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WO2014003535A1 - A microfluidic device - Google Patents

A microfluidic device Download PDF

Info

Publication number
WO2014003535A1
WO2014003535A1 PCT/MY2013/000107 MY2013000107W WO2014003535A1 WO 2014003535 A1 WO2014003535 A1 WO 2014003535A1 MY 2013000107 W MY2013000107 W MY 2013000107W WO 2014003535 A1 WO2014003535 A1 WO 2014003535A1
Authority
WO
WIPO (PCT)
Prior art keywords
substrate
working fluid
reservoir
flow
microchannel
Prior art date
Application number
PCT/MY2013/000107
Other languages
French (fr)
Inventor
Hing Wah Lee
Bien Chia Sheng Daniel
Ismahadi Syono MOHD
Original Assignee
Mimos Berhad
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mimos Berhad filed Critical Mimos Berhad
Publication of WO2014003535A1 publication Critical patent/WO2014003535A1/en

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0003—Constructional types of microvalves; Details of the cutting-off member
    • F16K99/0026—Valves using channel deformation
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0034—Operating means specially adapted for microvalves
    • F16K99/0055—Operating means specially adapted for microvalves actuated by fluids
    • F16K99/0059—Operating means specially adapted for microvalves actuated by fluids actuated by a pilot fluid
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0034—Operating means specially adapted for microvalves
    • F16K99/0063—Operating means specially adapted for microvalves using centrifugal forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0803—Disc shape
    • B01L2300/0806—Standardised forms, e.g. compact disc [CD] format
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0463—Hydrodynamic forces, venturi nozzles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K2099/0082—Microvalves adapted for a particular use
    • F16K2099/0084—Chemistry or biology, e.g. "lab-on-a-chip" technology

