CN111595758B - Ellipse cell detection device and detection method based on lens-free imaging - Google Patents
Ellipse cell detection device and detection method based on lens-free imaging Download PDFInfo
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Abstract
本发明公开了基于无透镜成像的椭圆细胞检测装置,包括上下设置的灯光盒和电路板保护盒,灯光盒中设置有LED光源、凸透镜、CMOS图像传感器,本发明能够针对无透镜成像系统采集细胞图像时存在分辨率低和衍射干扰严重的情况,准确检测出椭圆细胞。本发明椭圆细胞的检测方法,该方法应用本发明的基于无透镜成像的椭圆细胞检测装置进行椭圆细胞检测,包括制作、固定待测椭圆细胞样本,开启LED光源,CMOS图像传感器采集图像数据,处理图像数据,根据椭圆细胞长轴和短轴差异判断是否为正常椭圆细胞,本发明提高了椭圆形细胞测量的自动化程度,降低了操作的人工成本。
The invention discloses an ellipse cell detection device based on lensless imaging, which includes a light box and a circuit board protection box arranged up and down. The light box is provided with an LED light source, a convex lens, and a CMOS image sensor. The invention can collect cells for the lensless imaging system. In the case of low resolution and severe diffraction interference in the image, the elliptical cells can be detected accurately. The detection method of elliptic cells of the present invention, the method uses the elliptical cell detection device based on lensless imaging of the present invention to detect elliptical cells, including making and fixing the elliptical cell samples to be tested, turning on the LED light source, and collecting image data by a CMOS image sensor, processing The image data can judge whether it is a normal ellipse cell according to the difference between the long axis and the short axis of the ellipse cell. The invention improves the automation degree of ellipse cell measurement and reduces the labor cost of operation.
Description
技术领域technical field
本发明属于医学图像分析技术领域,涉及基于无透镜成像的椭圆细胞检测装置,还涉及椭圆细胞的检测方法。The invention belongs to the technical field of medical image analysis, relates to an ellipse cell detection device based on lensless imaging, and also relates to a detection method of the ellipse cell.
背景技术Background technique
血细胞形态参数对于疾病诊断、健康监测、新药研制是非常有价值的数据。通常获取这一数据的方法是采集细胞图像进行分析。常用的采集设备时光学显微镜。为了保证成像质量,光学显微镜不得不采用复杂的多透镜组。使得光学显微镜的小型化问题一直受限于透镜组。在面对突发疫情等紧急情况或采集现场检测等即时检测的应用场景中,较高的专业要求和制造成本成为了掣肘,不利于快速部署、低成本大规模部署和即时检测。Blood cell morphological parameters are very valuable data for disease diagnosis, health monitoring, and new drug development. The usual way to obtain this data is to acquire images of cells for analysis. A common acquisition device is an optical microscope. In order to ensure the imaging quality, optical microscopes have to use complex multi-lens groups. The problem of miniaturization of optical microscopes has been limited to lens groups. In the face of emergency situations such as sudden outbreaks or the application scenarios of real-time detection such as collection and on-site detection, high professional requirements and manufacturing costs have become constraints, which are not conducive to rapid deployment, low-cost large-scale deployment and real-time detection.
2006年,美国加州理工大学的Yang changhuei研究小组首次提出无透镜光流体显微芯片的概念。这一设备的优势在于使用图像传感器不仅降低了设备的制造和使用成本,还提高的便携性。在面对快速部署、低成本大规模部署和即时检测的应用场景中更具有优势。In 2006, Yang Changhuei's research group at California Institute of Technology first proposed the concept of a lensless optofluidic microchip. The advantage of this device is that the use of image sensors not only reduces the cost of manufacturing and using the device, but also improves portability. It has more advantages in the application scenarios of rapid deployment, low-cost large-scale deployment and instant detection.
