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Sacrificial polymers for nanofluidic channels in biological applications

Chip based bio/chemical analysis relies on networks of fluidic channels that are connected to reaction chambers and sensors. For sensitive detection it is important to scale down the size of the channels so that they approach the relevant length scales of the molecules of interest. Here we have made sealed channels on the 100 nm scale using nanoimprinting to pattern the sacrificial polymer polynor

A DNA prism : Physical principles for optimizing a microfabricated DNA separation device

Recently, we reported a microfabricated "DNA prism" device that continuously sorts large DNA molecules (61 kilobase pair to 209 kb) according to size in 15 seconds. In this paper, we develop models to understand and optimize the device. The device's complicated characteristics are explained poorly by a simple model based on the assumption that DNA molecules are fully stretched. Assuming DNA molecu

Gradient nanostructures for interfacing microfluidics and nanofluidics

It is difficult to introduce long genomic DNA molecules into nanometer scale fluidic channels directly from the macroscale world because of the steep entropic barrier caused by necessary stretching of the polymer. We present a very simple technique using optical lithography to fabricate continuous spatial gradient structures which smoothly narrow the cross section of a volume from the micron to th

Fabrication of 10 nm enclosed nanofluidic channels

We made uniform arrays of nanometer scale structures using nanoimprint lithography over large areas (100 mm wafers). The nanofluidic channels were further narrowed and sealed by techniques that are based on nonuniform deposition. The resulting sealed channels have a cross section as small as 10 nm by 50 nm, of great importance for confining biological molecules into ultrasmall spaces. These techni

Separation of 100-kilobase DNA molecules in 10 seconds

Long double-stranded DNA molecules were separated in microfabricated hexagonal arrays in less than 1 min, several orders of magnitude faster than by using conventional technology. DNA samples were first concentrated at the entrance to the array in a thin band by entropic focusing. They were then separated by pulsed field electrophoresis. T4 (168.9 kbp) and λ (48.5 kbp) DNAs could be resolved into

Near-field scanner for moving molecules

A new technology that provides high optical resolution as well as very high data rates for moving molecules is presented. An important aspect of the device is the dependence of both the near-field radiation pattern and the far-field transmission of a thin slit on the polarization of the incident light.

Hydrodynamics in 2 1/2 dimensions : Making jets in a plane

We show that a careful analysis of the Navier-Stokes equation in the low Reynolds number limit has two distinct solutions, one valid for a deep, thin curtain of flow and the other for a thin wide flow. We derive a solution to the latter situation and use the results to develop a new way to control fluid flows in thin, wide sheet flow.

Sorting biomolecules with microdevices

Micro- and nanofabrication techniques have provided an unprecedented opportunity to create a designed world in which separation and fractionation technologies which normally occur on the macroscopic scale can be optimized by designing structures which utilize the basic physics of the process, or new processes can be realized by building structures which normally do not exist without external desig

Sorting of biomolecules via microdevices

Micro and nano fabrication techniques have provided an unprecedented opportunity to create a designed world in which separation and fractionation technologies which normally occur on the macroscopic scale can be optimized by designing structures which utilize the basic physics of the process, or new processes can be realized by building structures which normally do not exist without external desig

Presence of vitronectin and activated complement factor C9 on ventriculoperitoneal shunts and temporary ventricular drainage catheters

Object. The pathogenesis of cerebrospinal fluid (CSF) shunt infection is characterized by staphylococcal adhesion to the polymeric surface of the shunt catheter. Proteins from the CSF-fibronectin, vitronectin, and fibrinogen-are adsorbed to the surface of the catheter immediately after insertion. These proteins can interfere with the biological systems of the host and mediate staphylococcal adhesi

