Enrichment of Cancer Cells Using Aptamers Immobilized on a Microfluidic Channel

Phillips, Joseph A.; Xu, Ye; Zheng, Xiu-Cheng; Fan, Z. Hugh; Tan, Weihong

doi:10.1021/ac802092j

Cited by 210 publications

(199 citation statements)

References 59 publications

(161 reference statements)

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“…Aptamers have been used in cell labeling studies (15,16) as well as in activating cell signaling pathways (17)(18)(19)(20). However, only recently, aptamers have been used in lab-on-chip devices to sort, isolate, and detect tumor cells (21). Here, we report results from an RNA aptamer substrate to isolate epidermal growth factor receptor (EGFR)-overexpressing primary human glioblastoma (hGBM) cells, as well as genetically engineered mouse glioma cells that photocopy human glioma.…”

Section: Introductionmentioning

confidence: 99%

Surface-Immobilized Aptamers for Cancer Cell Isolation and Microscopic Cytology

et al. 2010

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Exposing rare but highly malignant tumor cells that migrate from the primary tumor mass into adjacent tissue(s) or circulate in the bloodstream is critical for early detection and effective intervention(s). Here, we report on an aptamer-based strategy directed against epidermal growth factor receptor (EGFR), the most common oncogene in glioblastoma (GBM), to detect these deadly tumor cells. GBMs are characterized by diffuse infiltration into normal brain regions, and the inability to detect GBM cells renders the disease surgically incurable with a median survival of just 14.2 months. To test the sensitivity and specificity of our platform, anti-EGFR RNA aptamers were immobilized on chemically modified glass surfaces. Cells tested included primary human GBM cells expressing high levels of the wild-type EGFR, as well as genetically engineered murine glioma cells overexpressing the most common EGFR mutant (EGFRvIII lacking exons 2-7) in Ink4a/Arf-deficient astrocytes. We found that surfaces functionalized with anti-EGFR aptamers could capture both the human and murine GBM cells with high sensitivity and specificity. Our findings show how novel aptamer substrates could be used to determine whether surgical resection margins are free of tumor cells, or more widely for detecting tumor cells circulating in peripheral blood to improve early detection and/or monitoring residual disease after treatment.

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Section: Introductionmentioning

confidence: 99%

Surface-Immobilized Aptamers for Cancer Cell Isolation and Microscopic Cytology

et al. 2010

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“…[1][2][3][4][5][6][7] Despite allowing for the rapid isolation of these clinically relevant cell types, microfluidic methods are facing the challenge of releasing and recovering the isolated target cells for further biological analysis. 8 Due to the nature of low concentration of CTCs in whole cellular population after separation process, the acceptable efficiency of releasing cells should approach 100% for broader applications such as sensitively monitoring therapy response, diagnosis of early stage cancer, and analysis of genetic makeup.…”

Section: Introductionmentioning

confidence: 99%

Efficient elusion of viable adhesive cells from a microfluidic system by air foam

Lai

Shao

et al. 2014

Biomicrofluidics

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We developed a new method for releasing viable cells from affinity-based microfluidic devices. The lumen of a microchannel with a U-shape and user-designed microstructures was coated with supported lipid bilayers functionalized by epithelial cell adhesion molecule antibodies to capture circulating epithelial cells of influx solution. After the capturing process, air foam was introduced into channels for releasing target cells and then carrying them to a small area of membrane. The results show that when the air foam is driven at linear velocity of 4.2 mm/s for more than 20 min or at linear velocity of 8.4 mm/s for more than 10 min, the cell releasing efficiency approaches 100%. This flow-induced shear stress is much less than the physiological level (15 dyn/cm 2 ), which is necessary to maintain the intactness of released cells. Combining the design of microstructures of the microfluidic system, the cell recovery on the membrane exceeds 90%. Importantly, we demonstrate that the cells released by air foam are viable and could be cultured in vitro. This novel method for releasing cells could power the microfluidic platform for isolating and identifying circulating tumor cells. V C 2014 AIP Publishing LLC.

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“…For micelle-buffer incubation, a PDMS flow channel was used. PDMS devices were fabricated by using a process similar to what is described in the literature (19,20). The layout of the device was designed in AutoCAD and printed on a transparency by using a high-resolution printer.…”

Section: Synthesis Of Aptamer-lipidmentioning

confidence: 99%

DNA aptamer–micelle as an efficient detection/delivery vehicle toward cancer cells

Sefah

Liu

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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We report the design of a self-assembled aptamer-micelle nanostructure that achieves selective and strong binding of otherwise low-affinity aptamers at physiological conditions. Specific recognition ability is directly built into the nanostructures. The attachment of a lipid tail onto the end of nucleic acid aptamers provides these unique nanostructures with an internalization pathway. Other merits include: extremely low off rate once bound with target cells, rapid recognition ability with enhanced sensitivity, low critical micelle concentration values, and dual-drug delivery pathways. To prove the potential detection/delivery application of this aptamer-micelle in biological living systems, we mimicked a tumor site in the blood stream by immobilizing tumor cells onto the surface of a flow channel device. Flushing the aptamer-micelles through the channel demonstrated their selective recognition ability under flow circulation in human whole-blood sample. The aptamermicelles show great dynamic specificity in flow channel systems that mimic drug delivery in the blood system. Therefore, our DNA aptamer-micelle assembly has shown high potential for cancer cell recognition and for in vivo drug delivery applications.DNA aptamers | drug delivery | micelles | molecular specificity M any interesting nanomaterials, either natural or artificial, have been designed to perform unique functions through the process of molecular self-assembly. In nature, the apoptosome (1) is one such example. Individual apaf-1 protein does not have a biological function; however, when forming a complex with cytochrome-c, several individual proteins self-assemble into a wheel structure called an apoptosome. Once formed, the apoptosome can then recruit and activate the otherwise inactive procaspase-9 that can then activate other caspases and trigger a cascade of events leading to apoptosis. Learning from nature, chemists have created various artificial nanostructures. Micelle is one of such examples. Polymeric micelles have been subjected to extensive studies in the field of drug delivery, functioning as drug solibilizers and carriers (2). More recently, a micelle constructed as a hybrid from hydrophilic oligonucleotide and hydrophobic polymer (3, 4) has drawn close attention. In aqueous solutions, this type of amphiphilic block copolymer can self-assemble into a three-dimensional spherical micelle structure or a nanorod-like micelle structure. This type of micelle has been shown to efficiently carry a variety of cargos to cells, including antisense oligonucleotides (5) and drug molecules (6). To perform efficient targeted delivery, folic acid, a type of cancer cell recognition molecule modified on a piece of short, complementary DNA, was clicked onto the micelles based on Watson-Crick base pairing (6).Aside from Watson-Crick base pairing, single-stranded oligonucleotides can recognize other target molecules based on noncovalent interactions, such as hydrophobic interaction and hydrogen bonding. This type of oligonucleotide ligand is known as an ...

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Enrichment of Cancer Cells Using Aptamers Immobilized on a Microfluidic Channel

Cited by 210 publications

References 59 publications

Surface-Immobilized Aptamers for Cancer Cell Isolation and Microscopic Cytology

Surface-Immobilized Aptamers for Cancer Cell Isolation and Microscopic Cytology

Efficient elusion of viable adhesive cells from a microfluidic system by air foam

DNA aptamer–micelle as an efficient detection/delivery vehicle toward cancer cells

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