A nanostructured microfluidic device for plasmonic-assisted electrochemical detection of hydrogen peroxide released from cancer cells

Nanoscale ◽  
2021 ◽  
Author(s):  
Carolina del Real Mata ◽  
Roozbeh Siavash Moakhar ◽  
Sayed Iman Isaac Hosseini ◽  
Mahsa Jalali ◽  
Sara Mahshid

Non-invasive liquid biopsies offer hope for a rapid, risk-free, real-time glimpse into cancer diagnostics. Recently, hydrogen peroxide (H2O2) is identified as a cancer biomarker due to continued release from cancer...

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Skaidre Jankovskaja ◽  
Johan Engblom ◽  
Melinda Rezeli ◽  
György Marko-Varga ◽  
Tautgirdas Ruzgas ◽  
...  

AbstractThe tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker. Non-invasive topical sampling of Trp/Kyn can therefore serve as a promising concept for skin cancer diagnostics. By performing in vitro pig skin permeability studies, we conclude that non-invasive topical sampling of Trp and Kyn is feasible. We explore the influence of different experimental conditions, which are relevant for the clinical in vivo setting, such as pH variations, sampling time, and microbial degradation of Trp and Kyn. The permeabilities of Trp and Kyn are overall similar. However, the permeated Trp/Kyn ratio is generally higher than unity due to endogenous Trp, which should be taken into account to obtain a non-biased Trp/Kyn ratio accurately reflecting systemic concentrations. Additionally, prolonged sampling time is associated with bacterial Trp and Kyn degradation and should be considered in a clinical setting. Finally, the experimental results are supported by the four permeation pathways model, predicting that the hydrophilic Trp and Kyn molecules mainly permeate through lipid defects (i.e., the porous pathway). However, the hydrophobic indole ring of Trp is suggested to result in a small but noticeable relative increase of Trp diffusion via pathways across the SC lipid lamellae, while the shunt pathway is proposed to slightly favor permeation of Kyn relative to Trp.


2021 ◽  
Vol 12 ◽  
Author(s):  
Megan E. Barefoot ◽  
Netanel Loyfer ◽  
Amber J. Kiliti ◽  
A. Patrick McDeed ◽  
Tommy Kaplan ◽  
...  

Detection of cellular changes in tissue biopsies has been the basis for cancer diagnostics. However, tissue biopsies are invasive and limited by inaccuracies due to sampling locations, restricted sampling frequency, and poor representation of tissue heterogeneity. Liquid biopsies are emerging as a complementary approach to traditional tissue biopsies to detect dynamic changes in specific cell populations. Cell-free DNA (cfDNA) fragments released into the circulation from dying cells can be traced back to the tissues and cell types they originated from using DNA methylation, an epigenetic regulatory mechanism that is highly cell-type specific. Decoding changes in the cellular origins of cfDNA over time can reveal altered host tissue homeostasis due to local cancer invasion and metastatic spread to distant organs as well as treatment responses. In addition to host-derived cfDNA, changes in cancer cells can be detected from cell-free, circulating tumor DNA (ctDNA) by monitoring DNA mutations carried by cancer cells. Here, we will discuss computational approaches to identify and validate robust biomarkers of changed tissue homeostasis using cell-free, methylated DNA in the circulation. We highlight studies performing genome-wide profiling of cfDNA methylation and those that combine genetic and epigenetic markers to further identify cell-type specific signatures. Finally, we discuss opportunities and current limitations of these approaches for implementation in clinical oncology.


Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1274 ◽  
Author(s):  
Bee Luan Khoo ◽  
Charlotte Bouquerel ◽  
Pradeep Durai ◽  
Sarannya Anil ◽  
Benjamin Goh ◽  
...  

Bladder cancer (BC) is a disease that requires lifelong surveillance due to its high recurrence rate. An efficient method for the non-invasive rapid monitoring of patient prognosis and downstream phenotype characterization is warranted. Here, we develop an integrated procedure to detect aggressive mesenchymal exfoliated bladder cancer cells (EBCCs) from patients in a label-free manner. Using a combination of filtration and inertial focusing principles, the procedure allowed the focusing of EBCCs in a single stream-line for high-throughput separation from other urine components such as large squamous cells and blood cells using a microfluidic sorting device. Characterization of enriched cells can be completed within hours, suggesting a potential utility for real-time detection. We also demonstrate high efficiency of cancer cell recovery (93.3 ± 4.8%) and specific retrieval of various epithelial to mesenchymal transition (EMT) phenotype cell fractions from respective outlets of the microfluidic device. EMT is closely associated with metastasis, drug resistance and tumor-initiating potential. This procedure is validated with clinical samples, and further demonstrate the efficacy of bladder wash procedure to reduce EBCCs counts over time. Overall, the uniqueness of a rapid and non-invasive method permitting the separation of different EMT phenotypes shows high potential for clinical utility. We expect this approach will better facilitate the routine screening procedure in BC and greatly enhance personalized treatment.