Quantitation of bacterial adhesion to polymer surfaces by bioluminescence

Quantitation of microbes adhering to a surface is commonly used in studies of microbial adhesion to different surfaces. We have quantified different staphylococcal strains adhering to polymer surfaces by measuring bacterial ATP (adenosine triphosphate) by bioluminescence. The method is sensitive, having a detection limit of 104 bacterial cells. Viable counting of bacterial cells may yield falsely

Protein depositions on one hydrocephalus shunt and on fifteen temporary ventricular catheters

Biomaterials are commonly used in modern medicine. Proteins are adsorbed to the surface of the biomaterial immediately after insertion. This report demonstrates the presence of adsorbed proteins in one infected cerebrospinal shunt from a child with hydrocephalus and on fifteen temporary ventricular catheters from adult patients with spontaneous or traumatic brain injuries. Depositions of vitronect

Novel all-silicon sensor structure with integrated poly-Si electrodes

The interest in miniaturization of modern chemical and medical sensors is steadily increasing. However, when employing methods and fabrication procedures especially developed for microelectronics, one may encounter new and unpredictable problems for applications in aqueous media. For instance, in microelectronics often a dual metal layer system is employed for making electrical contacts. In a solu

Image widening not only a question of tip sample convolution

As the tip in the atomic force microscope is scanned over the sample surface an image results which contains information from the sample as well as from the tip. This mainly results in an increase of the apparent size of the sample. If the tip is reasonably sharp the contribution from the tip is small. In some cases the widening still persists in spite of a very sharp tip. In this letter, a model

Fabrication and characterization of a nanosensor for admittance spectroscopy of biomolecules

We have fabricated nanometer-sized interdigitated electrode patterns using electron beam lithography and liftoff techniques. The aim of the investigation was to find out whether the dimensions (i.e., the electrode separations) of the pattern would affect the admittance signal of the biomolecules in between the electrodes. Since the admittance signal scales with the geometrical factor A/d, where A

Direct observation of the tip shape in scanning probe microscopy

In this study we report on the first direct observation of the real shape of the atomic force microscopy (AFM) tip using the AFM technique itself, utilizing a specially designed sample geometry. This is the first report of the so-called inverse AFM mode in which the tip is actually used as the sample and vice versa. We propose how this method can, with a very high accuracy, be used for studying ob

Cost-effectiveness analysis of budesonide/formoterol compared with fluticasone in moderate-persistent asthma

In this economic evaluation, conducted alongside a randomized, double-blind clinical trial, economic data were collected from 339 patients with moderate-persistent asthma randomized to receive twice-daily, double-blind treatment with budesonide/formoterol 160/4.5 μg in a single inhaler (n = 166) or fluticasone propionate 250 μg (n = 173) for 12 weeks. The mean number of episode-free days (EFD) per

Cost differences for COPD with and without physician-diagnosis

Previous studies have presented divergent estimates of the cost of illness of COPD due to differences in methodology. The objective of this study was to examine differences between register-based estimates versus population-based estimates on the burden of COPD. This study therefore examined differences in costs of COPD among physician-diagnosed and un-diagnosed subjects. During a one-year period,

Retrospective incremental cost analysis of a hospital-based COPD Disease Management Programme in Sweden

This paper reports on a retrospective analysis of hospital-based healthcare costs associated with the management of chronic obstructive pulmonary disease (COPD). During the second half of 2001, Simrishamn Hospital, Sweden, implemented a structured Disease Management Programme (DMP) for COPD and a total of 784 patients with COPD, enrolled in the DMP, were included in the analysis. The goal was to r

Budesonide/formoterol in a single inhaler (Symbicort®) reduces healthcare costs compared with separate inhalers in the treatment of asthma over 12 months

This open, multinational, randomised, parallel-group, six-month extension conducted in the Swedish centres of a previous six-month study compared the costs of a total of 12 months of treatment with budesonide/formoterol in a single inhaler with budesonide plus formoterol separate inhalers in 320 adults with asthma. Patients received budesonide/formoterol (Symbicort® Turbuhaler®) 160/4.5 mg deliver