Definitions

  • This invention is related to a microfluidic device in the form of rotary compact disc, more particularly an apparatus having a structure that allow air from external environment to flow and generate pressure difference for actuate passive microvalve.
  • Microfluidic device is a powerful tool for handling biomolecules such as cells, DNA, RNA, proteins or neurons.
  • the microfluidic device have been applied in various molecular biology analysis such as Polymerase chain reaction (PCR), DNA analysis, nucleotide sequencing, protein separation, immunoassay and cellular analysis raging from disposable lob-on-chip to high through put microfluidic device.
  • PCR Polymerase chain reaction
  • microfluidic device to conduct analysis rely primarily on the development of microstructures or components such as microvalve or micropump. Therefore eventhough much attention has been paid for development of the microfluidic components, there are still limitations on issues such as actuation power in valve system and contamination of fluid sample as the fluid sample is been used as working fluid to actuate the valve system.
  • the invention suggested a microfluidic device with an elastic film in the microvalve which is actuated by pneumatic pressure to control the movement of the fluid samples.
  • the pneumatic pressure is supplied from the outer side of the microfluidic device and this will promote contamination of the fluid sample to happen while passing through the microfluidic structure.
  • Another disclose prior art suggest a microvalve with diaphragm and a valve seat.
  • the diaphragm is controlled by external actuated device which is a bladder device having fluid inside to control the diaphragm movement through direct means such as electrostatic or electromagnet and indirect means such as thermal actuation.
  • external actuated device which is a bladder device having fluid inside to control the diaphragm movement through direct means such as electrostatic or electromagnet and indirect means such as thermal actuation.
  • this invention applies different approaches in actuating the passive microvalve as compared to the present invention which utilize pressure difference generated from the airflow of external environment.
  • the purposed present invention is intended to overcome limitation on contamination of fluid sample and the power to actuate the microvalve against centrifugal force.
  • the present invention suggested a microfluidic device having a valve system different from fluid sample pathway and also a system where the fluid sample has the capability to flow against centrifugal force.
  • the first substrate has a main reservoir which contains the working fluid while the second substrate placed the secondary reservoir and also the diaphragm.
  • the microfluidic structure is located in the third substrate which consists of at least one sample reservoir for a sample fluid, micromixer, microchannel and microfilter.
  • the fourth substrate there are one microchannel With a constriction structure and at least two vent holes. Ail these substrates are bonded together through but not limited to adhesive, anodic, thermal, fusion or pressure bonding.
  • this microfluidic device When this microfluidic device are rotated, it will allow air from external environment to flow into the vent hole and generate pressure difference inside the first substrate in order to cause the movement of Working fluid inside the first substrate and actuate the passive microvalve, used for regulating the fluid flow in this microfluidic system which is coupled to an electric motor or servo.
  • the microvalve has structure of a diaphragm which will deform and expand upon application of pressure from the working fluid caused by the pressure difference in the main reservoir and second reservoir during operation.
  • the pressure difference of the working fluid in the both reservoirs are generated based on the Bernoulli's principle wherein the exist pressure difference in the external air in contact with the working fluid due to the differences in the speed of the air, hence the corresponding air pressure, formed through constriction in the microchannel design.
  • Figure 1 shows the isometric view of basic configuration for microfluidic device.
  • Figure s shows the top view of basic configuration for microfluidic device.
  • Figure 3 shows the cross section view of basic configuration for microfluidic device.
  • Figure 4 shows the design of the diaphragm structure.
  • Figure 5 shows the microfluidic structure and sample reservoir on the third substrate of the invention.
  • Figure 6 (a) shows the top view vent holes and constriction of microchannel on the fourth substrate
  • Figure 6 (b) shows the isometric view vent holes and constriction of microchannel on the fourth substrate
