New MEMS devices offer the opportunity not just to lower drug dosages by enhancing delivery efficiency but also to improve the safety of drug delivery. Medication delivery errors have been reported to contribute to 7,000 deaths in the United States each year and to cost society between $76 billion and $136 billion annually. Errors include improper dosages or dosing rates, administration of the wrong medication and administration of medication by improper means.
In a recent case study, errors were observed in half of the intravenous (IV) drug doses, with one-third of those being potentially harmful. Administrator error during selection or compounding can result from mislabeling, misread labels (e.g., choosing a drug with a similar spelling or pronunciation to the prescribed drug or misinterpreting an unclear abbreviation), unusual concentration requests, decimal-place dose mistakes, patient-tracking errors, excessive handoffs, memory lapses, miscommunication and insufficient training.
While numerous changes and recommendations have been made to reduce the incidence of medication errors, the number of reported mistakes continues to grow. To alleviate the situation, a multi-function MEMS sensor could be used as a means of controlling drug flow. Such a sensor could link to a comprehensive computer system that would track patient history, prescriptions and physicians' orders. In doing so, it could accomplish many of suggested improvements in the medication delivery process.
The new microfluidic device uses a hollow silicon tube that is vacuum-packaged so that it can resonate over metal capacitor plates. Fluids enter and exit the silicon microtube through holes in the bottom of the chip, while the electrical signals are taken off with conventional bond pads. By tracking the frequency of the resonator, the density or specific gravity of the fluid in the tube can be determined. Chemicals and drugs can be identified and chemical concentrations of binary solutions can be measured using this mass-based approach.
By capacitively monitoring the twist of the microtube, the mass flow going through the tube can be measured using the Coriolis effect. The Coriolis force is named for Gustav-Gaspard Coriolis, who in 1835 first described how Newton's laws of motion applied within a rotating frame of reference. This concept is used to explain how the rotation of the earth or other spinning platforms affects projectiles and other forms of motion. It also applies to resonating tubes that pivot about a fixed point with an angular frequency, such as the Coriolis mass flow sensor tube. If the mass flow of the liquid or drug in such a tube changes, the vibrating tube twists as a result of the Coriolis force. This twisting motion is sensed capacitively by the microsensor. By measuring the true mass flow of a liquid with respect to time, the dose volume and dose rate can be monitored and occlusions detected.
The silicon microtube is formed by patterning, etching and bonding silicon and glass wafers. The channel dimensions of the microtubes can be varied by design from tens to hundreds of microns to accommodate a wide range of flow rates. The volume of fluid being tested in the sensors manufactured to date ranges from 40 to 600 nanoliters.
The electrically conductive silicon tubes are positioned over thin metal plates, which are patterned on etched glass. The tube is designed as a U-shaped cantilever so that it can move or resonate vertically. One of the metal plates positioned under the tube electrostatically causes the silicon tubes to resonate while another capacitively senses the frequency of motion. The bonded stack of wafers is sealed in a vacuum. The chip-level vacuum package is needed to reduce air dampening of tube motion, which is significant at the micron-scale separation used in the construction of this sensor.
One problem encountered early on in the development of the resonant microsensor was a low quality factor, or Q, when conventional MEMS vacuum packaging was employed. A quality factor above 1,000 was desired to obtain sufficient signal resolution with the sensor. Initial test data on R&D samples was collected using a vacuum chamber and indicated that a cavity pressure of less than 100 mTorr would be needed to obtain an acceptable sensor signal. Historically, anodic wafer bonding produces cavity pressures in the 100- to 400-Torr range, while glass frit and solder sealing produces cavity pressures of 1 to 2 Torr. For this microfluidic device, a cavity pressure of 1.4 Torr was obtained with glass frit sealing, and because of squeeze-film damping and molecular interaction, the Q value was limited to 40 for this wide vertical resonator.
To reach the microcavity pressure goal, a novel approach to MEMS gettering was developed and added to the wafer-bonding process. (A getter is a device or material that absorbs an undesired gas.) A capping wafer, generally either silicon or glass, is patterned and etched to form a cavity that encloses the active micromachine, while also providing open access to the electrical bond pads. At this point the getter, called a NanoGetter, is applied and patterned on the top portion of the cavity.
The NanoGetter consists of a proprietary, multilayer structure. As the name implies, the thickness of the film layers is in the nanometer range, specifically 5 to 500 nm. Since thin-film deposition techniques are employed in a clean-room environment, the new getter is virtually particle-free. The thin-film deposition method also enhances the ability to integrate the getter into most typical MEMS processes. By using the new getter, the vacuum-packaging goal of the team was achieved.
Meters using resonant glass tubes to measure specific gravity, along with stainless-steel Coriolis mass-flow sensors, have been available for more than 25 years; but prices from $2,000 to $15,000 per meter and sizes from 28,000 cc up to 20 kg have prevented them from finding applications outside of chemical labs or industrial settings.
Manufacturability and reliability issues with the microchip-based fluid devices have been addressed for the lower-volume industrial user environment; but for use in medication monitoring, particularly in disposable applications, both the system size and price must come down significantly. Fabricating MEMS sensors as conventional ICs are fabricated is one way to achieve both the size and cost reductions needed for high-volume applications.
Using the microfluidic sensor's density measurement output enables drugs to be distinguished from one another based on their density and specific gravity or their concentration in water or a saline solution. When the Coriolis mass-flow sensor output is employed along with a timer, the dose volume delivered can be monitored, as can the dose rate, or how fast the drug is being injected into the patient. Occlusions due to particles or kinked tubing can also be detected by monitoring the flow rate.
When coupled with an infusion pump in a feedback loop, the sensor can control drug delivery. Current infusion pumps do not measure flow rate; they simply monitor revolutions in the syringe or peristaltic pump motor. Using a MEMS-based flow sensor will reduce the minimum flow rate or dose that can be accurately infused into a patient and thereby offer physicians a new means of ensuring safe drug delivery.
Doug Sparks (email@example.com) is the executive vice president of Integrated Sensing Systems Inc. (Ypsilanti, Mich.).