UCLA

Richard Feynman in his famous address “There’s plenty of room at the bottom” illuminated the potential that nano and micro technologies had in extending our reach into the microscopic world. Specifically, his vision of “a hundred tiny hands” where motions at the human scale can be de-amplified to the micro scale are alluring because biological systems, such as cells and bacteria, occupy this scale. Indeed the ability to achieve microscopic motion control is essential for developing miniaturized systems for biological assays.

Magnetic ratcheting serves as a superior technique for high throughput micromanipulation to develop miniaturized systems due to its specificity, biocompatibility, and highly parallelized nature. Ratcheting manipulation uses an external magnetic field combined with arrays of micro-pillars composed of a magnetically soft alloy to generate localized potential minima in which superparamagnetic particles become trapped. When the external field is directionally cycled in a ratcheting manner, the particles follow the shifting potential minima and traverse across the micro pillar array with piconewton scale forcing. Using this technique we have developed a high force (67pN) architecture to achieve highly parallelized manipulation (~3x105 manipulations/mm2) for transporting magnetically labeled cells and or probing subcellular phenomena with magnetic particles. Using a mechatronic system to generate the ratcheting field, magnetic particles can be automatically or manually piloted via a joystick interface. We have demonstrated highly resolved particle mediated interface with cells and also automated manipulation of magnetically labeled cells for performing automated single cell assays.

The system’s high force envelop also allows rapid transport and concentration of immunomagnetically labeled cells using nanoscale particles, enabling higher labeling efficiency and specificity. Using a funneling ratcheting array, endothelial cells labeled with 500nm particles were concentrated in a little as 15 minutes, showing potential as a point of care diagnostic and also operability in complex solutions such as blood. Additionally, our ratcheting manipulation system was used to achieve quantitative magnetic separation on micro-pillar arrays with gradient pitch. Here ratcheting was used to separate and concentrate cells based on surface expression but also enrich circulating tumor cells from clinical blood samples.

In addition to in vitro applications, we demonstrated a therapeutic use case in treatment of bacterial biofilm infections of intravenous catheters. Staphylococcus aureus biofilms gown on ratcheting substrates could be mechanically disrupted using magnetic particles combined with both static and dynamic forcing, potentially increasing antibiotic penetration into the biofilm matrix. Using this ratcheting “scrubbing” approach, a majority (~91%) of S. aureus biofilms were removed. This method of mechanically perturbing the adhered biofilm shows promise as a minimally invasive treatment for biofilm infected catheters.

Magnetic ratcheting is a powerful tool which can be used to construct miniaturized systems for high throughput single cell operations or for therapeutic use to provide localized force in a minimally invasive manner. Ratcheting provides a vehicle to extend our reach into the microscopic length scale to solve problems or gain knowledge; providing us a million tiny hands to reach into, explore, and engineer in the microscale world.