Biomedical subjects

James C Sturm

Publications and source records attributed to James C Sturm.

11 recordsLinked to original sources

PubMed2006

Deterministic hydrodynamics: taking blood apart.

We show the fractionation of whole blood components and isolation of blood plasma with no dilution by using a continuous-flow deterministic array that separates blood components by their hydrodynamic size, independent of their mass. We use the technology we developed of deterministic arrays which separate white blood cells, red blood cells, and platelets from blood plasma at flow velocities of 1,000 microm/sec and volume rates up to 1 microl/min. We verified by flow cytometry that an array using focused injection removed 100% of the lymphocytes and monocytes from the main red blood cell and platelet stream. Using a second design, we demonstrated the separation of blood plasma from the blood cells (white, red, and platelets) with virtually no dilution of the plasma and no cellular contamination of the plasma.

Blood Platelets↗

PubMed2006

Critical particle size for fractionation by deterministic lateral displacement.

The fractionation of small particles in a liquid based on their size in a micropost array by deterministic lateral displacement was recently demonstrated with unprecedented resolution (L. R. Huang, E. C. Cox, R. H. Austin and J. C. Sturm, Science, 2004, 304, 987-990, ). In this paper, we present a model of how the critical particle size for fractionation depends on the micropost geometry, depending specifically on the gap between posts, the offset of posts in one row with respect to another, and whether the fluid is driven by hydrodynamics or by electroosmosis. In general the critical particle diameter is much smaller than the gap, which prevents clogging. The model is supported by data with particles from 2.3 to 22 microm.

Chemical Fractionation↗

PubMed2006

A nanofluidic railroad switch for DNA.

We present a metamaterial consisting of a two-dimensional, asymmetric lattice of crossed nanochannels in fused silica, with channel diameters of 80 nm to 140 nm. When DNA is introduced, it is stretched and linearized. We show that the asymmetry in channel dimensions gives rise to a preferred direction for DNA orientation and a preferred direction for transport under dc electrophoresis. Interestingly, the preferred axis of orientation and transport can be switched by 90 degrees through application of an ac voltage. We explain the results in terms of an energy landscape for polyelectrolytes that consists of entropic and dielectrophoretic contributions and whose strength and sign can be tuned by changing the ac field strength.

DNA↗

PubMed2005

Statics and dynamics of single DNA molecules confined in nanochannels.

The successful design of nanofluidic devices for the manipulation of biopolymers requires an understanding of how the predictions of soft condensed matter physics scale with device dimensions. Here we present measurements of DNA extended in nanochannels and show that below a critical width roughly twice the persistence length there is a crossover in the polymer physics.

Bacteriophage lambda↗

PubMed2004

From the Cover: The dynamics of genomic-length DNA molecules in 100-nm channels.

We show that genomic-length DNA molecules imaged in nanochannels have an extension along the channel that scales linearly with the contour length of the polymer, in agreement with the scaling arguments developed by de Gennes for self-avoiding confined polymers. This fundamental relationship allows us to measure directly the contour length of single DNA molecules confined in the channels, and the statistical analysis of the dynamics of the polymer in the nanochannel allows us to compute the SD of the mean of the extension. This statistical analysis allows us to measure the extension of lambda DNA multimers with a 130-nm SD in 1 min.

DNA↗

PubMed2004

Continuous particle separation through deterministic lateral displacement.

We report on a microfluidic particle-separation device that makes use of the asymmetric bifurcation of laminar flow around obstacles. A particle chooses its path deterministically on the basis of its size. All particles of a given size follow equivalent migration paths, leading to high resolution. The microspheres of 0.8, 0.9, and 1.0 micrometers that were used to characterize the device were sorted in 40 seconds with a resolution of approximately 10 nanometers, which was better than the time and resolution of conventional flow techniques. Bacterial artificial chromosomes could be separated in 10 minutes with a resolution of approximately 12%.

Chemical Fractionation↗

PubMed2004

Micro- and nanofluidics for DNA analysis.

Miniaturization to the micrometer and nanometer scale opens up the possibility to probe biology on a length scale where fundamental biological processes take place, such as the epigenetic and genetic control of single cells. To study single cells the necessary devices need to be integrated on a single chip; and, to access the relevant length scales, the devices need to be designed with feature sizes of a few nanometers up to several micrometers. We will give a few examples from the literature and from our own research in the field of miniaturized chip-based devices for DNA analysis, including dielectrophoresis for purification of DNA, artificial gel structures for rapid DNA separation, and nanofluidic channels for direct visualization of single DNA molecules.

Cell Separation↗

PubMed2003

Tilted brownian ratchet for DNA analysis.

In this paper, we report a factor of 3 improvement in the resolution and a factor of 10 improvement in the speed of fractionation of approximately 100-kb DNA molecules in Brownian ratchet arrays. In our device, the electrophoretic flow is tilted at a small angle relative to the array axis. Tilting accelerates the fractionation speed because a higher fraction of the diffusing molecules is "ratcheted" at each step in the array. Molecules of lengths 48.5 and 164 kb can be separated in approximately 70 min with a resolution of approximately 3.8, using a 12-mm-long array. The Brownian ratchet arrays are not limited to DNA separation, but can, in principle, be used for any particle in this size range.

Chemical Phenomena↗

PubMed2002

Bacterial chromosome extraction and isolation.

We have used diffusive mixing and dielectrophoretic trapping to lyse Escherichia coli cells in a microfabricated environment and trap the E. coli chromosome. We characterize the conditions needed for efficient lysis of the cells, and conditions needed for the dielectrophoretic trapping of the chromatin without the trapping of cytoplasmic proteins.

Chromosomes, Bacterial↗

PubMed2002

Role of molecular size in ratchet fractionation.

We show the importance of finite particle size in microfluidic asymmetric continuous-flow diffusion arrays, specifically the critical nature of the particle size with respect to the barrier gaps. We show that particles much smaller than the barrier gap follow individual field lines through narrow gaps and are poorly fractionated. In contrast, particles comparable to the gap size lose memory of their incoming field line and can be fractionated with high resolution. We demonstrate this effect using a new technological approach to create very straight and narrow injection bands in such arrays, and completely resolve bands of DNA of lengths 48,500 and 16,7000 base pairs.

Bacteriophage T4↗

PubMed2002

A DNA prism for high-speed continuous fractionation of large DNA molecules.

The analysis and fractionation of large DNA molecules plays a key role in many genome projects. The standard method, pulsed-field gel electrophoresis (PFGE), is slow, with running times ranging from 10 hours to more than 200 hours. In this report, we describe a thumbnail-sized device that sorts large DNA fragments (61-209 kilobases (kb)) in 15 seconds, with a resolution of approximately 13%. An array of micron-scale posts serves as the sieving matrix, and integrated microfluidic channels spatially shape the electric fields over the matrix. Asymmetric pulsed fields are applied for continuous-flow operation, which sorts DNA molecules in different directions according to their molecular masses, much as a prism deflects light of different wavelengths at different angles. We demonstrate the robustness of the device by using it to separate large DNA inserts prepared from bacterial artificial chromosomes, a widely used DNA source for most genomics projects.

Chemical Fractionation↗