TWM273348U - Micro-separator for human blood - Google Patents

Description

M273348 IV. Creation Instructions (1) <New Technical Field> This creation is a new blood cell serum micro-separation element design. It is designed on a material the size of an optical disc, using a rotary drive such as an optical disc drive. The generated centrifugal force, combined with the valve formed by the surface tension between the fluid and the carrier material to control the timing of fluid flow, has the advantages of simple structure, small size, no moving parts, etc., and is easy to integrate with related microfluidic components. 〈Previous technology〉 The development of the entire micro-electromechanical industry, at present, the application and main development fields of nano / micro-electromechanical technology in the world can be roughly divided into ... Bio-MEMS, Microwave Electro-Mechanical (RF-MEMS), Optical micro-electromechanical (Optical-MEMS), etc., due to a series of advances in biotechnology, copying news such as sheep and cattle and presenting them to the world again and again, showing that biotechnology is definitely a major axis in the development of the scientific community in the next few years; especially The human genome project is a great project in the scientific community that has attracted the attention of all people. It has triggered a new wave of biochemical scientific research. The application and development of biochemical systems has been eagerly anticipated by the market. In the early 1990s, Andreas Manz, Jed Harrison, and others first produced mini-chips with a mini-chemical system; the f-chip system showed that it has the advantages of less sample volume, cheaper, and faster than the traditional method; These technologies were originally developed for biological analysis, but later they have also been used in traditional chemical immunoassays, environmental analysis, material measurement, etc., and they only require a small volume and fast Advantages of the reaction 'can be removed by more accurate and rapid fluid injection, better intermediate vehicle or product removal

Page 7 M273348 IV. Creative Instructions (2) 'Control of chemical reactions that are difficult to achieve with traditional reactors, such as better control of reaction variables. In these micro-devices, the microfluidic control system is a very key technology for the factory project. It provides the advantages of a small number of specimens, automation, rapid response, flat processing, and disposable type. It develops more complex and widely used fluid processing systems. In-depth discussion of the microfluidic principle phenomenon has been a doubtful question for helmets. An ideal microfluidic system must have complete analytical capabilities, from sample injection (including sample storage and injection), pretreatment (including concentration, mixing, dilution, and reaction) to final analysis. The typical sample flow rate is from nuc ^ roliters to picoHters. Because the flow rate is small, a special shape fluid device is usually required to rotate the fluid. Integrate various microfluidic devices such as micro-injection, micro-pumps, micro-valves, micro-mixers, micro-reactors, etc. to form a reduced analysis experiment and become the common goal and direction of various research units; the so-called micro- Design concept of analysis system (VTAS) or Lab 〇na chip. 0 Looking at the existing biochips on the market, the microfluidics technology platform is based on ele.Ctroosmosis and electro-osmosis. The method of isokinetic power drive (electrokinetic) is the mainstream and the most mature, as shown by various representative products. The shortcomings of the analysis of electric power drive technology are shown in the following table; Advantages: 1 Easy to control the fluid. Such as molecular separation, mixing, 2 · Can perform related biochemical processing, flow control, etc. . 3. Can be made on glass, quartz, polymer and other materials.

M273348 Fourth, creation instructions (3) Disadvantages: 1 susceptible to the physical and chemical characteristics of the fluid (such as ionic strength, pH value, etc.). 2. High voltage is required, which may easily cause damage to biochemical specimens. 3 · Only suitable for continuous fluids. 4 · High flow rate (greater than 1 microliter / second) cannot be delivered in a wide runner. = The electric drive method has the above disadvantages. The disc type microfluidic processing level = The structure is born from the response. The main structure is shown in the first figure. This level is flat: technology is produced on a traditional CD-size disc. The microfluidic processing element mainly uses centrifugal force, so it does not need any driving element to drive the flow of fluid. Therefore, if designed properly, the structure is quite simple and has the following advantages according to its characteristics: 1. Low power and space requirements. 2 · Not sensitive to the physical and chemical properties of the fluid used. 3. Allow the existence of air bubbles in the fluid; ^ With a variety of channel widths and flow rates (5 nl / sec ~ 01 ml / sec), ^ can be designed to meet the needs of high density and parallel design. Quantities: Γ performs the separation, mixing, shunting, adding, and flow control mechanisms required for biochemical detection. The creation of the C fluid system has considerable development potential, so this is because: the development of a blood separation element on this development platform, the first step in the inspection process is blood separation, and the blood in the blood &gt; month screening Possible diseases. <New content> The main purpose of this creation is to provide a disk microfluidic system

