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Skokie, IL, United States

Jang J.-W.,Northwestern University | Jang J.-W.,NanoInk Inc. | Zheng Z.,Northwestern University | Zheng Z.,Hong Kong Polytechnic University | And 5 more authors.
Nano Letters | Year: 2010

Poly(ethylene glycol) (PEG) polymer lens arrays are made by using dip-pen nanolithography to deposit nanoscale PEG features on hydrophobically modified quartz glass. The dimensions of the PEG lenses are controlled by tuning dwell time and polymer molecular weight. The PEG polymer lenses on the quartz substrate act as a phase-shift photomask for fabricating subwavelength scale features, ∼100 nm in width. Depending upon UV irradiation time during the photolithography, the photoresist nanostructures can be transitioned from well-shaped (short time) to ring-shaped (long time) features. The technique can be used to pattern large areas through the use of cantilever arrays. © 2010 American Chemical Society. Source

Bett C.K.,Louisiana State University | Ngunjiri J.N.,NanoInk Inc. | Serem W.K.,Louisiana State University | Fontenot K.R.,Louisiana State University | And 3 more authors.
ACS Chemical Neuroscience | Year: 2010

Neuronal cytotoxicity observed in Alzheimer's disease (AD) is linked to the aggregation of β-amyloid peptide (Aβ) into toxic forms. Increasing evidence points to oligomeric materials as the neurotoxic species, not Aβ fibrils; disruption or inhibition of Aβ self-assembly into oligomeric or fibrillar forms remains a viable therapeutic strategy to reduce Aβ neurotoxicity. We describe the synthesis and characterization of amyloid aggregation mitigating peptides (AAMPs) whose structure is based on the Aβ "hydrophobic core" Aβ17?20, with α,α- disubstituted amino acids (ααAAs) added into this core as potential disrupting agents of fibril self-assembly. The number, positional distribution, and side-chain functionality of ααAAs incorporated into the AAMP sequence were found to influence the resultant aggregate morphology as indicated by ex situ experiments using atomic force microscopy (AFM) and transmission electron microscopy (TEM). For instance, AAMP-5, incorporating a sterically hindered ααAA with a diisobutyl side chain in the core sequence, disrupted Aβ1?40 fibril formation. However, AAMP-6, with a less sterically hindered ααAA with a dipropyl side chain, altered fibril morphology, producing shorter and larger sized fibrils (compared with those of Aβ1?40). Remarkably, ααAA-AAMPs caused disassembly of existing Aβ fibrils to produce either spherical aggregates or protofibrillar structures, suggesting the existence of equilibrium between fibrils and prefibrillar structures. © 2010 American Chemical Society. Source

George S.,University of Illinois at Urbana - Champaign | Chaudhery V.,University of Illinois at Urbana - Champaign | Lu M.,University of Illinois at Urbana - Champaign | Takagi M.,University of Illinois at Urbana - Champaign | And 5 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2013

Enhancement of the fluorescent output of surface-based fluorescence assays by performing them upon nanostructured photonic crystal (PC) surfaces has been demonstrated to increase signal intensities by >8000×. Using the multiplicative effects of optical resonant coupling to the PC in increasing the electric field intensity experienced by fluorescent labels ("enhanced excitation") and the spatially biased funneling of fluorophore emissions through coupling to PC resonances ("enhanced extraction"), PC enhanced fluorescence (PCEF) can be adapted to reduce the limits of detection of disease biomarker assays, and to reduce the size and cost of high sensitivity detection instrumentation. In this work, we demonstrate the first silicon-based PCEF detection platform for multiplexed biomarker assay. The sensor in this platform is a silicon-based PC structure, comprised of a SiO2 grating that is overcoated with a thin film of high refractive index TiO2 and is produced in a semiconductor foundry for low cost, uniform, and reproducible manufacturing. The compact detection instrument that completes this platform was designed to efficiently couple fluorescence excitation from a semiconductor laser to the resonant optical modes of the PC, resulting in elevated electric field strength that is highly concentrated within the region <100 nm from the PC surface. This instrument utilizes a cylindrically focused line to scan a microarray in <1 min. To demonstrate the capabilities of this sensor-detector platform, microspot fluorescent sandwich immunoassays using secondary antibodies labeled with Cy5 for two cancer biomarkers (TNF-α and IL-3) were performed. Biomarkers were detected at concentrations as low as 0.1 pM. In a fluorescent microarray for detection of a breast cancer miRNA biomarker miR-21, the miRNA was detectable at a concentration of 0.6 pM. © The Royal Society of Chemistry 2013. Source

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 737.92K | Year: 2006

DESCRIPTION (provided by applicant): The goal of this research is to develop novel, biologically functional nanostructures that dramatically enhance the reproducibility, sensitivity, and spatial density of chip based assays. These nanostructures will improve applications ranging from point-of-care diagnosis to genomic arrays used in basic research by enabling the development of next generation screening technologies that are faster, more sensitive, more reliable, and possibly more cost effective than those presently available in the life sciences market. To accomplish the stated goals, Nanolnk will develop a patterning methodology based on Dip Pen Nanolithography (tm)(DPN(tm)) technology to generate sub-micron sized features on solid surfaces. The DPN method, built upon the technique of Atomic Force Microscopy (AFM), allows one to deposit materials uniformly in a direct-write fashion on surfaces with nanoscale spatial precision. This strategy offers significant advantages over current microarray printing technologies that suffer from poor spot to spot reproducibility in terms of size, shape, and oligonucleotide density, as well as reproducibility across microarray slides. In Phase I, Nanolnk demonstrated the feasibility of an approach based on DPN technology by generating sub-micron scale DNA nanostructures on glass surfaces. The resulting nanostructures were analyzed using existing fluorescence probe technology to provide benchmarking standards for comparison to conventional microarray assays. Concurrent with ink development and patterning optimization, microfabricated parallel multipen arrays were developed as a means for faster, simultaneous writing of multiple DNA inks. In Phase II, Nanolnk will develop a nanoarray fabrication platform consisting of a nanoarrayer instrument, parallel multipen arrays with integrated microfluidic inking systems and appropriate pen and surface modification chemistry to allow patterning with a variety of biomolecules. The Phase II effort will build on our success in Phase I and yield a flexible, nanoarray fabrication "system" with both near term and long term commercial potential. A commercialization partner has been identified for Phase III. This research project will develop a system for fabricating biochip microarrays that will offer more sensitive and reliable tools for medical research groups helping them to better understand the role of genes and proteins in human health. Improved methods of diagnosing and treating disease will result.

Jang J.-W.,Pukyong National University | Collins J.M.,NanoInk Inc. | Nettikadan S.,NanoInk Inc.
Advanced Functional Materials | Year: 2013

A new method for subcellular-sized protein patterning on a SiOx substrate is demonstrated by dip-pen nanolithography printed aldehyde-terminated alkylsilane template. The aldehyde-silane template is stable and durable; for example, subcellular scaled IgG protein array can be obtained using one-year old aldehyde-silane template. Moreover, single cell patterning is successfully carried out by extracellular material (ECM) protein microarray and nanoarray fabricated on an aldehyde-silane template. With more than half of chance, single- or double-cells are successfully attached on fibronectin protein nanoarrays in 21 × 21 μm 2 (7 × 7 dot array) and 42 × 42 μm2 (14 × 14 dot array). The fibronectin nanoarray with small area (21 × 21 μm2) shows the more rate of single cell attachment. Therefore, it is also demonstrated that cell patterning can be controlled by adjusting the nanostructure of ECM materials. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

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