DE102013201330A1 - Fluid transfer device for use in loading samples in high performance liquid chromatography instrument, uses axial displacement of piezoelectric actuator to operate internal valve and internal pump chamber of microfluidic device - Google Patents

Abstract

The fluid transfer device (100) includes a piezoelectric actuator (110) that is externally coupled to the microfluidic pump device (130). The actuator is axially displaced along a lengthwise axis (L) such that it operates the internal valve and the internal pump chamber (140) of the microfluidic device. A high-stiffness actuator (150), coupled to the piezoelectric actuator, dynamically adjusts position of the piezoelectric actuator relative to the microfluidic pump device. The axial displacement of the piezoelectric actuator is less than about 10 micrometers.

Description

BACKGROUND

Reciprocating micropumps are used for various applications, such as loading samples into liquid chromatography instruments. A typical micropump may include an inlet valve, a pumping chamber and an outlet chamber, wherein the pumping chamber pumps fluid by alternately expanding to receive the fluid through the inlet valve and contracting to expel the fluid through the outlet valve. Of course, "fluid" refers to liquids and / or gases. Generally, a reciprocating motion of a diaphragm or membrane forming part of the pumping chamber causes the pumping chamber to expand and contract. Various techniques for generating the reciprocating motion include, for example, the use of thermo-pneumatic, electrostatic, pneumatic, and piezoelectric actuators. The performance of conventional micropumps is generally limited by the largest dimension of a bubble that can be tolerated.

Conventional micropumps with piezoelectric actuators typically have a lateral expansion configuration that includes a flat piezoelectric disc having a first side attached to the diaphragm of a pumping chamber and a second side free in response to an electrical signal expand. A longitudinal axis of the piezoelectric disc is substantially parallel to an upper surface of the diaphragm so that the piezoelectric disc is effectively flat on the diaphragm. When a bias voltage is applied, the piezoelectric disc contracts laterally, causing a bending moment between the piezoelectric disc and the diaphragm. The bending moment bends the diaphragm, causing fluid to be expelled within the pumping chamber. While this configuration is relatively easy to manufacture and produces large deflections, it can not generate high pressures. For example, a conventional lateral strain micro-pump may generate about 0.06 bar to about 2 bars of pressure.

The inlet and outlet valves may be actively actuated in a similar manner as the pump chamber, e.g. using a piezoelectric actuator, or the inlet and outlet valves may be passive check valves. However, passive check valves are typically unsuitable for high pressure piezoelectric actuated micropumps because the amount of fluid pumped in each cycle is limited and a finite volume of fluid is needed to actuate the check valves. Piezoelectric actuated valves may be limited to differential pressures of approximately e.g. 3 bar. Many piezoelectrically actuated inlet and outlet valves rely on flex mode actuators to achieve a wide range of motion.

There are some examples of conventional micropumps that have piezoelectric actuators that expand and contract longitudinally, as opposed to laterally. Again, such micropumps typically include a flat piezoelectric disk having a longitudinal axis substantially parallel to the top surface of the diaphragm so that the piezoelectric disk is effectively flat on the diaphragm. However, when a bias voltage is applied, the piezoelectric disk expands vertically downward, causing a bending moment to bend the diaphragm. However, such configurations may be difficult to manufacture and have poor on / off flow ratios. Also, in one example, a thermally balanced piezoelectric actuator is located within the valve chamber. Although this micropump is capable of producing high on / off flow rate ratios and sealing against relatively high pressures, the piezoelectric actuator is placed under tension and the working fluid in the valve chamber is in contact with the piezoelectric actuator. Accordingly, the micropump is not suitable for high pressure systems in which a variety of liquids can be used, creating a risk of contamination. Further, since the piezoelectric actuator is inside in the valve chamber, the valve chamber can not be removed or replaced with respect to the piezoelectric actuator.

SUMMARY

In a representative embodiment, a fluid transfer device includes a piezoelectric actuator that is externally coupled to a microfluidic device. The piezoelectric actuator has an axial displacement along a longitudinal axis in response to application of a bias voltage, wherein the axial displacement of the piezoelectric actuator actuates one of an internal valve and an internal pumping chamber of the microfluidic device.

In another representative embodiment, a fluid transfer device includes a microfluidic device having a first valve and a first piezoelectric actuator coupled to the microfluidic device. The first valve has a valve chamber and operation of the first valve allows fluid entering or leaving the valve chamber through an opening. The first piezoelectric actuator is configured to expand along a first longitudinal axis in response to application of a first bias voltage to close the first valve, and to contract along the first longitudinal axis in response to a reduction in the applied first bias voltage to open the first Valve, wherein the first piezoelectric actuator is external to the microfluidic device.

In another representative embodiment, a fluid transfer device includes a planar microfluidic device, a first piezoelectric actuator, a second piezoelectric actuator, and a third piezoelectric actuator. The planar microfluidic device includes an inlet valve, a pumping chamber in fluid communication with the inlet valve via an inlet port, and an outlet valve in fluid communication with the pumping chamber via an outlet port. The first piezoelectric actuator is external to the microfluidic device and mechanically coupled to the inlet valve, the first piezoelectric actuator having a first axial displacement in response to selectively applying a first bias voltage causing the inlet valve to close via the mechanical coupling , The second piezoelectric actuator is mechanically coupled externally to the microfluidic device and to the pumping chamber, the second piezoelectric actuator having a second axial displacement in response to selectively applying a second bias voltage, which causes the pumping chamber to compress via the mechanical coupling , The third piezoelectric actuator is mechanically coupled externally to the microfluidic device and to the exhaust valve, the third piezoelectric actuator having a third axial displacement in response to selectively applying a third bias voltage causing the exhaust valve to close via the mechanical coupling , Thus, fluid from a device inlet port connected to the inlet valve is drawn into the pump chamber through the inlet port when the inlet valve is open, the pump chamber expands and the outlet valve is closed. Similarly, the fluid is expelled from the pumping chamber through the outlet port to a device outlet port connected to the outlet valve when the inlet valve is closed, compressing the pumping chamber and leaving the outlet valve open.

In another representative embodiment, a microfluidic device includes one of a pumping chamber and a valve chamber, which are partially defined by a flexible membrane and a piezoelectric actuator coupled to the microfluidic device. The piezoelectric actuator is configured to expand along a longitudinal axis in response to application of a bias voltage, the value of the bias voltage moving the flexible diaphragm to a position that compresses one of the pumping chamber and the valve chamber to restrict a flow of fluid the microfluidic device at a desired flow rate. The piezoelectric actuator is external to the microfluidic device.

BRIEF DESCRIPTION OF THE DRAWINGS

The illustrative embodiments are best understood from the following detailed description when read in conjunction with the accompanying drawings. It is emphasized that the various features are not necessarily drawn to scale. In fact, the dimensions may be arbitrarily increased or decreased for clarity of discussion. Wherever applicable and practicable, like reference numerals refer to similar elements.

1A and 1B 10 show cross-sectional diagrams illustrating a fluid transfer device according to a representative embodiment.

2A . 2 B and 2C Figure 10 are cross-sectional diagrams illustrating a fluid transfer device according to a representative embodiment.

3 FIG. 10 is a cross-sectional diagram illustrating a multi-valve fluid transfer device according to a representative embodiment. FIG.

4A and 4B FIG. 10 are cross-sectional diagrams illustrating a multi-valve, integrated fluid transfer device according to a representative embodiment. FIG.

5A and 5B 10 are cross-sectional diagrams illustrating multi-valve microfluidic devices of integrated fluid transfer devices, according to representative embodiments.

6 FIG. 10 is a cross-sectional diagram illustrating an actuator device according to a representative embodiment. FIG.

7 FIG. 12 is a cross-sectional diagram illustrating a multi-valve, integrated fluid transfer device according to a representative embodiment incorporating the actuator device of FIG 6 contains.

8A and 8B FIG. 10 are cross-sectional diagrams illustrating a valve chamber having a raised structure according to a representative embodiment. FIG.

9A and 9B FIG. 10 are cross-sectional diagrams illustrating a pumping chamber having a raised structure according to a representative embodiment. FIG.

10A and 10B FIG. 10 are cross-sectional diagrams illustrating a pumping chamber having a lowered structure according to a representative embodiment. FIG.

11A and 11B FIG. 10 are cross-sectional diagrams illustrating a pumping chamber having a gas-permeable membrane according to a representative embodiment. FIG.

12A and 12B 10 are cross-sectional diagrams illustrating a multi-valve, integrated fluid transfer device having a continuous flow according to a representative embodiment.

DETAILED DESCRIPTION

In the following detailed description, for purposes of explanation and not limitation, illustrative embodiments are set forth in order to provide a thorough understanding of embodiments in accordance with the present teachings. However, for one who has had the benefit of the present disclosure, it will become apparent that other embodiments in accordance with the present teachings that depart from the specific details disclosed herein may remain within the scope of the appended claims. In addition, descriptions of well-known devices and methods may be omitted so as not to obscure the description of the exemplary embodiments. Such methods and apparatus are within the scope of the present teachings.