  • FIG. 7 shows the flowchart for the working principle of the passive microvalve.
  • Figure 8 (a) shows the air enters the microchannel for regulating fluid flow in microfluidic platform.
  • Figure 8 (b) shows the air pushes working fluid from main reservoir to secondary reservoir.
  • FIG. 8 (c) shows the working fluid pushes diaphragm structure
  • Figure 8 (d) shows the diaphragm structure block the fluid flow.
  • Figure 9 shows the proposed invention as a microfluidic device.
  • FIG. 1 showed the basic configuration of the present invention.
  • the microfluidic device (10) in form of rotary compact disc is developed from four layer substrate which are attach together by using bonding technique such as but not limited to adhesive, anodic, thermal, fusion or pressure bonding.
  • the substrate is having a shape of, but not limited to circular, square or Hexagonal.
  • the materials that have been used for making the substrate is made of but not limited to material such as glass, polymer or silicon.
  • the isometric view of the microfluidic device has indicated that the microfluidic device (10) In form of rotary compact disc is developed by four layers substrate which each layer contains the specific structures for the microfluidic device to be function as miniaturised integrated diagnostic system.
  • the first substrate (20) contains at least main reservoir (22) and secondary reservoir (24) which is the place to -store working fluid (26) and also as flow passage for the working fluid (26).
  • the second substrate (30) indicated the location of the microvalve.
  • the microvalve used for the present invention is passive type of microvalve which is in the formed of diaphragm (32) structure and actuated by the working fluid (26) in the first substrate.
  • the third substrate (40) contain at least one reservoir (46) for fluid sample (44) and a microfluidic structure (42) as fluid sample pathway and the fourth substrate (50) indicated at least one microchannel (54) to work as an air flow passage to enter the microfluidic device and at least two vent holes (52) to allow air to enter the microchannel.
  • Figure 4 shows the design of the diaphragm structure which not limited to circular or square shape.
  • Figure 5 shows the microfluidic structure (42) such as microchannel (42A), micromixer (42B) or microfi!ter (42C) and at least one sample reservoir (44) for the sample fluid which is located at the third substrate.
  • the diaphragm to work as an ejector to the fluid sample (44) from the sample reservoir (46).
  • addition of pressure to the sample fluid (44) and reduction of the volume in the sample reservoir (46) causes the fluid sample (44) to be ejected and flow from the sample reservoir (46) towards the microfluidic structures (42).
  • Figure 6 (a) and 6 (b) shows the top and isometric view of the microchannel (54) on the fourth substrate (50).
  • the unique structure of the microchannel (54) of the fourth substrate (SO) is the element of having at least two vent holes (52) and the existent of constriction feature (56). The purposed of having both structure are to allow and accelerate air from external environment to flow and generate pressure difference inside the first substrate (20) in order to cause the movement of working fluid (26) in the first substrate (20).
  • microfluidic device substrate is rotated using a rotatable spindle or platen which is coupled by a motor or servo.
  • the rotation activity caused the generation of external environment air and then entered the microchannel (54) through the vent holes (52).
  • the external environment air then passes through the microchannel (54) to the constriction feature where air flow is accelerated which causes a pressure different in this case the pressure reduction of working fluid (26) inside the first substrate (20).
  • the working fluid (26) Due to the pressure different which is utilising the Bernoulli's principle to generate actuation energy, the working fluid (26) is pushed from the main reservoir (22) into secondary reservoir (24) if the pressures in both reservoirs are not balanced. If the pressure is balanced, the working fluid (26) is idle.
  • the working fluid (26) which is in a formed of liquid such as but not limited to water, paraffin oil or grease, then completely fill up the secondary reservoir (24) until having an ability to pressure the passive microvalve which is in diaphragm (32) structure. In this situation the pressure difference that generated from working fluid (26) is worked as an actuate means for the diaphragm (32) to expand.
  • the fluid sample (44) that will flowed inside the microfluidic structure (42) is in a liquid form such as but not limited to nucleotide DNA or RNA, protein or cell while the microfluidic structure (42) is in the form of microchannel, micromixer or microfilter.

