner that the scanning rate on the virtual surface VS is kept constant.”);
determining image scanning parameter information corresponding to each pixel point in the effective area (Norita, Column 8, Lines 64-67; “In writing data into the frame memory 60, the address controller 521 designates an address based on the position data Yg from the Y counter 512 and the position data Xg from the galvanometer mirror 12X.” Here the disclosed “position data Xg and Yg” are location for each individual pixel so correspond to “image scanning parameter information” of Application);
determining, according to the galvanometer scanning synchronization signal (sampling clock SPCLK) and the area range information (the region shown in Fig. 2 of Norita), scanning time information corresponding to the effective area (Norita, Column 7, Lines 43-45; “Thus, the one line scanning time H is equivalent to 320 periods (320=(128+16x2)x2)) of the sampling clock SPCLK.”; Lines 49-51; “The number of vertical pixels is 96. Assume that the flyback period (mirror restoration time) in Y direction is 4H. The scanning time V per screen is thus 100 H.”. To scan a 2D area, the disclosed method starts at time 0, finishes the entire area at time 96H, and returns to start position at time 100H. This information corresponds to “scanning time information” of Application); and
generating, by performing quantization processing on the image scanning parameter information and the scanning time information, the clock signal (Norita, Column 13, Lines 43-49; “The X counter 511 and the Y counter 512 are supplied with the sampling clock SPCLK from a frequency divider 541. The count (0 to 639) of the X counter 511 is used for controlling the drive of the main scanning. The count (0 to 99) of the Y counter 512, on the other hand, is used for controlling the drive of the subsidiary scanning and address designation.” Fig. 4 shows an example of the correspondence between time points and counts based on the sampling clock SPCLK, which is essentially a quantization process);
wherein the area range information at least comprises a starting position, an end position, and the number of pixel points (Norita, Fig. 1 (cited below) shows an example of the disclosed virtual surface VS with definite area range, with start and end positions (the upper-left and lower-right corner of VS), and Fig. 2 shows an example of the matrix that consists of number of pixel points (termed as “sp” in cited Fig. 1)).
Fig. 1 of Norita
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Norita does not clearly and explicitly disclose
sampling a fluorescence signal,
calculating, according to the area range information, galvanometer motion parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the starting position, the end position, and the number of pixel points, the galvanometer motion speed information corresponding to each pixel point in the effective area, and
calculating, according to the galvanometer motion parameter information corresponding to each pixel point in the effective area, image scanning parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the galvanometer motion speed information corresponding to each pixel point in the effective area, sampling time information corresponding to each pixel point in the effective area.
Fujinuma in the same field of endeavor discloses
sampling a fluorescence signal (Fujinuma, Para 0179; “… such a configuration makes it possible to sample a detection signal such as fluorescence with high accuracy …”), and
calculating, according to the galvanometer motion parameter information corresponding to each pixel point in the effective area, image scanning parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the galvanometer motion speed information corresponding to each pixel point in the effective area, sampling time information corresponding to each pixel point in the effective area (Fujinuma, Para 0255; “… a pixel-clock generating means 27 which discerns a change in pixel position corresponding to the irradiation point while discerning the change in pixel position corresponding to the irradiation point is synchronizing with the change in irradiation point scanned by the scanning means 11-2 and which outputs a trigger for timing at which a pixel position is changed to another pixel position, as a pixel clock …”. This disclosure suggests that timing of transiting from one pixel to the next pixel is determined based on change in irradiation point scanned by the scanning means 11-2 (i.e. galvanometer mirror in Fig. 26). Para 0269-0271 and Fig. 28 further discuss how the proper consideration of variable scanning speed in the method would lead to more accurate result; Para 0271: “As a result, it is possible to remove differences between the pixels in brightness even if scanning speeds of the scanning means 11-2 vary with scanning positions.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Norita, as suggested by Fujinuma, in order to apply the method for acquiring fluorescence signals and to determine sampling time for each pixel. One of ordinary skill in the art would have been motivated to make the modification of acquiring fluorescence signals for the benefit of enabling precise monitoring of cell physiology by using fluorescence microscopy, and to make the modification of determining sampling time for each pixel for the benefit of improved accuracy of acquired image intensity by adjusting exposure time of each pixel based on pixel-wise scanning speed (Fujinuma, Para 0268: “As described above, the scanning speed of the irradiation point moving in the imaging range varies with pixel positions. On the other hand, sampling of a detection signal is performed at a fixed timing. As a result, the pixels inevitably differ from one another in exposure time, in the number of samplings of the detection signal, and in integration time.”).