Page 9 M273348 IV. Creative Instructions (4) The new type of blood cell serum separation element used in the blood is driven by centrifugal force without any moving parts. It can separate the small flow of blood as required without occupying too much space. Large volume, can be integrated with other microfluidic components, eliminating other types of blockage, poor efficiency and other problems. <Embodiment>

The research and development of this disc-type biochemical sensing technology has been in foreign countries since about 1990, and has been making breakthroughs in the past one or two years. There have been products listed on the market. There are mainly three leading technology manufacturers: Gyros, Sweden, Tecan, Burstein, etc., among which patents on microfluidics are US4940527, US5006749, US5061381, US5122284, US5171695, US5173193, US5173262, US5186844, US5242606, US5242803, US5252294, US5275016, US53041, US5304348, US5304348 , US5409665, US5413732, US5426032, US5431303, US5432009, US5457063, US5472603, US5478750, US5496520 &gt; US5518930, US5590052, US5591643, US5599411, US5624597, US5639428, US 1943323248, US 1539323248, etc. Between 2001 and 2001, the patent content of US6302 1 34 was the most complete, and two specific embodiments for blood separation were provided in the text, as shown in Figures 1 to 11; the specific embodiments are shown in Figures 1 and 2. Blood From the operation status of the blood flow, both of which have a design in common, and that is separated from the serum storage tank storage of blood serum, are near the center position

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The far position is located in the outer part of the entire disc. The application structure of this disc type from the fluid system is limited by the direction of its driving force-centrifugal force. It is not easy to transfer the distant position to the position closer to the center of rotation, so it will be very difficult to design the components of other subsequent serum processing programs, which is the first problem. The first problem is that the valve formed by wax blocks is used for both, which not only increases the processing difficulty, but also requires a proper heating mechanism, which makes the overall structure design more complicated and costly. The f-th problem is for the situation of the specific embodiment 2. From the operation procedure of blood separation 2 ', it can be seen that after the speed is high enough to separate the blood, add ... The fluid in the 〇7 is sent to the blood, = 509, the serum level is raised and the serum is separated into the storage tank 514. Here, a problem arises when the fluid in the stabilization tank 507 is to be transferred to the blood = When the knife-off = 5 0 9, the flow path 5 1 2 is still full of air, and there are liquids in the upstream and downstream. ^ When the gas is squeezed, it shows an unstable interface, although at high speed f 2: f gas will still be affected. The upper liquid squeezes into the blood separation tank 509, half: it is quite difficult to control. For the future biochemical detection, precise control is required. Dozens of methods: automatic program control. Second, this high speed f makes it difficult to design the components. ^: m means &amp; ㉟ for the shortcomings mentioned above, the thirteenth figure is the conceptual design of the book, the base material 10 is 12 cm in diameter and is similar to the disc hair Γ ϊ Head 1 uses the surface tension as the valve design in the creation , To avoid its material being hydrophobic, currently used

M273348 Fourth, creation instructions (6) polydimethylsiloxane (PDMS), thickness is 0.6 mm; the entire element structure is 100, and the volume of a drop of blood is about 25 microliters, and the diameter of the injection groove is not too large. Due to the limitation of the number of components, the processing depth is set to 400 microns and the diameter is 8 mm; Figures 14 to 17 are schematic diagrams of the operation of blood separation components. Here, a description of its operation is given. First, 2 microliters of blood is transferred to the injection tank through the injection hole of the upper cover using a precision manual injector or an automated robotic arm, and then starts to rotate. Due to the size of the flow channel 108 It's quite big, so the speed does not need to be too high. About 200 ~ 300 rpm, blood will flow into the auxiliary filling tank 102. This speed does not cause the valve to produce abundant effects. After a few seconds, the liquid level of the auxiliary filling tank 102 exceeds The flow channel 丨 〇9 enters the blood separation tank 103, and finally forms as shown in Figure 15; in order to produce the maximum separation effect, and to prevent blood from flowing into the overflow channel 丨 丨The size of the auxiliary filling tank and the blood separation tank must be calculated and controlled during the design, so as to ensure that the situation in Figure 15 is generated, that is, the total blood volume of the auxiliary filling tank and the blood separation tank is equal to the blood volume injected. The liquid level is almost the same as at the inlet of the overflow channel. Immediately afterwards, the rotation rate is increased to about 15,000 revolutions per minute for blood cell serum separation. At this time, blood in both the auxiliary filling tank and the blood separation tank will undergo blood cell serum separation. In order to ensure complete blood separation Must continue for 2 ~ 3 minutes, and then increase the rotation rate to 2000 rpm to make the valve 105 work to assist the liquid in the filling tank to flow into the blood separation tank 103. Due to the design of the block 106, the injected liquid = Will cause the interface of the separated serum and blood cells to be damaged, and the compressed air will flow out from the gap above the block to cause pressure equilibrium. The injected liquid