Generally, it is understood that the drawings and the various elements illustrated therein are not drawn to scale. Further, relative terms such as "over," "under," "top," "bottom," "upper," "lower," "left," "right," "vertical," and "horizontal" are used to refer to to describe the various relationships of elements to one another as illustrated in the accompanying drawings. It is to be understood that these relative terms are intended to encompass different orientation of the device and / or elements in addition to the orientation illustrated in the drawings. For example, if the device were inverted with respect to the view in the drawings, one element described as "above" another element would now be, for example, "under" that element. Similarly, if the device were rotated 90 ° with respect to the view in the drawings, an element described as "vertical", e.g. now be "horizontal".

Various representative embodiments provide a planar microfluidic device coupled to one or more external piezoelectric actuators for producing a fluid pumping device or fluid transfer device, such as a micropump. For example, the microfluidic device may include an inlet, a first valve chamber, a pumping chamber, a second valve chamber and an outlet. A first piezoelectric actuator is configured to open and close a first valve in the first valve chamber, a second piezoelectric actuator is configured to compress and expand the pumping chamber, and a third piezoelectric actuator is configured to open and close a second valve in the third valve chamber. Each of the first, second, and third piezoelectric actuators is configured to axially expand and contract along an elongated longitudinal axis for interaction with the corresponding valve or pumping chamber.

By closing the second valve, opening the first valve, and expanding the pumping chamber, fluid is drawn in from the inlet. By closing the first valve, opening the second valve and compressing the pump chamber, fluid is expelled from the device. Accordingly, the fluid transfer device is capable of pumping fluid and generating a substantial pressure, e.g. in a range of about 50 bar to over about 1,000 bar pressure. The various embodiments may be used for high performance liquid chromatography (HPLC) instruments, for example, for loading samples and / or as the analytical pump itself.

1A and 1B FIG. 10 are cross-sectional diagrams illustrating a fluid transfer device including a piezoelectric actuator according to a representative embodiment. FIG.

Referring to 1A and 1B , Contains the fluid transfer device 100 a planar microfluidic pump device 130 which is an internal pumping chamber 140 , an inlet opening 131 and an outlet opening 132 having. The microfluidic pump device 130 also contains a flexible membrane 120 , which is the top wall of the internal pump chamber 140 forms. Like in Detail is described below, the flexible membrane 120 bent down (or deformed) from its initial position (shown in FIG 1A ) into a bent position (shown in FIG 1B ), Fluid from the pump chamber 140 through the outlet opening 132 ejecting, and is straightened upwards from its bent position to its initial position, fluid into the pumping chamber 140 through the inlet opening 131 sucking in to deliver a pumping action. The fluid may be a liquid or a gas, as would be apparent to those skilled in the art. The microfluidic pump device 130 may be formed of a durable material, such as stainless steel or other metal material. Alternatively, the microfluidic pump device 130 be formed of a different material, such as glass, ceramic, silicone or a polymer such as polyimide, polycarbonate or other plastic, without departing from the scope of the present teachings. Similarly, the flexible membrane 120 be formed of a flexible metal, such as a stainless steel. Alternatively, the flexible membrane 120 of materials such as polymers, glass, ceramics, and metals, or any combination thereof, without departing from the scope of the present teachings. In various embodiments, the internal surfaces of the microfluidic pumping device 130 (eg walls of the pump chamber 140 ) coated with a non-reactive coating, which may contain, for example, a polymer, ceramic, glass, metal or fluoropolymer coating.

The fluid transfer device 100 also includes a piezoelectric actuator 110 , which externally to the microfluidic pump device 130 about a boss 115 (English boss) is coupled. The piezoelectric actuator is externally coupled, in that it is completely outside the pump chamber 140 is arranged and therefore is not in contact with the working fluid in the pump chamber 140 is included or passes through them. The piezoelectric actuator 110 can therefore be used in high-pressure systems for which there is otherwise a risk of contamination of the piezoelectric actuator 110 if it is not external to the microfluidic pumping device 130 would. In various configurations, the external piezoelectric actuator 110 also from the microfluidic pump device 130 be removable. Therefore, the external coupling of the piezoelectric actuator allows 110 a simple replacement of the microfluidic pump device 130 ,

In the illustrated configuration, the piezoelectric actuator has 110 an elongated shape, wherein the length is greater than the width, as in 1A and 1B specified. A longitudinal axis L of the piezoelectric actuator 110 is substantially perpendicular to the upper surface (flexible membrane 120 ) of the microfluidic pump device 130 arranged. This deviates from a conventional system in which a longitudinal axis of the piezoelectric actuator is parallel to the upper surface of the microfluidic device so that it lies substantially flat on the microfluidic device. Although the piezoelectric actuator 110 As shown having a substantially rectangular shape, it should be understood that a variety of elongate shapes having a longitudinal axis L may be incorporated without departing from the scope of the present teachings.

The piezoelectric actuator has an axial displacement along the longitudinal axis L in response to a bias voltage being applied. For example, upon application of the bias voltage (eg, 100V), the piezoelectric actuator expands 110 from a contracted position (shown in FIG 1A ) to an extended position (shown in FIG 1B ) and forces the flexible membrane 120 to bend down into the pump chamber 140 to a distance, which of the axial displacement by means of the bosses 115 equivalent. The downward movement of the flexible membrane 120 thus compresses the pump chamber 140 so that the pump chamber 140 from an expanded position (shown in FIG 1A ) to a compressed position (shown in FIG 1B ) passes over. The movement from the expanded position to the compressed position causes the pump chamber 140 Fluid from the outlet port 132 ejects. The bosses 115 provides a transition from the cross section of the piezoelectric actuator 110 (eg rectangular) to a circular area, over which pressure on the flexible membrane 120 is created.

Similarly, when the bias voltage is reduced (eg, 0 volts is applied), which involves removing the bias voltage, the piezoelectric actuator contracts 110 from the extended position (shown in FIG 1B ) to its initial contracted position (shown in FIG 1A ), what is the flexible membrane 120 the microfluidic pump device 130 allows to straighten up and out of the pump chamber 140 to move out. The straightening movement of the flexible membrane 120 consequently, the pump chamber expands 140 so that the pump chamber 140 from its compressed position (shown in 1B ) to its initially expanded position (shown in FIG 1A ) passes over. The movement from the compressed position to the expanded position causes the pump chamber 140 Fluid through the inlet opening 131 sucks. The application of the bias voltage to the piezoelectric actuator 110 is repeated in a periodic manner to cause the pump chamber 140 alternately expanded and compressed, causing fluid to be sucked in and expelled through the inlet port 131 or the outlet opening 132 Delivering a pumping functionality.

In the illustrated illustrative embodiment, the fluid transfer device includes 100 also a highly rigid actuator 150 which is connected to the piezoelectric actuator 110 is coupled. The highly rigid actuator 150 may be a slow low compliance actuator configured to adjust a position of the piezoelectric actuator with respect to the microfluidic pump device 130 eg to make sure the piezoelectric actuator 110 is correctly positioned with respect to the microfluidic pumping device 130 , In addition, the high-stiffness actuator provides 150 a barrier that prevents the piezoelectric actuator 110 extending in an upward direction upon the application of the bias voltage, causing the axial deflection in the downward direction to occur around the flexible diaphragm 120 more efficient to bend. Similar to the piezoelectric actuator 110 is the highly rigid actuator 150 external to the microfluidic pumping device 130 , which makes it easy to replace the microfluidic part. The highly rigid actuator 150 can be adjusted, for example, to accommodate any slow thermal misalignment that occurs between the piezoelectric actuator 110 and the microfluidic pump device 130 occurs.

In the illustrated example, the high-stiffness actuator 150 implemented as an adjustable screw drive configured to adjust the position of the piezoelectric actuator 110 along the longitudinal axis L by correspondingly moving the screw drive in clockwise or counterclockwise directions. The screw drive can be realized by coupling a rotary motor to an adjustable screw with fine pitch, for example, such as a rotary stepping motor. Of course, other types of highly rigid actuators 150 can be incorporated or the highly rigid actuator can be omitted at all without departing from the scope of the present teachings. Other implementations of the highly rigid actuator 150 contain, for example, a pneumatic actuator, a thermal actuator or a wedge drive.

2A . 2 B and 2C FIG. 15 are cross-sectional diagrams illustrating a fluid transfer device including a piezoelectric actuator according to a representative embodiment. FIG.

Referring to 2A to 2C contains the fluid transfer device 200 a piezoelectric actuator 110 , a boss 115 and a highly rigid actuator 150 which are for the purpose of description as the same as with reference to 1A and 1B be adopted. The fluid transfer device 200 also includes a planar microfluidic valve device 230 which is an internal valve chamber 240 , a flexible membrane 220 , an inlet opening 231 and an outlet opening 232 having. The microfluidic valve device 230 also contains a valve 245 which is inside the valve chamber 240 is formed by the operation of the flexible membrane 220 and the preceding part 246 the outlet opening 232 , As described in detail below, the flexible membrane becomes 220 from its initial position (shown in FIG 2A ) is bent down (or deformed) to a bent position (shown in FIG 2 B ) mechanically to the protruding part 246 to contact, which prevents fluid from entering the inlet 231 entering or out of the outlet opening 232 exit and consequently the valve 245 effectively closes. The flexible membrane 220 is then straightened upwardly from the bent position to its initial position allowing fluid to enter the inlet port 231 enter and the outlet opening 232 to leave what the valve 245 opens effectively.