Norita and Fujinuma do not clearly and explicitly disclose calculating, according to the area range information, galvanometer motion parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the starting position, the end position, and the number of pixel points, the galvanometer motion speed information corresponding to each pixel point in the effective area.
Duma in the same field of endeavor discloses calculating, according to the area range information, galvanometer motion parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the starting position, the end position, and the number of pixel points, the galvanometer motion speed information corresponding to each pixel point in the effective area (Duma, Fig. 3(b) shows the speed of galvanometer mirror along a x axis (vx); in the time period of [0, T], the segments [0, ta] and [T/2, T/2+ta] are for sampling data of two lines for a 2D image, and the data points for the entire image can be acquired with sampling of more lines on different y-axis locations. Duman, Fig. 9(a2) shows the speed of galvanometer mirror along a y axis (vy). It is noted that vx and vy are derived based on area range information, including xa (see Eq. A.2) and ya (see Eq. 24)). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Norita and Fujinuma, as suggested by Duma, in order to determine scanning speed for each pixel. One of ordinary skill in the art would have been motivated to make the modification for the benefit of potential correction of image distortion caused by variable scanning speed by determining pixel-wise scanning speed (Duma, Page 459, Para 4; “From an optical point of view, the sinusoidal scan has a major drawback, as it implies a non-constant scanning speed for the entire oscillatory period. In imaging for example, this means that the pixels in OCT or CM are not equally spaced, therefore the image is distorted [26,38].”).
With regard to Claim 4, Norita, Fujinuma and Duma disclose the laser scanning imaging method according to Claim 1. Norita further discloses wherein the galvanometer motion parameter information comprises motion speed information of the galvanometer and spatial position information of a mirror of the galvanometer (Norita, Column 5, Lines 50-63; “The look-up table has stored therein conversion data for changing the rotational speed of the mirror, for example, in such a manner that the scanning rate on the virtual surface VS is kept constant. … the galvanometer mirror 12X includes a rotational angle sensor for accurately grasping the position of the light spot on the virtual surface VS.”. Furthermore, Fig. 3 shows multiple relevant parameters as a function of time, including rotational angle, and scanning spot along both main and subsidiary scanning directions).
With regard to Claim 5, Norita, Fujinuma and Duma disclose the laser scanning imaging method according to Claim 1. Norita further discloses wherein the image scanning parameter information comprises sampling position information corresponding to the each pixel point (Norita, Column 8, Lines 64-67; “In writing data into the frame memory 60, the address controller 521 designates an address based on the position data Yg from the Y counter 512 and the position data Xg from the galvanometer mirror 12X.” Here the disclosed “position data Xg and Yg” are sampling position for each individual pixel).
With regard to Claim 6, Norita, Fujinuma and Duma disclose the laser scanning imaging method according to Claim 4. Norita further discloses wherein the image scanning parameter information comprises sampling position information corresponding to the each pixel point (Norita, Column 8, Lines 64-67; “In writing data into the frame memory 60, the address controller 521 designates an address based on the position data Yg from the Y counter 512 and the position data Xg from the galvanometer mirror 12X.” Here the disclosed “position data Xg and Yg” are sampling position for each individual pixel).
With regard to Claim 9, Norita, Fujinuma and Duma disclose the laser scanning imaging method according to Claim 1. Norita further discloses wherein the area range information at least comprises a starting position and an end position (Norita, Fig. 1 (cited above) shows an example of the disclosed virtual surface VS with definite area range, with start and end positions (the upper-left and lower-right corner of VS). Fig. 31 further show that such area range can be specified by user), and the determining, according to the galvanometer scanning synchronization signal and the area range information, scanning time information corresponding to the effective area (Norita, Column 7, Lines 36-45; “FIG. 2 is a diagram showing the output image size … Thus, the one line scanning time H is equivalent to 320 periods (320=(128+16x2)x2)) of the sampling clock SPCLK.”; Lines 49-51; “The number of vertical pixels is 96. Assume that the flyback period (mirror restoration time) in Y direction is 4H. The scanning time V per screen is thus 100 H.”. To scan a 2D area, the disclosed method starts at time 0, finishes the entire area at time 96H, and returns to start position at time 100H. This information corresponds to “scanning time information” of Application) comprises:
determining, according to the starting position (the upper-left corner of the example image in Fig. 2) and a period of the galvanometer scanning synchronization signal (Norita, Column 7, Line 51; “The scanning time V per screen is thus 100 H.” Each H corresponds 320 periods of the sampling clock SPCLK), a starting moment corresponding to the effective area (the starting moment of the disclosed “scanning time V” or “100H”); and
determining, according to the end position (the lower-right corner of the example image in Fig. 2) and a period of the galvanometer scanning synchronization signal (Norita, Column 7, Line 51; “The scanning time V per screen is thus 100 H.” Each H corresponds 320 periods of the sampling clock SPCLK), an end moment corresponding to the effective area (either 100H (including the flyback period of 4H) or 96H (excluding the flyback period of 4H)).
