Recently, many researches on the "Lab on a Chip", the system which apply MEMS techniques and micro fabrication to medical and chemical field, were reported. In this system, chemical reaction/detection devices were minimized and integrated on one chip. However, since in conventional methods, a continuous flow in microchannels fabricated on a chip was used, dead volume of samples and reagents were not negligible. Further, a development and an integration of micropumps and microvalves were difficult problems.
On the other hand, since in a new method developed in this research, only a minimum volume of chemical solutions to react was put into micro droplets, this method has advantages in sample/reagent volume, reaction time, and cost. And, since these micro droplets were manipulated in chemically stable liquid, some problems, such as evaporation and contaminations, which were not negligible in case in the open air, can be avoided. Further, since micro droplets were manipulated independently, and two dimensionally by electrostatic force on the devices, on which electrodes were patterned, micro fluidic devices, such as micropumps, and microvalves, were not necessary and a structure of the device can be simple. Since using this method many chemical reactions can be caused on one chip simultaneously, the "Lab on a chip" device for combinatorial chemistry can be achieved.
Fig. 1 "Lab on a Chip" device for combinatorial chemistry
In this report, the principle of electrostatic manipulation, manipulation of micro droplets using the electrode devices, and chemical reactions caused by mixing of droplets were mentioned.
|(a) The principle||(b) The sequential voltages|
|Fig. 2 The principle of electrostatic manipulation|
The electrode of three or six-phase arrays device has a width of 0.2mm and pitches of 0.5mm, 0.75mm, 1.0mm, 2.0mm, and the electrode of nine-phase dots device has a width of 0.6mm and an average pitch of 1.0mm. Using the electrode dots device, micro droplets on the device can be manipulated independently, and two-dimensionally.
|Three-phase arrays device||Six-phase arrays device|
|Fig. 3 The electrode arrays device|
|Nine-phase dots device||Electrode dots|
|Fig. 4 The electrode dots device|
|A movie of electrostatic manipulation of droplets was shown in Fig.5. Droplets were water colored by ink, 1µl in volume, and surrounded by edible oil. The electrodes have a width of 1.0mm and an average pitch of 0.6mm. In this experiment, the sequential voltages: + + + - - -, 400V0-p, 1Hz (1 cycle) was used. Shown in a movie, applying the voltages only to a column, on which a left droplet had stayed, only a left droplet could be manipulated (a right droplet stayed where it was). Using the electrode dots device, each droplet can be manipulated independently.|
Alkalization of phenolphthalein was achieved on the nine-phase dot device (Fig.6). In figure, a right droplet was NaOH solution, and a lower droplet was phenolphthalein solution. Applying the sequential voltages to a center column and a center line, two droplets approached cross point, and mixed, and a mixed droplet changed into red color.
Luciferin-luciferase enzyme reaction was achieved on the six-phase array device (Fig.7). In figure, a left droplet was luciferase solution, and a right droplet was luciferin, ATP solution. Applying the sequential voltages to the electrodes, a luciferase droplet was transported rightward, and approached a luciferin, ATP droplet, and mixed. Mixing of droplets caused enzyme reaction, and luciferin luminesced.
|(a) right: NaOH, lower: phenolphthalein||(b) Mixing caused a reaction|
|Fig. 6 Alkalization of phenolphthalein|
|(a) left: luciferase, right: luciferin, ATP||(b) Mixing caused a reaction|
|Fig. 7 Luciferin-luciferase enzyme reaction|