Coating apparatus – With means to apply electrical and/or radiant energy to work... – Electrostatic and/or electromagnetic attraction or...
Utility Patent
1998-05-22
2001-01-02
Sells, James (Department: 1734)
Coating apparatus
With means to apply electrical and/or radiant energy to work...
Electrostatic and/or electromagnetic attraction or...
C118S621000, C118S308000
Utility Patent
active
06168666
ABSTRACT:
The present invention is directed to devices for electrostatically picking up and dispensing beads in a spatially resolved manner. Specifically, this disclosure describes a focused acoustic charger/dispenser for electrostatic bead transporter chucks, allowing focused and controlled distribution of beads for directed delivery aligned with bead collection zones. Electrostatic bead transporter chucks may be used to pick up, manipulate, transport, and then discharge or place beads or objects for use in creating pharmaceutical or chemical compositions, or in performing assays or chemical analysis.
Bead transporter chucks act as clamps to hold or retain an object or objects. Bead transporter chucks can provide superior performance for manipulating synthetic beads having typical diameters of 0.1-1 millimeters to in chemical synthesis, such as combinatorial chemistry for solid phase synthesis, or in an assay using nucleic acid amplification such as PCR (polymerase chain reaction) or other processes. In combinatorial chemistry, a multi-well array such as a microtiter plate allows screening or synthesis of many compounds simultaneously.
For example, bead transporter chucks allow deposition of beads on an array in a manner that is faster and more reliable than by the use of micropipettes, which can be inefficient, tedious, and time consuming. Another application for bead transporter chucks is synthesis of pharmaceutical compositions, especially when used to combine compounds to form compositions to be packaged into administration foims for humans or animals.
Beads containing one or more active ingredients may be deposited onto well known carriers or substrates to make pharmaceutical dosage forms. Such beads may take the form, for example, of [1] a powder, such as dry micronized forms made by air jet milling processes, where overall particle dimensions can be, for example, in the 1 to 10 micron range useful for dry powder respiratory administration of medicaments, with 4-8 microns preferred; [2] microspheres; [3] extremely small structures, including fullerenes, chelates, or nanotubes; or [4] liposomes and fatty droplets formed from lipids or cell membranes.
The use of bead transporter chucks provides a customized and precise method for formulating drug compositions. The transporter can be used when merging adjacent substrates carrying active ingredient to form multidosage packs, in which dosage may decrease or increase fiom one individual unit to the next, as in hormone-based (e.g., birth control) drugs or antibiotic remedies. Using an electrostatic bead transporter chuck, dosages may be easily established or determined by the number and/or type of beads dispensed onto each pharmaceutical carrier. Using bead transporter chucks to place active ingredients into pharmaceutical compositions can give high repeatability and is also advantageous when the active ingredients are not compatible, such as when the active ingredient is poorly soluble with the carrier, or where a formulation or carrier negatively affects the bioavailability of the active ingredient.
Although emphasis is placed in this disclosure on use of electrostatic bead transporter chucks that apply electric fields for bead retention and/or release, the teachings given here may be applied to chucks using other phenomena, such as the use of compressed gas or vacuum, or electrically/chemically switchable adhesives, in controlling beads. Electrostatic holding mechanisms, however, are benign to delicate bead structures, particularly when manipulating biologically active compounds where crushing, contamination, or oxidative damage must be minimized or eliminated.
The present invention can involve use of acoustic stimulation or acoustic dispensers, where acoustic energy, provided by a speaker or piezoelectric device, is used to great advantage in bead control, that is, propelling and/or tribocharging beads prior to, and especially during, electrostatic manipulation. Tribocharging beads, as known in the art, and described below, is more efficient and less damaging to the beads than corona or plasma charging, which typically requires high applied voltages of around 5 kV. Often, the sonically vibrating membrane or mesh used in such an acoustic bead dispenser can itself be used to tribocharge particles, eliminating the need to charge the beads prior to their entry into an acoustic dispenser. The use of acoustic dispensers allows polarity discrimination of beads, where wrongly charged beads are discouraged from being retained by the bead transporter chuck.
Bead transporter chucks offer precision in being able to have one, and only one bead attracted, transported, and discharged for each bead transporter chuck, or for each well, pixel, or individual spatial element of the bead transporter chuck. In many cases, each pixel can be considered a tiny bead transporter chuck that is selectively and independently controlled, such as planar chucks having individually addressable x and y coordinates. This includes individually addressable pixels for different (multiple) bead types.
Beads manipulated by these bead transporter chucks (or bead manipulating chucks) are easily and controllably releasable, with wrongly charged beads (objects or beads having a charge of the opposite polarity desired) not occupying bead retaining or collection zones on the bead transporter chuck. They function well for a wide range of bead diameters, including beads with general dimensions of 100 microns and up, and also including porous or hollow beads that have high charge/mass ratios. They also offer durability and re-usability, and good ease-of-use, including having selectively or wholly transparent elements for easy movement and alignment of the chuck with intended targets or carriers.
Bead transporter chuck designs that use simple attraction electrodes to pick up and discharge beads can, under certain conditions, encounter serious problems with bead density and control. One problem encountered is that many more beads than desired can be attracted to intended bead collection zones. During synthesis or analysis, instead of retaining one and only one bead per bead collection zone, multiple beads or even whole clumps of beads can be attracted to bead collection zones when using typical or desired attracting voltages needed for efficient manipulation of the beads. Alternatively, in seeking to avoid this bead clumping by reducing the applied (attraction) voltage, the attraction field can then be insufficient to cause beads to deposit in the required manner, i.e., one bead per hole, without either having beads attracted to unintended or wrong locations on the bead transporter chuck, or having wrongly charged beads attracted to the bead transporter chuck.
In the course of using bead transporter chucks for creating pharmaceutical or chemical compositions, or in performing assays or chemical analysis, certain problems arise and certain requirements have been identified.
First, charged beads must be freed from electrostatic image forces in order to leave any conductor to be picked up by the bead transporter chuck. As a charged bead approaches any metal or other conductive material, such as a conductive material inside the bead dispenser or container, an image charge of opposite polarity will accumulate on that conductive material. This happens when mobile charge carriers in the conductive surface are attracted by, or repelled by, the bead charge. This movement of charge in the conductive surface in response to a charged bead in the vicinity creates a potent image charge-induced holding force, or electrostatic image force. This electrostatic image force tends to keep the bead in tight contact with, or highly attracted to, the conductive material. It should be noted that dielectric beads in stationary tight contact with a conductive surface have a tendency to keep their charge for a period of days. With a bead close to any conductor, the electrostatic image force generated tends to be greater than that due to any applied field used to accelera
Burke William J.
Sarnoff Corporation
Sells James
LandOfFree
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