With regard to Claim 10, Norita, Fujinuma and Duma disclose the laser scanning imaging method according to Claim 1. Norita further discloses wherein the galvanometer comprises a first galvanometer and a second galvanometer (Norita, Column 5, Line 45; “galvanometer mirrors 12X, 12Y”), the first galvanometer and the second galvanometer are set to move in two mutually perpendicular directions respectively (Norita, Column 5, Lines 64-67; “… the direction of main scanning (X direction) is sometimes regarded as the horizontal direction and the direction of the subsidiary scanning (Y direction) as the vertical direction”), and the method further comprises:
determining, according to the galvanometer scanning synchronization signal (the sampling clock SPCLK) and the effective area (Norita, Column 7, Lines 36-45; “FIG. 2 is a diagram showing the output image size. The number of horizontal pixels of the image is 128. Taking the time required for the reversal of the driving direction of the galvanometer mirror 12X for the main scanning into consideration, each of the image ends has a margin equivalent to 16 pixels. … Thus, the one line scanning time H is equivalent to 320 periods (320=(128+16x2)x2)) of the sampling clock SPCLK.” This disclosure indicates how the sampling clock SPCLK is counted to control data sampling along the X direction.), a control signal for the second galvanometer (Norita, Column 7, Lines 45-46; “In controlling the main scanning, the sampling clock SPCLK is counted thereby to generate a drive signal.”);
controlling the driving unit to drive the first galvanometer to move in a first direction (Norita, Column 5, Lines 55-56; “The subsidiary scanning is carried out intermittently for each line of main scanning.” Column 7, Lines 51-53; “In the subsidiary scanning, like in the main scanning, the sampling clock SPCLK is counted thereby to generate a drive signal.” The disclosed “subsidiary scanning” is along the Y direction, controlled by a drive signal based on SPCLK); and
controlling, according to the control signal of the second galvanometer, the second galvanometer to move in a second direction (Norita, Fig. 3, the upper portion, shows an example of data sampling trajectory driven by drive signal, along the X direction).
With regard to Claim 11, Norita, Fujinuma and Duma disclose the laser scanning imaging method according to Claim 10. Norita further discloses wherein the determining, according to the galvanometer scanning synchronization signal and the effective area, a control signal for the second galvanometer comprises:
determining, according to the galvanometer scanning synchronization signal (the sampling clock SPCLK) and the parameter information related to the effective area (Norita, Column 7, Lines 36-48 discloses how the sampling clock is counted based on number of pixels per line that covers the imaging area along the X direction), the control signal for the second galvanometer (Norita, Column 7, Lines 45-46; “In controlling the main scanning, the sampling clock SPCLK is counted thereby to generate a drive signal.”).
With regard to Claim 12, Norita discloses a laser scanning imaging system (Norita, Fig. 1 shows a laser scanning imaging system), comprising:
a galvanometer (galvanometer mirrors 12X, 12Y in Fig. 1); and
a processor (Norita, Column 7, Lines 8-10; “The 3D measuring apparatus 1 comprises a CPU 51 having a microprocessor and a controller 52 for controlling the scanning and the data input/output.”), connected to the galvanometer, for executing the following steps: determining parameter information related to an effective area (Norita, Column 6, Lines 45-52; “… the position data Xg, Yg in X and Y directions, respectively, of each sampling period sp for address designation of the frame memory 60. As a result, instead of writing the detection data Yp simply in the order of generation, the pixel arrangement on the virtual screen providing an address space of the frame memory 60 coincides with the pixel arrangement of the virtual surface VS.”. For the disclosed “virtual surface VS”, position of evert pixel is pre-determined, as (Xg, Yg). Fig. 2 shows the matrix of the pixels), wherein the effective area comprises an imaging area satisfying a preset condition (Norita, Column 6, Lines 33-39; “In the case where the output of the photo-electric conversion device 25 is periodically sampled during the scanning period, the depth of the object Q (the position in the direction at right angles to the virtual surface VS) can be measured for each sampling period (basically, a spot) sp constituting one of the subdivisions of the virtual surface VS in X and Y directions.”. As demonstrated in cited Fig. 1, the disclosed “virtual surface VS” corresponds to the “imaging area” of Application);