Page 12 M273348 IV. Creation instructions (7) The optimal capacity is exactly the condition that the serum separated # in the blood separation tank 103 is completely discharged from the overflow channel 110, but because the human serum content is affected by different physiological conditions And physical differences, the content accounts for about 40 ~ 60% of the blood volume. In order to avoid causing blood cells to flow into the overflow channel 110, the blood volume in the auxiliary filling tank 102 is based on the blood in the blood separation tank 103. 40% of the capacity (the liquid level to the inlet of the overflow channel) is taken as the design value; after several tens of seconds, the distribution of the fluid is shown in the seventeenth figure.

M273348 on page 13 Brief description of the drawing 403… blood separation area 4 0 4… blood overflow tank 405… serum storage tank 4 0 6… capillary channel 407… capillary 40 6 and 408 connecting end 4 0 8… capillary channel 409… air runner 4 1 0… the connecting section in the air runner prevents liquid from flowing into 411… micro runner

412… Wax block for valve 413… Valve 5 0 1… blood injection tank 5 0 2, 5 0 3… metering capillary channel 5 04… overflow capillary channel 5 0 5… overflow groove 50 6… capillary connection Segment 50 7… stabilizing groove 5 0 8… flow channel 5 0 9… blood separation groove

510… capillary channel 511… capillary connecting section 512… microchannel 514… storage tank 515… air channel

Page 15 M273348 Schematic description 517 ... Storage tanks 518, 519 ... Drawing number description of new valve creation 10 ... PDMS material disc 12 cm in diameter 100 ... Blood separation element 1 0 1 ... Blood injection tank 102 ... Supplementary filling Tank 103… blood separation tank 104… serum storage tank

105… valve 106… block 107… air runner 108… runner 10 9… overflow channel 110… separation overflow channel

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Claims (1)

M273348 5. Scope of patent application!. ----- 1 · A new type of blood micro-separation element is used for disc biochemical ^ (a) — blood injection tank; dagger includes (b) — auxiliary filling tank; (c) A blood separation tank; (d) a blood block in the blood separation tank; (e)-a valve and two overflow channels. 2. The blood micro-separation element described in item 丨 of the scope of the patent application ^ The separation tank has a block, which can separate the separated blood cells from the liquid phase in the blood-filling tank. In addition, it can prevent the serum from being damaged. = Time to fill so that the liquid from the filling tank is smoothly injected into the blood separation tank. 'Bu also 3. As described in the scope of the patent application, the internal block of the blood micro-separator cell has a small distance from the upper wall surface =, the width of blood separation), as an air flow channel, to balance the relative fluid pressure I micron size 4. Blood micro-separation as described in item 1 of the patent application scope. The volume of both the tank and the blood separation tank needs to be carefully examined. The auxiliary filling and the blood separation tank are two. • At the inlet of the overflow channel, the blood injection volume of the filling tank is aided. 40% of the volume. · Temple blood separation tank volume 5 flashes! ΪThe blood micro-separation element described in item 1 of the patent scope, which has a-valve and its startup speed value needs to be higher than 1 dry knife has 6. If you apply for a patent basket彳, ask, the speed of the moon is away. The material used in this article is the blood micro-separation element. The material used for the bean can be similar to PDMS or stripped from the ground and used for the purpose. 乂 Use different hydrophobic materials after processing. Page 17 M273348 Page 18 Figure Fourteen Page 31