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • Dispersion Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Mechanical Engineering (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Micromachines (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

An improve microfluidic device (10) is configured to improve in microyalve system, the microfluidic device is in the form of rotary compact disc, comprising four substrate which a first substrate (20) having at least main reservoir (22) and secondary reservoir (24) containing working fluid (26), a second substrate (30) with at least a microvalve in the formed of diaphragm (32) structure which is actuated by the working fluid (26), a third substrate (40) with at least one reservoir (46) for fluid sample (44) and a microfluidic structure (42) as fluid sample pathway and a fourth substrate (50) with at least one microchannel (54) as an air flow passage. The microfluidic device has improved the valve system by applying a microchannel (54) that has at least two vent holes (52) and constriction feature (56) to allow and accelerate air from external environment to flow and generate pressure difference in order to cause the movement of said working fluid (26) for the working fluid to move the passive microvalve.

Description

A MICROFLUIDIC DEVICE
TECHNICAL FIELD OF INVENTION
This invention is related to a microfluidic device in the form of rotary compact disc, more particularly an apparatus having a structure that allow air from external environment to flow and generate pressure difference for actuate passive microvalve.
BACKGROUND OF THE INVENTION
Microfluidic device is a powerful tool for handling biomolecules such as cells, DNA, RNA, proteins or neurons. The microfluidic device have been applied in various molecular biology analysis such as Polymerase chain reaction (PCR), DNA analysis, nucleotide sequencing, protein separation, immunoassay and cellular analysis raging from disposable lob-on-chip to high through put microfluidic device.
The success of the microfluidic device to conduct analysis rely primarily on the development of microstructures or components such as microvalve or micropump. Therefore eventhough much attention has been paid for development of the microfluidic components, there are still limitations on issues such as actuation power in valve system and contamination of fluid sample as the fluid sample is been used as working fluid to actuate the valve system.
In one of the prior art, the invention suggested a microfluidic device with an elastic film in the microvalve which is actuated by pneumatic pressure to control the movement of the fluid samples. In this invention the pneumatic pressure is supplied from the outer side of the microfluidic device and this will promote contamination of the fluid sample to happen while passing through the microfluidic structure.
Another disclose prior art, suggest a microvalve with diaphragm and a valve seat. The diaphragm is controlled by external actuated device which is a bladder device having fluid inside to control the diaphragm movement through direct means such as electrostatic or electromagnet and indirect means such as thermal actuation. However, this invention applies different approaches in actuating the passive microvalve as compared to the present invention which utilize pressure difference generated from the airflow of external environment. The purposed present invention is intended to overcome limitation on contamination of fluid sample and the power to actuate the microvalve against centrifugal force. The present invention suggested a microfluidic device having a valve system different from fluid sample pathway and also a system where the fluid sample has the capability to flow against centrifugal force.
SUMMARY OF THE INVENTION
This invention recommends a microfluidic device comprises of four substrates with a rotary compact disc having a microchannel structure with at least two vent holes and a constriction feature. The first substrate has a main reservoir which contains the working fluid while the second substrate placed the secondary reservoir and also the diaphragm. The microfluidic structure is located in the third substrate which consists of at least one sample reservoir for a sample fluid, micromixer, microchannel and microfilter. In the fourth substrate, there are one microchannel With a constriction structure and at least two vent holes. Ail these substrates are bonded together through but not limited to adhesive, anodic, thermal, fusion or pressure bonding.
When this microfluidic device are rotated, it will allow air from external environment to flow into the vent hole and generate pressure difference inside the first substrate in order to cause the movement of Working fluid inside the first substrate and actuate the passive microvalve, used for regulating the fluid flow in this microfluidic system which is coupled to an electric motor or servo. The microvalve has structure of a diaphragm which will deform and expand upon application of pressure from the working fluid caused by the pressure difference in the main reservoir and second reservoir during operation. The pressure difference of the working fluid in the both reservoirs are generated based on the Bernoulli's principle wherein the exist pressure difference in the external air in contact with the working fluid due to the differences in the speed of the air, hence the corresponding air pressure, formed through constriction in the microchannel design.
Due to the pressure difference, air with the higher pressure will push the working fluid from the main reservoir into the secondary reservoir. When the secondary reservoir has been completely filled up, any subsequent addition of pressure from the external air will exert additional pressure to the diaphragm at the secondary reservoir. When the addition of pressure is able to overcome the mechanical stiffness of the diaphragm, the diaphragm will expand creating a reduction in the volumetric space of the connecting fluid flow passage (or microchannel). Gonsequently, the flow of the sample fluid will be reduced or stopped completely based on the expansion of the diaphragm.
BRIEF DESCRIPTION OF ACCOMPANYING DRAWINGS
To further clarify various aspects of some embodiments of the present invention, a more particular description of the invention will be rendered by references to specific embodiments thereof, which are illustrated in the appended drawings. It is appreciated that these drawings depict only typical embodiments of the invention and are therefore not to be considered limiting of its scope. The invention will be described and explained with additional specificity and detail through the accompanying drawings in which:
