Patent Application
20130345096
The present invention relates to a microfluidic chip automatic system, and more particularly to a microfluidic chip automatic system with an optical platform.
A biochip is a miniaturized device that allows specific biochemical reactions between specified biological materials (e.g. nucleic acid or protein) and other under-test biological samples by employing a microelectromechanical (MEMS) technology. After the reaction signals are quantified by various sensors, the possible biochemical reactions can be realized. In other words, the miniaturized device fabricated by a microelectromechanical technology and a biological technology is referred as the biochip. For example, the biochip is a microfluidic chip or a lab-on-a-chip. The applications of the biochip cover the disease diagnosis, the gene probe, the pharmaceutical technology, the microelectronic technology, the semiconductor technology, the computer technology, and the like.
Recently, due to the rapid development of biomedicine and the rising awareness of personal health, the demands on fast symptom detection and correct diagnosis are gradually increased. The medical organizations or research organizations pay much attention on seeking the platform for automatically and quickly acquire large numbers of detection data. With the development and maturity of the microelectromechanical technology, the microfluidic chip becomes a rapidly developing research field. By means of the microelectromechanical technology, a series of steps of carrying out the complicated biological reaction (e.g. sampling, sample handling, sample separation, reagent reaction and detection) can be integrated into a small microfluidic chip. In other words, the microfluidic chip has many benefits such as low cost, rapid detection and low reagent and sample consumption. Therefore, there is a need of providing a microfluidic chip automatic system.
Regardless of the synthesis stages or the detection stages of the biochips, the photochemical reaction plays an important role. In other words, the integration of an optical path system of the photochemical reaction into the microfluidic chip automatic system is an important subject of the present invention.
The present invention provides a microfluidic chip automatic system with an optical platform in order for automatically detecting biological molecule, accelerating the detecting process and detecting a large number of different samples.
The present invention also provides a microfluidic chip automatic system with an optical platform. The microfluidic chip automatic system is used for performing an optical imaging operation according to a predetermined pattern of a digital micromirror device of the optical platform. By guiding a light beam to a microfluidic chip on a sample platform, the position of carrying out the photochemical reaction on the sample platform can be effectively controlled.
In accordance with an aspect of the present invention, there is provided a microfluidic chip automatic system. The microfluidic chip automatic system includes a microfluidic chip platform and an optical platform. The microfluidic chip platform includes a microfluidic chip, a fluid source, a gas source, and a controller. The microfluidic chip includes a base layer, a fluid layer and a gas regulating layer. The base layer includes a microarray reaction zone. The fluid layer is disposed over the base layer, and includes plural flow channels for introducing and collecting a reagent. The gas regulating layer is disposed over the fluid layer for controlling open/close states of the flow channels, thereby controlling a flowing condition of a fluid in the fluid layer. The fluid source includes the reagent, which is introduced into the fluid layer of the microfluidic chip. The gas source provides a high pressure gas to the gas regulating layer of the microfluidic chip. The controller is connected with the gas source, and includes plural solenoid valves. A time sequence of charging the high pressure gas from the gas source into the microfluidic chip and discharging the high pressure gas from the microfluidic chip is controlled by the controller through the plural solenoid valves. The optical platform includes a light source, plural lenses, a digital micromirror device, a grating device and a reflective mirror. A light beam provided by the light source is guided to the microfluidic chip of the microfluidic chip platform. The digital micromirror device includes plural micromirrors. The optical switching states of the micromirrors are controlled by a computer, so that a position of the microfluidic chip to carry out a photochemical reaction is correspondingly controlled.
The above contents of the present invention will become more readily apparent to those ordinarily skilled in the art after reviewing the following detailed description and accompanying drawings, in which:
The present invention will now be described more specifically with reference to the following embodiments. It is to be noted that the following descriptions of preferred embodiments of this invention are presented herein for purpose of illustration and description only. It is not intended to be exhaustive or to be limited to the precise form disclosed.
The fluid layer 3 is made of polydimethyl siloxane (PDMS). The fluid layer 3 has a first surface 31 facing the base layer 2 and a second surface 32 facing the gas regulating layer 4. Moreover, the fluid layer 3 comprises plural solution inlets 33, plural micro channels 34, a buffer region 39, a diffluent region 35, a reactive region 36, and a solution outlet 37. The plural solution inlets 33 are formed in the second surface 32 of the fluid layer 3. The samples, reagents and washing solutions may be introduced into the fluid layer 3 through different solution inlets 33. The plural micro channels 34 are concavely formed in the first surface 31 of the fluid layer 3. In addition, the plural micro channels 34 are in communication with and arranged between the plural solution inlets 33 and the buffer region 39. The buffer region 39, the diffluent region 35 and the reactive region 36 are also concavely formed in the first surface 31 of the fluid layer 3. In addition, the buffer region 39 and the diffluent region 35 are in communication with each other. In order to mix the samples with the reagents, the mixed fluid is collected and mixed in the diffluent region 35. The reactive region 36 is in communication with the diffluent region 35, and aligned with the microarray reaction zone 20 of the base layer 2. The specific reaction between the under-test molecule of the sample and a probe molecule (not shown) occurs at the microarray reaction zone 20, so that the under-test molecule can be detected. Furthermore, the solution outlet 37 is formed in the second surface 32 of the fluid layer 3. The waste solution produced by the specific reaction is exhausted out from the solution outlet 37.
