WO1999042804A2 - Procede d'aspiration et de distribution microfluidique - Google Patents

Procede d'aspiration et de distribution microfluidique Download PDF

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Publication number
WO1999042804A2
WO1999042804A2 PCT/US1999/003677 US9903677W WO9942804A2 WO 1999042804 A2 WO1999042804 A2 WO 1999042804A2 US 9903677 W US9903677 W US 9903677W WO 9942804 A2 WO9942804 A2 WO 9942804A2
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WO
WIPO (PCT)
Prior art keywords
fluid
aspirate
pressure
valve
dispense
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Application number
PCT/US1999/003677
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English (en)
Other versions
WO1999042804A3 (fr
Inventor
Tony Lemmo
Don Rose
Original Assignee
Cartesian Technologies, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cartesian Technologies, Inc. filed Critical Cartesian Technologies, Inc.
Priority to AU27757/99A priority Critical patent/AU2775799A/en
Publication of WO1999042804A2 publication Critical patent/WO1999042804A2/fr
Publication of WO1999042804A3 publication Critical patent/WO1999042804A3/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • B01L3/0268—Drop counters; Drop formers using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L13/00—Cleaning or rinsing apparatus
    • B01L13/02—Cleaning or rinsing apparatus for receptacle or instruments
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • B01L3/0265—Drop counters; Drop formers using valves to interrupt or meter fluid flow, e.g. using solenoids or metering valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00378—Piezo-electric or ink jet dispensers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00608—DNA chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries

Definitions

  • the present invention provides aspirating and dispensing methodology in accordance with one preferred method or embodiment which overcomes some or all of the above-mentioned disadvantages by actively controlling the hydraulic pressure in the aspirate-dispense system.
  • this active control utilizes a series of operations that adjust a positive displacement pump and/or a drop-on-demand valve of the aspirate-dispense system or apparatus.
  • these operations provide repeatable, accurate and efficient performance, and minimize wastage and dilution of reagent.
  • the present invention provides an apparatus adapted to aspirate and/or dispense predetermined quantities of a fluid specimen from a source and onto a target.
  • the apparatus includes a wash fluid source, such as distilled water.
  • An aspirate/dispense tube is provided in fluid communication with the wash fluid source and has an open end adapted to be dipped into the fluid specimen source and then positioned over the target.
  • a positive displacement pump is provided interposed between the wash fluid source and the aspirate/dispense tube and is adapted to displace or withdraw predetermined quantities of wash fluid.
  • a valve is provided interposed between the positive displacement pump and the aspirate/dispense tube.
  • Figure 2 is a cross-sectional detail view of the syringe pump of Figure 1;
  • Figure 3 is a schematic illustration of a solenoid valve dispenser for use in the system of Figure 1;
  • FIG. 1 is a schematic drawing of a microfluidic aspirate-dispense apparatus or system 10 having features in accordance with one preferred embodiment of the present invention.
  • the aspirate-dispense system 10 generally comprises a dispenser 12 and a positive displacement syringe pump 22 intermediate a reservoir 16.
  • the dispenser 12 generally comprises a dispenser 12 and a positive displacement syringe pump 22 intermediate a reservoir 16.
  • the dispenser generally comprises a dispenser 12 and a positive displacement syringe pump 22 intermediate a reservoir 16.
  • the positive displacement pump 22 meters the volume and/or flow rate of the reagent aspirated and, more critically, of the reagent dispensed.
  • the reservoir 16 contains a wash or system fluid 14, such as distilled water, which fills most of the aspirate-dispense system 10.
  • a robot arm may be used to maneuver the aspirate-dispense system 10 or alternatively the aspirate-dispense system 10 and/or its associated components may be mounted on movable X,
  • the pump 22 is preferably a high-resolution, positive displacement syringe pump hydraulically coupled to the dispenser 12.
  • pump 22 may be any one of several varieties of commercially available pumping devices for metering precise quantities of liquid.
  • a syringe-type pump 22, as shown in Figure 1 is preferred because of its convenience and commercial availability.