receiving a galvanometer scanning synchronization signal (Specification, Para 0005, specifies “galvanometer scanning synchronization signal” to be “a square wave representing a change in the direction of the motion of the galvanometer”. The claimed “signal” corresponds to the “sampling clock SPCLK” disclosed in Norita, Column 5, Lines 47-49: “The electromagnetic mechanism is supplied with a drive voltage representing the count of the clock SPCLK …”. Norita, Fig. 4 shows an example of SPCLK as a square wave) generated by a driving unit (Norita, Fig. 6, frequency divider 541 as a component of controller 52, which outputs sampling clock SPCLK);
generating, based on the galvanometer scanning synchronization signal and the parameter information related to the effective area, a clock signal (Norita, Column 7, Lines 37-46; “The number of horizontal pixels of the image is 128. … In controlling the main scanning, the sampling clock SPCLK is counted thereby to generate a drive signal.”; Lines 49-53; “The number of vertical pixels is 96. … In the subsidiary scanning, like in the main scanning, the sampling clock SPCLK is counted thereby to generate a drive signal.”; Column 8, Lines 44-45; “The X counter 511 and the Y counter 512 are supplied with a sampling clock SPCLK from a frequency divider 541.” These disclosures disclose “drive signal” along 2 directions are implemented as “X counter 511 and Y counter 512” (also see Fig. 6), and correspond to the “clock signal” of Application); and
sampling, according to the clock signal, a signal received through galvanometer scanning (Norita, Column 6, Lines 42-45; “… the detection data Yp which is a quantized output of the photo-electric conversion device 25 is written in the frame memory 60 as a specific data DD.” Here the disclosed “detection data Yp” corresponds to the sampled signal (by the block “A/D” in the cited Fig. 1)), and obtaining fluorescence image information of the effective area (Norita, Column 6, Lines 60-61; “The detection data Yp written in the frame memory 60 is read for displaying the distance image …”);
wherein the parameter information comprises area range information of the effective area (Norita, Fig. 1 (cited above) shows an example of the disclosed virtual surface VS with definite area range, which is also termed as “scanning range”);
wherein the processor executing the step of the generating, based on the galvanometer scanning synchronization signal and the parameter information related to the effective area, a clock signal, further comprises executing the following steps:
determining galvanometer motion parameter information corresponding to each pixel point in the effective area (Norita, Column 5, Lines 50-53; “The look-up table has stored therein conversion data for changing the rotational speed of the mirror, for example, in such a manner that the scanning rate on the virtual surface VS is kept constant.”);
determining image scanning parameter information corresponding to each pixel point in the effective area (Norita, Column 8, Lines 64-67; “In writing data into the frame memory 60, the address controller 521 designates an address based on the position data Yg from the Y counter 512 and the position data Xg from the galvanometer mirror 12X.” Here the disclosed “position data Xg and Yg” are location for each individual pixel so correspond to “image scanning parameter information” of Application);
determining, according to the galvanometer scanning synchronization signal (sampling clock SPCLK) and the area range information (the region shown in Fig. 2 of Norita), scanning time information corresponding to the effective area (Norita, Column 7, Lines 43-45; “Thus, the one line scanning time H is equivalent to 320 periods (320=(128+16x2)x2)) of the sampling clock SPCLK.”; Lines 49-51; “The number of vertical pixels is 96. Assume that the flyback period (mirror restoration time) in Y direction is 4H. The scanning time V per screen is thus 100 H.”. To scan a 2D area, the disclosed method starts at time 0, finishes the entire area at time 96H, and returns to start position at time 100H. This information corresponds to “scanning time information” of Application); and
generating, by performing quantization processing on the image scanning parameter information and the scanning time information, the clock signal (Norita, Column 13, Lines 43-49; “The X counter 511 and the Y counter 512 are supplied with the sampling clock SPCLK from a frequency divider 541. The count (0 to 639) of the X counter 511 is used for controlling the drive of the main scanning. The count (0 to 99) of the Y counter 512, on the other hand, is used for controlling the drive of the subsidiary scanning and address designation.” Fig. 4 shows an example of the correspondence between time points and counts based on the sampling clock SPCLK, which is essentially a quantization process);
wherein the area range information at least comprises a starting position, an end position, and the number of pixel points (Norita, Fig. 1 (cited above) shows an example of the disclosed virtual surface VS with definite area range, with start and end positions (the upper-left and lower-right corner of VS), and Fig. 2 shows an example of the matrix that consists of number of pixel points (termed as “sp” in cited Fig. 1)).
