Enhanced Isolation and Release of Circulating Tumor Cells Using Nanoparticle Binding and Ligand Exchange in a Microfluidic Chip

Park, Myoung‐Hwan; Reátegui, Eduardo; Li, Wei; Tessier, Shannon N.; Wong, Keith H.K.; Jensen, Anne Eeg; Thapar, Vishal; Ting, David T.; Toner, Mehmet; Stott, Shannon L.; Hammond, Paula T.

doi:10.1021/jacs.6b12236

Cited by 229 publications

(190 citation statements)

References 55 publications

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“…In order to capture and analyze CTCs among a billion normal blood cells, multiple isolation methods have been developed, which generally utilize differences among cell physical properties or surface biomarkers of cancer cells . Several technology platforms have been developed, which involve microfluidic devices that enhance cell‐surface contact, immunomagnetic beads based on capture biomolecules immobilized on beads, several functionalized nanostructured surfaces based on cell‐substrate affinity, and microfilter devices for isolating tumor cells based on the different sizes . However, most of the aforementioned CTCs capture and isolation methods have some drawbacks and limitations.…”

Section: Introductionmentioning

confidence: 99%

Biospecific Monolayer Coating for Multivalent Capture of Circulating Tumor Cells with High Sensitivity

Chen

et al. 2019

Adv Funct Materials

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The isolation and detection of rare circulating tumor cells (CTCs) from patient peripheral blood can help to monitor the metastatic spread of carcinoma and evaluate therapeutic outcomes. However, it is technically challenging to isolate CTCs due to extreme rarity in blood. Current techniques typically have to utilize complex instrumentation to capture CTCs, resulting in nonapplicability. Inspired from the mussel adhesion, a polyglycerol-based block polymer is used to fabricate a biospecific and bioinert interface for isolating CTCs with high selectivity and efficiency. Benefitting from the antifouling polyglycerol, the resulting monolayer coating greatly suppresses the nonspecific cells adhesion. Compared with one anti-epithelial cell adhesion molecule (anti-EpCAM), the CTCs' capture efficiency was improved to 95% when multiple receptors, i.e. anti-EpCAM/Human epithelial receptor 2 (Her2)/Epithelial Growth Factor receptor (EGFR) are employed, even for low EpCAM-expressing CTCs. The CTCs detection limit on the presented surface is as low as 1 cell mL −1 . Furthermore, CTCs are isolated from breast cancer patients' blood sample with a high selectivity. Also, the CTCs can be released and still keep proliferation capability for downstream analysis. This multifunctional block polymer surface coating is quite cost effective and highly applicable for CTCs' isolation in the clinic, which can provide a new prospect for designing the next-generation of bio/nanointerfaces for biomedical studies.

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Section: Introductionmentioning

confidence: 99%

Biospecific Monolayer Coating for Multivalent Capture of Circulating Tumor Cells with High Sensitivity

Chen

et al. 2019

Adv Funct Materials

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“…Second, the aptamer-modified AuNP surface acts as ar ough interface to enhance local topographic interactions. [14] Moreover, AuNPs can protect DNAp robes from nuclease degradation, [15] improving the stability of aptamers.Finally,the Au À Sbond can be readily disrupted by excess biocompatible thiol molecules,w ithout compromising cell viability, [16] thereby enabling effective release for further analysis.…”

mentioning

confidence: 99%

Bioinspired Engineering of a Multivalent Aptamer‐Functionalized Nanointerface to Enhance the Capture and Release of Circulating Tumor Cells

Song,

Shi,

Huang

et al. 2019

Angew Chem Int Ed

198

209

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Circulating tumor cell (CTC)-enrichment by using aptamers has an umber of advantages,b ut the issue of compromised binding affinities and stabilities in real samples hinders its wide applications.Inspired by the high efficiency of the prey mechanism of the octopus,weengineered adeterministic lateral displacement (DLD)-patterned microfluidic chip modified with multivalent aptamer-functionalized nanospheres (AP-Octopus-Chip) to enhance capture efficiency.T he multivalent aptamer-antigen binding efficiency improves 100-fold and the capture efficiency is enhanced more than 300 % compared with am onovalent aptamer-modified chip.M oreover,t he captured cancer cells can be released through athiol exchange reaction with up to 80 %e fficiency and 96 % viability,whichisfully compatible with downstream mutation detection and CTC culture.Using the chip,wewere able to find CTCs in all cancer samples analyzed.

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“…The facile and highly efficient release of captured target cells is crucial for carrying out downstream profiling of CTCs. As shown in Figure S4 (Supporting Information), the captured cells could be released with an efficiency as high as 99 ± 0.0% ( n = 3), which is a difficult standard for many antibody‐based methods to meet and/or is reached only through use of complex designs . The high cell‐release efficiency of the PBA‐CIH could be attributed to the noncovalent interaction with the cells made possible by the microinterfaces of the imprinted sites and the reversible affinity fostered by the molecular recognition between the 3‐AAPBA on the hydrogel and the glycans on the cell surface.…”

Section: Methodsmentioning

confidence: 99%

Antibody‐Free Hydrogel with the Synergistic Effect of Cell Imprinting and Boronate Affinity: Toward the Selective Capture and Release of Undamaged Circulating Tumor Cells

Liu

Dong

et al. 2020

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The selective and highly efficient capture of circulating tumor cells (CTCs) from blood and their subsequent release without damage are very important for the early diagnosis of tumors and for understanding the mechanism of metastasis. Herein, a universal strategy is proposed for the fabrication of an antibody‐free hydrogel that has a synergistic effect by featuring microinterfaces obtained by cell imprinting and molecular recognition conferred by boronate affinity. With this artificial antibody, highly efficient capture of human hepatocarcinoma SMMC‐7721 cells is achieved: as many as 90.3 ± 1.4% (n = 3) cells are captured when 1 × 105 SMMC‐7721 cells are incubated on a 4.5 cm2 hydrogel, and 99% of these captured cells are subsequently released without any loss of proliferation ability. In the presence of 1000 times as many nontarget cells, namely, leukaemia Jurkat cells, the SMMC‐7721 cells can be captured with an enrichment factor as high as 13.5 ± 3.2 (n = 3), demonstrating the superior selectivity of the artificial antibody for the capture of the targeted CTCs. Most importantly, the SMMC‐7721 cells can be successfully captured even when spiked into whole blood, indicating the great promise of this approach for the further molecular characterization of CTCs.

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Enhanced Isolation and Release of Circulating Tumor Cells Using Nanoparticle Binding and Ligand Exchange in a Microfluidic Chip

Cited by 229 publications

References 55 publications

Biospecific Monolayer Coating for Multivalent Capture of Circulating Tumor Cells with High Sensitivity

Biospecific Monolayer Coating for Multivalent Capture of Circulating Tumor Cells with High Sensitivity

Bioinspired Engineering of a Multivalent Aptamer‐Functionalized Nanointerface to Enhance the Capture and Release of Circulating Tumor Cells

Antibody‐Free Hydrogel with the Synergistic Effect of Cell Imprinting and Boronate Affinity: Toward the Selective Capture and Release of Undamaged Circulating Tumor Cells

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