skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


  • NSF Public Access
  • Search Results
  • Few-Layer Graphene-Based Optical Nanobiosensors for the Early-Stage Detection of Ovarian Cancer Using Liquid Biopsy and an Active Learning Strategy

This content will become publicly available on March 1, 2026

Title: Few-Layer Graphene-Based Optical Nanobiosensors for the Early-Stage Detection of Ovarian Cancer Using Liquid Biopsy and an Active Learning Strategy
Ovarian cancer survival depends strongly on the time of diagnosis. Detection at stage 1 must be the goal of liquid biopsies for ovarian cancer detection. We report the development and validation of graphene-based optical nanobiosensors (G-NBSs) that quantify the activities of a panel of proteases, which were selected to provide a crowd response that is specific for ovarian cancer. These G-NBSs consist of few-layer explosion graphene featuring a hydrophilic coating, which is linked to fluorescently labeled highly selective consensus sequences for the proteases of interest, as well as a fluorescent dye. The panel of G-NBSs showed statistically significant differences in protease activities when comparing localized (early-stage) ovarian cancer with both metastatic (late-stage) and healthy control groups. A hierarchical framework integrated with active learning (AL) as a prediction and analysis tool for early-stage detection of ovarian cancer was implemented, which obtained an overall accuracy score of 94.5%, with both a sensitivity and specificity of 0.94.  more » « less
Award ID(s):
2129617
PAR ID:
10657831
Author(s) / Creator(s):
; ; ; ; ; ;
Publisher / Repository:
MDPI
Date Published:
Journal Name:
Cells
Volume:
14
Issue:
5
ISSN:
2073-4409
Page Range / eLocation ID:
375
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; ; ; ; (, Journal of Clinical Oncology)
    e20551 Background: Enzyme activity is at the center of all biological processes. When these activities are misregulated by changes in sequence, expression, or activity, pathologies emerge. Misregulation of protease enzymes such as Matrix Metalloproteinases and Cathepsins play a key role in the pathophysiology of cancer. We describe here a novel class of graphene-based, cost effective biosensors that can detect altered protease activation in a blood sample from early stage lung cancer patients. Methods: The Gene Expression Omnibus (GEO) tool was used to identify proteases differentially expressed in lung cancer and matched normal tissue. Biosensors were assembled on a graphene backbone annotated with one of a panel of fluorescently tagged peptides. The graphene quenches fluorescence until the peptide is either cleaved by active proteases or altered by post-translational modification. 19 protease biosensors were evaluated on 431 commercially collected serum samples from non-lung cancer controls (69%) and pathologically confirmed lung cancer cases (31%) tested over two independent cohorts. Serum was incubated with each of the 19 biosensors and enzyme activity was measured indirectly as a continuous variable by a fluorescence plate reader. Analysis was performed using Emerge, a proprietary predictive and classification modeling system based on massively parallel evolving “Turing machine” algorithms. Each analysis stratified allocation into training and testing sets, and reserved an out-of-sample validation set for reporting. Results: 256 clinical samples were initially evaluated including 35% cancer cases evenly distributed across stages I (29%), II (26%), III (24%) and IV (21%). The case controls included common co-morbidies in the at-risk population such as COPD, chronic bronchitis, and benign nodules (19%). Using the Emerge classification analysis, biosensor biomarkers alone (no clinical factors) demonstrated Sensitivity (Se.) = 92% (CI 82%-99%) and Specificity (Sp.) = 82% (CI 69%-91%) in the out-of-sample set. An independent cohort of 175 clinical cases (age 67±8, 52% male) focused on early detection (26% cancer, 70% Stage I, 30% Stage II/III) were similarly evaluated. Classification showed Se. = 100% (CI 79%-100%) and Sp. = 93% (CI 80%-99%) in the out-of-sample set. For the entire dataset of 175 samples, Se. = 100% (CI 92%-100%) and Sp. = 97% (CI 92%-99%) was observed. Conclusions: Lung cancer can be treated if it is diagnosed when still localized. Despite clear data showing screening for lung cancer by Low Dose Computed Tomography (LDCT) is effective, screening compliance remains very low. Protease biosensors provide a cost effective additional specialized tool with high sensitivity and specificity in detection of early stage lung cancer. A large prospective trial of at-risk smokers with follow up is being conducted to evaluate a commercial version of this assay. 
    more » « less
  2. ; ; ; ; ; ; ; ; ; ; et al (, Cancer Research)
    AACR (Ed.)