  • a wide variety of other direct current fluid source means may be used, however, to achieve the benefits and advantages as disclosed herein. These may include, without limitation, rotary pumps, peristaltic pumps, squash-plate pumps, and the like, or an electronically regulated fluid current source.
  • the syringe pump 22 generally comprises a syringe housing 62 of a predetermined volume and a plunger 64 which is sealed against the syringe housing by 0-rings or the like.
  • the plunger 64 mechanically engages a plunger shaft 66 having a lead screw portion 68 adapted to thread in and out of a base support (not shown).
  • a base support not shown.
  • Any number of suitable motors or mechanical actuators may be used to drive the lead screw 68.
  • a stepper motor 26 ( Figure 1) or other incremental or continuous actuator device is used so that the amount and/or flow rate of fluid or reagent can be precisely regulated.
  • the syringe pump 22 is connected to the reservoir 16 and the dispenser 12 using tubing 23 provided with luer-type fittings for connection to the syringe and dispenser.
  • Various shut-off valves 25 and/or check valves may also be used, as desired or needed, to direct the flow of fluid 14 to and from the reservoir 16, syringe pump 22 and dispenser 12.
  • the dispenser 12 may be any one of a number of dispensers well known in the art for dispensing a liquid, such as a solenoid valve dispenser, a piezoelectric dispenser, a fluid impulse dispenser, a heat actuated dispenser or the like.
  • a solenoid dispenser 12 schematically illustrated in Figure 3, is preferred.
  • the solenoid valve dispenser 12 generally comprises a solenoid-actuated drop- on-demand valve 20, including a valve portion 34 and a solenoid actuator 32, hydraulically coupled to a tube or tip 36 and nozzle 38.
  • the solenoid valve 20 is energized by one or more electrical pulses 13 provided by a pulse generator 19.
  • a detailed description of one typical solenoid valve dispenser can be found in U.S. Patent No. 5,741,554, incorporated herein by reference.
  • the wash fluid reservoir 16 may be any one of a number of suitable receptacles capable of allowing the wash fluid 14, such as distilled water, to be siphoned into pump 22.
  • the reservoir may be pressurized, as desired, but is preferably vented to the atmosphere, as shown, via a vent opening 15.
  • the particular size and shape of the reservoir 16 is relatively unimportant.
  • a siphon tube 17 extends downward into the reservoir 16 to a desired depth sufficient to allow siphoning of wash fluid 14.
  • the siphon tube 17 extends as deep as possible into the reservoir 16 without causing blockage of the lower inlet portion of the tube 17.
  • the lower inlet portion of the tube 17 may be cut at an angle or have other features as necessary or desirable to provide consistent and reliable siphoning of wash fluid 14.
  • the hydraulic coupling between the pump 22 and the dispenser 12 provides for the situation where the input from the pump 22 exactly equals the output from the dispenser 12 under steady state conditions. Therefore, the positive displacement system uniquely determines the output volume of the system while the operational dynamics of the dispenser 12 serve to transform the output volume into ejected drop(s) having size, frequency and velocity.
  • the models included herein depict the basic theory of operation of the positive displacement dispense/aspirate system of Figure 1. Of course, the models may also apply to other direct current fluid source dispensing devices for dispensing small quantities of fluid. These models examine the design and operation of the dispensing system from a mathematical, physical, circuit and block diagram perspective representation, with each perspective being equivalent but offering a distinct view of the system.
  • the positive displacement pump 22 is placed in series with the dispenser 12 ( Figures 1 and 4) and has the benefit of forcing the dispenser 12 to admit and eject a quantity and/or flow rate of reagent as determined (under steady state conditions) solely by the positive displacement pump 22.
  • the syringe pump 22 acts as a forcing function for the entire system, ensuring that the desired flow rate is maintained regardless of the duty cycle, frequency or other operating parameters of the dispensing valve, such as the solenoid-actuated valve 20. This is certainly true for steady state operation, as discussed in more detail below. However, for non- steady state operation, it has been discovered that the elastic capacitance of the feedline and precipitated gaseous bubbles in the system can cause transient changes in dispensing pressure and system behavior.
  • a major part of the hydraulic compressibility or compliance within the system 10 ( Figures 1 and 4) is due to precipitated air.
