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基于微电机的双重适体分析,用于早期经济高效的新生儿败血症诊断。

Micromotor-based dual aptassay for early cost-effective diagnosis of neonatal sepsis.

机构信息

Department of Analytical Chemistry, Physical Chemistry and Chemical Engineering, Faculty of Sciences, University of Alcalá, Ctra. Madrid-Barcelona, Km. 33.600, Alcalá de Henares, 28802, Madrid, Spain.

Department of Neonatology, Instituto del Niño y del Adolescente, Hospital Clínico San Carlos-IdISSC, 28040, Madrid, Spain.

出版信息

Mikrochim Acta. 2024 Jan 19;191(2):106. doi: 10.1007/s00604-023-06134-x.

Abstract

Given the long-life expectancy of the newborn, research aimed at improving sepsis diagnosis and management in this population has been recognized as cost-effective, which at early stages continues to be a tremendous challenge. Despite there is not an ideal-specific biomarker, the simultaneous detection of biomarkers with different behavior during an infection such as procalcitonin (PCT) as high specificity biomarker with one of the earliest biomarkers in sepsis as interleukin-6 (IL-6) increases diagnostic performance. This is not only due to their high positive predictive value but also, since it can also help the clinician to rule out infection and thus avoid the use of antibiotics, due to their high negative predictive value. To this end, we explore a cutting-edge micromotor (MM)-based OFF-ON dual aptassay for simultaneous determination of both biomarkers in 15 min using just 2 μL of sample from low-birth-weight neonates with gestational age less than 32 weeks and birthweight below 1000 g with clinical suspicion of late-onset sepsis. The approach reached the high sensitivities demanded in the clinical scenario (LOD = 0.003 ng/mL, LOD = 0.15 pg/mL) with excellent correlation performance (r > 0.9990, p < 0.05) of the MM-based approach with the Hospital method for both biomarkers during the analysis of diagnosed samples and reliability (Er < 6% for PCT, and Er < 4% for IL-6). The proposed approach also encompasses distinctive technical attributes in a clinical scenario since its minimal sample volume requirements and expeditious results compatible with few easy-to-obtain drops of heel stick blood samples from newborns admitted to the neonatal intensive care unit. This would enable the monitoring of both sepsis biomarkers within the initial hours after the manifestation of symptoms in high-risk neonates as a valuable tool in facilitating prompt and well-informed decisions about the initiation of antibiotic therapy.These results revealed the asset behind micromotor technology for multiplexing analysis in diagnosing neonatal sepsis, opening new avenues in low sample volume-based diagnostics.

摘要

鉴于新生儿的预期寿命较长,因此针对该人群的脓毒症诊断和治疗的研究已被认为具有成本效益,而在早期阶段,这仍然是一个巨大的挑战。尽管目前尚无理想的特异性生物标志物,但同时检测感染过程中具有不同行为的生物标志物,例如降钙素原(PCT)作为脓毒症最早的生物标志物之一,以及白细胞介素-6(IL-6),可以提高诊断性能。这不仅是因为它们具有较高的阳性预测值,而且还因为它们还可以帮助临床医生排除感染,从而避免使用抗生素,因为它们具有较高的阴性预测值。为此,我们探索了一种基于微电机(MM)的开-关双适体测定法,用于在 15 分钟内同时测定这两种生物标志物,只需从胎龄小于 32 周且出生体重低于 1000 克的低出生体重儿中使用 2μL 的样本即可,并且临床怀疑患有晚发性败血症。该方法达到了临床所需的高灵敏度(LOD=0.003ng/mL,LOD=0.15pg/mL),并且在分析诊断样本时,基于 MM 的方法与医院方法之间具有出色的相关性能(r>0.9990,p<0.05),对于两种生物标志物均具有可靠性(PCT 的 Er<6%,IL-6 的 Er<4%)。该方法还具有独特的技术属性,因为它需要的样本量最少,并且结果快速,与从新生儿重症监护病房入院的新生儿足跟采血得到的少量容易获得的血液样本兼容。这将使我们能够在高危新生儿出现症状后的最初几个小时内监测这两种脓毒症生物标志物,作为促进及时做出明智的抗生素治疗决策的有价值的工具。这些结果揭示了微电机技术在诊断新生儿败血症中的多重分析中的资产,为基于低样本量的诊断开辟了新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b755/10798920/d0a371763da6/604_2023_6134_Fig1_HTML.jpg

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