Microfluidic cell sorting by stiffness to examine heterogenic responses of cancer cells to chemotherapy

Islam, Muhymin; Mezencev, Roman; McFarland, Brynn; Brink, Hannah; Campbell, Betsy; Tasadduq, Bushra; Waller, Edmund K.; Lam, Wilbur A.; Alexeev, Alexander; Sulchek, Todd

doi:10.1038/s41419-018-0266-x

Cited by 56 publications

(42 citation statements)

References 63 publications

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“…Cancer diseases comprise of a mixed genotypic cells population that respond differently to the drug treatment over chemoresistant subpopulations. Recent studies show that microfluidic approaches have been chosen to explain the complex biological mechanisms in chemoresistant cancer cells through differences in cellular stiffness after progressive drug exposure . Also, seminal studies have displayed the measurement of tumorigenicity of breast cancer cells through silicon resonant microelectromechanical systems sensors and Atomic force microscopy .…”

Section: Resultsmentioning

confidence: 99%

Optical study of chemotherapy efficiency in cancer treatment via intracellular structural disorder analysis using partial wave spectroscopy

Almabadi

Nagesh

Sahay

et al. 2018

Journal of Biophotonics

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As cancer progresses, macromolecules, such as DNA, RNA or lipids, inside cells undergo spatial structural rearrangements and alterations. Mesoscopic light transport-based optical partial wave spectroscopy (PWS) was recently introduced to quantify changes in the nanoscale structural disorder in biological cells. The PWS measurement is performed using a parameter termed as "disorder strength" (L ), which represents the degree of nanoscale structural disorder inside the cells. It was shown that cancerous cells have higher disorder strength than normal cells. In this work, we first used the PWS to analyze the hierarchy of different types of prostate cancer cells, namely, C4-2, DU-145 and PC-3, by quantifying their average disorder strengths. Results expectedly showed that L values increases in accordance with the increasing aggressiveness/tumorigenicity levels of these cells. Using the L parameter, we then analyzed the chemoresistance properties of these prostate cancer cells to docetaxel drug compared to their chemosensitivity. Results show that chemoresistant cancer cells have increased L values, that is, higher disorder strength, relative to chemosensitive cancer cells. Thus, use of the L metric can be effective in determining the efficacy of particular chemotherapy.

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Section: Resultsmentioning

confidence: 99%

Optical study of chemotherapy efficiency in cancer treatment via intracellular structural disorder analysis using partial wave spectroscopy

Almabadi

Nagesh

Sahay

et al. 2018

Journal of Biophotonics

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“…Significant advancements in microfluidic technology over the past two decades led to an increased use of microfluidic-based separation and concentration of particles/cells from a heterogeneous mixture sample in biological, chemical, environmental, and clinical applications 17–20 . The strategy of using microfluidic devices for sample preprocessing has been widely applied before post-analysis such as in flow cytometry, PCR, surface plasmon resonance (SPR), and spectrophotometry 14,21–25 . Microfluidic separation and concentration techniques are divided into two categories based on the use of the following external force fields: active and passive techniques.…”

Section: Introductionmentioning

confidence: 99%

Viscoelastic Separation and Concentration of Fungi from Blood for Highly Sensitive Molecular Diagnostics

Nam

Jang

Hong

et al. 2019

Sci Rep

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Isolation and concentration of fungi in the blood improves sensitivity of the polymerase chain reaction (PCR) method to detect fungi in blood. This study demonstrates a sheathless, continuous separation and concentration method of candida cells using a viscoelastic fluid that enables rapid detection of rare candida cells by PCR analysis. To validate device performance using a viscoelastic fluid, flow characteristics of 2 μm particles were estimated at different flow rates. Additionally, a mixture of 2 μm and 13 μm particles was successfully separated based on size difference at 100 μl/min. Candida cells were successfully separated from the white blood cells (WBCs) with a separation efficiency of 99.1% and concentrated approximately 9.9-fold at the center outlet compared to the initial concentration (~2.5 × 10 7 cells/ml). Sequential 1st and 2nd concentration processes were used to increase the final number of candida cells to ~2.3 × 10 9 cells/ml, which was concentrated ~92-fold. Finally, despite the undetectable initial concentration of 10 1 CFU/ml, removal of WBCs and the additional buffer solution enabled the quantitative reverse transcription (RT)-PCR detection of candida cells after the 1st concentration (Ct = 31.43) and the 2nd concentration process (Ct = 29.30).

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“…This achievement highlights how the exploitation of differential physical properties of cancer cells can lead to the development of diagnostic tools and prognosis. In addition, differential sorting of these cells has also demonstrated therapy response, in which stiff cells are more sensitive to chemotherapy than softer cells [ 177 ]. Further research is necessary to pinpoint the mechanisms by which cells react to external mechanical cues [ 171 ], to be able not only to establish diagnostic tools but also propose emerging alternative cancer therapies based on mechanotherapy.…”

Section: Emerging Systems Of Tme Reprogrammingmentioning

confidence: 99%

Integrating the Tumor Microenvironment into Cancer Therapy

Sanegre

Lucantoni

Burgos‐Panadero

et al. 2020

Cancers

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Tumor progression is mediated by reciprocal interaction between tumor cells and their surrounding tumor microenvironment (TME), which among other factors encompasses the extracellular milieu, immune cells, fibroblasts, and the vascular system. However, the complexity of cancer goes beyond the local interaction of tumor cells with their microenvironment. We are on the path to understanding cancer from a systemic viewpoint where the host macroenvironment also plays a crucial role in determining tumor progression. Indeed, growing evidence is emerging on the impact of the gut microbiota, metabolism, biomechanics, and the neuroimmunological axis on cancer. Thus, external factors capable of influencing the entire body system, such as emotional stress, surgery, or psychosocial factors, must be taken into consideration for enhanced management and treatment of cancer patients. In this article, we review prognostic and predictive biomarkers, as well as their potential evaluation and quantitative analysis. Our overarching aim is to open up new fields of study and intervention possibilities, within the framework of an integral vision of cancer as a functional tissue with the capacity to respond to different non-cytotoxic factors, hormonal, immunological, and mechanical forces, and others inducing stroma and tumor reprogramming.

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Microfluidic cell sorting by stiffness to examine heterogenic responses of cancer cells to chemotherapy

Cited by 56 publications

References 63 publications

Optical study of chemotherapy efficiency in cancer treatment via intracellular structural disorder analysis using partial wave spectroscopy

Optical study of chemotherapy efficiency in cancer treatment via intracellular structural disorder analysis using partial wave spectroscopy

Viscoelastic Separation and Concentration of Fungi from Blood for Highly Sensitive Molecular Diagnostics

Integrating the Tumor Microenvironment into Cancer Therapy

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