Each of the piezoelectric actuator 110 , the bosses 115 and the highly rigid actuator 150 is external to the microfluidic valve device 230 as discussed above. For example, the piezoelectric actuator 110 externally coupled, in that it is completely outside the valve chamber 240 is arranged and therefore is not in contact with the fluid which is in the valve chamber 245 and / or the valve 245 is included or passes. The piezoelectric actuator 110 , the bosses 115 and the highly rigid actuator 150 can also from the microfluidic valve device 230 be removable.

The microfluidic valve device 230 may be formed of a durable material, such as stainless steel or another metal. Alternatively, the microfluidic pump device 230 be formed of a different material, such as glass, ceramic, silicone or a polymer such as polyimide, polycarbonate or other plastic, without departing from the scope of the present teachings. Similarly, the flexible membrane 220 be formed of a flexible metal, such as stainless steel. Alternatively, the flexible membrane 220 be formed of a different material, such as polymers, glass, ceramics and metals or any combination thereof, without departing from the scope of the present teachings. As discussed above, in various embodiments, the internal surfaces of the microfluidic pumping device may 230 (eg walls of the valve chamber 240 ) with a non-reactive coating, which is a polymer, Ceramics, glass, metal or a fluoropolymer coating may be coated, for example.

As discussed above, the piezoelectric actuator has 110 an axial displacement along a longitudinal axis L in response to application of a bias voltage (not shown). For example, the piezoelectric actuator expands 110 upon application of the bias voltage (eg, 100V) from a contracted position (shown in FIG 2A ) to an extended position (shown in FIG 2 B ) what the flexible membrane 220 the microfluidic valve device 230 this forces you down into the valve chamber 240 to bend at a distance, which is the axial displacement by means of the bosses 115 equivalent. As noted above, the flexible membrane covers 220 thereby the above part 246 the outlet opening 232 what the valve 245 effectively closes (shown in 2 B ). Similarly, when the bias voltage application is reduced (eg, 0V is applied), the piezoelectric actuator contracts 110 from the extended position (shown in FIG 2 B ) into its initial contracted position (shown in FIG 2A ), what is the flexible membrane 220 the microfluidic valve device 230 allowed to move up from the valve chamber 240 to move out. The upward movement of the flexible membrane 220 thus expanding the valve chamber 240 and puts the previous part 246 free what the valve 245 effectively opens (shown in 2A ). An opening of the valve 245 displaces the valve chamber 242 able to fluid through the inlet opening 231 suck. The application of the bias voltage to the piezoelectric actuator 110 is repeated in a periodic manner to cause the valve 245 alternately opens and closes, allowing the fluid to be sucked in and expelled through the inlet port 231 or the outlet opening 232 , which provides a fluid pumping functionality.

The fluid transfer device 200 may also be configured to allow variable flow restriction (or variable flow modulation) of the fluid. Referring to 2C For example, a preliminary bias voltage (eg, 50V) may be applied to the piezoelectric actuator 110 be applied to provide axial deflection along the longitudinal axis L between the fully contracted position (shown in FIG 2A ) and the fully extended position (shown in FIG 2 B ). The preliminary bias voltage is between the bias voltage (eg, 0 V) for fully contracting the piezoelectric actuator 110 and the bias voltage (eg, 100V) for fully expanding the piezoelectric actuator 110 , The amount of expansion of the piezoelectric actuator 110 may be a linear function or a non-linear function of the preliminary bias voltage, depending on the particular implementation.

Application of the preliminary bias voltage forces the flexible membrane 220 the microfluidic valve device 230 to bend down into the valve chamber 240 by a distance, which is the axial deflection over the bosses 115 corresponds, for example, about half the distance to the protruding part 246 in the example shown. Continuously applying the preliminary bias voltage turns the flexible membrane 220 in this position over the protruding part 246 held, creating a boundary, which is a flow of liquid from the inlet port 231 to the outlet port 232 through the fluid transfer device 200 established. In other words, the preliminary bias voltage is applied to the piezoelectric actuator 110 continuously applied to maintain a constant axial deflection and to cause the fluid transfer device 200 provides the flow limiting functionality.

In the illustrated embodiment, increasing the preliminary bias voltage further completes the limitation, and thus reduces the fluid flow, and reducing the preliminary bias voltage further opens the boundary, and thus increases the fluid flow to achieve the desired flow rate. The fluid flow may be enabled by a pumping action of other fluid transfer devices, such as the pumping action described above with respect to FIGS 1A - 2 B which is in fluid communication with the fluid transfer device 200 are to which the preliminary bias voltage is applied. Examples of fluid transfer devices in fluid communication with each other are described below with reference to FIGS 3 - 5B . 7 and 12A - 12B ,

In various embodiments, the fluid transfer device 100 similarly configured for flow modulation. For example, it expands, referring to 1B , the piezoelectric actuator 110 upon applying the bias voltage (eg, 100V) to the extended position, forcing the flexible membrane 120 , down into the pump chamber 140 to bend. By maintaining the application of the bias voltage, the flexible membrane becomes 120 held in this position, which creates a boundary which a flow of fluid from the inlet port 131 to the outlet opening 132 through the fluid transfer device 100 established. Similarly, the flow can be modulated by applying a bias bias voltage (eg, 50V) between the bias voltage (eg, 0V) to fully contract the piezoelectric actuator 110 and the bias voltage (eg, 100V) for fully expanding the piezoelectric actuator 110 , Continuously applying the preliminary bias voltage causes the piezoelectric actuator 110 a position between that completely Contraction and fully expanded (not shown), depending on the desired flow rate.

3 FIG. 10 is a cross-sectional diagram illustrating a multi-valve fluid transfer device according to a representative embodiment. FIG.

Referring to 3 contains a fluid transfer device 300 an intake valve device 301 , a pump device 302 and an exhaust valve device 303 , which are shown as separate microfluidic devices in fluid communication with each other through the fluid conduits 306 respectively. 307 , In the illustrated embodiment, the inlet valve means 301 be substantially the same as the fluid transfer device 200 , in the 2A - 2C is shown, and the pump device 302 may be substantially the same as the fluid transfer device 100 , what a 1A and 1B is shown. The outlet valve device 303 may be similar to the fluid transfer device 200 , in the 2A - 2C except that the inlet port and the outlet port are reversed, as discussed below. In an alternative embodiment, the inlet valve device 301 , the pump device 302 and the exhaust valve device 303 be made as a single integrated unit, an example of which in 4A and 4B is shown.

The inlet valve device 301 contains a first piezoelectric actuator 311 , which is mechanically coupled to a flexible membrane 321 the microfluidic valve device 331 about a boss 316 for operating the intake valve 346 in the intake valve chamber 341 , As discussed above, the first piezoelectric actuator has 311 a first axial displacement along its longitudinal axis in response to selectively applying a first bias voltage (not shown). That is, the sequential application and reduction (eg, removal) of the first bias voltage causes the piezoelectric actuator 311 expands and contracts accordingly, and the flexible membrane 321 the microfluidic valve device 331 Bends and straightens alternately the inlet valve 346 to close and open. When it is closed, the inlet valve prevents 346 Fluid from being sucked into the inlet port 324 , which is the device inlet opening 361 the fluid transfer device 300 corresponds to or to be ejected from the outlet port 325 by pressing the flexible membrane 321 against the preceding part 347 , When it is open, the inlet valve allows 346 in that fluid is sucked in to the inlet opening 324 and ejected from the outlet port 325 ,

The pump device 302 contains a second piezoelectric actuator 312 which mechanically with the flexible membrane 322 the microfluidic pump device 332 is coupled via a boss 317 for operating the pump chamber 342 , As discussed above, the second piezoelectric actuator has 312 a second axial displacement along its longitudinal axis in response to selectively applying a second bias voltage (not shown). That is, sequentially applying and reducing (eg, removing) the second bias voltage causes the piezoelectric actuator 312 expands and contracts accordingly which causes the flexible membrane 322 the microfluidic valve device 332 bends and straightens to alternately compress and expand the pumping chamber 342 , When compressed, the pump chamber abuts 342 Fluid from the outlet port 327 out, ie during the intake valve 346 (discussed above) is closed to prevent fluid from entering the inlet 326 is sucked in, and the exhaust valve 348 (discussed above) is open to allow the fluid from the outlet port 327 to be expelled. When it expands, the pump chamber sucks 342 Fluid through the inlet opening 326 on, for example, while the exhaust valve 348 (discussed above) is closed, which prevents fluid from passing through the outlet port 327 is discharged, and the intake valve 346 (discussed above) is open to allow fluid through the inlet port 326 is sucked in.

The outlet valve device 303 contains a third piezoelectric actuator 313 , which mechanically to a flexible membrane 323 the microfluidic valve device 333 is coupled via a boss 318 for operating the intake valve 348 in the intake valve chamber 343 , As discussed above, the third piezoelectric actuator has 313 a third axial displacement along its longitudinal axis in response to selectively applying a third bias voltage (not shown). That is, sequentially applying and reducing (eg, removing) the third bias voltage causes the piezoelectric actuator 313 expands and contracts accordingly and the flexible membrane 323 the microfluidic valve device 333 bends and straightens to alternate the exhaust valve 348 to close and open. When it is closed, the exhaust valve prevents 348 in that fluid to the inlet port 328 is sucked in or ejected from the outlet opening 329 that of the device outlet opening 362 the fluid transfer device 300 corresponds by pressing the flexible membrane 323 against a protruding part 349 , When it is open, the exhaust valve allows 348 in that fluid to the inlet port 328 is sucked in and out of the outlet opening 329 is ejected.

