An integrated drug-delivery probe with in-line flow measurement.
Li, Yang
2007
Abstract
This research has developed an integrated drug-delivery probe containing an inline thermal flowmeter. Research efforts have focused on improving the probe yield and flowmeter sensitivity. Microchannels for drug delivery are formed in the body of the probe by undercutting a selectively-etched boron-doped silicon and/or dielectric masking structure and then sealing the mask openings using deposited dielectrics. Methods to improve the etching process used for undercutting the channels have been investigated. Channel formation has been explored as a function of etch type, mask opening size, grid width, and screen geometry. Using a screen trench masking structure, together with reducing the previously-used 4mum-wide ribs to 2mum and increasing the trench openings from 1.4mum to 2mum, has improved channel yield to above 90%. <italic> In vivo</italic> testing has demonstrated their effectiveness and robustness in use. Ways to improve the flowmeter sensitivity have been investigated based on thermal modeling, and integrated anemometers with a variety of new features have been designed and fabricated. For polysilicon strip heaters 20mum long, 2mum wide, and 1mum thick having a resistance of 37kO and a temperature coefficient of resistance (TCR) of -5000ppm, the flowmeter produces an output of 40muV/mm/sec over a range of several nL/sec when operating at an input power of 0.18mW with a channel cross-sectional area of 318mum<super>2</super>. A resolution of 1.3nL/sec is achieved, corresponding to a flow velocity of 4.2mm/sec. To further improve flowmeter performance, a process for making buried channels based on a trench refill and CMP process is proposed. Based on this process, a drug-delivery probe with a 50mum<super>2</super> cross-sectional area and partial- or all-dielectric channel sidewalls, and an integrated flowmeter was fabricated. <italic>In vivo</italic> testing showed the probe has excellent drug-delivery and neural-recording functions and is appropriate for acute or chronic applications. For a 10mum long, 2mum wide, 1mum thick polysilicon strip heater with a resistance of 16kO and a TCR of -5000ppm, the flowmeter detects 280pL/sec at 0.1mW and 160pL/sec at 0.2mW. In all of these cases, the heater temperature is limited such that the temperature rise in tissue at a distance of 25mum from the probe is less than 2°C, even ignoring capillary cooling. This avoids any possibility of tissue damage due to local heating. For situations where the flowmeter is situated on the back of the probe above the brain cortex and higher local heating can be tolerated for the short times that the flowmeter is active, flow sensitivity can be improved below 100pL/sec while still limiting the temperature rise in tissue to less than 2°C a distance of 200mum below the flowmeter.Subjects
Drug Delivery Flow In-line Integrated Measurement Microchannel Probe
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