  • the nominal solubility of air in liquids is in the range of about 2%. Even a small amount of this air converted to bubbles within the hydraulic system will dominate the compliance of the system 10.
  • the dissolved air represents an important variable in determining the compliance or elastic capacitance, C, and hence determining the actuations of the drop-on-demand valve 20 ( Figures 3 and 4) and syringe pump 22 ( Figures 1 and 4) to bring the system to the desired predetermined and/or steady state pressure conditions (as discussed in greater detail herein below).
  • the reagents used with the method of the present invention can be degassed, by using known surfactants.
  • the aspirate-dispense apparatus 10 ( Figure 1) can also be configured to minimize the formation and accumulation of gaseous bubbles within the fluid residing in the system 10 and particularly in the feedline 23 and dispenser 12.
  • the components of the aspirate-dispense system 10 can be configured so that the fluid movements within the system avoid sharp local pressure drops, and hence gaseous bubble precipitation.
  • the components may be configured such that none or few "dead spots" are encountered by the fluid, thereby discouraging bubble accumulation within the system.
  • bubble removal means such as a suitably configured bubble trap, may be used. Nevertheless, despite whatever measures are taken, there will be at least some elastic compliance in the system which can cause transient variations in performance. These are discussed in more detail below.
  • Capillary flow resistance applies to flow through sections of tubes and pipes.
  • Orifice flow resistance applies to constrictions or changes in flow direction.
  • Capillary resistance can be represented by the following:
  • R c is the capillary flow resistance
  • Q is the flow rate
  • a c is the cross-sectional area
  • u is the mean velocity of flow
  • ⁇ is the flow resistivity
  • L c is the capillary length
  • ⁇ is the viscosity
  • r c is the radius of the circular capillary.
  • R 0 is the orifice flow resistance
  • p is the fluid density
  • a render is the cross-sectional area
  • C d is the discharge coefficient
  • the fluid velocity profile is parabolic with zero velocity at the capillary wall and the maximum velocity at the center.
  • the mean velocity u is one half the maximum velocity.
  • the fluid has mass and inertia, there is a time constant associated with the buildup of flow in the tube. This is modeled as an inductance in series with the resistance.
  • the derivation of the inertial time constant, r is illustrated in Modeling Axisymmetric Flows, S. Middleman, Academic Press, 1995, Page 99, incorporated herein by reference.
  • the time constant, r can be defined as:
  • the system 10 generally includes a stepper motor 26, a syringe pump 22, a feedline 23, and a drop-on-demand valve 20, with a solenoid actuator 32 and a valve portion 34, coupled to a tip 36 and a nozzle 38.
  • the syringe pump 22 ( Figures 1 and 4) of the system acts as a fluid current source and forces a given volume per step into the system.
  • the force available from the stepper motor 26 ( Figures 1 and 4) is essentially infinite, due to the large gear ratio to the syringe input. The input is impeded from the forces feeding back from the system. Since volume, V, is the integral of the flow rate:
  • the syringe pump is therefore a current source rather than a pressure (voltage) source. Since any impedance in series with a current source has no effect on the flow rate, this has the beneficial effect of removing the influence of the impedance of the feed line (resistance and inductance) on the flow rate.
  • this solves a major problem that would be present if a pressure source were used as the driving function.
  • the feedline impedance would offer a changing and/or unpredictable resistance to flow and could give rise to hydraulic hammer pressure pulses and varying pressure drops across the feedline which could affect the flow rate through the dispense system, and hence the fluid output.
  • a current source such as the syringe pump, the effect of changes in fluid impedance is substantially negligible or none on the flow rate, and thus accurate fluid volumes can be readily dispensed.
  • a simplified circuit analogue representation 40 of the dispense system 10 (Figure 1) is shown in Figure 5.
  • the syringe pump 22 forces a total flow rate of Q, into the system.
  • the flow is comprised of Q c and Q_.
  • Q. is the flow that is driven into the elastic capacitance C t of the system and Q Sunday is the flow rate that is output from the nozzle 38 of the system.
  • the inductance L, and resistance R are the totals of all elements within the valve 20, tip 36, nozzle 38 and feedline 23.