Norita does not clearly and explicitly disclose
sampling a fluorescence signal,
calculating, according to the area range information, galvanometer motion parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the starting position, the end position, and the number of pixel points, the galvanometer motion speed information corresponding to each pixel point in the effective area, and
calculating, according to the galvanometer motion parameter information corresponding to each pixel point in the effective area, image scanning parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the galvanometer motion speed information corresponding to each pixel point in the effective area, sampling time information corresponding to each pixel point in the effective area.
Fujinuma in the same field of endeavor discloses
sampling a fluorescence signal (Fujinuma, Para 0179; “… such a configuration makes it possible to sample a detection signal such as fluorescence with high accuracy …”), and
calculating, according to the galvanometer motion parameter information corresponding to each pixel point in the effective area, image scanning parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the galvanometer motion speed information corresponding to each pixel point in the effective area, sampling time information corresponding to each pixel point in the effective area (Fujinuma, Para 0255; “… a pixel-clock generating means 27 which discerns a change in pixel position corresponding to the irradiation point while discerning the change in pixel position corresponding to the irradiation point is synchronizing with the change in irradiation point scanned by the scanning means 11-2 and which outputs a trigger for timing at which a pixel position is changed to another pixel position, as a pixel clock …”. This disclosure suggests that timing of transiting from one pixel to the next pixel is determined based on change in irradiation point scanned by the scanning means 11-2 (i.e. galvanometer mirror in Fig. 26). Para 0269-0271 and Fig. 28 further discuss how the proper consideration of variable scanning speed in the method would lead to more accurate result; Para 0271: “As a result, it is possible to remove differences between the pixels in brightness even if scanning speeds of the scanning means 11-2 vary with scanning positions.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Norita, as suggested by Fujinuma, in order to apply the method for acquiring fluorescence signals and to determine sampling time for each pixel. One of ordinary skill in the art would have been motivated to make the modification of acquiring fluorescence signals for the benefit of enabling precise monitoring of cell physiology by using fluorescence microscopy, and to make the modification of determining sampling time for each pixel for the benefit of improved accuracy of acquired image intensity by adjusting exposure time of each pixel based on pixel-wise scanning speed (Fujinuma, Para 0268: “As described above, the scanning speed of the irradiation point moving in the imaging range varies with pixel positions. On the other hand, sampling of a detection signal is performed at a fixed timing. As a result, the pixels inevitably differ from one another in exposure time, in the number of samplings of the detection signal, and in integration time.”).
Norita and Fujinuma do not clearly and explicitly disclose calculating, according to the area range information, galvanometer motion parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the starting position, the end position, and the number of pixel points, the galvanometer motion speed information corresponding to each pixel point in the effective area.
Duma in the same field of endeavor discloses calculating, according to the area range information, galvanometer motion parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the starting position, the end position, and the number of pixel points, the galvanometer motion speed information corresponding to each pixel point in the effective area (Duma, Fig. 3(b) shows the speed of galvanometer mirror along a x axis (vx); in the time period of [0, T], the segments [0, ta] and [T/2, T/2+ta] are for sampling data of two lines for a 2D image, and the data points for the entire image can be acquired with sampling of more lines on different y-axis locations. Duman, Fig. 9(a2) shows the speed of galvanometer mirror along a y axis (vy). It is noted that vx and vy are derived based on area range information, including xa (see Eq. A.2) and ya (see Eq. 24)). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Norita and Fujinuma, as suggested by Duma, in order to determine scanning speed for each pixel. One of ordinary skill in the art would have been motivated to make the modification for the benefit of potential correction of image distortion caused by variable scanning speed by determining pixel-wise scanning speed (Duma, Page 459, Para 4; “From an optical point of view, the sinusoidal scan has a major drawback, as it implies a non-constant scanning speed for the entire oscillatory period. In imaging for example, this means that the pixels in OCT or CM are not equally spaced, therefore the image is distorted [26,38].”).
With regard to Claim 15, Norita, Fujinuma and Duma disclose the laser scanning imaging system according to Claim 12. Norita further discloses wherein the galvanometer motion parameter information comprises motion speed information of the galvanometer and spatial position information of a mirror of the galvanometer (Norita, Column 5, Lines 50-63; “The look-up table has stored therein conversion data for changing the rotational speed of the mirror, for example, in such a manner that the scanning rate on the virtual surface VS is kept constant. … the galvanometer mirror 12X includes a rotational angle sensor for accurately grasping the position of the light spot on the virtual surface VS.”. Furthermore, Fig. 3 shows multiple relevant parameters as a function of time, including rotational angle, and scanning spot along both main and subsidiary scanning directions).