Figure 1 shows the isometric view of basic configuration for microfluidic device. Figure s shows the top view of basic configuration for microfluidic device. Figure 3 shows the cross section view of basic configuration for microfluidic device. Figure 4 shows the design of the diaphragm structure.
Figure 5 shows the microfluidic structure and sample reservoir on the third substrate of the invention.
Figure 6 (a) shows the top view vent holes and constriction of microchannel on the fourth substrate
Figure 6 (b) shows the isometric view vent holes and constriction of microchannel on the fourth substrate
Figure 7 shows the flowchart for the working principle of the passive microvalve.
Figure 8 (a) shows the air enters the microchannel for regulating fluid flow in microfluidic platform.
Figure 8 (b) shows the air pushes working fluid from main reservoir to secondary reservoir.
Figure 8 (c) shows the working fluid pushes diaphragm structure
Figure 8 (d) shows the diaphragm structure block the fluid flow.
Figure 9 shows the proposed invention as a microfluidic device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention will be described in detail with the accompanying drawing of the preferred embodiment of the present invention. Figure 1, 2 and 3 showed the basic configuration of the present invention. The microfluidic device (10) in form of rotary compact disc is developed from four layer substrate which are attach together by using bonding technique such as but not limited to adhesive, anodic, thermal, fusion or pressure bonding. The substrate is having a shape of, but not limited to circular, square or Hexagonal. The materials that have been used for making the substrate is made of but not limited to material such as glass, polymer or silicon.
As been shown by figure 1 , the isometric view of the microfluidic device has indicated that the microfluidic device (10) In form of rotary compact disc is developed by four layers substrate which each layer contains the specific structures for the microfluidic device to be function as miniaturised integrated diagnostic system. The first substrate (20) contains at least main reservoir (22) and secondary reservoir (24) which is the place to -store working fluid (26) and also as flow passage for the working fluid (26). The second substrate (30) indicated the location of the microvalve. The microvalve used for the present invention is passive type of microvalve which is in the formed of diaphragm (32) structure and actuated by the working fluid (26) in the first substrate. The third substrate (40) contain at least one reservoir (46) for fluid sample (44) and a microfluidic structure (42) as fluid sample pathway and the fourth substrate (50) indicated at least one microchannel (54) to work as an air flow passage to enter the microfluidic device and at least two vent holes (52) to allow air to enter the microchannel.
Figure 4 shows the design of the diaphragm structure which not limited to circular or square shape.
Figure 5 shows the microfluidic structure (42) such as microchannel (42A), micromixer (42B) or microfi!ter (42C) and at least one sample reservoir (44) for the sample fluid which is located at the third substrate. The diaphragm to work as an ejector to the fluid sample (44) from the sample reservoir (46). Upon expansion of the diaphragm structure (32), addition of pressure to the sample fluid (44) and reduction of the volume in the sample reservoir (46) causes the fluid sample (44) to be ejected and flow from the sample reservoir (46) towards the microfluidic structures (42).
Figure 6 (a) and 6 (b) shows the top and isometric view of the microchannel (54) on the fourth substrate (50). Refemng to the figure 6, the unique structure of the microchannel (54) of the fourth substrate (SO) is the element of having at least two vent holes (52) and the existent of constriction feature (56). The purposed of having both structure are to allow and accelerate air from external environment to flow and generate pressure difference inside the first substrate (20) in order to cause the movement of working fluid (26) in the first substrate (20).
The fundamental of the working principle of the microfludic device is explained in figure 7, figure 8(a), 8(b), 8(c) and 8(d). The microfluidic device substrate is rotated using a rotatable spindle or platen which is coupled by a motor or servo. The rotation activity caused the generation of external environment air and then entered the microchannel (54) through the vent holes (52). The external environment air then passes through the microchannel (54) to the constriction feature where air flow is accelerated which causes a pressure different in this case the pressure reduction of working fluid (26) inside the first substrate (20). Due to the pressure different which is utilising the Bernoulli's principle to generate actuation energy, the working fluid (26) is pushed from the main reservoir (22) into secondary reservoir (24) if the pressures in both reservoirs are not balanced. If the pressure is balanced, the working fluid (26) is idle. The working fluid (26) which is in a formed of liquid such as but not limited to water, paraffin oil or grease, then completely fill up the secondary reservoir (24) until having an ability to pressure the passive microvalve which is in diaphragm (32) structure. In this situation the pressure difference that generated from working fluid (26) is worked as an actuate means for the diaphragm (32) to expand. The actuated diaphragm (32), creating a reduction in the volumetric space of the microti uidic structure (42) and as the consequence the fluid sample (44) inside the microfluidic structure (42) will reduced or stopped completely in the third substrate. However, it is to state that the flow of the fluid sample (44) inside of the microfluidic structure (42) is not interfered directly by actuate means that generated by the working fluid (26). The fluid sample (44) that will flowed inside the microfluidic structure (42) is in a liquid form such as but not limited to nucleotide DNA or RNA, protein or cell while the microfluidic structure (42) is in the form of microchannel, micromixer or microfilter.
While the preferred embodiment of the present invention and the advantages have been disclosed in the above detailed description, the invention is not limited to but only with the scope of the appended claim.

