Isolation and mutational analysis of circulating tumor cells from lung cancer patients with magnetic sifters and biochips

Earhart, Christopher M.; Hughes, Casey E.; Gaster, Richard S.; Ooi, Chin Chun; Wilson, Robert; Zhou, Lisa; Humke, Eric W.; Xu, Lingyun; Wong, Dawson J.; Willingham, Stephen B.; Schwartz, Erich; Weissman, Irving L.; Jeffrey, Stefanie S.; Neal, Joel W.; Rohatgi, Rajat; Wakelee, Heather A.; Wang, Shan X.

doi:10.1039/c3lc50580d

Cited by 145 publications

(107 citation statements)

References 42 publications

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“…To validate use of the Ephesia chip as a CTC enrichment platform, Autebert et al isolated CTCs from 6/8 prostate cancer and 4/5 breast cancer patient samples and compared their results to CellSearch; they achieved similar or higher CTC counts in 10/13 samples. Another microfluidic-based immunomagnetic capture technology that features a unique architecture is the Magnetic Sifter (Earhart et al, 2013). In contrast to other microfluidic designs, the Magnetic Sifter uses a vertical flow configuration that sieves the sample through a dense array of 3808 square magnetic pores (40 Â 40 mm) arranged in a honeycomb pattern.…”

Section: Epispotmentioning

confidence: 99%

Circulating tumor cell technologies

2016

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Cancer CTC capture CTC clustersImmunoaffinity enrichment A B S T R A C TCirculating tumor cells, a component of the "liquid biopsy", hold great potential to transform the current landscape of cancer therapy. A key challenge to unlocking the clinical utility of CTCs lies in the ability to detect and isolate these rare cells using methods amenable to downstream characterization and other applications. In this review, we will provide an overview of current technologies used to detect and capture CTCs with brief insights into the workings of individual technologies. We focus on the strategies employed by different platforms and discuss the advantages of each. As our understanding of CTC biology matures, CTC technologies will need to evolve, and we discuss some of the present challenges facing the field in light of recent data encompassing epithelial-to-mesenchymal transition, tumor-initiating cells, and CTC clusters.

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Section: Epispotmentioning

confidence: 99%

Circulating tumor cell technologies

2016

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“…Micro/nano-cantilevers [1,2], stripe/wires [3,4], and pores [5,6] are some of the platforms. There are also magnetic particle-based Food and Drug Admisnistration (FDA) approved isolation technologies available in the market [7], and in the literature, many microfluidic devices have been developed for the separation of various biomolecules [4,8,9].…”

Section: Introductionmentioning

confidence: 99%

Detection of Proteins Using Nano Magnetic Particle Accumulation-Based Signal Amplification

İçöz

Mzava

2016

Applied Sciences

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Abstract:We report a biosensing method based on magnetic particles where coated magnetic particles are used for immunomagnetic separation, and uncoated magnetic particles are used for signal enhancement. To quantify the signal amplification, optical micrographs are analyzed to measure changes in pixel area and pixel intensity. Microcontact-printed surface receptors are arranged in alternating lines on gold chips, enabling differential calculations. In a model experiment, target molecules-streptavidin-are first captured and separated by biotin-coated magnetic particles, and then exposed to a gold surface functionalized with biotin-coupled bovine serum albumin, forming a sandwich assay. Applying a magnetic field and introducing uncoated magnetic particles resulted in accumulation around magnetic particles in the sandwich assay and enhancement of the contrast to noise ratio at least by eight-fold in a range of 0.1-100 µM.

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“…Magnetic techniques mix antibody-functionalized nanoparticles Hayes et al 2006) or rods with a blood sample (Talasaz et al 2009;Powell et al 2012;Earhart et al 2014), often after pre-processing steps such as centrifugation or dilution; the antibodies on the particle or rod surfaces bind with the antigens on the cell surface and then can be separated from the bulk sample by applying a magnetic field. Microdevice techniques engineer device geometries on the scale of the target cells and use combinations of diffisional mixing, cell-wall interactions, and varying shear stress to isolate rare cells by bringing them into contact with a fixed, antibody-functionalized device wall; these devices have used micron-scale obstacles in linear arrays (Nagrath et al 2007) and radial arrays (Murlidhar et al 2014), herringbone-like device floors to increase and control the frequency of interactions between the cells and the capture surface.…”

Section: Introductionmentioning

confidence: 99%

A transfer function approach for predicting rare cell capture microdevice performance

Smith

Kirby

2015

Biomed Microdevices

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Rare cells have the potential to improve our understanding of biological systems and the treatment of a variety of diseases; each of those applications requires a different balance of throughput, capture efficiency, and sample purity. Those challenges, coupled with the limited availability of patient samples and the costs of repeated design iterations, motivate the need for a robust set of engineering tools to optimize application-specific geometries. Here, we present a transfer function approach for predicting rare cell capture in microfluidic obstacle arrays. Existing computational fluid dynamics (CFD) tools are limited to simulating a subset of these arrays, owing to computational costs; a transfer function leverages the deterministic nature of cell transport in these arrays, extending limited CFD simulations into larger, more complicated geometries. We show that the transfer function approximation matches a full CFD simulation within 1.34 %, at a 74-fold reduction in computational cost. Taking advantage of these computational savings, we apply the transfer function simulations to simulate reversing array geometries that generate a "notch filter" effect, reducing the collision frequency of cells outside of a specified diameter range. We adapt the transfer function to study the effect of off-design boundary conditions (such as a clogged inlet in a microdevice) on overall performance. Finally, we have validated the transfer function's predictions for lateral displacement within the array using particle tracking and polystyrene beads in a microdevice.

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Isolation and mutational analysis of circulating tumor cells from lung cancer patients with magnetic sifters and biochips

Cited by 145 publications

References 42 publications

Circulating tumor cell technologies

Circulating tumor cell technologies

Detection of Proteins Using Nano Magnetic Particle Accumulation-Based Signal Amplification

A transfer function approach for predicting rare cell capture microdevice performance

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