With regard to Claim 16, Norita, Fujinuma and Duma disclose the laser scanning imaging system according to Claim 12. Norita further discloses wherein the image scanning parameter information comprises sampling position information corresponding to the each pixel point (Norita, Column 8, Lines 64-67; “In writing data into the frame memory 60, the address controller 521 designates an address based on the position data Yg from the Y counter 512 and the position data Xg from the galvanometer mirror 12X.” Here the disclosed “position data Xg and Yg” are sampling position for each individual pixel).
With regard to Claim 19, Norita, Fujinuma and Duma disclose the laser scanning imaging system according to Claim 12. Norita further discloses wherein the area range information at least comprises a starting position and an end position (Norita, Fig. 1 (cited above) shows an example of the disclosed virtual surface VS with definite area range, with start and end positions (the upper-left and lower-right corner of VS). Fig. 31 further show that such area range can be specified by user), and
the processor executing the step of the determining, according to the galvanometer scanning synchronization signal and the area range information, scanning time information corresponding to the effective area (Norita, Column 7, Lines 36-45; “FIG. 2 is a diagram showing the output image size … Thus, the one line scanning time H is equivalent to 320 periods (320=(128+16x2)x2)) of the sampling clock SPCLK.”; Lines 49-51; “The number of vertical pixels is 96. Assume that the flyback period (mirror restoration time) in Y direction is 4H. The scanning time V per screen is thus 100 H.”. To scan a 2D area, the disclosed method starts at time 0, finishes the entire area at time 96H, and returns to start position at time 100H. This information corresponds to “scanning time information” of Application), further comprises executing the following steps:
determining, according to the starting position (the upper-left corner of the example image in Fig. 2) and a period of the galvanometer scanning synchronization signal (Norita, Column 7, Line 51; “The scanning time V per screen is thus 100 H.” Each H corresponds 320 periods of the sampling clock SPCLK), a starting moment corresponding to the effective area (the starting moment of the disclosed “scanning time V” or “100H”); and
determining, according to the end position (the lower-right corner of the example image in Fig. 2) and a period of the galvanometer scanning synchronization signal (Norita, Column 7, Line 51; “The scanning time V per screen is thus 100 H.” Each H corresponds 320 periods of the sampling clock SPCLK), an end moment corresponding to the effective area (either 100H (including the flyback period of 4H) or 96H (excluding the flyback period of 4H)).
With regard to Claim 20, Norita discloses a non-volatile storage medium, storing a computer program (Norita, Column 8, Lines 35-36; “FIG. 6 is a block diagram showing a functional configuration of the controller 52.”. To one ordinary skill in the field, a computer program stored in a non-volatile storage medium is intrinsically available for implementing the method), wherein the computer program, when executed by a processor (Norita, Column 7, Lines 8-10; “The 3D measuring apparatus 1 comprises a CPU 51 having a microprocessor and a controller 52 for controlling the scanning and the data input/output.”), executes the following steps:
determining parameter information related to an effective area (Norita, Column 6, Lines 45-52; “… the position data Xg, Yg in X and Y directions, respectively, of each sampling period sp for address designation of the frame memory 60. As a result, instead of writing the detection data Yp simply in the order of generation, the pixel arrangement on the virtual screen providing an address space of the frame memory 60 coincides with the pixel arrangement of the virtual surface VS.”. For the disclosed “virtual surface VS”, position of evert pixel is pre-determined, as (Xg, Yg). Fig. 2 shows the matrix of the pixels), wherein the effective area comprises an imaging area satisfying a preset condition (Norita, Column 6, Lines 33-39; “In the case where the output of the photo-electric conversion device 25 is periodically sampled during the scanning period, the depth of the object Q (the position in the direction at right angles to the virtual surface VS) can be measured for each sampling period (basically, a spot) sp constituting one of the subdivisions of the virtual surface VS in X and Y directions.”. As demonstrated in cited Fig. 1, the disclosed “virtual surface VS” corresponds to the “imaging area” of Application);
receiving a galvanometer scanning synchronization signal (Specification, Para 0005, specifies “galvanometer scanning synchronization signal” to be “a square wave representing a change in the direction of the motion of the galvanometer”. The claimed “signal” corresponds to the “sampling clock SPCLK” disclosed in Norita, Column 5, Lines 47-49: “The electromagnetic mechanism is supplied with a drive voltage representing the count of the clock SPCLK …”. Norita, Fig. 4 shows an example of SPCLK as a square wave) generated by a driving unit (Norita, Fig. 6, frequency divider 541 as a component of controller 52, which outputs sampling clock SPCLK);