The inlet valve device 301 , the pump device 302 and the exhaust valve device 303 contain highly rigid actuators 351 . 352 respectively. 353 , which with the corresponding first, second and third piezoelectric actuators 311 . 312 and 313 are coupled. Each one of the highly rigid actuators 351 . 352 and 353 may be a slow low compliance actuator configured to adjust a position of the first, second and third piezoelectric actuators 311 . 312 and 313 as discussed above with respect to the high stiffness actuator 115 in 1A - 2C , In the example shown, the highly rigid actuators 351 . 352 and 353 implemented as adjustable screw drives configured to adjust the position of the first, second and third piezoelectric actuators 311 . 312 and 313 along the respective longitudinal axes by moving the screw drive in corresponding clockwise or counterclockwise directions.

The operation of the intake valve device 301 and the exhaust valve device 303 is coordinated with the operation of the pump device 302 to prevent movement of fluid from the device inlet port 361 to the device outlet port 362 through the fluid transfer device 300 to enable. For example, as described above, fluid from the device outlet port becomes fluid 362 eject the first and second bias voltages to the first and second piezoelectric actuators, respectively 311 respectively. 312 created, causing that the inlet valve 346 the inlet valve device closes and causing the pump chamber 342 the pump device 302 compressed. At the same time, the third bias voltage becomes the third piezoelectric actuator 313 reduced (eg 0 volts is applied), causing the exhaust valve 348 the exhaust valve device 303 opens what it is the fluid in the pump chamber 342 allows, through the device outlet opening 362 over the outlet opening 327 withdraw. To deliver fluid to the device inlet port 361 to suck in, the first and second bias voltages become the first and second piezoelectric actuators, respectively 311 respectively. 312 reduced (eg 0 V is applied), causing the exhaust valve 346 the intake valve device 301 opens and causing the pump chamber 342 the pump device 302 expanded. At the same time, the third bias voltage to the third piezoelectric actuator 313 created, causing that the exhaust valve 348 the exhaust valve device 303 closes what allows the fluid into the pump chamber 342 through the device inlet port 361 over the inlet opening 326 to be sucked.

In alternative embodiments, one or more of the intake valve device operates 301 , the outlet valve device 303 and the pump device 302 as a variable flow modulator, as described above. For example, one or more of the first to third bias voltages may be maintained as a preliminary bias voltage, causing the corresponding first to third piezoelectric actuators 311 - 313 expand and the first to third flexible membrane 321 - 323 hold in a fixed position, restricting fluid flow by a desired amount. This also applies to the illustrative implementations, which are referred to below 4A - 5B . 7 and 12A - 12B are discussed.

In various embodiments, the timing of application and reduction (eg, removal) of the first, second, and third bias voltages may be controlled by a controller (not shown), such as a processor or central processing unit (CPU), application-specific integrated Application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or combinations thereof, using software, firmware, hardwired logic circuits, or combinations thereof. For example, the control device may be configured to determine a rate at which the first to third bias voltages to the corresponding first to third piezoelectric actuators 311 - 313 should be created to achieve the desired pumping rate and to apply the specific rate accordingly. Similarly, the controller may be configured to determine an extent of one or more of the first through third piezoelectric actuators 311 - 313 , which corresponds to a desired flow rate, and for controlling the application of the first to third bias voltages for moving the first to third flexible diaphragms to the proper position for restricting the flow of the fluid to the desired flow rate.

When a processor or CPU is used, a memory (not shown) is added for storing executable software / firmware and / or executable code which signals from the controller to the first, second and third actuators 311 - 313 controls. The memory may be any number, type, and combination of non-volatile read only memory (ROM) and volatile random access memory (RAM), and may store various types of information, such as computer programs and software algorithms, that may be used by the computer Processor or the CPU are executable. The memory may be any number, type, and combination of tangible computer readable storage media, such as a disk drive, an electrically programmable read only memory (EPROM); an electrically erasable and programmable read only memory (EEPROM), a CD, a DVD, a universal serial bus (USB), a drive, and the like. The first, second and third bias voltages may be the same or different voltage sources and / or may be the same or different from each other, depending on the characteristics of the corresponding one of the first, second and third actuators 311 - 313 as will be apparent to one skilled in the art.

In various embodiments, the deflection of each of the first, second and third piezoelectric actuators 311 . 312 and 313 limited to less than about 100 μm and may be less than about 10 μm in various configurations. The volume of fluid flowing from the device outlet port 362 at each pump stroke is therefore relatively small, typically on the order of about 20 nanoliters, for example. However, the first, second and third piezoelectric actuators 311 . 312 . 313 capable of operating at relatively high frequencies, eg, from about 10 cycles / sec to about 10,000 cycles / sec, allowing fluid flow above about 10 μL / min.

4A and 4B 10 are cross-sectional diagrams describing a multi-valve, integrated fluid transfer device formed as a single unit, according to a representative embodiment. Especially 4B shows the cross-sectional view of 4A along the line A-A '.

Referring to 4A contains the fluid transfer device 400 an intake valve device 401 , a pump device 402 and an exhaust valve device 403 , which is an integrated, planar microfluidic device 410 share. That is, in the illustrated embodiment, the inlet valve chamber 441 , the pump chamber 442 and the outlet valve chamber made as separate regions in the single microfluidic device 410 , The microfluidic device 410 contains three separate layers or plates, which serve as a membrane plate 420 , Orifice plate 430 and connecting plate 440 each of which may be patterned on one or both sides, eg using electrochemical etching. The structured membrane plate 420 , the orifice plate 430 and the connection plate 440 are aligned and interconnected to the various features of the integrated fluid transfer device 400 including the device inlet port 461 , the inlet valve chamber 441 , the pump chamber 442 , the outlet valve chamber 443 and the device outlet port 462 as well as the inlet and outlet ports 424 - 429 and fluid lines 404 - 408 , which provides fluid communication of the device inlet port 461 , the inlet valve chamber 441 , the pump chamber 442 , the outlet valve chamber 443 and the device outlet port 462 allow each other.

The inlet valve chamber 441 and the exhaust valve chamber 443 contain a corresponding inlet valve 446 and exhaust valve 448 By bending and straightening first and third flexible areas 421 and 423 the membrane plate 420 operate by operating the first and third piezoelectric actuators 411 respectively. 413 , The pump chamber works similarly 442 by bending and straightening a second flexible area 422 the membrane plate 420 by operating the second piezoelectric actuator 412 , The membrane plate 420 , the orifice plate 430 and the connection plate 440 may be formed of metal or other flexible material, such as stainless steel sheets, for example. If metal is used, the membrane plate can 420 , the orifice plate 430 and the connection plate 440 aligned and fused together using high temperature metal diffusion bonding.

As in 4B shown, the first, second and third flexible area 421 . 422 and 423 be circular in shape. Protruding parts 447 and 449 may similarly be circular in shape and centered within the first and third flexible regions 421 respectively. 423 , The first, second and third flexible areas 421 . 422 and 423 may be of the same size, having diameters of from about 1.0 mm to 10 mm, for example, and in particular from about 4.0 mm to about 5.0 mm. In alternative configurations, the first, second and third flexible regions may be 421 . 422 and 423 have shapes other than circles and / or may have different sizes from each other, without departing from the scope of the present teachings.

In particular, the inlet valve device contains 401 the first piezoelectric actuator 411 , the first flexible area 421 the membrane plate 420 about a boss 416 is mechanically coupled to operate the inlet valve 446 in the intake valve chamber 441 , As discussed above, the first piezoelectric actuator has 411 a first axial displacement along its longitudinal axis in response to selectively applying a first bias voltage (not shown) so that sequentially applying and reducing (eg, removing) the first bias voltage causes the piezoelectric actuator 411 expands and contracts accordingly, and the first flexible area 421 bends and straightens to alternate the inlet valve 446 to close and open. When it is closed, the inlet valve prevents 446 that fluid into the inlet opening 421 (which with the device inlet opening 461 over the line 405 connected) to be sucked in or from the outlet opening 425 To be ejected by pressing the first flexible part 421 against the preceding part 447 , When it is open, the inlet valve allows 446 the fluid, to the inlet port 424 to be sucked in, and from the outlet port 425 to be expelled.

The pump device 402 contains the second piezoelectric actuator 412 , which mechanically to the second flexible area 422 the membrane plate 420 about a boss 417 is mechanically coupled to operate the pump chamber 442 , As discussed above, the second piezoelectric actuator has 412 a second axial displacement along its longitudinal axis in response to a selective application of a second bias voltage (not shown) such that the sequential application and reduction (eg, removal) of the second bias voltage causes the piezoelectric actuator 412 expands and contracts accordingly and the second flexible part 422 bends and straightens to alternate the pump chamber 442 to compress and expand. When compressed, the pump chamber abuts 442 Fluid from the outlet port 427 off, eg while the inlet valve 446 (discussed above) is closed to prevent the fluid from entering the inlet 426 is sucked in, and the exhaust valve 448 (discussed above) is open to allow the fluid from the outlet port 427 is ejected. When it expands, the pump chamber sucks 442 Fluid through the inlet opening 426 on, for example, while the exhaust valve 448 (discussed below) is closed, which prevents fluid from passing through the outlet 427 is discharged, and the intake valve 446 (discussed above) to allow the fluid to pass through the inlet port 426 to be sucked.