Moreover, each of the plural micro valves 45 is aligned with a corresponding micro channel 34. Each of the plural micro valves 45 comprises a valve pore 451 and a valve chamber 452. The valve pore 451 is formed in the second surface 42 of the gas regulating layer 4. The valve chamber 452 is concavely formed in the first surface 41 of the gas regulating layer 4 and disposed over the corresponding circular membranes 34a of the micro channel 34. The valve pore 451 is connected with a silicone tube and a solenoid valve (not shown). Consequently, a gas may be introduced into the valve chamber 452 through the silicone tube and the valve pore 451. The gas may force the fluid layer 3 underlying the valve chamber 452 to be moved downwardly, so that the circular membranes 34a of the micro channel 34 is compressed to block the fluid within the micro channel 34. In other words, the micro valve 45 is opened or closed by selectively charging the gas into the valve chamber 452 or discharging the gas from the valve chamber 452. On the other hand, once the gas is discharged, the compressed fluid layer 3 is moved upwardly and returned to the original position. Consequently, a negative pressure is generated to facilitate the fluid to flow within the micro channel 34.
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Moreover, the fluid layer 3 further comprises a liquid collecting channel 38. The liquid collecting channel 38 is concavely formed in the first surface 31 of the fluid layer 3. Moreover, the liquid collecting channel 38 is in communication with and arranged between the reactive region 36 and the solution outlet 37. Moreover, the gas regulating layer 4 further comprises a liquid collecting valve 47. The liquid collecting valve 47 is aligned with the collecting channel 38. The liquid collecting valve 47 comprises a valve pore 471 and a valve chamber 472. The valve pore 471 is formed in the second surface 42 of the gas regulating layer 4. The valve chamber 472 is concavely formed in the first surface 41 of the gas regulating layer 4, and disposed over the liquid collecting channel 38. The valve pore 471 is connected with a silicone tube and a solenoid valve (not shown). Consequently, a gas may be introduced into the valve chamber 472 through the silicone tube and the valve pore 471. The gas may force the fluid layer 3 underlying the valve chamber 472 to be moved downwardly, so that the liquid collecting channel 38 is blocked. On the other hand, once the gas is discharged, the compressed fluid layer 3 is moved upwardly and returned to the original position. Meanwhile, a negative pressure is generated to facilitate the fluid to flow to the solution outlet 37 through the liquid collecting channel 38, and thus waste solution produced by the specific reaction is exhausted out from the solution outlet 37. In other words, the liquid collecting valve 47 is opened or closed by selectively charging the gas into the valve chamber 472 or discharging the gas from the valve chamber 472.
In an embodiment, the thickness of the fluid layer 3 is about 42 μm, the depth of the micro channel 34 is about 10 μm˜18 μm, the thickness of the gas regulating layer 4 is about 4 mm, and the depths of the valve chambers 452, 472 and the pump chambers 462 are about 100 μm. The above dimensions are not restricted. It is noted that the numbers and arrangements of the solution inlets 33, the micro channels 34, the second slot 44 and the micropump group 46 may be varied according to the practical requirements.
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In an embodiment, the solenoid valve 72 is a 3 port solenoid valve. The on/off states of the solenoid valves 72 are controlled by a solenoid valve control program (e.g. Lab View software). By the solenoid valve 72, an electronic potential energy which is digitally inputted into or outputted from a timing interface card may be converted into different gas pressure levels (e.g. 0˜0.15 MPa).
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The light source 91 is used for providing a light beam. An example of the light source 91 includes but is not limited to a high pressure mercury lamp. In case that the light source 91 is a high pressure mercury lamp, the light beam is a UV light beam. The first lens group 92 is arranged between the light source 91 and the digital micromirror device 93 for guiding the light beam from the light source to the digital micromirror device 93. Moreover, the first lens group 92 comprises at least two lenses. In this embodiment, the first lens group 92 comprises three lenses 921, 922 and 923. After the curvatures of these lenses are precisely calculated according to the imaging requirements, the efficacy of guiding the light beam is enhanced. In an embodiment, the three lenses 921, 922 and 923 are all plano-convex lenses. Alternatively, in some other embodiments, the three lenses 921, 922 and 923 are all biconvex lenses. Alternatively, in some other embodiments, the three lenses 921, 922 and 923 may be selected from the combination of biconvex lenses and plano-convex lenses.