generating, based on the galvanometer scanning synchronization signal and the parameter information related to the effective area, a clock signal (Norita, Column 7, Lines 37-46; “The number of horizontal pixels of the image is 128. … In controlling the main scanning, the sampling clock SPCLK is counted thereby to generate a drive signal.”; Lines 49-53; “The number of vertical pixels is 96. … In the subsidiary scanning, like in the main scanning, the sampling clock SPCLK is counted thereby to generate a drive signal.”; Column 8, Lines 44-45; “The X counter 511 and the Y counter 512 are supplied with a sampling clock SPCLK from a frequency divider 541.” These disclosures disclose “drive signal” along 2 directions are implemented as “X counter 511 and Y counter 512” (also see Fig. 6), and correspond to the “clock signal” of Application); and
sampling, according to the clock signal, a signal received through galvanometer scanning (Norita, Column 6, Lines 42-45; “… the detection data Yp which is a quantized output of the photo-electric conversion device 25 is written in the frame memory 60 as a specific data DD.” Here the disclosed “detection data Yp” corresponds to the sampled signal (by the block “A/D” in the cited Fig. 1)), and obtaining fluorescence image information of the effective area (Norita, Column 6, Lines 60-61; “The detection data Yp written in the frame memory 60 is read for displaying the distance image …”);
wherein the parameter information comprises area range information of the effective area (Norita, Fig. 1 (cited above) shows an example of the disclosed virtual surface VS with definite area range, which is also termed as “scanning range”);
wherein the generating, based on the galvanometer scanning synchronization signal and the parameter information related to the effective area, a clock signal comprises:
determining galvanometer motion parameter information corresponding to each pixel point in the effective area (Norita, Column 5, Lines 50-53; “The look-up table has stored therein conversion data for changing the rotational speed of the mirror, for example, in such a manner that the scanning rate on the virtual surface VS is kept constant.”);
determining image scanning parameter information corresponding to each pixel point in the effective area (Norita, Column 8, Lines 64-67; “In writing data into the frame memory 60, the address controller 521 designates an address based on the position data Yg from the Y counter 512 and the position data Xg from the galvanometer mirror 12X.” Here the disclosed “position data Xg and Yg” are location for each individual pixel so correspond to “image scanning parameter information” of Application);
determining, according to the galvanometer scanning synchronization signal (sampling clock SPCLK) and the area range information (the region shown in Fig. 2 of Norita), scanning time information corresponding to the effective area (Norita, Column 7, Lines 43-45; “Thus, the one line scanning time H is equivalent to 320 periods (320=(128+16x2)x2)) of the sampling clock SPCLK.”; Lines 49-51; “The number of vertical pixels is 96. Assume that the flyback period (mirror restoration time) in Y direction is 4H. The scanning time V per screen is thus 100 H.”. To scan a 2D area, the disclosed method starts at time 0, finishes the entire area at time 96H, and returns to start position at time 100H. This information corresponds to “scanning time information” of Application); and
generating, by performing quantization processing on the image scanning parameter information and the scanning time information, the clock signal (Norita, Column 13, Lines 43-49; “The X counter 511 and the Y counter 512 are supplied with the sampling clock SPCLK from a frequency divider 541. The count (0 to 639) of the X counter 511 is used for controlling the drive of the main scanning. The count (0 to 99) of the Y counter 512, on the other hand, is used for controlling the drive of the subsidiary scanning and address designation.” Fig. 4 shows an example of the correspondence between time points and counts based on the sampling clock SPCLK, which is essentially a quantization process);
wherein the area range information at least comprises a starting position, an end position, and the number of pixel points (Norita, Fig. 1 (cited above) shows an example of the disclosed virtual surface VS with definite area range, with start and end positions (the upper-left and lower-right corner of VS), and Fig. 2 shows an example of the matrix that consists of number of pixel points (termed as “sp” in cited Fig. 1)).
Norita does not clearly and explicitly disclose
sampling a fluorescence signal,
calculating, according to the area range information, galvanometer motion parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the starting position, the end position, and the number of pixel points, the galvanometer motion speed information corresponding to each pixel point in the effective area, and
calculating, according to the galvanometer motion parameter information corresponding to each pixel point in the effective area, image scanning parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the galvanometer motion speed information corresponding to each pixel point in the effective area, sampling time information corresponding to each pixel point in the effective area.