The outlet valve device 403 contains the third piezoelectric actuator 413 which mechanically with the third flexible part 423 the membrane plate 420 is coupled via a boss 418 for operating the intake valve 448 in the intake valve chamber 443 , As discussed above, the third piezoelectric actuator has 413 a third axial displacement along its longitudinal axis in response to selectively applying a third bias voltage (not shown) such that sequential application and reduction (eg, removal) of the third bias voltage causes the piezoelectric actuator 413 expands and contracts accordingly and the third flexible part 423 bends and straightens to alternate the exhaust valve 448 to close and open. When it is closed, the exhaust valve prevents 448 the fluid thereupon to the inlet port 428 to be sucked in or from the outlet opening 429 (which is connected to the device outlet opening 462 over the line 408 ) by pushing the third flexible part 423 against the preceding part 449 ,

When it is open, the exhaust valve allows 448 it the fluid, to the inlet port 428 to be sucked in and out of the outlet opening 429 to be expelled.

The inlet valve device 401 , the pump device 402 and the exhaust valve device 403 contain highly rigid actuators 451 . 452 respectively. 453 , which with the corresponding first, second and third piezoelectric actuator 411 . 412 and 413 are coupled. Each one of the highly rigid actuators 451 . 452 and 453 may be a slow low compliance actuator configured to adjust a position of the corresponding first, second and third piezoelectric actuators 411 . 412 and 413 as above with respect to the high stiffness actuator 150 in 1A to 2 B discussed. In the examples shown, the highly rigid actuators 451 . 452 and 453 implemented as adjustable screw drives configured to adjust the position of the first, second and third piezoelectric actuators 411 . 412 and 413 along the corresponding longitudinal axis by appropriately moving the screw drive in clockwise or counterclockwise directions.

The operation of the intake valve device 401 and the exhaust valve device 403 are coordinated with the operation of the pump device 402 by a control device (not shown) for permitting movement of fluid from the device inlet port 461 to the device outlet port 462 through the fluid transfer device 400 substantially the same as described above with respect to the fluid transfer device 300 represented in 3 , Therefore, the specific details regarding the structure and / or operation of the controller (and associated memory) are not repeated. A micropump acting as a fluid transfer device 400 may, for example, generate pressure of from about 50 bar to over about 1000 bar.

An entire compliance of the fluid transfer device 400 is determined in part by the amount of fluid from the valve openings, eg the outlet opening 425 of the inlet valve 446 and the inlet opening 428 the exhaust valve 448 is transferred. The intake and exhaust valves 446 and 448 also have fluidic connections, eg inlet opening 424 and outlet opening 429 , which are connected to the inlet and outlet valve chambers 441 respectively. 443 couple. To reduce the amount of fluid dragged out is the pump chamber 442 With both, the outlet opening 425 of the inlet valve 446 (over the line 406 ) and the inlet opening 428 the exhaust valve 448 (over the line 407 ) connected. In this way the fluid playing in the inlet and outlet valve chambers plays 441 and 443 is not involved in determining the overall compliance of the fluid transfer device 400 , In an illustrative configuration, the depth of the pump chamber 442 on the order of about 10 μm to about 100 be μm, for example, to reduce the corresponding chamber volume. For applications in which the compliance of the fluid transfer device 400 not critical, the depth of the pump chamber can 442 be larger and / or the pump chamber 442 can with the device inlet 461 or the device outlet opening 462 outside the corresponding outlet opening 425 and inlet opening 428 be connected.

5A and 5B 12 are cross-sectional diagrams illustrating multi-valve planar microfluidic devices of integrated fluid transfer assemblies according to representative embodiments. Exactly shows 5A a cross section of a planar microfluidic device 510a and 5B shows a cross section of a planar microfluidic device 510b each of which is a membrane plate 420 which is removable via a sealing layer as discussed below.

Referring to 5A contains the planar microfluidic device 510a the membrane plate 420 , the orifice plate 430 and the connection plate 440 which are structured, aligned and interconnected to produce the various features of an integrated fluid transfer device as discussed above with respect to the fluid transfer device 400 and the corresponding planar microfluidic device 410 in 4A and 4B , In addition, a bottom surface of the membrane plate 420 removably connected to an upper surface of the orifice plate 430 through a sealing layer containing a series of O-rings, including a first O-ring 571 , a second O-ring 572 and a third O-ring 573 , The first O-ring 571 surrounds the first flexible area 421 for sealing the circumference of the inlet valve chamber 441 , the second O-ring 572 surrounds the second flexible area 422 for sealing the circumference of the pump chamber 442 and the third O-ring 573 surrounds the third flexible area 423 for sealing the circumference of the outlet valve chamber 443 , Each of the first, second and third O-rings 571 - 573 may be formed of a resilient polymer, such as Viton ^®, PTFE, Kalrez ^®, for example. Consequently, the respective seals are formed by compressing the membrane plate 420 against the first, second and third O-ring 571 - 573 What makes it possible for the membrane plate 420 to the orifice plate 430 is well-sealed. Otherwise, the formation and operation of the planar microfluidic device 510a essentially the same as discussed above with respect to the planar microfluidic device 410 ,

Similarly, referring to 5B Contains the planar microfluidic device 510b the membrane plate 420 , the orifice plate 430 and the connection plate 440 which are structured, aligned and interconnected to produce the various features of an integrated fluid transfer device as described above with respect to the fluid transfer device 400 and the corresponding planar microfluidic device 410 from 4A and 4B , In addition, a bottom surface of the membrane plate 420 removably connected to an upper surface of the orifice plate 430 through a sealing layer, which is a sealing membrane 570 contains, which may be formed of a polymer such as polyimide, PEEK, PAEK, or Vespel ^®, for example. Consequently, the seals which are the inlet valve chamber 441 , the pump chamber 442 and the exhaust valve 443 surrounded, formed by compressing the membrane plate 420 against the sealing membrane 570 What makes it possible for the membrane plate 420 to the orifice plate 430 is well-sealed. Otherwise, the formation and operation of the planar microfluidic device 510b essentially the same as discussed above with respect to the planar microfluidic device 410 ,

6 FIG. 10 is a cross-sectional diagram illustrating an actuating device according to a representative embodiment. FIG. For example, the actuating device includes a piezoelectric actuator and a highly rigid actuator for driving a planar microfluidic device, wherein the piezoelectric actuator and the high-stiffness actuator, which in 6 are shown, detailed configurations of the piezoelectric actuator 110 and the highly rigid actuator 150 which were discussed above with reference to 1 to 2 , the first, second and third piezoelectric actuators 311 - 313 and the first, second and third high-stiffness actuators 351 - 353 discussed above with reference to 3 and / or the first, second and third piezoelectric actuators 411 - 413 and the first, second and third high-stiffness actuators 451 - 453 discussed above with reference to the 4A and 4B ,

Referring to 6 includes an actuator 600 an illustrative high-stiffness actuator assembly 650 and an illustrative piezoelectric actuator assembly 610 , In the illustrated embodiment, the high-stiffness actuator assembly 650 a screw drive, eg containing a rotary motor 652 which is on a frame 680 is attached and coupled with an adjusting screw 654 with fine pitch (eg M3, 0.2 mm pitch), by a strain relief 656 , The strain relief 656 For example, takes a misalignment of the rotary motor 652 and the adjusting screw 654 on. The adjusting screw is through the frame 680 screwed and can be biased against the thread with a screw preload 658 , which is shown schematically as a spring. A first ball bearing surface 659 is machined or bonded to a distal end of the adjustment screw 654 , When the adjusting screw 654 is extended, sits the first ball bearing surface 659 in a first matching pedestal 671 the piezoelectric actuator assembly 610 and thus transmits the deflection of the adjusting screw 654 on the piezoelectric assembly 610 ,

The first counter-pedestal 671 is on a first carrier plate 672 attached, which is free, in the longitudinal (vertical) direction relative to the frame 680 to move. However, the first carrier plate is 672 laterally constrained so that it is unable to rotate, eg, about a longitudinal axis of the piezoelectric actuator 611 as discussed below. Accordingly, when the adjusting screw 654 rotates, in a clockwise or counterclockwise direction, the associated torque from the first carrier plate 672 recorded and will not be in the piezoelectric actuator 611 coupled. For example, the piezoelectric actuator 611 made of sintered material (s) and would therefore be susceptible to breakage when subjected to rotation or tension by operation of the adjusting screw 654 , The first carrier plate 672 is with the frame 680 by a first spring carrier 682 connected, shown schematically as two springs on each side of the first support plate 672 , The first spring carrier 682 pulls the first carrier plate 672 and the attached second counter socket 673 in contact with a second ball bearing surface 674 attached to one end of the piezoelectric actuator 611 is attached.

