Magnetic High Throughput System
We are developing a magnetic bead-based system that will be applicable to a range of studies focusing on the rheological properties of biofluids and biomaterials, to cell mechanoresponse, drug carrier transport and magnetic drug delivery. The system will be developed for a 96 specimen plate compatible with existing infrastructure for HTS and will permit the exploration of small molecule, protein and genetic libraries for mechanical phenotype. The magnetic system consists of a force generation system and an imaging platform. The force generation system takes the form of a magnetic block that supplies magnetic flux to a multiwell plate. The imaging system is a commercial high resolution fluorescence/brightfield inverted microscope that we will adapt for HTS studies.
Multiwell Magnetic Plate: The development of the MHTS system requires: (1) a means for generating magnetic excitation and for delivering the resulting magnetic flux to the specimen wells and (2) a means for suitably shaping the magnetic field within the specimen well to achieve the desired force profile.
The former is instrument-specific and relatively costly, while the latter is experiment-specific and can be relatively inexpensive. Our 3Dfm system was designed with the philosophy that separating the systems allows maximum flexibility in the tailoring the magnetic field for a range of experiments. Accordingly, the design of (1) takes the form of a magnetic drive block of high permeability magnetic material shaped to accommodate an array of excitation coil electromagnets, along with a corresponding array of magnetic paths for channeling the flux to a common interface at the bottom of the wells of a multiwell plate. As a single component of the entire instrument, a drive block can afford to be substantially intricate and sophisticated to provide the necessary magnetomotive force, bandwidth, thermal control, etc.
The design of (2) must account for the disparate requirements of the experiments that could be conducted with the MHTS. Accordingly, it takes the form of multiwell plates with pole plates sealed to the bottoms of their wells. The pole plates consist of thin foil magnetic structures laminated to thin glass plates of high optical quality. The pole plate plane forms the interface to (1). The magnetic structures can be photolithographically patterned to produce pole shapes suited to the various experiments. This design of the magnetics is the subject of our granted patents and the pending patent for the high throughput system. Successfully fabricated multiwell plates are shown in Figure 5.
Magnetics Block: Current that circulates in an excitation coil gives rise to a magnetomotive force (MMF) driving the magnetic flux. The density of magnetic flux is proportional to its MMF, and inversely to the reluctance (magnetic resistance) encountered by the flux line over the length of its loop. CISMM designs endeavor to provide low reluctance to maximize the force acquired for a given applied current. Thus, iron posts can be formed to guide the flux from the front end of a coil to the pole plate, and other posts to guide it back to the bulk of the iron block which provides an easy return path to the back of the coil. In operation, the drive block is positioned above a well plate, then lowered so the posts pass through their respective wells to contact the pole plate. Figure 6b shows our 4×4 drive block prototype in place, as viewed from beneath a bottomless well plate.
Spero, R. C., L. Vicci, et al. (2008). “High throughput system for magnetic manipulation of cells, polymers, and biomaterials.” Review of Scientific Instruments 79(8): 083707.