2014 ◽  
Vol 3 (3) ◽  
Author(s):  
Laura T. Kerr ◽  
Katarina Domijan ◽  
Ivor Cullen ◽  
Bryan M. Hennelly

AbstractBiomolecular changes associated with cancer progression can be identified using Raman spectroscopy, allowing for this technique to be utilized as a non-invasive tool for the diagnosis of bladder cancer. Applications of Raman spectroscopy for diagnostics in real-time have consistently produced higher sensitivities and specificities than current clinical methods. This technique can be applied


2016 ◽  
Vol 8 (42) ◽  
pp. 7614-7622 ◽  
Author(s):  
Saidhbhe L. O'Riordan ◽  
Kelly Mc Laughlin ◽  
John P. Lowry

The in vitro physiological performance factors of a catalase-based microelectrochemical biosensor, developed for real-time neurochemical monitoring of hydrogen peroxide.


2020 ◽  
Vol 21 (7) ◽  
pp. 2401 ◽  
Author(s):  
Nicolai T. Sand ◽  
Tobias B. Petersen ◽  
Sara R. Bang-Christensen ◽  
Theresa D. Ahrens ◽  
Caroline Løppke ◽  
...  

Early detection and monitoring of cancer progression is key to successful treatment. Therefore, much research is invested in developing technologies, enabling effective and valuable use of non-invasive liquid biopsies. This includes the detection and analysis of circulating tumor cells (CTCs) from blood samples. Recombinant malaria protein VAR2CSA (rVAR2) binds a unique chondroitin sulfate modification present on the vast majority of cancers and thereby holds promise as a near-universal tumor cell-targeting reagent to isolate CTCs from complex blood samples. This study describes a technical approach for optimizing the coupling of rVAR2 to magnetic beads and the development of a CTC isolation platform targeting a range of different cancer cell lines. We investigate both direct and indirect approaches for rVAR2-mediated bead retrieval of cancer cells and conclude that an indirect capture approach is most effective for rVAR2-based cancer cell retrieval.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3525-3525
Author(s):  
Dadasaheb B Akolkar ◽  
Timothy Crook ◽  
Raymond Page ◽  
Darshana Patil ◽  
Sewanti Limaye ◽  
...  

3525 Background: Despite the development of targeted therapy agents and immune checkpoint inhibitors (ICI), cytotoxic anticancer agents remain the mainstay of treatment in several solid organ cancers. However, instances of innate and acquired resistance towards these anticancer agents can lead to treatment failures, which remain undetectable until clinical or radiological manifestation of symptoms suggestive of disease progression. There are presently no viable means or markers to detect or monitor for chemoresistance in real time. Owing to this unmet need, cancer treatment strategies face risks of failure and poor outcomes. Methods: We obtained 15 mL blood from 3,662 patients with various solid organ cancers, of various states and including treatment-naïve and pretreated patients. Circulating Tumor Associated Cells (C-TACs) were enriched and harvested from PBMCs using an epigenetically activating medium that is cytotoxic towards non-malignant epithelial and hematolymphoid cells in blood, but confers survival benefit on apoptosis resistant cells of tumorigenic origin (Circulating Tumor Associated Cells, C-TACs). In a subset of patients, fresh tumor tissue was also obtained from which viable tumor derived cells (TDCs) were obtained. Viable TDCs and C-TACs were treated with a panel of anticancer agents and the surviving cell fraction estimated to determine chemoresistance. Results: Among the 1,325 therapy naïve patients, resistance towards treatment agents was observed in C-TACs from 56.3 % of samples. Among 2,201 pretreated patients’ samples, resistance towards treatment agents was observed in C-TACs from 77.8% of samples. The increased resistance in C-TACs from pretreated patients indicated that the C-TACs had been resistance-educated by prior therapies. In a subset of patients, Chemoresistance profile of C-TACs was observed to be 96.9% concordant with that of tumor derived cells (TDCs) which were concurrently obtained from tumor tissue indicating that C-TACs accurately represent chemo-antecedents of the tumor. Conclusions: Non-invasive chemoresistance profiling of C-TACs is a viable strategy to monitor treatment efficacy in real time. Adoption of this strategy in the clinic will not only guide treatment selection with reduced risk of failure, but will also enable timely therapeutic course correction upon detection of acquired chemoresistance.


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