The piezoelectric actuator 611 is effectively the core of the actuator 600 , The piezoelectric actuator 611 may be any of a variety of piezo actuators, either recessed or blank, formed from any of a variety of piezoelectric materials. For example, the piezoelectric actuator 611 be a stacked piezoelectric actuator, such as the piezoelectric actuator AE0505D16F, available from Thorlabs, or a piezoelectric tube, such as the piezoelectric tube actuator PT-120, available from Physik Instrumente, although other types of piezoelectric actuators can be installed without the circumference to depart from the present teachings. In 6 the piezoelectric actuator is shown with a strain gauge 612 , The resistance of the strain gauge 612 changes when the piezoelectric actuator 611 extends to the application of a voltage across first and second voltage lines 615 and 616 or contracts for a reduction in voltage from the first and second voltage lines 615 and 616 , The strain gauge 612 is shown schematically, with a constant current through the first strain gauge line 616 can be applied and the strain gauge resistance can be monitored by measuring the voltage between the first strain gauge line 613 and the second strain gauge lead 614 is induced. In one embodiment, the strain gauge may 612 be arranged in a resistance bridge, eg with two active sensors and two dummy resistors.

Because very little torque on the piezoelectric actuator 611 should be applied, a mechanical contact is made with the piezoelectric actuator 611 through the second ball bearing surface 674 attached to one end of the piezoelectric actuator 611 is fixed, as discussed above, and a third ball bearing surface 675 at the opposite end of the piezoelectric actuator 611 is attached. The third ball bearing surface 675 contacted a third counter socket 676 , which on the second support plate 677 is attached. The second carrier plate 677 can with the frame 680 be connected by a second spring carrier 684 schematically illustrated as two springs on each side of the second carrier plate 677 , Consequently, allowed when the adjustment screw 654 is withdrawn, the first spring carrier 682 and the second spring carrier 684 the piezoelectric actuator 611 , to move freely in the longitudinal (vertical) direction, which is particularly significant when a corresponding microfluidic device (not shown in FIG 6 ) is either removed or used. Examples of the corresponding microfluidic device include microfluidic pump devices 130 and 333 represented in 1A . 1B and 3 ; Microfluidic valve devices 230 . 331 and 333 represented in 2A . 2 B . 2C and 3 ; and integrated microfluidic devices 410 . 510a and 510b represented in 4A . 4B . 5A and 5B as discussed above. The positions of the first spring carrier 682 and / or the second spring carrier 684 can be chosen, leaving a fourth counter-pedestal 679 slightly (eg, some Newtons of force) against a diaphragm or bearing carrier mounted on the diaphragm of the corresponding microfluidic device attached to the piezoelectric actuator assembly 610 is attached, is pressed.

The strain gauge 612 can for example serve two purposes. First, the strain gauge monitors 612 the extension of the piezoelectric actuator 610 and allows the piezoelectric actuator 610 moves accurately. This is helpful in that the piezoelectric actuator 610 in particular when implemented as a stacked piezoelectric actuator 610 , can show significant creep and hysteresis with the applied voltage. For this reason, in order to precisely meter the fluid expelled from the corresponding microfluidic device, it is necessary to measure the physical deflection of the piezoelectric actuator 610 to measure and place a control loop around the voltage applied to the piezoelectric actuator 610 is created. When a bias voltage of the order of, for example, about 100V across the first and second voltage lines 615 and 616 is applied, the piezoelectric actuator 610 extend by a few microns. For example, if the piezoelectric actuator 610 implemented as a piezoelectric actuator AE0505D16F, as mentioned above, applying 100 V causes the piezoelectric actuator 610 by about 12 microns expands. While a substantial portion of this 12 micron deflection occurs simultaneously with the applied voltage, there will be a few microns of additional deflection occurring over the period of minutes as the piezoelectric actuator 610 continues to "crawl".

Second, the strain gauge delivers 612 a feedback to the rotary motor 652 by, for example, a control device (not shown) for positioning the adjusting screw 654 , For example, when a corresponding microfluidic device is under the piezoelectric actuator 610 is applied, a small additional force on the piezoelectric actuator 610 applied, which is detectable as a small compression of the piezoelectric actuator 610 , The first ball bearing surface 659 attached to the adjusting screw 654 is not in contact with the first mating base at this stage 671 , When it is desired to actuate the corresponding microfluidic device, the rotary motor becomes 652 driven and a resistance signal of the strain gauge 612 is being supervised. Until the first ball bearing surface 659 the first counter-pedestal 671 contacted, there will be no resistance change. However, when a contact is made, the adjusting screw becomes 654 the piezoelectric actuator 611 compress and press down on the membrane of the corresponding microfluidic device. The compression of the piezoelectric actuator 611 gets from the strain gauge 612 detected as a decrease in resistance. Consequently, a resistance setpoint of the strain gauge 612 used to determine the appropriate preload from the adjustment screw 654 ,

In monitoring the compression of the piezoelectric actuator 611 at zero applied bias, the strain gauge can 612 also be used to monitor a thermal drift that can occur. As the piezoelectric actuator 611 may be a few inches long, a temperature change of a few degrees may cause the distal end of the piezoelectric actuator 611 varies by a few microns, in amount similar to the deflection of the piezoelectric actuator 611 , The motor 652 can compensate for this thermal drift by ensuring that the signal of the strain gauge 612 zero bias remains constant. In various embodiments, operation and / or monitoring of the rotary motor 652 , the strain gauge 612 and a voltage source (not shown) connected to the first and second voltage lines 615 and 616 is connected, by a control device (not shown) to be performed. The controller may include a processor or a CPU, ASICs, FPGAs, or combinations thereof, using software, firmware, hardwired logic, or combinations thereof, which may be similar or the same as the controller described above with respect to FIG 3 was discussed.

7 FIG. 12 is a cross-sectional diagram illustrating a multi-valve, integrated fluid transfer device according to a representative embodiment incorporating the actuator device of FIG 6 contains.

Referring to 7 includes the multi-valve integrated fluid transfer device 700 three actuator devices, a first actuator device 701 , a second actuator device 702 and a third actuator device 703 connected to a corresponding microfluidic device 410 are coupled. It is understood that each of the first, second and third actuator devices 701 . 702 and 703 essentially the same as the piezoelectric actuator 600 referring to the above 6 was discussed and therefore its description is not repeated. Similar is the microfluidic device 410 with reference to above 4A and 4B has been discussed and therefore the description will not be repeated.

In the illustrated embodiment, the microfluidic device is 410 inserted or attached to the external first, second and third actuator device 701 . 702 and 703 , After a fluidic connection has been made with the device inlet port 461 and the device outlet port 462 , are the adjustable screws 654a . 654b and 654c the first, second and third actuator device 701 . 702 and 703 corresponding to the intake valve chamber 441 , the pump chamber 442 and the exhaust valve chamber 443 extended until the appropriate extensometer 612a . 612b and 612c reach their corresponding setpoints.

The integrated fluid transfer device 700 is primed by flowing fluid at low pressure through the inlet chamber 441 , the pump chamber 442 and the exhaust valve chamber 443 , The piezoelectric actuator 611a which is the inlet valve 446 is extended by applying 100 V to the inlet valve 446 close. The piezoelectric actuator 611b , which is the pump chamber 442 is extended by applying a continuously variable voltage of less than 100 V to compress the pump chamber 442 , The expansion of the piezoelectric actuators 611a and 611 can be monitored using the appropriate strain gauges 612a and 612 and the applied voltage may be controlled to provide a continuous flow of fluid.

When the piezoelectric actuator 611b , which is the pump chamber 442 corresponds, reaches its full extent, becomes the piezoelectric actuator 611c , which is the outlet valve 448 equals, extended by applying 100 V to the exhaust valve 448 close and the piezoelectric actuator 611a which is the inlet valve 446 is contracted by applying 0 V to the previously open inlet valve 446 , In the meantime, the piezoelectric actuator 611b , which is the pump chamber 442 equal to, contracted by applying 0 V, which is the pump chamber 442 allowed to expand. The pumping operation then continues by repeating the alternate application of 100V and 0V to the piezoelectric actuators 611a - 611c , That is, the piezoelectric actuator 611a which is the inlet valve 426 corresponds, in turn, is extended by applying 100 V to the inlet valve 426 close while the piezoelectric actuator 611c , which is the outlet valve 428 corresponds, is contracted again by applying 0 V to the exhaust valve 428 to open.

In the present example, the piezoelectric actuator 611b , which is the pump chamber 442 equals about 6 microns at each pump cycle, causing about 20 nL from the device outlet 462 be ejected. It is relatively straightforward, the piezoelectric actuators 611a - 611c to control 1/1000 of their travel path using the appropriate strain gauges 612a - 612c , and thus it is possible to control the fluid flow with 20 picoliter / min accuracy in the present example. In addition, the piezoelectric actuators 611a - 611c able to operate at high frequencies and reliable operation is possible up to 100 Hz, corresponding to a flow rate of 120 μL / min.

In various configurations, the deflection of the piezoelectric actuator 611b be relatively small relative to the size of the pump chamber 442 , It is important in such a configuration that the integrated fluid transfer device 700 or otherwise, air bubbles may degrade the performance. Fluids used, for example, with HPLC instruments are usually degassed before entering the integrated fluid transfer device 700 which makes it easier to aspirate because small air bubbles tend to diffuse back into the fluid. However, air bubbles in the fluid should still be minimized. A vivid process to a pump chamber and valves, such as the pump chamber 442 , the inlet valve 446 and the exhaust valve 448 the microfluidic device 410 That is, to prime to mitigate the formation of air bubbles in the fluid is described below.

