Microchip delivery systems

Figure 6 In vitro and in vivo performance of an anticancer drug-loaded microchip delivery system (A) In vitro release of BCNU into phosphate buffer pH 7.2. The reservoirs contained either pure BCNU or binary BCNU PEG blends. The dashed lines indicate the time points of device activation (opening 50% of the reservoirs). (B) Evolution of the tumor size in rat flanks upon SC implantation of BCNU PEG-loaded microchips, containing 0.67, 1.2, or 2.0 mg drug and being activated 11 and 16 days post tumor implantation (50% of the reservoirs being opened at each time), or upon SC injection of die same amounts of BCNU and PEG, or upon SC implantation of a microchip containing 2 mg BCNU, but which was not activated. For reasons of comparison, also a nontreated control group is included. Source From Ref. 49.

Implants for controlled release of drugs (nonbiodegradable) Implantable biosensor-drug delivery system Microfiuidics device for drug delivery Controlled-release microchip Implants that could benefit from local drug release Vascular stents coronary, carotid, and peripheral vascular Ocular implants Dental implants Orthopedic implants... 

Figure 5 Microchip-based drug delivery systems (A) Schematic presentation of the device stracture with cathodes, anodes, and drag reservoirs. (B) Photographs of the front and back sides of a microchip, the coin serves as a reference for the dimensions of the system. Source From Refs. 43 and 44.

Figure 3. Microfluidic Device. (A) Time lapse illustrating repulsion the ejection of 1.9 pm fluorescent polystyrene microsphere particles from an electroactive microwell. After dissolution of the membrane, the fluorescent particles can be seen in the well. White hnes outline the gold electrodes features. Images are taken every 2 s (total of 10 s). (B) Schematic of the electroactive microwell drug delivery system developed here. Scale bar represents 2 mm. (C) Micro fluidic device with electrical leads connected to thin copper wires. Inset Magnified view of microchip from above looking at the region near the membrane. (D) To illustrate the electrokinetic transport processes involved in the ejection stage, a finite element analysis of time-dependent species transport of the system is shown. Images show cut view of species concentration every 60 s up to 300 s after the ejection process.

In one approach, the microchip interface was constmcted from modified 1/16-inch high-performance liquid chromatography (HPLC) fittings [30]. It incorporates a freestanding liquid junction formed via continuous delivery of a flow of suitable solvent which carries the separation effluent through a pneumatically assisted electrospray needle located in front of the MS orifice. In some cases, stmctural features of microchips can be utilized as parts of the ion source (e.g., ESI emitter). Thus, the resulting coupled microchip-MS systems are more compact, and the delay time between the on-chip incubation and MS detection can be decreased. For example, a capillary nanoESI emitter was successfully incorporated into a microchip CE channel for on-line CE-MS analysis [31]. Such microchip-MS systems do not require the use of external pumps because analytes can be driven toward the ion source (ESI or nanoESI) by means of electroosmosis and electrophoresis [32]. 

Health care and a health delivery system based on WBSN requires multidisciplinary research and development in biology, physiology, physics, chemistry, micro/nano-technologies, material sciences, industrial sectors like medical devices, electronics, microchips, technical textiles, and telecommunications and related engineering disciplines. Thus, a close interdisciplinary collaboration between biomedical sensors... 

Mass spectrometric detection has also been directly interfaced with microchip separations for drug detection. These studies, detecting imipramine and desipramine in fortified human plasma, show analysis of spiked analytes in clinical sample matrices for drug detection [3]. These widely used tricyclic antidepressants inhibit the reuptake of the neurotransmitters serotonin and norepinephrine in the central nervous system. Unfortunately, the 5-mg/mL detection limit found for these antidepressants with this method is not low enough to detect typical clinical levels of the drugs. Combinatorial library characterization and preclinical drug delivery studies should benefit, however, since the concentra-... 

A dispensing system fitted with a counting mechanism also is available (Fig. 6). It allows the consumer to monitor each actuation, beginning from the first priming stroke until delivery of the last dose. A dispensing system for controlled substances, such as morphine, can be equipped with a lock-out system. The microchip controlled actuation mode takes into account the patient s specific requirements, such as amount of drug and frequency of administration. Other relevant data are recorded and can be evaluated later by a physician. 

Microchip drug delivery is an impressive method for drug dehv-ery (51). The time window is large without the need for patient intervention. A microchip system has the capability to store a large number of drugs, control the time at which release begins, and control the rate at which the chemicals are released. 

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