Cadle Brian A, Rasmus Kristin C, Varela Juan A, Leverich Leah S, O'Neill Casey E, Bachtell Ryan K, Cooper Donald C
Institute for Behavioral Genetics.
Subst Abuse. 2010;4:21-33. doi: 10.4137/sart.s5025. Epub 2010 Sep 21.
Here we describe the first report of using low-cost cellular or web-based digital cameras to image and quantify standardized rapid immunoassay strips as a new point-of-care diagnostic and forensics tool with health applications. Quantitative ratiometric pixel density analysis (QRPDA) is an automated method requiring end-users to utilize inexpensive (∼ $1 USD/each) immunotest strips, a commonly available web or mobile phone camera or scanner, and internet or cellular service. A model is described whereby a central computer server and freely available IMAGEJ image analysis software records and analyzes the incoming image data with time-stamp and geo-tag information and performs the QRPDA using custom JAVA based macros (http://www.neurocloud.org). To demonstrate QRPDA we developed a standardized method using rapid immunotest strips directed against cocaine and its major metabolite, benzoylecgonine. Images from standardized samples were acquired using several devices, including a mobile phone camera, web cam, and scanner. We performed image analysis of three brands of commercially available dye-conjugated anti-cocaine/benzoylecgonine (COC/BE) antibody test strips in response to three different series of cocaine concentrations ranging from 0.1 to 300 ng/ml and BE concentrations ranging from 0.003 to 0.1 ng/ml. This data was then used to create standard curves to allow quantification of COC/BE in biological samples. Across all devices, QRPDA quantification of COC and BE proved to be a sensitive, economical, and faster alternative to more costly methods, such as gas chromatography-mass spectrometry, tandem mass spectrometry, or high pressure liquid chromatography. The limit of detection was determined to be between 0.1 and 5 ng/ml. To simulate conditions in the field, QRPDA was found to be robust under a variety of image acquisition and testing conditions that varied temperature, lighting, resolution, magnification and concentrations of biological fluid in a sample. To determine the effectiveness of the QRPDA method for quantifying cocaine in biological samples, mice were injected with a sub-locomotor activating dose of cocaine (5 mg/kg; i.p.) and were found to have detectable levels of COC/BE in their urine (160.6 ng/ml) and blood plasma (8.1 ng/ml) after 15-30 minutes. By comparison rats self-administering cocaine in a 4 hour session obtained a final BE blood plasma level of 910 ng/ml with an average of 62.5 infusions. It is concluded that automated QRPDA is a low-cost, rapid and highly sensitive method for the detection of COC/BE with health, forensics, and bioinformatics application and the potential to be used with other rapid immunotest strips directed at several other targets. Thus, this report serves as a general reference and method describing the use of image analysis of lateral flow rapid test strips.
在此,我们首次报告了使用低成本的手机或基于网络的数码相机对标准化快速免疫分析试纸条进行成像和定量分析,将其作为一种具有健康应用价值的新型即时诊断和法医工具。定量比率像素密度分析(QRPDA)是一种自动化方法,要求终端用户使用价格低廉(约1美元/条)的免疫检测试纸条、常见的网络或手机相机或扫描仪,以及互联网或移动网络服务。文中描述了一种模式,即中央计算机服务器和免费的IMAGEJ图像分析软件会记录并分析传入的图像数据,同时带有时间戳和地理标签信息,并使用基于Java的自定义宏执行QRPDA(http://www.neurocloud.org)。为了演示QRPDA,我们开发了一种标准化方法,使用针对可卡因及其主要代谢物苯甲酰爱康宁的快速免疫检测试纸条。使用包括手机相机、网络摄像头和扫描仪在内的多种设备采集标准化样本的图像。我们对三个品牌的市售染料偶联抗可卡因/苯甲酰爱康宁(COC/BE)抗体检测试纸条进行了图像分析,以响应三种不同系列的可卡因浓度,范围从0.1至300 ng/ml,以及BE浓度范围从0.003至0.1 ng/ml。然后利用这些数据创建标准曲线,以便对生物样本中的COC/BE进行定量分析。在所有设备上,QRPDA对COC和BE的定量分析被证明是一种灵敏、经济且比气相色谱 - 质谱法、串联质谱法或高压液相色谱法等更昂贵方法更快的替代方法。检测限确定为0.1至5 ng/ml之间。为了模拟现场条件,发现在各种图像采集和测试条件下,包括温度、光照、分辨率、放大倍数以及样本中生物流体浓度的变化,QRPDA都很稳健。为了确定QRPDA方法对生物样本中可卡因定量分析的有效性,给小鼠注射亚运动激活剂量的可卡因(5 mg/kg;腹腔注射),发现在15 - 30分钟后其尿液(160.6 ng/ml)和血浆(8.1 ng/ml)中可检测到COC/BE水平。相比之下,在4小时实验中自行注射可卡因的大鼠,其最终血浆中BE水平为910 ng/ml,平均注射62.5次。结论是,自动化QRPDA是一种低成本、快速且高度灵敏的检测COC/BE的方法,具有健康、法医和生物信息学应用价值,并且有可能用于针对其他多个靶点的其他快速免疫检测试纸条。因此,本报告作为一份通用参考资料和方法,描述了侧向流动快速检测试纸条的图像分析应用。