The device outlet opening 462 should first over the device inlet 461 be positioned. For example, the microfluidic device 410 be rotated (eg, by about 90 °) so that the device outlet opening 462 essentially above the device inlet opening 461 is arranged. An organic fluid, such as methanol, may be used to prime and then be replaced with the desired operating fluid, such as water, acetonitrile and methanol, for example. The entire microfluidic device 410 can be pumped out before it is aspirated and then backfilled with carbon dioxide (CO ₂ ), which dissolves more easily in most fluids. Also, the inner surfaces of the intake and exhaust valve chambers 441 and 443 and the pump chamber 442 coated with a hydrophilic or hydrophobic polymer to aid in aspiration. The hydrophilic or hydrophobic polymer may be patterned to ensure that no bubbles are trapped when the fluid enters the inlet valve chamber 441 , the pump chamber 442 and / or the outlet valve chamber 443 entry.

Additionally, mechanical features may be in one or more of the inlet and outlet valve chambers 441 and 443 and / or the pump chamber 442 be incorporated, such as illustratively raised structures (which may include, for example, multiple ribs) shown in 8A to 9B and vividly recessed structures (which may include, for example, multiple grooves) shown in FIG 10A to 10B , The raised structures stop the growth of fluid droplets as the fluid enters the inlet and outlet valve chambers 441 and 443 and / or the pump chamber 442 entry. The fluid does not go into the next section until the area between each raised part or rib of the raised structure and a corresponding inlet (or previous raised part) is completely filled with fluid. In this way, inlet and outlet valve chambers 441 and 443 and / or the pump chamber 442 filled with very little trapped air.

8A and 8B 10 show cross-sectional diagrams illustrating a valve chamber having a raised structure according to a representative embodiment. In particular shows 8B the cross section of 8A along the line B-B '. Referring to 8A and 8B contains a representative inlet valve chamber 841 an inlet valve 846 which is formed by bending and straightening a flexible membrane 821 on a protruding part 847 in response to operation of a piezoelectric actuator (not shown) as discussed above. Fluid enters the inlet valve chamber 841 through the inlet opening 824 and exits the inlet valve chamber 841 through the outlet opening 825 , The inlet valve chamber 841 Also includes a raised structure having first and second ribs or raised portions 845 and 846 which are raised concentric circles, which are the protruding part 847 surround. Of course, more or less raised parts may be included without departing from the scope of the present teachings.

9A and 9B FIG. 10 are cross-sectional diagrams illustrating a pumping chamber having a raised structure according to a representative embodiment. FIG. In particular shows 9B the cross section of 9A along the line C-C '. Referring to 9A and 9B is a representative pump chamber 942 formed by bending and straightening a flexible membrane 922 in response to operation of a piezoelectric actuator (not shown) as discussed above. Fluid enters the pump chamber 942 through the inlet opening 925 and leaves the pump chamber 942 through an outlet opening 927 , The pump chamber 942 contains a raised structure, which contains first to fifth raised parts 951 - 955 having. In the illustrated example, the third raised part passes through 953 the inner diameter of the pump chamber 942 while the first and second raised parts 951 and 952 from the third sublime part 953 turn left and the fourth and fifth raised parts 954 and 955 bend from the third sublime part 953 right away. Of course, more or less raised parts may be included without departing from the scope of the present teachings.

10A and 10B 10 are cross-sectional diagrams illustrating a pumping chamber having a recessed structure according to a representative embodiment. In particular shows 10B the cross section of 10A along the line D-D '. Referring to 10A and 10B is the representative pump chamber 1042 formed by bending and straightening a flexible membrane 1022 in response to the operation of a piezoelectric actuator (not shown) as discussed above. Fluid enters the pump chamber 1042 through the inlet opening 1026 and leaves the pump chamber 1042 through the outlet opening 1027 , The pump chamber 1072 Also includes an etched recessed structure, which first to fifth grooves or recessed parts 1051 - 1055 having. In the example shown, the third recessed part passes through 1053 the inner diameter of the pump chamber 1042 while the first and second recessed parts 1051 and 1052 from the third recessed part 1053 turn left and the fourth and fifth recessed parts 1054 and 1055 from the third recessed part 1053 turn right away. Of course, more or less recessed parts may be included without departing from the scope of the present teachings.

In another embodiment, the pump chamber and / or the valve chamber may include a gas permeable membrane. For example 11A and 11B Cross-sectional diagrams illustrating a pumping chamber having a gas-permeable membrane according to a representative embodiment. In particular shows 11B the cross section of 11A along the line E-E '. Referring to 11A and 11B , is a representative pump chamber 1142 formed by bending and straightening a flexible membrane 1122 in response to operation of a piezoelectric actuator (not shown) as discussed above. Fluid enters the pump chamber 1142 through the inlet opening 1126 and leaves the pump chamber 1142 through the outlet opening 1127 , The stacked membrane plate 1120 , the orifice plate 1130 and the connection plate 1140 are structured on one or both sides to the pump chamber 1142 , the inlet opening 1126 and the outlet opening 1127 to form as shown. In addition, the gas permeable membrane 1125 formed between the membrane plate 1120 and the orifice plate 1130 , which allows trapped air bubbles (or other gases), the pump chamber 1142 leave while the fluid is retained. The gas permeable membrane 1125 may be formed of various membrane materials, such as Nafion ^®, silicone rubber, agarose or porous Teflon ^®, for example, although other materials may be included, without departing from the scope of the present teachings. The material used depends, at least in part, on the fluid being pumped and the internal pressure of the pump chamber 1142 ,

For certain implementations, such as in HPLC instruments, the fluid transfer device should have a continuous flow. The fluid transfer devices 300 . 400 respectively. 700 as related to 3 . 4A . 4B and 7 for example, can not provide a continuous flow because the external fluid flow stops when the corresponding pump chamber 342 . 442 is filled. In contrast to this are 12A and 12B Cross-sectional diagrams showing a multi-valve, integrated fluid transfer device having a continuous flow, according to a representative embodiment. In particular shows 12B the cross section of 12A along the line F-F '.

Referring to 12A contains the integrated fluid transfer device 1200 an intake valve device 1201 , a first pumping device 1202 , an exhaust valve device 1203 and a second pump device 1204 , which is an integrated planar microfluidic device 1210 share. That is, in the illustrated embodiment, the inlet valve chamber 1241 , the first pump chamber 1242 , the outlet valve chamber 1243 and the second pump chamber 1244 made as separate regions in the single microfluidic device 1210 , The integrated fluid transfer device 1200 , as in 12A and 12B can be referred to as a binary pump, for example.

As above with respect to 4A and 4B discussed contains the microfluidic device 1210 three separate layers or plates, which serve as a membrane plate 1220 , Orifice plate 1230 and connecting plate 1240 each of which may be patterned on one or both sides, eg, using electrochemical etching, to accommodate the various features of the integrated fluid transfer devices 1200 when aligned and interconnected. These features include the device inlet port 1261 , the inlet valve chamber 1241 , the first pump chamber 1242 , the outlet valve chamber 1243 and the second pump chamber 1244 and the device outlet port 1262 as well as inlet and outlet openings 1224 - 1229 and 1276 - 1277 and fluid lines 1205 - 1209 showing the fluid communication of the device inlet ports 1261 , the inlet valve chamber 1241 , the first pump chamber 1242 , the outlet valve chamber 1243 , the second pump chamber 1244 and the device outlet port 1262 enable each other.

It is understood that each of the inlet valve device 1201 , the first pump device 1202 , the outlet valve device 1203 and the second pump device 1204 a corresponding external piezoelectric actuator having axial deflections along its longitudinal axis, such as the first piezoelectric actuator 411 referring to the above 4A was discussed (as well as a corresponding highly rigid actor and / or bosses). However, the piezoelectric actuators are in 12A not shown, for clarity and to simplify the description. The structure and functionality of the piezoelectric actuators are essentially the same as discussed above.

The inlet valve chamber 1241 and the exhaust valve chamber 1243 contain a corresponding inlet valve 1246 and exhaust valve 1248 By bending and straightening first and third flexible areas 1221 and 1223 the membrane plate 1220 operate by operating corresponding piezoelectric actuators (not shown). Similarly, the first pump chamber work 1242 and the second pump chamber 1244 by bending and straightening second and fourth flexible areas 1222 and 1224 the membrane plate 1220 by operating respective piezoelectric actuators (not shown). As in 12B shown, the first to fourth flexible area 1221 - 1224 for example, be circular in shape. The protruding parts 1247 and 1249 may be equally circular in shape and may be within the first and third flexible regions 1221 respectively. 1223 be centered. The first to fourth flexible areas 1221 - 1224 may be the same or different in size and / or shape as discussed above. Otherwise, the structure and operation of the intake valve 1246 and the exhaust valve 1248 be substantially the same as that of the intake valve 446 and the exhaust valve 448 and the structure and operation of the first pump chamber 1242 and the second pump chamber 1244 are essentially the same as those of the pumps 442 as above with respect to 4A and 4B discussed. Therefore, the descriptions are not repeated herein.

The operation of the intake valve device 1201 and the exhaust valve device 1203 are coordinated with the operation of the first pump device 1202 and the second pump device 1204 by a control device (not shown) for permitting movement of fluid from the device inlet port 1261 to the device outlet port 1262 through the fluid transfer device 1200 substantially as above with respect to the fluid transfer device 300 , in the 3 is discussed.

