Micropump delivery

Micropump delivery rates are as low as few nl/s and can be controlled accurately by the pulsed current passing through the platinum electrodes. Electrochemical gas production can be precisely... 

Zahn, J.D., et al. 2004. Continuous on-chip micropumping for microneedle enhanced drug delivery. Biomed Microdevices 6 183. 

Silicon micropumps offer major advantages in terms of system miniaturization and control over low flow rates with a stroke volume 160 nL.14 The micropump has the characteristics of very small in size, implantability in the human body, low flow rates (in the range of 10 pL/min), moderate pressure generation from the microactuator to move the drug, biocompatibility, and most important, a reliable design for safe operation. The implantable device is particularly suitable (over the injectable drug delivery systems) for patients with Parkinson s disease, Alzhiemer s disease, diabetes, and cancer, as well as chronically ill patients, because the catheter that is attached to the device can transport drug to the required site. 

In polymeric membrane and matrix-based micropumps, the membrane or the matrix makes the essential component of the delivery device that controls the rate of release. In matrix controlled delivery, the rate of the hydrolytic breakdown of the matrix is the governing process. In polymeric membrane-controlled release, the rate of hydration of the membrane and the subsequent diffusion of drug are the rate-controlling steps. 

Maillefer, D., Rey-Mermet, G., Hirschi, R. A high-performance silicon micropump for an implantable drug delivery system. 12th IEEE MEMS 1999, Technical Digest, Orlando, FL, 1999. 

Yih TC, Wei C, Hammad B. Modeling and characterization of a nanoUter drug-delivery MEMS micropump with circular bossed membrane. Nanomedicine 2005 1 164-75. 

A review of micro-electromechanical systems (MEMS)-based delivery systems provides more detailed information of present and future possibilities (52). This covers both micropumps [electrostatic, piezoelectric, thermopneumatic, shape memory alloy bimetallic, and ionic conductive polymer films (ICPF)] and nonmechanical micropumps [magnetohydrodynamic (MHD), electrohydrodynamic (EHD), electroosmotic (EO), chemical, osmotic-type, capillary-type, and bubble-type systems]. The biocompatibility of materials for MEMS fabrication is also covered. The range of technologies available is very large and bodes well for the future. 

T. Korenaga, X.-J. Zhou, T. Moriwake, H. Muraki, T. Naito, S. Sanuki, Computer-controlled micropump suitable for precise microliter delivery and complete in-line mixing, Anal. Chem. 66 (1994) 73. 

The controlled-release micropump (Figure 2) is a recently invented device that uses the principles of membrane transport and controlled release of drugs to deliver insulin at variable rates (20,26). With a suitable supply of insulin connected to the pump, the concentration and/or pressure difference across the membrane results in diffusion or bulk transport through the membrane ). This process is the basal delivery and requires no external power source. Augmented delivery is achieved by repeated compression of the foam membrane by the coated mild-steel piston. The piston is the core of the solenoid, and compression is effected when current is applied to the solenoid coil. Interruption of the current causes the membrane to relax, drawing more drug into the membrane in preparation for the next compression cycle. 

To improve the delivery, 13-mm-diameter rate-controlling membranes held in a Swinnex filter chamber (Millipore Corp.) were inserted in the delivery line between the insulin reservoir and the micropump. The effective membrane area was 0.7 cm2. Membranes investigated were l- xm and 8- xm pore size polycarbonate filters (Nucle-pore Corp.), 0.45- xm cellulosic microporous filters (Amicon Corp.), Cuprophane PT-150 (from Ultra-Flow 145 Dialyser, Travenol Laboratories), and 0.2- xm and 1.2- xm pore size cellulose acetate filters (Schleicher and Schuell OE 66 and ST 69). 

Care had to be taken to fill the micropump with liquid since the presence of air bubbles in any of the lines would reduce the delivery rate. The portion of the pump below the membrane was filled with insulin-free phosphate buffered saline containing 0.5% (w/v) m-cresol (a preservative) via a tube connected to the pump outlet. When this portion was full, the membrane was laid onto the membrane support portion of the chamber, and the upper half of the chamber was reconnected to the controlled-release micropump. The upper half of the chamber constituted the 1-cm3 upstream reservoir for these experiments and was filled with radioactive feed solution through a needle inserted horizontally into the side of the membrane chamber. The top of the chamber was connected to a plastic three-way valve using the appropriate Luer-lok connections to permit filling. The valve was turned to seal the chamber and eliminate the pressure difference before the experiment. One of the ports of the valve was used... 

Pressure-Difference Driving Force. The effect of a l- xm polycarbonate microporous filter on basal and augmented delivery in the controlled-release micropump due to a pressure difference is shown in Figure 3. As the pressure difference was lowered (i.e., as the liquid level dropped in the falling head permeameter) the basal flow rate was reduced to less than 0.2 mL/day (pressure difference, approximately 0.8 cm H20). At this basal rate, operation with a 100-U/mL reservoir becomes practical. More importantly, the degree of augmentation was increased to more than 10 X from the... 

The mechanism of action of the controlled-release micropump is unclear. With a pressure difference, the rapid oscillatory movement of the piston during augmented delivery may be responsible for the increased delivery rate by lowering the overall resistance of the micropump to bulk flow (35). When only a concentration difference exists, on the other hand, augmentation can be attributed to a pressure difference superimposed during piston movement on the basal concentration difference, or to a mixing effect associated with piston movement. The physical relationship between piston movement and augmentation remains to be defined. 

A number of concerns regarding open-loop delivery of insulin in general, and delivery of insulin by the controlled-release micropump, in particular, remain to be resolved. The optimum site of insulin delivery (intravenous... 

Liquid Chromatography System. The solvent delivery system was constructed of two lO-mL stainless-steel syringe pumps (MPLC Micropump, Brownlee Labs, Santa Clara, CA). By splitting the pump effluent between the mlcrocolumn and a restricting capillary (1 20-1 2000), Isocratlc separations were achieved reproduclbly at column flowrates as low as 0.005 pL/mln, and gradient separations as low as 0.1 pL/mln. Samples of 0.5 to 50 nL volume were Introduced by the split Injection technique with a 1- L valve Injector (Model ECI4W1., Valeo Instruments Co., Inc., Houston,... 

Microactuators, Fig. 4 In-plane micropump for drug delivery composed of diffuser, nozzle, pumping chamber, and electrothermal microactuator (Image courtesy of Texas Microfactory Lab, ARRI-UTA)... 

One of the earliest types of rotary micropumps developed for microfluidics applications, drug delivery in particular, is the jet-type magnetically driven fluid micropump. It is based on a rotary micromotor which is attached to a toothed rotor (Fig. 1). Basically, it is a micro version of conventional positive displacement pump. Flow rates up to 24 pL/min at a pressure of 10 kPa have been obtained using this design [4]. 

---