无透镜设备有两个问题需要解决:1.由于商用图像传感器的像素尺寸与血液细胞十分接近,造成了由无透镜成像系统采集到的细胞图像分辨率较低;2.衍射干扰较小的接触式成像要求成像样品到图像传感器的距离必须缩小到几个可见光波长,对于商用传感器很难实现,不得不采用具有干扰的衍射成像。因此,如何在使用商用传感器的情况下,获得准确的细胞形态参数成为了研究难点。There are two issues to be solved for lensless devices: 1. The resolution of cell images collected by lensless imaging systems is low due to the fact that the pixel size of commercial image sensors is very close to that of blood cells; 2. Contacts with less diffraction interference Traditional imaging requires that the distance from the imaging sample to the image sensor must be reduced to a few wavelengths of visible light, which is difficult to achieve for commercial sensors, and diffraction imaging with interference has to be used. Therefore, how to obtain accurate cell morphological parameters when using commercial sensors has become a research difficulty.
发明内容Contents of the invention
本发明的目的是提供基于无透镜成像的椭圆细胞检测装置,能够针对无透镜成像系统采集细胞图像时存在分辨率低和衍射干扰严重的情况,准确检测出椭圆细胞。The purpose of the present invention is to provide an elliptical cell detection device based on lensless imaging, which can accurately detect elliptical cells in view of the low resolution and serious diffraction interference when the lensless imaging system collects cell images.
本发明的另一目的是提供椭圆细胞的检测方法,可以准确检测出椭圆细胞。Another object of the present invention is to provide a method for detecting oval cells, which can accurately detect oval cells.
本发明所采用的第一种技术方案是,基于无透镜成像的椭圆细胞检测装置,包括上下设置的灯光盒和电路板保护盒,灯光盒中由上向下依次设置有位于同一轴线上的LED光源、凸透镜、CMOS图像传感器,CMOS图像传感器位于电路板保护盒上,电路板保护盒中设置有与CMOS图像传感器连接的CMOS图像传感器电路。The first technical solution adopted by the present invention is an ellipse cell detection device based on lensless imaging, including a light box and a circuit board protection box arranged up and down, and LEDs on the same axis are sequentially arranged in the light box from top to bottom. A light source, a convex lens, and a CMOS image sensor. The CMOS image sensor is located on a circuit board protection box, and a CMOS image sensor circuit connected to the CMOS image sensor is arranged in the circuit board protection box.
本发明第一种技术方案的特点还在于,The feature of the first technical solution of the present invention is also that,
灯光盒与电路板保护盒旋转连接,灯光盒可在电路板保护盒上转动,灯光盒侧壁开设在有开口,电路板保护盒上固定有与灯光盒开口匹配的遮光板。The light box is rotatably connected with the circuit board protection box, the light box can rotate on the circuit board protection box, the side wall of the light box is provided with an opening, and the circuit board protection box is fixed with a shading plate matching the opening of the light box.
CMOS图像传感器外周设置有样本垫。A sample pad is provided on the periphery of the CMOS image sensor.
样本垫上设置有样本卡槽。A sample card slot is arranged on the sample pad.
本发明椭圆细胞的检测方法,该方法应用本发明的基于无透镜成像的椭圆细胞检测装置进行椭圆细胞检测,具体按照以下步骤实施:The detection method of elliptic cells of the present invention, the method uses the elliptical cell detection device based on lensless imaging of the present invention to detect elliptical cells, specifically implemented according to the following steps:
步骤1、制作待测椭圆细胞样本;Step 1, making the elliptical cell sample to be tested;
步骤2、将待测椭圆细胞样本置于CMOS图像传感器上,并固定于样本卡槽中,旋转灯光盒使其开口与遮光板形成封闭采集室;
步骤3、开启LED光源,使LED光源发出的光线经凸透镜聚拢垂直射向待测椭圆细胞样本;
步骤4、打开CMOS图像传感器,将采集到的图像数据经数据接口导出到CMOS图像传感器电路的处理模块上;Step 4, open the CMOS image sensor, and export the image data collected to the processing module of the CMOS image sensor circuit through the data interface;
