Glioblastoma Multiforme heterogeneity profiling with solid-state micropores.

Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. It is characterized by widespread heterogeneity at the cellular and molecular levels. The detection of this heterogeneity is valuable for accurate diagnosis.

Self-induced back action actuated nanopore electrophoresis (SANE).

We present a novel method to trap nanoparticles in double nanohole (DNH) nanoapertures integrated on top of solid-state nanopores (ssNP). The nanoparticles were propelled by an electrophoretic force from the cis towards the trans side of the nanopore but were trapped in the process when they reached the vicinity of the DNH-ssNP interface. The self-induced back action (SIBA) plasmonic force existing between the tips of the DNH opposed the electrophoretic force and enabled simultaneous optical and electrical sensing of a single nanoparticle for seconds.

Classification of cancer cells using computational analysis of dynamic morphology.

Background And Objective: Detection of metastatic tumor cells is important for early diagnosis and staging of cancer. However, such cells are exceedingly difficult to detect from blood or biopsy samples at the disease onset. It is reported that cancer cells, and especially metastatic tumor cells, show very distinctive morphological behavior compared to their healthy counterparts on aptamer functionalized substrates.

Functionalization of nanotextured substrates for enhanced identification of metastatic breast cancer cells.

Metastasis is the major cause of low survival rates among cancer patients. Once cancer cells metastasize, it is extremely difficult to contain the disease. We report on a nanotextured platform for enhanced detection of metastatic cells.

Enhanced proliferation of PC12 neural cells on untreated, nanotextured glass coverslips.

Traumatic injury to the central nervous system is a significant health problem. There is no effective treatment available partly because of the complexity of the system. Implementation of multifunctional micro- and nano-device based combinatorial therapeutics can provide biocompatible and tunable approaches to perform on-demand release of specific drugs.

An accelerated framework for the classification of biological targets from solid-state micropore data.

Micro- and nanoscale systems have provided means to detect biological targets, such as DNA, proteins, and human cells, at ultrahigh sensitivity. However, these devices suffer from noise in the raw data, which continues to be significant as newer and devices that are more sensitive produce an increasing amount of data that needs to be analyzed. An important dimension that is often discounted in these systems is the ability to quickly process the measured data for an instant feedback.

Differentiating Metastatic and Non-metastatic Tumor Cells from Their Translocation Profile through Solid-State Micropores.

Cancer treatment, care, and outcomes are much more effective if started at early stages of the disease. The presence of malignant cancer cells in human samples such as blood or biopsied tissue can be used to reduce overtreatment and underdiagnosis as well as for prognosis monitoring. Reliable quantification of metastatic tumor cells (MTCs) and non-metastatic tumor cells (NMTCs) from human samples can help in cancer staging as well.

Electromechanical transducer for rapid detection, discrimination and quantification of lung cancer cells.

Tumor cells are malignant derivatives of normal cells. There are characteristic differences in the mechanophysical properties of normal and tumor cells, and these differences stem from the changes that occur in the cell cytoskeleton during cancer progression. There is a need for viable whole blood processing techniques for rapid and reliable tumor cell detection that do not require tagging.

One-step tumor detection from dynamic morphology tracking on aptamer-grafted surfaces.

In this paper, we report a one-step tumor cell detection approach based on the dynamic morphological behavior tracking of cancer cells on a ligand modified surface. Every cell on the surface was tracked in real time for several minutes immediately after seeding until these were finally attached. Cancer cells were found to be very active in the aptamer microenvironment, changing their shapes rapidly from spherical to semi-elliptical, with much flatter spread and extending pseudopods at regular intervals.

Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels.

Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different.

Nanotextured polymer substrates show enhanced cancer cell isolation and cell culture.

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.

Nucleic acid aptamers in cancer research, diagnosis and therapy.

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.

Micro+nanotexturing of substrates to enhance ligand-assisted cancer cell isolation.

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.

Parallel recognition of cancer cells using an addressable array of solid-state micropores.

Early stage detection and precise quantification of circulating tumor cells (CTCs) in the peripheral blood of cancer patients are important for early diagnosis. Early diagnosis improves the effectiveness of the therapy and results in better prognosis. Several techniques have been used for CTC detection but are limited by their need for dye tagging, low throughput and lack of statistical reliability at single cell level.

3D structural integrity and interactions of single-stranded protein-binding DNA in a functionalized nanopore.

Biomarker-binding nucleotide sequences, like aptamers, have gained recent attention in cancer cell isolation and detection works. Self-assembly and 3D conformation of aptamers enable them to selectively capture and bind diseased cells and related biomarkers. One mode of utilizing such an extraordinary selective property of the aptamers is by grafting these in nanopores.

Quantitative classification of tumor cell morphological changes on selectively functionalized biochips.

Proteomics information of cancer has shown that abnormalities at the levels of growth factors, receptors, intracellular mediators and transcription factors play major role in the disease progression. We report a directly quantifiable approach to measure tumor cell behavior on functionalized chips. The chips were functionalized with aptamer molecules that were selective against epidermal growth factor receptor (EGFR), a commonly overexpressed cancer biomarker.

Cell detachment: post-isolation challenges.

Rare cells already have become established indicators for disease diagnosis, to help track prognosis, and in developing personalized therapy. Numerous techniques have been developed to effectively and specifically detect and sort rare cells and cell isolation techniques have gained much attention among researchers in the last few decades. Recent developments in nanotechnologies and microfluidics have been used with great promise towards these goals.

Synthesis of nano-textured biocompatible scaffolds from chicken eggshells.

Cell adhesion, morphology and growth are influenced by surface topography at nano and micrometer scales. Nano-textured surfaces are prepared using photolithography, plasma etching and long polymer chemical etching which are cost prohibitive and require specialized equipment. This article demonstrates a simple approach to synthesize nano-textured scaffolds from chicken eggshells.

Proliferation and migration of tumor cells in tapered channels.

Tumor cells depict two deviant tendencies; over-proliferation and vigorous migration. A tapered channel device is designed and fabricated for in vitro studies. We report inhibited proliferation and migration of human glioblastoma (hGBM) cells when exposed to an aptamer that is known to bind epidermal growth factor receptors (EGFR).

Capture, isolation and release of cancer cells with aptamer-functionalized glass bead array.

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 polydimethylsiloxane (PDMS) channel.

Electrical detection of cancer biomarker using aptamers with nanogap break-junctions.

Epidermal growth factor receptor (EGFR) is a cell surface protein overexpressed in cancerous cells. It is known to be the most common oncogene. EGFR concentration also increases in the serum of cancer patients.

Electrical fingerprinting, 3D profiling and detection of tumor cells with solid-state micropores.

Solid-state micropores can provide direct information of ex vivo or in vitro cell populations. Micropores are used to detect and discriminate cancer cells based on the translocation behavior through micropores. The approach provides rapid detection of cell types based on their size and mechano-physical properties like elasticity, viscosity and stiffness.

GPU-based real-time detection and analysis of biological targets using solid-state nanopores.

The emergence of nanoscale devices has provided robust interfaces to biomolecules that faithfully transduce and define fundamental interactions of living systems. Measuring single-event behavior of important targets like DNA, and diseased cells has been achieved with a number of devices and systems. An important dimension to these systems, often discounted, is real-time computational decision-making from measured data.

Biocompatible nanolayered polymerization of MEMS devices.

Deposition of polymeric and biocompatible nanolayers on the solid-state substrates is done using a simple vacuum chamber. The chemical characteristics of the deposited nanolayer are analyzed using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The surface morphology of the nanolayers is analyzed using contact angle goniometer and scanning electron microscopy.