    Abstract Cancer is an intricate disease accountable for the deaths of over 10 million people per year in the United States of America. Several scientific studies showed that the cancer stem cell (CSC) markers have prognostic significance in various cancers and are crucial for designing anticancer drugs to lower cancer death. However, there was a lack of rapid, accurate identification, and analysis, of the prognostic cancer stem cell (CSC) biomarkers in numerous cancer patients. In our laboratory, we identified and analyzed prognostic lung cancer stem cell markers (LCSCs) by using the Immunofluorescence microtissue array (IMA) technique in different lung cancer patient’s tissue biopsy samples and observed that the increased expression of LCSCs principally, CD44 and CD80 in stage IIIA lung cancer tissues compared to normal lung biopsy tissues. We also investigated pancreatic cancer stem cell biomarkers (PAN CSCs) namely CD44 and CD80 with the IMA technique in pancreatic biopsy tissues. The CD44 fluorescence proved an increased expression in adenocarcinoma pancreatic cell tissues when compared to CD80. We also studied and analyzed the stage progression with ovarian cancer stem cell biomarkers (OCSCs) chiefly CD54 and CD44 using the IMA technique in ovarian cancer patients and normal biopsy tissues. The increased expression of CD44 and CD54 were observed in Stage III ovarian cancer tissues compared to normal ovarian tissue indicating the potential role of these OCSC’s biomarkers for the prognosis of ovarian cancer pathogenesis. Our results of prognostic cancer stem cell biomarkers of lung, pancreatic, and ovarian cancers have been analyzed by one-way ANOVA and bioinformatics software (Reactome, Cytoscape PSICQUIC services, STRING) to find underlying molecular mechanism of target gene regulation of increased expression of prognostic CSCs which may give a clue for the prevention and treatment of these cancers. Further research is warranted for these lung, pancreatic, and ovarian CSCs which could be valuable for clinical trials and drug discovery against these CSC biomarkers at early-stage development. Citation Format:Madhumita Das, Kymkecia Henry, Djarie Armstrong, Charle Truman, Charlie Kendrick, Maya S. Saunders, Juan E. Anderson, Malcolm J. Lovett, Rose Stiffin, Ayivi Huisso, Donrie Purcell, Marco Ruiz, Paulo Chaves, Jayanta Kumar Das. Immunofluorescence microtissue array (IMA) for detection of prognostic cancer stem cell biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7077. 
    more » « less
  3. ; ; ; ; ; ; ; (, Obstetrics & Gynecology)
    OBJECTIVE:To determine biomarkers other than CA 125 that could be used in identifying early-stage ovarian cancer. DATA SOURCES:Ovid MEDLINE ALL, EMBASE, Web of Science Core Collection, ScienceDirect, Clinicaltrials.gov, and CAB Direct were searched for English-language studies between January 2008 and April 2023 for the concepts of high-grade serous ovarian cancer, testing, and prevention or early diagnosis. METHODS OF STUDY SELECTION:The 5,523 related articles were uploaded to Covidence. Screening by two independent reviewers of the article abstracts led to the identification of 245 peer-reviewed primary research articles for full-text review. Full-text review by those reviewers led to the identification of 131 peer-reviewed primary research articles used for this review. TABULATION, INTEGRATION, AND RESULTSOf 131 studies, only 55 reported sensitivity, specificity, or area under the curve (AUC), with 36 of the studies reporting at least one biomarker with a specificity of 80% or greater specificity or 0.9 or greater AUC. CONCLUSION:These findings suggest that although many types of biomarkers are being tested in ovarian cancer, most have similar or worse detection rates compared with CA 125 and have the same limitations of poor detection rates in early-stage disease. However, 27.5% of articles (36/131) reported biomarkers with better sensitivity and an AUC greater than 0.9 compared with CA 125 alone and deserve further exploration. 
    more » « less
  4. ; ; ; (, Sensors & transducers)
    Most of the cancers are curable if they are detected at early stages. The early stage detection of cancers can significantly improve the patient treatment outcomes and thus helps to decrease the. To achieve the early detection of specific cancer, the biochip is incorporated with an innovative sensing mechanism and surface treated microchannels. The sensing mechanism employed in the Point of Care (POC) biochip is designed to be highly specific and sensitive. The surface treated microchannel helps to control the self-driven flow of the blood sample. Cancer antibodies with enhanced specificity and affinity are immobilized on the surface of the nano circuit in the microchannel. When the blood sample flows in the microchannel over the cancer antibodies, the corresponding cancer antigens from the blood form the antigen-antibody complex. These antigen-antibody interactions are captured with the variation in the electrical properties of the gold nano circuit using the sensing mechanism in the biochip. The point of care (POC) micro biochip is designed as an in-situ standalone device to diagnose ovarian cancer at the early stages by sensing the cancer antigens in the blood sample drawn from a finger prick. The POC biochip can help to diagnose, the existence of cancer and also its severity using the qualitative and the quantitative results of the sensing mechanism in the biochip. 
    more » « less
  5. ; ; ; ; ; (, ChemMedChem)
    Abstract The central role of iron in tumor progression and metastasis motivates the development of iron‐binding approaches in cancer chemotherapy. Disulfide‐based prochelators are reductively activated upon cellular uptake to liberate thiol chelators responsible for iron sequestration. Herein, a trimethyl thiosemicarbazone moiety and the imidazole‐2‐thione heterocycle are incorporated in this prochelator design. Iron binding of the corresponding tridentate chelators leads to the stabilization of a low‐spin ferric center in 2 : 1 ligand‐to‐metal complexes. Native mass spectrometry experiments show that the prochelators form stable disulfide conjugates with bovine serum albumin, thus affording novel bioconjugate prochelator systems. Antiproliferative activities at sub‐micromolar levels are recorded in a panel of breast, ovarian and colorectal cancer cells, along with significantly lower activity in normal fibroblasts. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email