步骤5、对导出的图像数据使用霍夫变换算法检测经过衍射干扰后呈现圆形的椭圆细胞的图像的圆心,并以它为中心建立矩形坐标系,对图像进行分割检测细胞衍射环;
步骤6、在步骤5的基础上进行亚像素插值运算得到亚像素图像,并以步骤5中得到的圆心坐标为中心,将亚像素图像从矩形坐标系转换为极坐标系;
步骤7、通过超分辨率算法确定衍射亮环最强光强点到细胞衍射环中心的距离的曲线;
步骤8、根据步骤6的距离曲线,计算出衍射亮环的光强最大值点,表征衍射亮环的位置;
步骤9、以极坐标系参数θ从0度增加至360度,按照设置的步长递增,依次重复步骤7~8,直到得到360度的半径数据,将360度的半径数据组成一个半径序列{x′pk1(θ1),x′pk2(θ2),…,x′pkn(θn)},x′pkn(θn)表示极坐标系参数θ对应的半径值,n为不为0的自然数
步骤10、通过两个半径之和表征衍射环直径,即匹配半径得到衍射环在角度α1,α2,…,αi处的直径长度,i是不为0的自然数:Step 10. Characterize the diameter of the diffraction ring by the sum of the two radii, that is, match the radius to obtain the diameter length of the diffraction ring at angles α 1 , α 2 ,...,α i , where i is a natural number other than 0:
式(10)中,D1(α1),D2(α2),…,Di(αi)是衍射环在角度α1,α2,…,αi处的直径长度;In formula (10), D 1 (α 1 ), D 2 (α 2 ),…,D i (α i ) are the diameter lengths of the diffraction ring at angles α 1 , α 2 ,…,α i ;
定义集合A来表示这些数据:Define a collection A to represent these data:
A={D1(α1),D2(α2),…,Di(αi)} (11);A={D 1 (α 1 ), D 2 (α 2 ),..., D i (α i )} (11);
步骤11、进行椭圆细胞的匹配识别,椭圆长轴位置的阴影长度表示为:Step 11, carry out the matching recognition of the ellipse cells, the shadow length of the long axis position of the ellipse is expressed as:
Dmaj(αmaj)=min(A) (12)D maj (α maj )=min(A) (12)
假设π/4<αmaj<3π/4,定义集合B表示为Assuming π/4<α maj <3π/4, the definition set B is expressed as
B={D1(β1),D2(β2),…,Di(βi)} (13)B={D 1 (β 1 ), D 2 (β 2 ),..., D i (β i )} (13)
椭圆短轴位置处阴影的长度可以表示为:The length of the shadow at the position of the minor axis of the ellipse can be expressed as:
Dmin(αmin)=min(B)D min (α min ) = min(B)
定义参数M表示椭圆细胞长轴和短轴之间的差异:Define the parameter M to represent the difference between the major and minor axes of the elliptical cells:
M=|Dmaj(αmaj)-Dmin(αmin)|M=|D maj (α maj )-D min (α min )|
定义阈值MT,如果M>MT,那么判断是正常的椭圆细胞,否则为其他细胞。Define the threshold M T , if M>M T , then it is judged to be a normal elliptical cell, otherwise it is other cells.
本发明第二种技术方案的特点还在于,The feature of the second technical solution of the present invention is also that,
步骤7具体为,根据图像数据本身携带的光强信息,得到光强和距离衍射发生点的长度的映射关系,衍射发生点即细胞的边缘,这个关系表示在二维坐标系中会出现多个波峰,每一个波峰代表了一个衍射亮环,以波峰的最大值点表征衍射亮环的位置;
根据径向超分辨率和周向超分辨率得到衍射亮环最强光强点到细胞衍射环中心的距离的曲线:径向超分辨率是找到衍射亮环对应波峰的最快上升点和最快下降点,以这两个点的斜率的交点来修正波峰最大值点的位置;周向超分辨率,通过高斯平滑进行降噪,进而得到衍射亮环修正后的表征位置;通过衍射亮环的表征位置计算出衍射亮环到细胞衍射环的距离,得到衍射亮环最强光强点到细胞衍射环中心的距离的曲线。According to the radial super-resolution and circumferential super-resolution, the curve of the distance from the strongest light intensity point of the diffraction bright ring to the center of the cell diffraction ring is obtained: the radial super-resolution is to find the fastest rising point and the fastest decline of the peak corresponding to the diffraction bright ring point, use the intersection of the slopes of these two points to correct the position of the peak maximum point; circumferential super-resolution, denoise through Gaussian smoothing, and then obtain the corrected representative position of the diffraction bright ring; calculate the representative position of the diffraction bright ring Calculate the distance from the diffraction bright ring to the cell diffraction ring, and obtain the curve of the distance from the strongest light intensity point of the diffraction bright ring to the center of the cell diffraction ring.
