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PRADA: Portable Reusable Accurate Diagnostics with nanoAntennas for Multiplexed Biomarker Screening of Preterm Labor

PRADA: Portable Reusable Accurate Diagnostics with nanoAntennas for Multiplexed Biomarker Screening of Preterm Labor
PRADA:便携式可重复使用的纳米天线精确诊断,用于早产的多重生物标志物筛查
批准号:
10229351
负责人:
Rizia Bardhan
金额:
$22.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-08-01 至 2023-07-31

项目摘要

项目成果

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中文摘要
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英文摘要
Project Summary/Abstract: Spontaneous preterm labor (PTL, <37 weeks gestation) is the leading cause of neonatal and infant mortality globally, representing ~60% of all infant deaths. The physiopathology of PTL remains poorly understood due to the heterogeneities associated with the risk factors including maternal age, multiple gestation, and co-morbidities among others. Current clinical standard to identify women at high risk of PTL include cervical length assessment, and screening for fetal fibronectin in the cervicovaginal fluid. However, these approaches are inadequate and often fail to identify women who may deliver preterm. Recent patient metadata studies have identified multiple biomarkers correlated to PTL but risk scoring based on single biomarkers has shown low positive predictive values and have been ineffective in PTL prediction. The scientific premise of the proposed study is that there is an urgent clinical need for accurate diagnostics with multiplexed biomarker detection capabilities that are simultaneously affordable to facilitate routine bedside screening for all patients. Further by benchmarking the biodiagnostic against commercial assays using the same sample type from the same patients will minimize inter- and intra-assay variation, which remains a challenge in current bedside diagnostics. The objective of this study is to address this unmet need with an innovative biodiagnostic, PRADA, which combines high sensitivity, specificity, multiplexing, use of low sample volumes, and low cost. PRADA, portable reusable accurate diagnostics with nanoantennas, consists of magnetic microbeads capture probes functionalized with polyclonal antibodies, and near-infrared resonant gold nanostar “antennas” barcoded with Raman tags and labeled with peptides to detect the biomarkers via surface-enhanced Raman spectroscopy (SERS). PRADA has successfully demonstrated multiplexed detection of 3 PTL biomarkers including alpha- fetoprotein (AFP), corticotrophin releasing hormone (CRH) and granulocyte macrophage colony-stimulating factor (GM-CSF) in pregnant patient serum. PRADA achieved ultrasensitive limit of detection (LOD, 1.7 pg/ml GM-CSF) ideal for risk stratification, and when compared to commercial Luminex and ELISA, PRADA showed far lower LODs. Further, PRADA is also reusable (due to the use of magnetic beads), lowering the overall cost by allowing >15 uses of a single microfluidic device. This work will leverage innovative PRADA to quantitatively detect 6 serum biomarkers which are the most predictive of PTL including C-reactive protein (CRP), AFP, IL-10, IL-6, CRH, and GM-CSF benchmarked against Luminex and ELISA (Aim 1). Further, we will validate multiplexing with PRADA in serum of patients recruited for this study in the 18 – 35 years age group with singleton pregnancy and gestation age 19 – 36 weeks (Aim 2). A maternal risk score will be established categorizing patients into high and low risk groups, and the scoring will be compared to their existing diagnosis to determine the accuracy of PRADA. Our central hypothesis is PRADA will enable a robust bedside diagnosis that accurately predicts the onset of PTL, identifies patients who need immediate treatment, and minimizes unnecessary intervention for those at low risk. PRADA is clinically translatable as gold nanoparticles are already in clinical trials (NCT00436410, NCT00356980) and integrated in commercial assays (First response pregnancy tests), and SERS has demonstrated utility in commercial sensors (Oxonica, Renishaw Diagnostics etc.). This impactful project will leverage the expertise of the PI (Bardhan) in nanoparticle diagnostics and SERS, with the complementary expertise of co-investigators Dr. Leon Bellan (microfluidics), Dr. Jeff Reese (mechanisms of PTL), and Dr. J. Michael Newton (PTL patient treatment).
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
DOI: 10.1021/acsami.3c04260
发表时间: 2023-08
期刊: ACS applied materials & interfaces
影响因子: 9.5
作者: [Lilly Synan;S. Ghazvini;Saji Uthaman;Gabriel Cutshaw;Che-Yu Lee;Joshua R. Waite;Xiaona Wen;S. Sarkar;Eugene C Lin;M. Santillan;D. Santillan;Rizia Bardhan]
通讯作者: Lilly Synan;S. Ghazvini;Saji Uthaman;Gabriel Cutshaw;Che-Yu Lee;Joshua R. Waite;Xiaona Wen;S. Sarkar;Eugene C Lin;M. Santillan;D. Santillan;Rizia Bardhan
Developing Multimodal Multiplexed ImmunoPET-Raman Probes to Guide Immunotherapies
  • 批准号:
    10256611
  • 项目类别:
  • 资助金额:
    $31.12万
  • 财政年份:
    2020
  • 负责人:
    Rizia Bardhan
  • 依托单位:
Developing Multimodal Multiplexed ImmunoPET-Raman Probes to Guide Immunotherapies
  • 批准号:
    10447750
  • 项目类别:
  • 资助金额:
    $29.61万
  • 财政年份:
    2020
  • 负责人:
    Rizia Bardhan
  • 依托单位:
海外基金