Micro Fluidics

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Technologies and methods for Micro Dispensing and Fluidics or handling sub-microliter volumes of liquids are essential components of high throughput research. Numerous recent advances in MEMS and Nano-technology have enabled the successful miniaturization of many liquid handling elements (i.e. chips, arrays, etc.), which have triggered an even greater necessity to interface MICRO and MACRO worlds.

TechElan has developed a number of novel devices and techniques capable of handling sub-microliter (> 20 nl) volumes of liquids. This range of Micro Dispensing lies between the "ink jet" nano-technology and the syringe/pipette types of dispensation.

The challenge of micro-volume dispensation can be analyzed using the formula for capillary action.

h - Column height ; r - Radius of capillary;

t - Surface tension (dyn/cm); ρ - Liquid density (g/ml)

g - Gravity force 9.8 m/sec²

In this formula, h (the height of liquid column in the capillary) represents the force with which the liquid is resisting to be dispensed. Thus, in order to dispense a smaller droplet, one will have to reduce its ability to "stick" to the dispensing nozzle. The limited choices are:

	Increase the radius of the nozzle - which is very difficult due to the small dimension of the droplet
	Reduce the liquid density if possible
	Render the nozzle surface so it’s liquid repelling
	Supply sufficient kinetic energy to the droplet and assist gravity in overcoming "stickiness".

The last condition defines a general approach to developing successful micro-volume dispensers. As a rule, the well-controlled pressurization of liquid (by fluid, gas or mechanical impact) provides an adequate source of kinetic energy. A tight control over the pressure range is required to avoid low-pressure dispensation problems (i.e. droplet formation, side shooting) or over- pressurization problems (i.e. atomization, satellite formation). Certain "pressurization limits" are empirically established for different types of dispensers.

Various means of supplying kinetic energy to a small droplet (dispensing micro-volumes) are described in the Non-Contact Dispensation section of this web site.

Supplying kinetic energy to individual droplets makes the dispensation of sub-micro-liter volumes possible, but an equally important requirement is:

The continuous verification of individual dispensation and a closed loop feedback control.

Multiple reasons for dispensation malfunctions:

	Reagent variations (viscosity, particulates, contamination);
	Ambient conditions (temperature, pressure);
	Controlling variables (pressurization, timing, driving voltage);
	Dispenser malfunction (clogged nozzle, valve, liquid channel).

Manifestation of dispensation problems:

	Volume variations (from occlusion to leaking);
	Formation of satellites - atomization (cross contamination);
	Formation and fall of a droplet (up to 5 µl)

A "real time" feedback control system, which detects and compensates for the majority of possible malfunctions, is an absolute requirement for reliable sub-microliter dispensation.

A number of supporting high-speed video clips (high-speed modem may be required) will show the possible problems during dispensation of micro-volumes.

Video 1: Ideal dispensation stream

Video 2: Satellite formation

Video 3: Low kinetic energy

Video 4: Over-pressurization

Video 5: Droplet fragmentation

Such a real-time feedback control system is implemented in the design of the Universal Dispensing/Aspirating Device . It uses a high sensitivity measurement of the reaction momentum (mV) of the system caused by the individual dispensation (patent pending). This method employs commercially available (or custom made) force sensors, which have no contact with the working fluid.

Other alternative monitoring techniques use pressure drops in the liquid channel in the immediate vicinity of the dispensing valve. (US Patent 6,357,636) The disadvantage of this method is the necessity for immediate contact with the working liquid (reagent).

Another technique of monitoring the dispensation process is to measure the flow towards the dispensing valve (www.Seyonic.com, or patent application WO0233423). This method also requires the immediate contact with the reagent or an intermediate liquid. Measurement of flow does provide volume information, however it cannot distinguish between a single dispensation event and the accumulation of individual dispensations into a hanging droplet.

Finally, there is another mode of providing better dispensation accuracy. It is to assure the individual dispensation of a predetermined volume. One of such techniques, described in US Patent 5916524, is called "positive displacement", where a syringe pump is used to force out a predetermined volume of liquid.

TechElan has introduced a novel method for dispensing a large array (matrix) of liquid using small liquid volumes pre-allocated in separate wells and simultaneously forcing these volumes out of the dispenser.