本发明的有益效果是:The beneficial effects of the present invention are:
本发明基于无透镜成像的椭圆细胞检测装置,结构稳定,装置简易;置面向快速部署、低成本大规模部署和即时检测等应用场景;具有成本低,便携性高的优点;能够针对无透镜成像系统采集细胞图像时存在分辨率低和衍射干扰严重的情况,准确检测出椭圆细胞,实现了椭圆细胞检测装置的小型化。The elliptical cell detection device based on lensless imaging of the present invention has a stable structure and simple device; it is oriented to application scenarios such as rapid deployment, low-cost large-scale deployment and instant detection; it has the advantages of low cost and high portability; it can be used for lensless imaging When the system collects cell images, there are low resolution and serious diffraction interference, and the elliptical cells are accurately detected, which realizes the miniaturization of the elliptical cell detection device.
本发明椭圆细胞的检测方法,简单清晰,可操作性强,提高了椭圆形细胞测量的自动化程度,降低了操作的人工成本。The detection method of the ellipse cell of the present invention is simple and clear, has strong operability, improves the automation degree of the ellipse cell measurement, and reduces the labor cost of operation.
附图说明Description of drawings
图1是本发明基于无透镜成像的椭圆细胞检测装置的结构示意图。FIG. 1 is a schematic structural diagram of an ellipse cell detection device based on lensless imaging according to the present invention.
图中,1.灯光盒,2.LED光源,3.凸透镜,4.样本卡槽,5.遮光板,6.样本垫,7.CMOS图像传感器,8.电路板保护盒,9.样本垫。In the figure, 1. Light box, 2. LED light source, 3. Convex lens, 4. Sample card slot, 5. Shading plate, 6. Sample pad, 7. CMOS image sensor, 8. Circuit board protection box, 9. Sample pad .
具体实施方式Detailed ways
下面结合附图和具体实施方式对本发明进行详细说明。The present invention will be described in detail below in conjunction with the accompanying drawings and specific embodiments.
本发明基于无透镜成像的椭圆细胞检测装置,如图1所示,包括上下设置的灯光盒1和电路板保护盒8,灯光盒1与电路板保护盒8旋转连接,灯光盒1可在电路板保护盒8上转动,灯光盒1侧壁开设在有开口,电路板保护盒8上固定有与灯光盒1开口匹配的遮光板5,灯光盒1中由上向下依次设置有位于同一轴线上的LED光源2、凸透镜3、CMOS图像传感器7,CMOS图像传感器7外周设置有样本垫9,样本垫9上设置有样本卡槽4,CMOS图像传感器7位于电路板保护盒8上,电路板保护盒8中设置有与CMOS图像传感器7连接的CMOS图像传感器电路。The present invention is based on the elliptical cell detection device without lens imaging, as shown in Figure 1, including a light box 1 and a circuit
本发明椭圆细胞的检测方法,该方法应用并本发明的基于无透镜成像的椭圆细胞检测装置进行椭圆细胞检测,具体按照以下步骤实施:The detection method of elliptic cells of the present invention, the method is applied and the elliptical cell detection device based on lensless imaging of the present invention is used for detection of elliptical cells, specifically implemented according to the following steps:
步骤1、制作待测椭圆细胞样本6。Step 1, making the
步骤2、将待测椭圆细胞样本6置于CMOS图像传感器7上,并固定于样本卡槽4中,旋转灯光盒1使其开口与遮光板形成封闭采集室。
步骤3、开启LED光源2,使LED光源2发出的光线经凸透镜3聚拢垂直射向待测椭圆细胞样本6。
步骤4、打开CMOS图像传感器7,将采集到的图像数据经数据接口导出到CMOS图像传感器电路的处理模块上。Step 4, turn on the
步骤5、对导出的图像数据使用霍夫变换算法检测血细胞圆心,并依据血细胞圆心对图像进行分割,检测血细胞衍射环。
步骤6、在步骤5的基础上进行亚像素插值运算得到亚像素图像,并以步骤5中得到的圆心坐标为中心,将亚像素图像从矩形坐标系转换为极坐标系。
步骤7、通过超分辨率算法确定衍射亮环最强光强点到细胞衍射环中心的距离的曲线;
步骤7具体为,根据图像数据本身携带的光强信息,得到光强和距离衍射发生点的长度的映射关系,衍射发生点即细胞的边缘,这个关系表示在二维坐标系中会出现多个波峰,每一个波峰代表了一个衍射亮环,以波峰的最大值点表征衍射亮环的位置;
