Recent advances in microfluidic methods in cancer liquid biopsy

Iliescu, Florina Silvia; Poenar, Daniel Puiu; Yu, Fang; Ni, Ming; Chan, Kiat Hwa; Cima, Irina; Taylor, Hayden; Cima, Igor; Iliescu, Ciprian

doi:10.1063/1.5087690

Cited by 39 publications

(29 citation statements)

References 457 publications

(579 reference statements)

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“…The only FDA-approved technique for CTC isolation is the CellSearch ® system which relies on the detection of the expression of the cell surface epithelial marker EpCAM to isolate CTCs from whole blood. However, the expression of EpCAM is often downregulated or absent in malignant epithelial CTCs undergoing epithelial-to-mesenchymal transition or in malignancies of non-epithelial origin (30). Compared with the FDA-approved CellSearch ® system, the eVBF device is not dependent on the expression of cell surface markers.…”

Section: Discussionmentioning

confidence: 99%

High‑throughput and continuous flow isolation of rare circulating tumor cells and clusters in gastric cancer from human whole blood samples using electromagnetic vibration‑based filtration

Xue

Ren

et al. 2020

Oncol Rep

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Circulating tumor cells (CTCs) or CTC clusters are considered as suitable and relevant targets for liquid biopsy as they more accurately indicate cancer progression, the therapeutic effects of treatment and allows for monitoring of cancer metastasis in real-time. Among the various methods for isolating CTCs, size-based filtration is one of the most convenient methods. However, cell clogging makes the filtration process less efficient. In the present study, an electromagnetic vibration-based filtration (eVBF) device was developed that efficiently isolated rare CTCs and CTC clusters from clinical blood samples of patients with gastric cancer. Using human blood samples spiked with human gastric cancer cells, the parameters of this device such as vibrating amplitude and flow rate were optimized. Putative CTCs were detected using a conventional filtration method and the eVBF device from the peripheral blood samples of patients with gastric cancer. Continuous flow isolation of CTCs was evaluated by a simulated blood flow system. The eVBF device utilized the electromagnetic force to generate a periodic vibration that prevented the cell clogging and improved the filtering efficiency. The optimized eVBF device with the high-amplitude vibration exhibited a recovery efficiency of 80-90% from whole blood samples spiked with 100 or 1,000 gastric cancer cells per ml. Using the eVBF device, CTCs were detected in 100% of patients (10/10) with gastric cancer, and the positive detection rate of the eVBF device was 30% higher compared with the conventional filtration method. Furthermore, CTC clusters were detected in 40% (4/10) of CTC-positive patient samples, and the integrity of CTC clusters was preserved using the eVBF device. The eVBF device allowed for high-throughput (1 ml/min) and continuous flow isolation of CTCs without the addition of any antibodies, any chemical reagents or any pretreatment processes. Thus, the eVBF device provides an efficient tool for isolating rare CTCs and CTC clusters from patients with cancer, highlighting its potential for use in cancer diagnosis, treatment and cancer biology research.

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Section: Discussionmentioning

confidence: 99%

High‑throughput and continuous flow isolation of rare circulating tumor cells and clusters in gastric cancer from human whole blood samples using electromagnetic vibration‑based filtration

Xue

Ren

et al. 2020

Oncol Rep

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“…Although CTCs have been preferred in the microfluidic-based sensor research for cancer diagnosis, alternative biomarkers, including microRNAs (miRNAs), circulating tumor DNA, or cancer-related proteins, can also provide important clinical information in this regard [ 95 , 99 ].…”

Section: Diagnostic Applicationsmentioning

confidence: 99%

Biosensors-on-Chip: An Up-to-Date Review

et al. 2020

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Generally, biosensors are designed to translate physical, chemical, or biological events into measurable signals, thus offering qualitative and/or quantitative information regarding the target analytes. While the biosensor field has received considerable scientific interest, integrating this technology with microfluidics could further bring significant improvements in terms of sensitivity and specificity, resolution, automation, throughput, reproducibility, reliability, and accuracy. In this manner, biosensors-on-chip (BoC) could represent the bridging gap between diagnostics in central laboratories and diagnostics at the patient bedside, bringing substantial advancements in point-of-care (PoC) diagnostic applications. In this context, the aim of this manuscript is to provide an up-to-date overview of BoC system development and their most recent application towards the diagnosis of cancer, infectious diseases, and neurodegenerative disorders.

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“…Most of the works have been developed around the analysis of blood-based biomarkers. However, precise information about malignancies can also be found through liquid biopsies [ 76 ] by isolating and analyzing rare cells, classical protein biomarkers, exosomes, circulating-free nucleic acids, tumor-derived vesicles or proteins, and metabolites [ 77 ].…”

Section: Microfluidics Tools: Single-cell Approachmentioning

confidence: 99%

Visualization and Measurements of Blood Cells Flowing in Microfluidic Systems and Blood Rheology: A Personalized Medicine Perspective

Pinho

Carvalho

Gonçalves

et al. 2020

JPM

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Hemorheological alterations in the majority of metabolic diseases are always connected with blood rheology disturbances, such as the increase of blood and plasma viscosity, cell aggregation enhancement, and reduction of the red blood cells (RBCs) deformability. Thus, the visualizations and measurements of blood cells deformability flowing in microfluidic devices (point-of-care devices) can provide vital information to diagnose early symptoms of blood diseases and consequently to be used as a fast clinical tool for early detection of biomarkers. For instance, RBCs rigidity has been correlated with myocardial infarction, diabetes mellitus, hypertension, among other blood diseases. In order to better understand the blood cells behavior in microfluidic devices, rheological properties analysis is gaining interest by the biomedical committee, since it is strongly dependent on the interactions and mechanical cells proprieties. In addition, the development of blood analogue fluids capable of reproducing the rheological properties of blood and mimic the RBCs behavior at in vitro conditions is crucial for the design, performance and optimization of the microfluidic devices frequently used for personalized medicine. By combining the unique features of the hemorheology and microfluidic technology for single-cell analysis, valuable advances in personalized medicine for new treatments and diagnosis approach can be achieved.

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Recent advances in microfluidic methods in cancer liquid biopsy

Abstract: Note: This paper is part of the special issue on Microfluidics, Circulating Biomarkers and Cancer.

Cited by 39 publications

References 457 publications

High‑throughput and continuous flow isolation of rare circulating tumor cells and clusters in gastric cancer from human whole blood samples using electromagnetic vibration‑based filtration

High‑throughput and continuous flow isolation of rare circulating tumor cells and clusters in gastric cancer from human whole blood samples using electromagnetic vibration‑based filtration

Biosensors-on-Chip: An Up-to-Date Review

Visualization and Measurements of Blood Cells Flowing in Microfluidic Systems and Blood Rheology: A Personalized Medicine Perspective

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