Background Detection of a small number of circulating tumor cells is important, especially at the early stages of cancer. The small number of CTCs is hard to detect as very few approaches are sensitive enough to differentiate these from the pool of other cells. Improving the affinity of a selective surface-functionalized molecule is important given the sparsity of CTCs in vivo. There are a number of proteins and aptamers that provide such a high affinity but using a surface nano-texturing increases this affinity even further. Method This work reports an approach to improve affinity of tumor cell capture by using novel aptamers against cell-membrane over-expressed Epidermal Growth Factor Receptors (EGFR) on a nano-textured polydimethylsiloxane (PDMS) substrate. Surface immobilized aptamers are used to specifically capture tumor cells from physiological samples. Results The nano-texturing of PDMS increased surface roughness at the nanoscale. This increased the effective surface area and resulted in a significantly higher degree of surface functionalization. The phenomenon resulted in increased density of immobilized EGFR specific RNA aptamer molecules and provided significantly higher efficiency to capture cancer cells from a mixture. The data showed that CTCs could be captured and enriched leading to higher yield, yet higher background. Conclusion The comparison of glass slides, plain PDMS and nano-textured PDMS functionalized with aptamers show that a two-fold approach of using aptamers on nano-textured PDMS can be an important factor for cancer cytology devices especially for the idea of lab-on-chip towards higher yield in capture efficiency.

Aptamers are single-stranded DNA or RNA oligomers, identified from a random sequence pool, with the ability to form unique and versatile tertiary structures that bind to cognate molecules with superior specificity. Their small size, excellent chemical stability and low immunogenicity enable them to rival antibodies in cancer imaging and therapy applications. Their facile chemical synthesis, versatility in structural design and engineering, and the ability for site-specific modifications with functional moieties make aptamers excellent recognition motifs for cancer biomarker discovery and detection. Moreover, aptamers can be selected or engineered to regulate cancer protein functions, as well as to guide anti-cancer drug design or screening. This review summarizes their applications in cancer, including cancer biomarker discovery and detection, cancer imaging, cancer therapy, and anti-cancer drug discovery. Although relevant applications are relatively new, the significant progress achieved has demonstrated that aptamers can be promising players in cancer research.

Early detection and isolation of circulating tumor cells (CTC) can enable better prognosis for cancer patients. A Hele-Shaw device with aptamer functionalized glass beads is designed, modeled, and fabricated to efficiently isolate cancer cells from a cellular mixture. The glass beads are functionalized with anti-epidermal growth factor receptor (EGFR) aptamer and sit in ordered array of pits in PDMS channel. A PDMS encapsulation is then used to cover the channel and flow through cell solution. The beads capture cancer cells from flowing solution depicting high selectivity. The cell-bound glass beads are then re-suspended from the device surface followed by the release of 92% cells from glass beads using combination of soft shaking and anti-sense RNA. This approach ensures that the cells remain in native state and undisturbed during capture, isolation and elution for post-analysis. The use of highly selective anti-EGFR aptamer with the glass beads in an array and subsequent release of cells with antisense molecules provide multiple levels of binding and release opportunities that can help in defining new classes of CTC enumeration devices.

Detection of circulating tumor cells (CTCs) in the early stages of cancer is a great challenge because of their exceedingly small concentration. There are only a few approaches sensitive enough to differentiate tumor cells from the plethora of other cells in a sample like blood. In order to detect CTCs, several antibodies and aptamers have already shown high affinity. Nanotexture can be used to mimic basement membrane to further enhance this affinity. This article reports an approach to fabricate nanotextured polydimethylsiloxane (PDMS) substrates using micro reactive ion etching (micro-RIE). Three recipes were used to prepare nanotextured PDMS using oxygen and carbon tetrafluoride. Micro-RIE provided better control on surface properties. Nanotexturing improved the affinity of PDMS surfaces to capture cancer cells using surface immobilized aptamers against cell membrane overexpressed with epidermal growth factor receptors. In all cases, nanotexture of PDMS increased the effective surface area by creating nanoscale roughness on the surface. Nanotexture also enhanced the growth rate of cultured cells compared to plain surfaces. A comparison among the three nanotextured surfaces demonstrated an almost linear relationship between the surface roughness and density of captured tumor cells. The nanotextured PDMS mimicked biophysical environments for cells to grow faster. This can have many implications in microfluidic platforms used for cell handling.

This paper presents a simple approach to create a two-tiered surface for superior cancer cell isolation. The idea is inspired by the interactions of cells with a nanotextured basement membrane. The texture mimicked the extracellular matrix and basement membrane for superior target cell adhesion. Prepared micro+nanotextured surfaces showed enhanced cell capture. Preparation of the two-tiered surface was done using micro- and nanotexturing and was easily reproducible. It has been shown before that the larger surface area of a nanotextured surface assists the cell's attachment through surface-anchored ligands. Taking it a step further, ligand functionalized two-level micro+nanotextured surfaces improved the sensitivity of the cancer cell isolation over simple flat nanotexturing. The isolation efficiency increased by 208% compared to the surface with a single-level nanotexture. The two-tiered surface was compatible with previously reported nanotextured devices used for cancer cell isolation. Micro-texture on the glass surface was created using simple sand gritting, followed by reactive ion etching (RIE) of the entire surface. The approach could create large surface areas within a short time while maintaining superior cell isolation efficiency.