Kahn Maria, LaRue Nicole, Zhu Changcheng, Pal Sampa, Mo Jack S, Barrett Lynn K, Hewitt Steve N, Dumais Mitchell, Hemmington Sandra, Walker Adrian, Joynson Jeff, Leader Brandon T, Van Voorhis Wesley C, Domingo Gonzalo J
PATH Diagnostics Group, Seattle, Washington, United States of America.
Center for Emerging and Re-emerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, United States of America.
PLoS One. 2017 May 26;12(5):e0177885. doi: 10.1371/journal.pone.0177885. eCollection 2017.
A large gap for the support of point-of-care testing is the availability of reagents to support quality control (QC) of diagnostic assays along the supply chain from the manufacturer to the end user. While reagents and systems exist to support QC of laboratory screening tests for glucose-6-phosphate dehydrogenase (G6PD) deficiency, they are not configured appropriately to support point-of-care testing. The feasibility of using lyophilized recombinant human G6PD as a QC reagent in novel point-of-care tests for G6PD deficiency is demonstrated.
Human recombinant G6PD (r-G6PD) was expressed in Escherichia coli and purified. Aliquots were stored at -80°C. Prior to lyophilization, aliquots were thawed, and three concentrations of r-G6PD (representing normal, intermediate, and deficient clinical G6PD levels) were prepared and mixed with a protective formulation, which protects the enzyme activity against degradation from denaturation during the lyophilization process. Following lyophilization, individual single-use tubes of lyophilized r-G6PD were placed in individual packs with desiccants and stored at five temperatures for one year. An enzyme assay for G6PD activity was used to ascertain the stability of r-G6PD activity while stored at different temperatures.
Lyophilized r-G6PD is stable and can be used as a control indicator. Results presented here show that G6PD activity is stable for at least 365 days when stored at -80°C, 4°C, 30°C, and 45°C. When stored at 55°C, enzyme activity was found to be stable only through day 28.
Lyophilized r-G6PD enzyme is stable and can be used as a control for point-of-care tests for G6PD deficiency.
即时检测支持方面的一个巨大差距在于,从制造商到最终用户的供应链中缺乏用于支持诊断检测质量控制(QC)的试剂。虽然存在支持葡萄糖 - 6 - 磷酸脱氢酶(G6PD)缺乏症实验室筛查检测质量控制的试剂和系统,但它们的配置并不适合支持即时检测。本文证明了使用冻干重组人G6PD作为G6PD缺乏症新型即时检测中的质量控制试剂的可行性。
人重组G6PD(r - G6PD)在大肠杆菌中表达并纯化。分装后储存在 - 80°C。冻干前,将分装物解冻,制备三种浓度的r - G6PD(代表正常、中间和缺乏的临床G6PD水平),并与一种保护制剂混合,该保护制剂可保护酶活性在冻干过程中不被变性降解。冻干后,将冻干r - G6PD的单支一次性使用管与干燥剂一起放入单独包装中,并在五个温度下储存一年。使用G6PD活性酶测定法确定r - G6PD活性在不同温度下储存时的稳定性。
冻干r - G6PD稳定,可作为对照指标。此处给出的结果表明,r - G6PD活性在 - 80°C、4°C、30°C和45°C储存时至少365天稳定。在55°C储存时,发现酶活性仅在第28天前稳定。
冻干r - G6PD酶稳定,可作为G6PD缺乏症即时检测的对照。