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Metastatic breast cancer is responsible for most breast cancer-related deaths. Disseminated cancer cells have developed an intrinsic ability to resist anchorage-dependent apoptosis (anoikis). Anoikis is caused by the absence of cellular adhesion, a process that underpins lumen formation and maintenance during mammary gland development and homeostasis. In healthy cells, anoikis is mostly governed b
Just like current software systems, models are characterised by increasing complexity and rate of change. Yet, these models only become useful if they can be continuously evaluated and validated. To achieve sufficiently low response times for large models, incremental analysis is required. Reference Attribute Grammars (RAGs) offer mechanisms to perform an incremental analysis efficiently using dyn
We present a label-free method capable of rapidly sorting particles based on their densities. Our device relies on deterministic lateral displacement (DLD) and achieves density fractionation by the use of T-shaped posts. By combining it with a lateral density gradient we achieve a density separation that is independent of size within a range given by the device geometry. Herein we present a proof-
The inherent properties of cells and micro-organisms is an under-explored source of specificity for particle sorting. In contrast to standard immunolabeling it allows us to perform fractionation without any chemical preparation of the sample. This improves the accessibility and affordability of the technology. Our contribution in the field is to extend the scope of deterministic lateral displaceme
We have developed an assay, based on nanofluidic channels and fluorescence microscopy, for optical mapping of DNA based on competitive binding between two molecules - one fluorescent and one sequence selective. From the experimental data we can extract binding constants for the two competing DNA binders, which may be subsequently used to calculate a theoretical reference map of any DNA with known
We present a deterministic-lateral-displacement (DLD) device that extends the capabilities of this traditionally sizebased particle separation technique to also be sensitive to density. By the use of T-shaped posts instead of the normally cylindrical posts the particle trajectory through the device will be a function of its vertical position which in turn is determined by the buoyancy of the parti
We have studied a selection of factors influencing the damage of DNA in nanochannels during fluorescence imaging. For cutting and nicking of DNA we show that the DNA is shortened during imaging. To avoid photodamage over the course of several hours of a typical experiment, we demonstrate the importance of an oxygen free gas to propel the buffer solution through the device. Finally, by varying the
Stretching DNA in nanochannels allows for direct, visual studies of genomic DNA at the single molecule level. In order to facilitate the study of the interaction of linear DNA with proteins in nanochannels, we have implemented a highly effective passivation scheme based on lipid bilayers. We show long-term passivation of nanochannel surfaces to several relevant reagents and demonstrate that the pe
To better understand how deformable and non-spherical particles behave in sorting devices based on deterministic lateral displacement we generate models of biological particles with tunable size, shape and mechanical properties using stop-flow lithography and we explore how these parameters play a role in our separation devices. Hollow and solid cylinders are compared with respect to their deforma
We present a simple and rapid microfluidic device capable of extracting and concentrating the parasite causing the fatal disease sleeping sickness (SS) from blood. The device is based on deterministic lateral displacement (DLD) and constructed with a single inlet with flow induced by an ordinary syringe. The simplicity is crucial as the device is intended for use in the resource depraved areas whe
In this work we present an integrated system for whole chromosome analysis of single bacterium. Using whole genome barcoding techniques, which offer direct and rapid microscopic visualization of the entire genome in one field-of-view, we aim to rapidly identify individual bacterium. We are developing our device to achieve the crucial, and difficult process of isolating a bacterium, removing the DN
A new chip design for handling and studying chromosomal DNA is described. Folding the nanochannels enables us to image an entire yeast chromosome in a single field of view. Together with existing mapping techniques our new design opens up the possibility of directly analyzing entire chromosomes in a single field of view using fluorescence microscopy. This would enable, for example, identification
Stretching of DNA in nanoscale confinement allows for direct visualization of the genetic contents of the DNA on the single DNA molecule level. DNA stretched in nanoscale confinement also allows for studies of DNA-protein interactions and DNA polymer physics in confined environments. This chapter describes the basic steps to fabricate the nanostructures, to perform the experiments, and to analyze
Deterministic Lateral Displacement (DLD) devices have been used to separate particles based on size [1] and shape [2]. Here we show how DLD devices can also be used to separate particles based on their ability to deform under shear forces. Varying experimental conditions allows us to vary the relative contributions of size, morphology and deformability. The ability to distinguish between cells bas
We present a simple and inexpensive device capable of extracting and concentrating the parasite causing sleeping sickness from blood. The device is aimed at being used in rural resource depraved areas where the disease is endemic; therefore simplicity is of paramount importance. The device is based on deterministic lateral displacement with a single inlet and flow induced by a syringe. Through an
Objectives: COPD is a common and disabling disease that entails high costs for society. The objectives of this study were to measure the societal costs of COPD in Sweden, and to examine the relationship between severity of illness and costs. Methods: The costs of COPD were examined using a well-defined and representative cohort of subjects with mild, moderate, and severe COPD. Regular telephone in
How good is your best chimpanzee impression? Go to the zoo and you probably wouldn’t be surprised to see people copying chimpanzees in order to grab their attention. But our latest research, which recently won the Ig Nobel Prize for Anthropology, suggests you are just as likely to see chimpanzees imitating the human visitors.
Background: It remains uncertain whether the increasing incidence of inflammatory bowel disease (IBD) during the last decades has been accompanied by an alteration in the presentation, course, and prognosis of the disease. To answer this question, 3 consecutive population-based IBD cohorts from Copenhagen, Denmark (1962-2005), were assessed and evaluated. Methods: Phenotype, initial disease course
Background: The Stanford integrated psychosocial assessment for transplantation (SIPAT) is a validated psychosocial evaluation tool in the transplant population. Objective: We evaluated SIPAT in predicting post-left ventricular assist device (LVAD) outcomes, including cumulative re-admissions, driveline infections, pump malfunction, pump thrombosis, gastrointestinal bleeding, major bleeding, strok
We present two new data structures for computing values of an n-variate polynomial P of degree at most d over a finite field of q elements. Assuming that d divides q- 1 , our first data structure relies on (d+ 1) n + 2 tabulated values of P to produce the value of P at any of the qn points using O(nqd2) arithmetic operations in the finite field. Assuming that s divides d and d / s divides q- 1 , o