根据径向超分辨率和周向超分辨率得到衍射亮环最强光强点到细胞衍射环中心的距离的曲线:径向超分辨率是找到衍射亮环对应波峰的最快上升点和最快下降点,以这两个点的斜率的交点来修正波峰最大值点的位置;周向超分辨率,通过高斯平滑进行降噪,进而得到衍射亮环修正后的表征位置;通过衍射亮环的表征位置计算出衍射亮环到细胞衍射环的距离,得到衍射亮环最强光强点到细胞衍射环中心的距离的曲线。According to the radial super-resolution and circumferential super-resolution, the curve of the distance from the strongest light intensity point of the diffraction bright ring to the center of the cell diffraction ring is obtained: the radial super-resolution is to find the fastest rising point and the fastest decline of the peak corresponding to the diffraction bright ring point, use the intersection of the slopes of these two points to correct the position of the peak maximum point; circumferential super-resolution, denoise through Gaussian smoothing, and then obtain the corrected representative position of the diffraction bright ring; calculate the representative position of the diffraction bright ring Calculate the distance from the diffraction bright ring to the cell diffraction ring, and obtain the curve of the distance from the strongest light intensity point of the diffraction bright ring to the center of the cell diffraction ring.
步骤8、根据步骤6的距离曲线,计算出衍射亮环的光强最大值点,表征衍射亮环的位置。
步骤9、以极坐标系参数θ从0度增加至360度,按照设置的步长递增,如每次增加1度,依次重复步骤7~8,直到得到360度的半径数据,将360度的半径数据组成一个半径序列{x′pk1(θ1),x′pk2(θ2),…,x′pkn(θn)},x′pkn(θn)表示极坐标系参数θ对应的半径值,n为不为0的自然数。
步骤10、通过两个半径之和表征衍射环直径,匹配半径得到衍射环在角度α1,α2,…,αi处的直径长度,i是不为0的自然数:Step 10. Characterize the diameter of the diffraction ring by the sum of the two radii, and match the radii to obtain the diameter length of the diffraction ring at angles α 1 , α 2 ,..., α i , where i is a natural number other than 0:
式(10)中,D1(α1),D2(α2),…,Di(αi)是衍射环在角度α1,α2,…,αi处的直径长度;In formula (10), D 1 (α 1 ), D 2 (α 2 ),…,D i (α i ) are the diameter lengths of the diffraction ring at angles α 1 , α 2 ,…,α i ;
定义集合A来表示这些数据:Define a collection A to represent these data:
A={D1(α1),D2(α2),…,Di(αi)} (11)。A={D 1 (α 1 ), D 2 (α 2 ), . . . , D i (α i )} (11).
步骤11、进行椭圆细胞的匹配识别,椭圆长轴位置的阴影长度表示为:Step 11, carry out the matching recognition of the ellipse cells, the shadow length of the long axis position of the ellipse is expressed as:
Dmaj(αmaj)=min(A) (12)D maj (α maj )=min(A) (12)
假设π/4<αmaj<3π/4,定义集合B表示为Assuming π/4<α maj <3π/4, the definition set B is expressed as
B={D1(β1),D2(β2),…,Di(βi)} (13)B={D 1 (β 1 ), D 2 (β 2 ),..., D i (β i )} (13)
椭圆短轴位置处阴影的长度可以表示为:The length of the shadow at the position of the minor axis of the ellipse can be expressed as:
Dmin(αmin)=min(B)D min (α min ) = min(B)
定义参数M表示椭圆细胞长轴和短轴之间的差异:Define the parameter M to represent the difference between the major and minor axes of the elliptical cells:
M=|Dmaj(αmaj)-Dmin(αmin)|M=|D maj (α maj )-D min (α min )|
定义阈值MT,如果M>MT,那么判断是正常的椭圆细胞,否则为其他细胞。Define the threshold M T , if M>M T , then it is judged to be a normal elliptical cell, otherwise it is other cells.
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