Volume Verified Pipetting (VVP) represents the very latest in air-based, independent volume liquid handling technology. Highly sensitive micro-sensors measure the pressure differential through a fluidic line, accurately detecting even single nanoliter volumes. By monitoring and adjusting to the flow in real-time, all pipetting processes can be controlled and finely tuned for any liquid.
Flow sensor technology is based on the measurement of the pressure difference across an integrated fluidic restriction. A silicon chip consisting of two piezo-resistive pressure sensors, connected by a micro-channel, forms the actual flow sensor device. The signals available are inlet and outlet pressure and fluid temperature.
In order to address different flow ranges, a family of sensor devices with different restriction geometry has been developed. The three basic output signals, together with the calibration factor for the restriction and the temperature corrected viscosity of the liquid, are used to calculate the volumetric flow.
Flow Sensor Design
VVP uses has a flow sensor based on a differential pressure measurement across a flow restriction. The sensor’s low dead volume, high speed, resolution, and accuracy allow it to control submicroliter to nanoliter liquid quantities. Integrated by means of hybrid assembly techniques, this sensor is well suited to the need for extreme miniaturization of the dosing functions in high-density, multichannel instruments.
The differential pressure caused by viscous liquid flowing across the micromachined channel is expressed at low Reynolds numbers by:
Figure 1. The flow sensor is constructed of bonded silicon and glass wafers with throughholes for fluidic connection.
p = pressure drop (Pa)
Qv = volumetric flow rate (m3/s)
C = dimensionless friction factor
µ = (temperature-dependent) fluid dynamic viscosity (Pa)
L = channel length (m)
A = channel cross section (m2)
Hydraulic Diameter [m]
As shown in the equation above, the the volumetric flow rate is a linear function of the pressure difference between each end of the channel. It depends only of the restriction geometry and of the fluid dynamic viscosity.
The full-scale flow sensitivity of the sensor can be modified by altering the geometry of the channel, (length and cross section).
The VVP Flow Sensor
The flow sensor is modeled on a modified commercial low-pressure device [2, 3]. As a final step in processing the sensor wafers, a flow restrictor is etched between two adjacent pressure sensors on the backside. The silicon wafer is subsequently bonded onto a glass wafer with throughholes for the fluidic connections (see Figure 1). The size of the chip is 3 by 10.0 by 0.8 mm3.
The sensor is then diced from the wafer and mounted stress-free onto a ceramic substrate using silicone sealant joints. Again, it has throughholes for the fluidic interconnections. Electrical contacts are made to a metallization pattern that is screen printed on the ceramic substrate. The sensor assembly is thus fully compatible with hybrid assembly techniques, ensuring high reliability and a large-volume capability. In addition, the liquid is completely isolated from the electrical side of the sensor—a key feature for microfluidic components.
The pressure sensor’s piezoresistors are connected as a Wheatstone bridge and connected to programmable integrated circuits  onto the ceramic substrate. Both inlet and outlet pressure signals are provided; Amplified output is programmable at calibration from 200 mbar to 1.5 bar full scale. The flow rate is calculated by subtracting the outlet from the inlet pressure. Depending on the design parameters selected for the fluidic restrictor, full-scale flow rates from 5 to 60 µL/s (water) can be achieved. The flow sensor chip is assembled in the form of a hybrid module with intelligent electronics integrated on the ceramic substrate, providing amplified 0– 5 V pressure signals. The module dimensions are 7.5 by 35 by 2.5 mm3.
As noted earlier, the flow rate output is a function of the pressure difference across the micromachined channel and the liquid viscosity. For the sensor to operate properly, it therefore must compensate for temperature effects on the piezoresistive pressure sensors and on the viscosity of the fluid passing through the sensor. This compensation ensures an accurate liquid flow measurement over the instrument temperature range (20°C–50°C). As these two temperature effects are independent, they are dealt with at different levels. The pressure sensor parameters are handled locally on the ceramic substrate, and the viscosity effect, on the system level.
The piezoresistive pressure sensor sensitivity and offset variation over temperature are well known and can easily be compensated to below 1% of the full-scale pressure output. Using commercially available ASICs, the compensation scheme is programmed-in during calibration and provides an amplified 0–5 V standard output signal. The ASICs are mounted onto the ceramic substrate along with the silicon sensor. Because the pressure-temperature calibration is performed on fully assembled modules with direct programming of the compensation coefficients, no subsequent manufacturing step, such as resistor trimming, is required. The overall temperature residual error of the pressure sensor stays below 1% full scale over the whole temperature range (see Figure 2).
Figure 2. The output of the sensor is linear with the flow rate of water, independent of the temperature.
Figure 3. The sensor measures a flow pulse resulting from a 25 ms opening of the valve.
To compensate for viscosity, the flow output must be corrected using an accurate measurement of the actual liquid temperature in the sensor. A temperature probe is integrated in the sensor chip. Consequently, the fluid temperature signal is used externally, at the system level, to correct the flow output so that it takes viscosity into account. Data on fluid viscosity over temperature for most liquids can be found in . If values are not available for a particular solvent or mixture, a specific calibration is performed. Figure 3 shows the result of the flow rate measurement over temperature, before and after the compensation is applied. The external viscosity correction allows the sensor to accurately measure the flow rate with an overall accuracy better than 2% of the full-scale flow. Figure 4 shows the output of the sensor vs. water flow rate. Through careful correction of the temperature effects on the liquid flow sensor, accurate measurement of very small flow rate is achieved.
Figure 6. The integrated flow signal shows a dispensed volume of 90 nl. The sensor’s fast response permits direct feedback control of the valve opening in real time.
Drug discovery and medical diagnostics equipment are fueling the major drive toward miniaturization of liquid handling systems, and the Seyonic flow sensor is a key element in controlling minute liquid quantity. The hybrid assembly techniques allow the integration of the sensors and intelligent signal conditioning very close to the point of use, thus increasing speed by reducing dead volume and allowing for a high density of measurement points.
References M.A. Boillat et al. 1995. “A Differential Pressure Liquid Flow Sensor for Flow Regulation and Dosing Systems,” Proc IEEE Micro Electro Mechanical Sys tems:350-352. M.A. Boillat et al. 1999. “High Precision Piezo-Resistive Sensing Techniques for Micro-Dosing Applications”, Proc. Sensor Expo, Cleveland, Ohio Sept.14-16, 1999 pp. 249-251. B. Konrad, P. Arquint, B. van der Schoot, 2001. “Miniature Flow sensor Has Electronic Temperature Compensation” www.Maxim-ic.com, Application Note AN884 t; CRC Handbook of Chemistry and Physics, 61th edition, p. F51