Dullaert-de Boer Maria, Akkerman Onno W, Vermeer Marloes, Hess Dorine L J, Kerstjens Huib A M, Anthony Richard M, van der Werf Tjip S, van Soolingen Dick, van der Zanden Adri G M
Laboratory for Medical Microbiology and Public Health, Hengelo, The Netherlands.
University of Groningen, University Medical Center Groningen, Department of Pulmonary diseases and Tuberculosis, Groningen, The Netherlands.
PLoS One. 2018 Jan 12;13(1):e0190847. doi: 10.1371/journal.pone.0190847. eCollection 2018.
Real time PCR has become a dominant method for the highly sensitive detection of pathogens in clinical material. Real time PCR can generate a fluorescence signal by using fluorescence labelled probes, allowing us to detect and semi quantify the amount of amplified DNA. Here we test the variability of the detection system and cost implications of three different versions of the LightCycler® 480 (LC480), focusing on the intensity of fluorescence and Cq in monoplex and multiplex rtPCRs. For gastro-intestinal pathogens there was no correlation between the intensity of fluorescence and the Cq value in the different LC480 types. For probes with the dyes FAMTM, HEXTM, Cy5 and Red610 a higher fluorescence intensity was seen in LC480 type II and III compared to LC480 type I. After lowering the probe concentration for the Cy5 dye three-fold (from 0.3μM to 0.1μM) the Cq value remains the same and the intensity of fluorescence decreases. For the LC480 type II and III the difference in fluorescence intensity was much more extreme. The concentration of the different labelled probes can be lowered at least six-fold in LC480 type II and III cyclers while maintaining a fluorescence intensity as high as achieved in the LC480 type I with undiluted probe. In conclusion, the strength of the fluorescence signal of the LightCycler® 480 type III is superior to that of LightCycler® 480 types I and II, allowing the use of lower probe concentrations for all dyes, particularly for the dyes Red610 and Cy5. This results in a two thirds reduction in PCR probe costs. Switching to these newer machines for real-time PCR can reduce dye labelled probe consumption and thus reduce costs significantly.
实时荧光定量PCR已成为临床样本中病原体高灵敏度检测的主要方法。实时荧光定量PCR可通过使用荧光标记探针产生荧光信号,使我们能够检测并半定量扩增DNA的量。在此,我们测试了三种不同版本的罗氏LightCycler® 480(LC480)检测系统的变异性及其成本影响,重点关注单重和多重逆转录PCR中荧光强度和Cq值。对于胃肠道病原体,不同类型的LC480中荧光强度与Cq值之间没有相关性。对于使用FAMTM、HEXTM、Cy5和Red610染料的探针,与LC480 I型相比,在LC480 II型和III型中观察到更高的荧光强度。将Cy5染料的探针浓度降低三倍(从0.3μM降至0.1μM)后,Cq值保持不变,荧光强度降低。对于LC480 II型和III型,荧光强度差异更为显著。在LC480 II型和III型仪器中,不同标记探针的浓度可至少降低六倍,同时保持与未稀释探针的LC480 I型中一样高的荧光强度。总之,罗氏LightCycler® 480 III型的荧光信号强度优于I型和II型,所有染料均可使用更低的探针浓度,特别是Red610和Cy5染料。这使得PCR探针成本降低三分之二。改用这些更新的仪器进行实时PCR可减少染料标记探针的消耗,从而显著降低成本。