Bead or particle manipulating chucks

Details Bead or particle manipulating chucks Bead or particle manipulating chucks

1999-09-10

2001-09-25

Fleming, Fritz (Department: 2836)

Electricity: electrical systems and devices

Electric charge generating or conducting means

Use of forces of electric charge or field

C361S233000

Reexamination Certificate

active

06295194

ABSTRACT:

The present invention is directed to devices for electrically picking up and dispensing electrically charged beads or particles in a spatially resolved manner. Specifically, this disclosure describes novel electrode configurations and operation techniques for electrostatic transporter chucks that pick up, manipulate, transport, and then discharge or place beads, particles or objects for use in creating pharmaceutical or chemical compositions, or in performing assays or chemical analysis. The invention provides for use of guide electrodes and guide fields to aid in moving, switching, shifting or manipulating beads or particles from an originating electrode to a target electrode, with lateral motions and other bead manipulation possible in up to three dimensions, as described below.
Electrostatic transporter chucks can be used to pick up, manipulate, transport, and then discharge or place beads, particles or objects for use in creating pharmaceutical or chemical compositions, or in performing assays or chemical analysis.
Transporter chucks act as clamps to hold or retain an object or objects. Transporter chucks provide superior performance for manipulating synthetic beads or particles having typical diameters of 100-300 microns in chemical synthesis, such as combinatorial chemistry for solid phase synthesis, or in an assay using 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, transporter chucks allow deposition of beads or particles on an array in a manner that is fast and reliable. Another application for transporter chucks is synthesis of pharmaceutical compositions, especially when used to combine compounds to form compositions to be packaged into administration forms for humans or animals.
Beads or particles containing one or more active ingredients can be deposited onto well known carriers or substrates to make pharmaceutical dosage forms. Such beads or particles can 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, such as 4-8 microns; [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 transporter chucks provides a customized and precise method for formulating drug compositions. The transporter chucks can be used when merging adjacent substrates carrying active ingredient to form multidosage packs, in which dosage can decrease or increase from one individual unit to the next, as in hormone-based (e.g., birth control) drugs or antibiotic remedies. Using an electrostatic transporter chuck, dosages can be established or determined by the number or type of beads or particles dispensed onto each pharmaceutical carrier, or by using electrical, optical, or mechanical dosage sensing. Using transporter chucks to place active ingredients into pharmaceutical compositions can yield high repeatability and is also advantageous when 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 transporter chucks that apply electric fields for bead retention or release, the teachings given here can be applied to chucks that also use other phenomena, such as the use of compressed gas or vacuum, or electrically/chemically switchable adhesives, in controlling beads or particles or substrates. Electrostatic or quasi-electrostatic holding mechanisms, however, are often more benign to delicate bead structures than traditional mechanical techniques, particularly when manipulating biologically active compounds where crushing, contamination, or oxidative damage should be minimized or eliminated.
Typically, beads or particles to be transported or manipulated are tribo-charged (through frictional encounters and collisions, such as rubbing or bumping) into or through charge induction. Other forms of charging, such as corona or plasma charging, can be used.
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. Such energy can help propel or tribocharge beads or particles prior to or during electrostatic manipulation. Tribocharging beads or particles, as known in the art, and described below, can be more efficient and less damaging to the beads or particles 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 the particles, eliminating the need to charge the beads or particles prior to their entry into the acoustic dispenser. The use of acoustic dispensers allows polarity discrimination of beads or particles, where wrongly charged beads or particles are discouraged from being retained by the transporter chuck.
Some transporter chucks offer precision in being able to have one, and only one bead attracted, transported, and discharged for each transporter chuck, or for each well, pixel, or individual spatial element of the transporter chuck. In many cases, each pixel can be considered a tiny transporter chuck that is selectively and independently controlled, such as planar chucks having individually addressable x and y coordinates. Such transporter chucks can include individually addressable pixels for different (multiple) bead types.
Beads or particles manipulated by these transporter chucks (or manipulating chucks) are easily and controllably releasable, with wrongly charged beads or particles (objects or beads having a charge of the opposite polarity desired) not occupying bead retaining or collection zones on the transporter chuck. Such transporter chucks function well for a wide range of bead diameters, including beads or particles with general dimensions of 100 microns up to a few millimeters or more, and also including porous or hollow beads or particles that have high charge/mass ratios. Such transporter chucks also offer durability and re-usability, and ease-of-use, including having selectively or wholly transparent elements for movement and alignment of the chuck with intended targets or carriers.
Often, instead of depositing beads or particles singly, transporter chucks are used to attract and place powder, such as powder containing active ingredient, on a substrate, such an edible substrate for use in pharmaceutical dosage forms.
Electrodes used for attracting beads or particles can vary widely in construction and structure. Bead attracting electrodes, can, for example, be directly exposed, or covered by a dielectric (for example, to prevent ionic breakdown (sparking) in air and to make use of the properties of dielectrics to enhance bead charge holding capacity). To control the amount of charged beads or particles that can be attracted, an indirect method can also be used where a bead attraction electrode attracts beads or particles indirectly, using capacitive coupling to a pad or floating electrode. The instant invention can be applied to any number of transporter chuck designs, but for illustration purposes, a simple chuck is shown here to attract beads or particles directly by way of one or more directly biased (non-floating) electrodes.
Methods for use of transporter chucks and acoustic bead dispensers are set forth, for example, in Sun, “Chucks and Methods for Positioning Multiple Objects on a Substrate,” U.S. Pat. No. 5,788,814, issued Aug. 4, 1998; Sun et al., “Method of Making Pharmaceutical Using Electrostatic Chuck,” U.S. Pat. No. 5,858,099, issued

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