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.


Title: Emerging on‐chip electrokinetic based technologies for purification of circulating cancer biomarkers towards liquid biopsy: A review
Abstract Early detection of cancer can significantly reduce mortality and save lives. However, the current cancer diagnosis is highly dependent on costly, complex, and invasive procedures. Thus, a great deal of effort has been devoted to exploring new technologies based on liquid biopsy. Since liquid biopsy relies on detection of circulating biomarkers from biofluids, it is critical to isolate highly purified cancer‐related biomarkers, including circulating tumor cells (CTCs), cell‐free nucleic acids (cell‐free DNA and cell‐free RNA), small extracellular vesicles (exosomes), and proteins. The current clinical purification techniques are facing a number of drawbacks including low purity, long processing time, high cost, and difficulties in standardization. Here, we review a promising solution, on‐chip electrokinetic‐based methods, that have the advantage of small sample volume requirement, minimal damage to the biomarkers, rapid, and label‐free criteria. We have also discussed the existing challenges of current on‐chip electrokinetic technologies and suggested potential solutions that may be worthy of future studies.  more » « less
Award ID(s):
2046037
PAR ID:
10446847
Author(s) / Creator(s):
 ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
ELECTROPHORESIS
Volume:
43
Issue:
1-2
ISSN:
0173-0835
Format(s):
Medium: X Size: p. 288-308
Size(s):
p. 288-308
Sponsoring Org:
National Science Foundation
More Like this
  1. 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
  2. null (Ed.)
    Advanced materials and chemo-specific designs at the nano/micrometer-scale have ensured revolutionary progress in next-generation clinically relevant technologies. For example, isolating a rare population of cells, like circulating tumor cells (CTCs) from the blood amongst billions of other blood cells, is one of the most complex scientific challenges in cancer diagnostics. The chemical tunability for achieving this degree of exceptional specificity for extra-cellular biomarker interactions demands the utility of advanced entities and multistep reactions both in solution and in the insoluble state. Thus, this review delineates the chemo-specific substrates, chemical methods, and structure–activity relationships (SARs) of chemical platforms used for isolation and enumeration of CTCs in advancing the relevance of liquid biopsy in cancer diagnostics and disease management. We highlight the synthesis of cell-specific, tumor biomarker-based, chemo-specific substrates utilizing functionalized linkers through chemistry-based conjugation strategies. The capacity of these nano/micro substrates to enhance the cell interaction specificity and efficiency with the targeted tumor cells is detailed. Furthermore, this review accounts for the importance of CTC capture and other downstream processes involving genotypic and phenotypic CTC analysis in real-time for the detection of the early onset of metastases progression and chemotherapy treatment response, and for monitoring progression free-survival (PFS), disease-free survival (DFS), and eventually overall survival (OS) in cancer patients. 
    more » « less
  3. Abstract IntroductionAbnormal angiogenesis is central to vascular disease and cancer, and noninvasive biomarkers of vascular origin are needed to evaluate patients and therapies. Vascular endothelial growth factor receptors (VEGFRs) are often dysregulated in these diseases, making them promising biomarkers, but the need for an invasive biopsy has limited biomarker research on VEGFRs. Here, we pioneer a blood biopsy approach to quantify VEGFR plasma membrane localization on two circulating vascular proxies: circulating endothelial cells (cECs) and circulating progenitor cells (cPCs). MethodsUsing quantitative flow cytometry, we examined VEGFR expression on cECs and cPCs in four age-sex groups: peri/premenopausal females (aged < 50 years), menopausal/postmenopausal females (≥ 50 years), and younger and older males with the same age cut-off (50 years). ResultscECs in peri/premenopausal females consisted of two VEGFR populations: VEGFR-low (~ 55% of population: population medians ~ 3000 VEGFR1 and 3000 VEGFR2/cell) and VEGFR-high (~ 45%: 138,000 VEGFR1 and 39,000–236,000 VEGFR2/cell), while the menopausal/postmenopausal group only possessed the VEGFR-low cEC population; and 27% of cECs in males exhibited high plasma membrane VEGFR expression (206,000 VEGFR1 and 155,000 VEGFR2/cell). The absence of VEGFR-high cEC subpopulations in menopausal/postmenopausal females suggests that their high-VEGFR cECs are associated with menstruation and could be noninvasive proxies for studying the intersection of age-sex in angiogenesis. VEGFR1 plasma membrane localization in cPCs was detected only in menopausal/postmenopausal females, suggesting a menopause-specific regenerative mechanism. ConclusionsOverall, our quantitative, noninvasive approach targeting cECs and cPCs has provided the first insights into how sex and age influence VEGFR plasma membrane localization in vascular cells. 
    more » « less
  4. Abstract Sepsis is responsible for the highest economic and mortality burden in critical care settings around the world, prompting the World Health Organization in 2018 to designate it as a global health priority. Despite its high universal prevalence and mortality rate, a disproportionately low amount of sponsored research funding is directed toward diagnosis and treatment of sepsis, when early treatment has been shown to significantly improve survival. Additionally, current technologies and methods are inadequate to provide an accurate and timely diagnosis of septic patients in multiple clinical environments. For improved patient outcomes, a comprehensive immunological evaluation is critical which is comprised of both traditional testing and quantifying recently proposed biomarkers for sepsis. There is an urgent need to develop novel point‐of‐care, low‐cost systems which can accurately stratify patients. These point‐of‐critical‐care sensors should adopt a multiplexed approach utilizing multimodal sensing for heterogenous biomarker detection. For effective multiplexing, the sensors must satisfy criteria including rapid sample to result delivery, low sample volumes for clinical sample sparring, and reduced costs per test. A compendium of currently developed multiplexed micro and nano (M/N)‐based diagnostic technologies for potential applications toward sepsis are presented. We have also explored the various biomarkers targeted for sepsis including immune cell morphology changes, circulating proteins, small molecules, and presence of infectious pathogens. An overview of different M/N detection mechanisms are also provided, along with recent advances in related nanotechnologies which have shown improved patient outcomes and perspectives on what future successful technologies may encompass. This article is categorized under:Diagnostic Tools > Biosensing 
    more » « less
  5. A biomarker is a physiological observable marker that acts as a stand-in and, in the best-case scenario, forecasts a clinically significant outcome. Diagnostic biomarkers are more convenient and cost-effective than directly measuring the ultimate clinical outcome. Cancer is among the most prominent global health problems and a major cause of morbidity and death globally. Therefore, cancer biomarker assays that are trustworthy, consistent, precise, and verified are desperately needed. Biomarker-based tumor detection holds a lot of promise for improving disease knowledge at the molecular scale and early detection and surveillance. In contrast to conventional approaches, surface plasmon resonance (SPR) allows for the quick and less invasive screening of a variety of circulating indicators, such as circulating tumor DNA (ctDNA), microRNA (miRNA), circulating tumor cells (CTCs), lipids, and proteins. With several advantages, the SPR technique is a particularly beneficial choice for the point-of-care identification of biomarkers. As a result, it enables the timely detection of tumor markers, which could be used to track cancer development and suppress the relapse of malignant tumors. This review emphasizes advancements in SPR biosensing technologies for cancer detection. 
    more » « less