Many current chemical and biochemical analyses, for example, analyzing the chemical constitution of a substance, monitoring the progress of chemical and biochemical reactions, and determining the presence of trace components of biological fluids, require the sampling of solutions. Often, such analyses require the use of minute volumes of samples and reagents. Current techniques dispense such volumes as micro-droplets, often placing many such micro-droplets in close proximity to each other in an array on the surface of, or inside of, a substrate or well, such as a slide, micro-card, chip, or membrane. High-density arrays (or micro-arrays) enable many reactions to occur in parallel fashion.
Handling and dispensing fluid in femto-liter (10−15) volumes, however, requires appropriately sized structures and control systems. Also, these structures and control systems should be electronically controllable because of the precision needed to properly handle such small fluid volumes.
One type of device developed for dispensing small quantities of fluid is referred to as an electro-spray device. In general, electro-spray devices use electrostatics to draw fluid from a capillary opening of the electro-spray device to an extracting electrode positioned nearby. The extracting electrode is typically an instrument or an electrode at the entry to an instrument (e.g., a mass spectrometer), separate from the electro-spray device, that samples the fluid drawn from the capillary. The instrument is placed within a few millimeters of the electro-spray device and electrically charged so as to function as the collector of the fluid and as the source of the electrical potential that produces a high electric field and induces the fluid to leave the electro-spray device.
More specifically, an electrical potential difference is applied between the extracting electrode and a conductive or partly conductive fluid in the capillary of the electro-spray device. The electrical potential difference generates an electric field that is concentrated at the end of the capillary. Electric field lines emanate from the end of the capillary and extend toward the extracting electrode. A volume of the fluid in the capillary is pulled from the end of the capillary into the shape of a cone, known as a Taylor cone. Droplets form at the tip of the Taylor cone and are drawn to the extracting electrode.
The magnitude of the electrical potential difference required to induce electro-spray depends upon the surface tension of the fluid in the capillary, a diameter of the capillary, and the distance of the capillary from the extracting electrode. Typically, the needed electric field is on the order of approximately 106 V/m.
A disadvantage common to many implementations of electro-spray devices is the high voltages needed to produce the electric field that achieves electro-spray. For some electro-spray devices, these voltages range from 500 volts to several kilovolts. Such high voltages can cause arcing between the capillary and the extracting electrode, causing the ongoing analysis to fail and posing a risk of damage to the electro-spray device and the sampling instrument. Moreover, some electro-spray devices have multiple capillaries for producing electro-spray, but the high voltages prevent independent operation of individual capillaries because the electric field generated at one capillary interferes with its neighboring capillaries. The high voltages also set a lower limit for the volume of fluid that can flow. Current fluid transfer capabilities are in the nano-liter to pico-liter range, but cannot achieve volumes in the femto-liter range.
Thus, there remains a need for a system and method for handling and dispensing minute volumes of fluid in the femto-liter range that can operate at voltages lower than the current electro-spray devices described above.
USPTO Backgrounds
USPTO Backgrounds