The digital micromirror device 93 comprises plural micromirrors 931 (see
The grating device 94 comprises an adjustable grating window 941 for allowing a portion of the patterned light beam to go through. Since the size of the grating window 941 is adjustable, the light amount to be introduced into the grating window 941 can be controlled in order to increase the light contrast and the resolution of the image. Of course, the size of the grating window 941 may be adjusted according to the practical requirements.
After the patterned light beam is transmitted through the grating window 941 of the grating device 94, the patterned light beam is directed to the second lens 95. By the second lens 95, the patterned light beam is guided to the reflective mirror 96. The reflective mirror 96 is used for changing the path of the patterned light beam, so that the patterned light beam is directed in a direction toward the sample platform 18. Then, the patterned light beam is directed to the sample platform 18 through the third lens 97. In an embodiment, the third lens 97 is a focusing lens.
By integrating the microfluidic chip platform A with the optical platform B, the microfluidic chip automatic system of the present invention may be applied to the fabrication of a biochip. For example, for defining a microarray structure in the biochip, it is necessary to form a photoresist pattern layer on a substrate of a chip. Firstly, a photoresist layer (e.g. an epoxy-based photoresist material layer such as a SU-8 photoresist layer) is formed on a surface of the substrate. Then, by using the optical platform B to irradiate a specified position of the photoresist layer, the photoresist layer is subjected to polymerization. After a developing solution is used to remove the unpolymerized photoresist layer, the photoresist pattern layer is fabricated. Then, biological materials (e.g. nucleic acid or protein) are bonded onto the photoresist pattern layer, so that the biochip is fabricated. Since the photoresist pattern layer is formed by the maskless lithography optical platform of the present invention, it is not necessary to use the conventional costly photomask. Moreover, since the photoresist pattern layer is produced by a maskless lithography process, each spot of the microarray structure has a diameter smaller than 300 μm and the fabricating process is simplified.
Moreover, the microfluidic chip automatic system of the present invention may be applied to the synthesis of DNA. After a DNA is irradiated to generate broken bonds and the protective groups at the 5′-end of the nucleotide are removed, the nucleotide molecules (e.g. A, T, C, G) to be linked are subjected to a synthesizing reaction. After the unreacted nucleotide molecules are washed off, the steps of irradiating, adding nucleotide molecules and washing are repeatedly done. Consequently, the DNA with a desired sequence is synthesized. By using the microfluidic chip platform A to control each reaction step and using the optical platform B to control the irradiating position, the linking position of the nucleotide molecules on the chip in each synthesizing step can be determined. Consequently, plural DNA molecules with different sequences may be synthesized on the chip in the same fabricating process. In such way, a DNA chip for screening disease or detecting biologic molecules is prepared.
From the above descriptions, the present invention provides a microfluidic chip automatic system. The microfluidic chip automatic system comprises a microfluidic chip platform and an optical platform. A solenoid valve control program is installed in a computer for controlling on/off states of plural solenoid valves, thereby further controlling the flowing condition of the fluid in a microfluidic chip. In other words, the microfluidic chip automatic system of the present invention is capable of automatically detecting biological molecules and precisely carrying out the photochemical reaction. Since a series of steps of carrying out the complicated biological reaction are integrated into a small-area microfluidic chip, the behaviors of liquid on the micro scale may facilitate control of molecular diffusion and interaction. In other words, the microfluidic chip has many benefits such as low cost, rapid detection and low reagent and sample consumption. Moreover, the microfluidic chip automatic system of the present invention is capable of accelerating the detecting process and detecting a large number of different samples. In other words, the microfluidic chip automatic system of the present invention is effective for fast symptom detection and correct diagnosis. Moreover, since the optical platform is integrated into the microfluidic chip automatic system, the microfluidic chip automatic system can be used to control the photochemical reaction so as to be applied to the fabrication of a biochip. For example, the microfluidic chip automatic system of the present invention may be used to form a photoresist pattern layer on a substrate of a chip or synthesize DNA. In other words, the microfluidic chip automatic system of the present invention has industrial applicability.
While the invention has been described in terms of what is presently considered to be the most practical and preferred embodiments, it is to be understood that the invention needs not be limited to the disclosed embodiment. On the contrary, it is intended to cover various modifications and similar arrangements included within the spirit and scope of the appended claims which are to be accorded with the broadest interpretation so as to encompass all such modifications and similar structures.
| Number | Date | Country | Kind |
|---|---|---|---|
| 101212200 | Jun 2012 | TW | national |
