Simultaneous transcranial magnetic stimulation and single-neuron recording in alert non-human primates.

Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report new methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally perturbed by stimulation artifact in awake monkeys (Macaca mulatta). We recorded action potentials within ∼1 ms after 0.4-ms TMS pulses and observed changes in activity that differed significantly for active stimulation as compared with sham stimulation. This methodology is compatible with standard equipment in primate laboratories, allowing easy implementation. Application of these tools will facilitate the refinement of next generation TMS devices, experiments and treatment protocols.

Optical Control of Magnetic Feshbach Resonances by Closed-Channel Electromagnetically Induced Transparency

Optical control of interactions in ultracold gases opens new fields of research by creating ``designer" interactions with high spatial and temporal resolution. However, previous optical methods using single optical fields generally suffer from atom loss due to spontaneous scattering. This thesis reports new optical methods, employing two optical fields to control interactions in ultracold gases, while suppressing spontaneous scattering by quantum interference. In this dissertation, I will discuss the experimental demonstration of two optical field methods to control narrow and broad magnetic Feshbach resonances in an ultracold gas of $^6$Li atoms. The narrow Feshbach resonance is shifted by $30$ times its width and atom loss suppressed by destructive quantum interference. Near the broad Feshbach resonance, the spontaneous lifetime of the atoms is increased from $0.5$ ms for single field methods to $400$ ms using our two optical field method. Furthermore, I report on a new theoretical model, the continuum-dressed state model, that calculates the optically induced scattering phase shift for both the broad and narrow Feshbach resonances by treating them in a unified manner. The continuum-dressed state model fits the experimental data both in shape and magnitude using only one free parameter. Using the continuum-dressed state model, I illustrate the advantages of our two optical field method over single-field optical methods.

Independent individual addressing of multiple neutral atom qubits with a micromirror-based beam steering system

We demonstrate a scalable approach to addressing multiple atomic qubits for use in quantum information processing. Individually trapped 87Rb atoms in a linear array are selectively manipulated with a single laser guided by a microelectromechanical beam steering system. Single qubit oscillations are shown on multiple sites at frequencies of ≃3.5 MHz with negligible crosstalk to neighboring sites. Switching times between the central atom and its closest neighbor were measured to be 6-7 μs while moving between the central atom and an atom two trap sites away took 10-14 μs. © 2010 American Institute of Physics.

Magnetophoretic circuits for digital control of single particles and cells.

The ability to manipulate small fluid droplets, colloidal particles and single cells with the precision and parallelization of modern-day computer hardware has profound applications for biochemical detection, gene sequencing, chemical synthesis and highly parallel analysis of single cells. Drawing inspiration from general circuit theory and magnetic bubble technology, here we demonstrate a class of integrated circuits for executing sequential and parallel, timed operations on an ensemble of single particles and cells. The integrated circuits are constructed from lithographically defined, overlaid patterns of magnetic film and current lines. The magnetic patterns passively control particles similar to electrical conductors, diodes and capacitors. The current lines actively switch particles between different tracks similar to gated electrical transistors. When combined into arrays and driven by a rotating magnetic field clock, these integrated circuits have general multiplexing properties and enable the precise control of magnetizable objects.

Acoustic and Magnetic Techniques for the Isolation and Analysis of Cells in Microfluidic Platforms

Cancer comprises a collection of diseases, all of which begin with abnormal tissue growth from various stimuli, including (but not limited to): heredity, genetic mutation, exposure to harmful substances, radiation as well as poor dieting and lack of exercise. The early detection of cancer is vital to providing life-saving, therapeutic intervention. However, current methods for detection (e.g., tissue biopsy, endoscopy and medical imaging) often suffer from low patient compliance and an elevated risk of complications in elderly patients. As such, many are looking to “liquid biopsies” for clues into presence and status of cancer due to its minimal invasiveness and ability to provide rich information about the native tumor. In such liquid biopsies, peripheral blood is drawn from patients and is screened for key biomarkers, chiefly circulating tumor cells (CTCs). Capturing, enumerating and analyzing the genetic and metabolomic characteristics of these CTCs may hold the key for guiding doctors to better understand the source of cancer at an earlier stage for more efficacious disease management.

The isolation of CTCs from whole blood, however, remains a significant challenge due to their (i) low abundance, (ii) lack of a universal surface marker and (iii) epithelial-mesenchymal transition that down-regulates common surface markers (e.g., EpCAM), reducing their likelihood of detection via positive selection assays. These factors potentiate the need for an improved cell isolation strategy that can collect CTCs via both positive and negative selection modalities as to avoid the reliance on a single marker, or set of markers, for more accurate enumeration and diagnosis.

The technologies proposed herein offer a unique set of strategies to focus, sort and template cells in three independent microfluidic modules. The first module exploits ultrasonic standing waves and a class of elastomeric particles for the rapid and discriminate sequestration of cells. This type of cell handling holds promise not only in sorting, but also in the isolation of soluble markers from biofluids. The second module contains components to focus (i.e., arrange) cells via forces from acoustic standing waves and separate cells in a high throughput fashion via free-flow magnetophoresis. The third module uses a printed array of micromagnets to capture magnetically labeled cells into well-defined compartments, enabling on-chip staining and single cell analysis. These technologies can operate in standalone formats, or can be adapted to operate with established analytical technologies, such as flow cytometry. A key advantage of these innovations is their ability to process erythrocyte-lysed blood in a rapid (and thus high throughput) fashion. They can process fluids at a variety of concentrations and flow rates, target cells with various immunophenotypes and sort cells via positive (and potentially negative) selection. These technologies are chip-based, fabricated using standard clean room equipment, towards a disposable clinical tool. With further optimization in design and performance, these technologies might aid in the early detection, and potentially treatment, of cancer and various other physical ailments.