On chip dilution system
View Patent ↗An on-chip chemical compound dilution system for providing dilution of a chemical compound in a microfluidic application includes at least one sample well for providing a selected chemical compound to be diluted, a dilution well for providing a diluent for diluting the chemical compound, a network of channels for carrying the chemical compound and diluent, a first syringe pump for effecting dilution, a second syringe pump, a detector and a plurality of valves for selectively controlling the flow of liquid through the channels. The dilution system may be a multiple-stage dilution system for precisely mixing a plurality of chemical compounds in a diluent. The dilution system allows for accurate calibration to compensate for variations due to manufacturing, thereby providing precise dilution ratios. The dilution system further enables flushing to allow re-use of the system with another chemical compound.
1. A method for diluting a sample, comprising:
providing a dilution system having:
a sample well for holding chemical standard;
a dilution well for providing a diluent;
a dilution channel for transmitting the diluent;
a sample channel for transmitting the chemical standard to the dilution channel to form a diluted chemical standard;
a high precision variable flow valve for varying the flow of diluent through the dilution channel, wherein the variable flow valve has a plurality of settings corresponding to different dilution ratios; and
a detector capable measuring the ratio of standard chemicals to diluent when chemical standards are introduced into the system through the sample well;
setting the variable flow valve to a first setting corresponding to a first dilution ratio;
introducing the chemical standard into the sample well to cause dilution of the chemical standard at the first dilution ratio; and
measuring a ratio of the chemical to diluent using the detector.
2. The method of claim 1 , wherein the variable flow valve comprises:
an aperture formed in a side wall of the dilution channel;
a membrane covering the aperture; and
an external actuator for deflecting the membrane through the aperture a predetermined amount to vary the resistance of the channel to flow.
3. The method of claim 2 , wherein the external actuator comprises a base and a cylindrical head for contacting the membrane.
4. The method of claim 1 , further comprising the step of introducing a second chemical to the system, wherein the second chemical mixes with the first diluted chemical.
5. The method of claim 1 , further comprising the step of creating an aliquot region for mixing the diluent and chemical.
6. The method of claim 5 , wherein the aliquot region is formed by a plurality of on-off valves.
7. The method of claim 1 , further comprising the steps of:
setting the variable flow valve to a second setting corresponding to a second dilution ratio; and
introducing a chemical into the system to cause dilution of the chemical at the second dilution ratio.
8. A method of calibrating an on-chip dilution system, comprising:
providing a dilution system comprising a sample well for providing a chemical compound, a dilution well for providing a diluent, a dilution channel for transmitting the diluent, a sample channel for transmitting the chemical compound to the dilution channel to form a diluted chemical compound, a variable flow valve for controlling the flow of diluent through the dilution channel and a detector for analyzing the diluted chemical compound; and
calibrating the variable flow valve to correlate a setting on the variable flow valve to a dilution ratio for the system.
9. The method of claim 8 , wherein the step of calibrating comprises the steps of:
providing a known chemical standard in the sample well;
providing a diluent in the dilution well;
setting the variable flow valve to a first setting;
diluting the known chemical standard with diluent to form a diluted chemical standard having a first dilution ratio;
detecting the diluted chemical standard to determine the first dilution ratio; and
correlating the first setting to the first dilution ratio.
10. The method of claim 9 , wherein the step of calibrating further comprises:
setting the variable flow valve to a second setting;
diluting the known chemical standard with diluent to form a diluted chemical standard having a second dilution ratio;
detecting the diluted chemical standard to determine the second dilution ratio; and
correlating the second setting to the second dilution ratio.
11. The method of claim 10 further comprising the step of generating a calibration curve graphing a relationship between a plurality of settings of the variable flow valve and the dilution ratio for the system.
12. The method of claim 8 , wherein the variable flow valve comprises an aperture formed in a side wall of the dilution channel, a membrane covering the aperture and an external actuator for deflecting the membrane through the aperture a predetermined amount to vary the resistance of the dilution channel to flow.
13. The method of claim 12 , wherein the step of calibrating comprises determining a relationship between the dilution ratio of the system and an amount of deflection of the membrane in the variable flow valve.