Fujinuma in the same field of endeavor discloses
sampling a fluorescence signal (Fujinuma, Para 0179; “… such a configuration makes it possible to sample a detection signal such as fluorescence with high accuracy …”), and
calculating, according to the galvanometer motion parameter information corresponding to each pixel point in the effective area, image scanning parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the galvanometer motion speed information corresponding to each pixel point in the effective area, sampling time information corresponding to each pixel point in the effective area (Fujinuma, Para 0255; “… a pixel-clock generating means 27 which discerns a change in pixel position corresponding to the irradiation point while discerning the change in pixel position corresponding to the irradiation point is synchronizing with the change in irradiation point scanned by the scanning means 11-2 and which outputs a trigger for timing at which a pixel position is changed to another pixel position, as a pixel clock …”. This disclosure suggests that timing of transiting from one pixel to the next pixel is determined based on change in irradiation point scanned by the scanning means 11-2 (i.e. galvanometer mirror in Fig. 26). Para 0269-0271 and Fig. 28 further discuss how the proper consideration of variable scanning speed in the method would lead to more accurate result; Para 0271: “As a result, it is possible to remove differences between the pixels in brightness even if scanning speeds of the scanning means 11-2 vary with scanning positions.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Norita, as suggested by Fujinuma, in order to apply the method for acquiring fluorescence signals and to determine sampling time for each pixel. One of ordinary skill in the art would have been motivated to make the modification of acquiring fluorescence signals for the benefit of enabling precise monitoring of cell physiology by using fluorescence microscopy, and to make the modification of determining sampling time for each pixel for the benefit of improved accuracy of acquired image intensity by adjusting exposure time of each pixel based on pixel-wise scanning speed (Fujinuma, Para 0268: “As described above, the scanning speed of the irradiation point moving in the imaging range varies with pixel positions. On the other hand, sampling of a detection signal is performed at a fixed timing. As a result, the pixels inevitably differ from one another in exposure time, in the number of samplings of the detection signal, and in integration time.”).
Norita and Fujinuma do not clearly and explicitly disclose calculating, according to the area range information, galvanometer motion parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the starting position, the end position, and the number of pixel points, the galvanometer motion speed information corresponding to each pixel point in the effective area.
Duma in the same field of endeavor discloses calculating, according to the area range information, galvanometer motion parameter information corresponding to each pixel point in the effective area, which comprises calculating, according to the starting position, the end position, and the number of pixel points, the galvanometer motion speed information corresponding to each pixel point in the effective area (Duma, Fig. 3(b) shows the speed of galvanometer mirror along a x axis (vx); in the time period of [0, T], the segments [0, ta] and [T/2, T/2+ta] are for sampling data of two lines for a 2D image, and the data points for the entire image can be acquired with sampling of more lines on different y-axis locations. Duman, Fig. 9(a2) shows the speed of galvanometer mirror along a y axis (vy). It is noted that vx and vy are derived based on area range information, including xa (see Eq. A.2) and ya (see Eq. 24)). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Norita and Fujinuma, as suggested by Duma, in order to determine scanning speed for each pixel. One of ordinary skill in the art would have been motivated to make the modification for the benefit of potential correction of image distortion caused by variable scanning speed by determining pixel-wise scanning speed (Duma, Page 459, Para 4; “From an optical point of view, the sinusoidal scan has a major drawback, as it implies a non-constant scanning speed for the entire oscillatory period. In imaging for example, this means that the pixels in OCT or CM are not equally spaced, therefore the image is distorted [26,38].”).
With regard to Claim 21, Norita, Fujinuma and Duma disclose the laser scanning imaging method according to Claim 1. Norita further discloses wherein the effective area is the imaging area that needs to be displayed for the user (Norita, Fig. 2: the imaging area displayed to user is the central area with matrix of 128x96); and the effective area is a part of the entire scanning area (Norita, Column 7, Lines 38-41; “Taking the time required for the reversal of the driving direction of the galvanometer mirror 12X for the main scanning into consideration, each of the image ends has a margin equivalent to 16 pixels”. The disclosed “margin” on each end of the image is not counted as displayed area).
With regard to Claim 22, Norita, Fujinuma and Duma disclose the laser scanning imaging method according to Claim 1. Norita further discloses wherein wherein a result of the fluorescence image information of the effective area is changed in the following ways:
changing a number of pixels in the effective area without changing a preset values of a starting position and an end position (Norita, Column 21, Lines 1-4; “The sampling period and the scanning rate are not necessarily operatively correlated to each other. Specifically, the angle of visibility and the pixel size (resolution) can be set independently of each other.” In this disclosure, change of “pixel size” alone would correspond to the claimed “changing number of pixels without changing starting and end positions”), or
changing a distance between the starting position and the end position without changing the number of pixels (Norita, Fig. 31A and 31B shows 2 modes with a same matrix size of 128x96 but different angles of visibility (and therefore range) on both the directions).
Conclusion
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/L.Z./ Examiner, Art Unit 3798
/PASCAL M BUI PHO/ Supervisory Patent Examiner, Art Unit 3798