Claims

1. A microfluidie device (10) in form of rotary compact disc, comprising:
a first substrate (20) with at least main reservoir (22) and secondary reservoir (24) containing working fluid (26);
a Second substrate (30) with at least a microvalve in said formed of diaphragm (32) structure which is actuated by said working fluid (26) in said first substrate (20);
a third substrate (40) with at least one reservoir (46) for fluid sample (44) and a microfluidie structure (42); and
a fourth substrate (50) with at least one microchannel (54) as an air flow passage;
characterized in that, said mierochannel (54) of said fourth substrate (50) which is attached with said third substrate (40) and further attached to first substrate (20) having at least two vent holes (52) and constriction feature (56)on said microchannel (54) to allow and accelerate air from external environment to flow and generate pressure difference inside said first substrate (20) in order to cause the movement of said working fluid (26) in said first substrate (20) into main reservoir (22) and further filling said second reservoir (24) for said working fluid (26) to cause expansion ofmicrovalve at said second substrate (30)for controlling said fluid sample (44) flow inside said third substrate (40).
2. A microfludic device (10) as claimed in claim 1, wherein said air flow from external environment is generated during rotation activity of said substrate of said microfluidie deVice (10).
3. A microfludic device (10) as claimed in claim 2, wherein said rotation activity is activated by a motor or servo which is coupled at rotatabie spindle or platen means.
4. A microfludic device (10) as claimed in claim 2, wherein said substrate is having a shape of, but not limited to circular, square or hexagonal.
5. A microfludic device (10) as claimed in claim 4, wherein said substrate is attached together by using bonding technique such as but not limited to adhesive, anodic, thermal, fusion or pressure bonding.
6. A microfludic device (10) as claiitied in claim 4, wherein said substrate is made of but not limited to material such as glass, polymer or silicon.
7. A microfludic device (10) as claimed in claim 1 , wherein said microfluidie structure is Consists of at least micromixer, microchannel or microfilter.
8. A microfludic device (10) as claimed in claim 1 , wherein said working fluid (26) is in a formed of liquid such as but not limited to water, paraffin oil or grease.
9, A microfludic device (10) as claimed in claim 1 , wherein said fluid sample is a liquid Such as, but not limited to nucleotide DNA or RNA, protein, or cell.
10. A microfludic device (10) as claimed in claim 1 , wherein said fluid sample (44) flow regulation is achieved by means of;
a. Entering of external environment air that generated during rotation activity through said vent hole (52) of said microchannel (54);
b. Flowing of external environment air flow inside said microchannel (54) and passes through constriction generating acceleration flow which correspond to reduction of fluid pressure;
c. Moving of working fluid (26) from main reservoir (22) into secondary reservoir (24) due to higher pressure from said air;
d. Filling of working fluid (26) in secondary reservoir (24)in a complete manner wherein subsequent addition of pressure from external air causes said diaphragm (32) to expand; and
e. Expending of said diaphragm (32) reduce space in said microfluidic structure (42) for fluid sample (44) flow passing causing reduction or stopping of said fluid sample (44) flow.
A method of flow regulation as claimed in claim 10, wherein the constriction is a structure of narrowing or reducing dimension of diameter, width or feature size along its length. A method of flow regulation as claimed in claim 10, wherein the expansion of diaphragm (32) from the working fluid (26) in the secondary reservoir (24) is achieved when the pressure from addition of the working fluid (26) is higher than the stiffness of the diaphragm (32).
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