An illustrative operation of the integrated fluid transfer device 1200 which provides a continuous flow of fluid will be described below. In the illustrated embodiment, the microfluidic device is 1210 inserted in or attached to the corresponding external piezoelectric actuators (not shown). Having a fluidic connection with the device inlet port 1261 and the device outlet port 1262 are made, the adjustable screws or other external high-stiffness actuators (not shown), which the intake valve chamber 1241 , the first pump chamber 1242 , the outlet valve chamber 1243 and the second pump chamber 1244 Extend until their corresponding strain gauges reach their respective setpoints as discussed above. The integrated fluid transfer device 1200 is sucked by flowing fluid under low pressure through the inlet valve chamber 1241 , the first pump chamber 1242 , the outlet valve chamber 1243 and the second pump chamber 1244 , Initially, a piezoelectric actuator, which is the exhaust valve device 1203 corresponds, by applying 100 V extended to the exhaust valve 1248 close.

In a first action, a piezoelectric actuator, which is the inlet valve device 1210 corresponds, contracted by applying 0 V, to open the inlet valve 1246 and then a piezoelectric actuator, which is the first pumping device 1202 corresponds, similarly contracted for filling the first pump chamber 1242 with fluid. The piezoelectric actuator, which is the inlet valve device 1201 is then expanded by applying 100V to the inlet valve 1246 and the chamber piezoelectric actuator which is the first pumping device 1202 corresponds, is slightly extended to the pressure in the first pump chamber 1242 with the pressure on the second pump chamber 1244 to balance approximately. This state is maintained until completion of a second action described in the following paragraph, which should be performed substantially concurrently with the first action.

In the second action, a piezoelectric actuator, which is the second pumping device 1204 is extended by applying a continuously variable voltage of less than 100V to compress the second pumping chamber 1244 , The expansion of the piezoelectric actuator is monitored, eg, using a strain gauge, and the applied voltage is controlled to provide the continuous flow of fluid. When the piezoelectric reaches full extension, the piezoelectric actuator, which is the exhaust valve device 1203 corresponds, contracted by applying 0 V to open the exhaust valve 1248 ,

In a third action, a piezoelectric actuator, which is the first pump device 1202 is extended by applying a continuously variable voltage of less than 100V to compress the first pumping chamber 1241 , The expansion of the piezoelectric actuator is monitored, eg, using a strain gauge, and the applied voltage is controlled to provide a continuous flow of fluid that is greater than the desired flow. When the piezoelectric actuator of the first pump device 1202 reaches its full extent, the process is repeated, for example by restarting with the expansion of the piezoelectric actuator, which the exhaust valve device 1203 by applying 100V to close the exhaust valve 1248 and then performing the first to fourth actions, wherein the fourth action is to be performed substantially concurrently with the third action.

In the fourth action, the piezoelectric actuator, which is the second pump device 1204 , contracted by applying a continuously variable voltage of less than 100 V, which is the second pumping chamber 1244 allowed to expand. The applied voltage is controlled, for example, using strain gauges of the piezoelectric actuators corresponding to the first and second pumping devices 1202 and 1204 for pumping a continuous flow of fluid at the desired level. Because the first pump chamber 1242 generates a larger flow of fluid than the desired flow, the second pump chamber 1244 fill with fluid during the fourth action. The integrated fluid transfer device 1200 is thus able to provide a continuous flow.

Of course, various alternative configurations and / or arrangements of one or more fluid transfer devices may be incorporated without departing from the scope of the present teachings. For example, a fluid transfer device may include an intake valve device, followed by a plurality of interconnected pump devices, followed by an exhaust valve device. This configuration multiplies the displacement volume of a pumping chamber in a single pumping device by, however, more pumping devices contained between the inlet and outlet valve devices. Several interconnected pumping devices have an advantage over simply increasing the lateral size of a single pumping chamber, which can reduce the stiffness of the flexible diaphragm in the pumping device, making it more susceptible to undesirable mechanical deformation at high backpressures.

Furthermore, a plurality of fluid transfer devices, e.g. configured in accordance with one or more of the embodiments discussed herein, in parallel and / or in series combinations to provide additional benefits. For example, the plurality of fluid transfer devices may be connected in parallel with corresponding device inlet ports connected together and corresponding device outlet ports connected together. The individual fluid transfer devices can then be operated synchronously or asynchronously. Synchronized actuation increases a volumetric flow rate by multiplying the flow rate of a single fluid transfer device by, however, many fluid transfer devices connected in parallel with each other. Asynchronous (or staggered) actuation may include pulsed vapors for continuous flow and / or e.g. generate time-varying flow rates.

Similarly, the plurality of fluid transfer devices may be connected in series with multiple inlet and outlet valve devices configured separately by one or more pump devices so that the outlet port of each outlet valve device is connected to the inlet port of a subsequent inlet valve device. This stepped configuration allows pumping against higher pressures. Each respective pump chamber (s) of the interconnected fluid transfer devices would incrementally add its individual maximum achievable pressure to the pressure generated by the pump chamber (s) of the previous fluid transfer device (s). Therefore, the maximum achievable pressure would be equal to the sum of the maximum achievable pressures of the constituent equivalent transfer devices.

While specific embodiments are disclosed herein, variations are possible which remain within the concept and scope of the invention. Such variations would become apparent upon inspection of the specification, drawings, and claims herein. The invention is therefore not intended to be limited except within the scope of the appended claims.

Claims (15)

Fluid transfer device ( 100 . 200 ) comprising: a piezoelectric actuator ( 110 ), which externally with a microfluidic device ( 130 . 230 The piezoelectric actuator has an axial displacement along a longitudinal axis in response to application of a bias voltage, wherein the axial displacement of the piezoelectric actuator of one of an internal valve ( 240 . 245 ) and an internal pump chamber ( 140 ) of the microfluidic device. Device according to claim 1, further comprising at least one of the following features: a highly rigid actuator ( 150 ) coupled to the piezoelectric actuator and configured to dynamically adjust a position of the piezoelectric actuator relative to the microfluidic device. Apparatus according to claim 1 or 2, wherein the axial displacement of the piezoelectric actuator is less than about 10 microns. The device of claim 1, wherein the bias voltage is applied to the piezoelectric actuator in a periodic manner to cause one of the internal valve and the internal pump chamber to provide fluid pumping functionality. The device of claim 1, wherein the bias voltage applied to the piezoelectric actuator continuously changes to maintain a constant axial deflection and to cause one of the internal valve and the internal pump chamber to provide flow restriction functionality. Fluid transfer device ( 300 . 400 ), comprising: a microfluidic device ( 301 . 401 ), which is a first valve ( 346 . 446 ) containing a valve chamber ( 341 . 441 ), wherein operation of the first valve allows fluid to enter the valve chamber through an orifice (10). 324 . 325 . 424 . 425 ) enter or exit; and a first piezoelectric actuator ( 311 . 411 ) coupled to the microfluidic device and configured to expand along a first longitudinal axis in response to application of a first bias voltage to close the first valve and to contract along the first longitudinal axis in response to a reduction in the first applied first bias voltage for opening the first valve, wherein the first piezoelectric actuator is external to the microfluidic device. The device of claim 6, wherein the first piezoelectric actuator comprises one of a stacked piezoelectric actuator or a piezoelectric tube. Device according to one of claims 6 or 7, further comprising: a highly rigid actuator ( 351 . 451 ), which is coupled to the piezoelectric actuator and is configured to adjust a position of the piezoelectric actuator with respect to the microfluidic device, wherein the high stiffness actuator is external to the microfluidic device. Device according to claim 8, wherein the high-stiffness actuator has an adjustable screw drive ( 351 . 451 . 650 ) configured to adjust the position of the piezoelectric actuator along the longitudinal axis, the adjustable screw drive comprising a rotary motor coupled to a fine pitch screw in contact with the piezoelectric actuator. Device according to one of claims 8 or 9, further comprising: a strain gauge ( 612 ) disposed between the first piezoelectric actuator and the high stiffness actuator, wherein the strain gauge is configured to detect compression of the first piezoelectric actuator and provide feedback to the high stiffness actuator for adjusting the position of the first piezoelectric actuator relative to the microfluidic device on the detected compression. Device according to one of claims 6 to 10, wherein the microfluidic device further comprises a pump chamber ( 342 . 442 ) which communicates with the valve chamber via an opening ( 326 . 426 ), wherein operation of the first valve allows fluid to enter or exit the pump chamber through the opening. The device of claim 11, further comprising: a second piezoelectric actuator ( 312 . 412 ) coupled to the microfluidic device and configured to expand and contract along a second longitudinal axis in response to selectively applying a second bias voltage to compress and expand the pumping chamber ( 342 . 442 ), wherein the second piezoelectric actuator is external to the microfluidic device. The apparatus of claim 11 or 12, wherein at least one of the pumping chamber and the valve chamber has a raised structure configured to arrest the growth of droplets as the fluid enters the at least one of the pumping chamber and the valve chamber. The apparatus of any one of claims 11 to 13, wherein at least one of the pumping chamber and the valve chamber has a recessed structure configured to arrest growth of droplets as the fluid enters the at least one of the pumping chamber and the valve chamber. Device according to one of claims 11 to 14, wherein at least one of the pump chamber and the valve chamber, a gas-permeable membrane ( 1125 ) configured to allow air bubbles trapped in the fluid to exit the at least one of the pumping chamber and the valve chamber.

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