  • the valve resistance R v varies with the actuation displacement of the valve 20 during operation from forces applied by the solenoid actuator 32. When the valve 20 is closed, the valve resistance R v is infinite.
  • the pressure in the feedline 23 is P
  • the pressure at the nozzle 38 is P n .
  • FIG. 6A A block diagram or control system representation 42 of the dispense system 10 (Figure 1) is shown in Figure 6A. This is perhaps the best way to see why the output fluid volume is synchronized to the syringe input.
  • this block diagram model 42 represents a feedback loop, in which the difference between Q, and 0. drives the flow into the elastic capacitance, Q c . If the flow out of the nozzle 38 is not exactly the same as the flow input, Qnd then the pressure in the feedline 23 , P f , will change. The feedback loop forces the value of P, to be whatever is necessary, at steady state, to maintain the output flow rate, Q linen, to equal the input flow rate, Q t . This is true regardless of the value of R t .
  • the block diagram model 42 ( Figure 6A) indicates that the system has the potential for damped oscillations in flow.
  • the elastic capacitance is an integrator and the inertial time constant, r, in the loop can give rise to the possibility of underdamped oscillations in transient flow. These oscillations may show up in pressure readings in the feedline 23 ( Figures 1 and 4).
  • the magnitude of the oscillations is dependent on the damping, which, in turn, is dependent on the flow resistance and the resonate frequency of the system.
  • W(s) transfer function of the system expressed in the Laplace domain
  • control block diagram 42 ( Figure 6A) can also be represented by a simplified equivalent block diagram 60 ( Figure 6B) with a block element 61 ( Figure 6B).
  • the control or block element 61 ( Figure 6B) incorporates the reduced forward transfer function of equation (14).
  • the feedback transfer function H for the block diagram 42 ( Figure 6A) may be expressed as follows:
  • Equation (16) can be simplified to yield the closed-loop transfer function in a reduced form, as shown below by equation (17):
  • K the gain and Z(s) and P(s) are polynomials which yield the zeros and poles.
  • FIG. 6C shows a sketch of a root locus diagram 72 for the control system representation 42 ( Figure 6A).
  • the root locus diagram 72 is plotted in the s-plane and includes a real axis 74, Re(s), an imaginary axis 76, lm(s), and a sketch of the root locus 78.
  • the determination of the root locus relies on a knowledge of the zeros and poles of the control system.
  • the root locus 78 ( Figure 6C) will have two branches and two zeros at infinity.
  • the nozzle 38 may be positioned over a waste receptacle (not shown) and the drop-on-demand valve 20 (Figure 3) opened and closed rapidly without operating the syringe pump 22 ( Figures 1 and 2).
  • the opening of the valve 20 causes some system fluid 14 ( Figure 1) and/or any residual aspirated source fluid from the prior aspirate function to be dispensed into the waste position due to the dispense steady state pressure (line 124) or any residual pressure within the system 10 ( Figure 1).
  • the residual pressure (line 124) dissipates and the system pressure stabilizes to a value near zero.
  • this "venting" of system pressure can concurrently serve as a wash function.
  • the valve 20 ( Figure 3) may remain closed while the syringe pump 22 ( Figures 1 and 2) is operated in the reverse direction, as required to release system pressure.
  • the residual pressure may also be released by providing a separate relief valve (not shown) for the syringe pump 22 ( Figure 1) and/or the shut-off valve 25 (Figure 1) can be opened to release system fluid 14 ( Figure 1) back into the reservoir 16 ( Figure 1).
  • a vacuum dry may be used to remove any excess fluid that may have adhered to the outer surface of the nozzle 38 and/or tip 36 (Figure 3) during aspiration and wash cycles.
  • Figure 11 schematically illustrates a system 79 for performing such a vacuum dry.
  • the system 79 generally includes a pump 80 connected to one or more vacuum apertures 82.
  • the nozzle 38 and/or tip 36 ( Figure 3) is inserted into a vacuum aperture 82 ( Figure 11).
  • the pump 80 ( Figure 11) is activated for a predetermined amount of time and provides enough suction to remove or suck any excess fluid sticking to the outer surface of the nozzle 38 and/or tip 36 ( Figure 3) without disturbing the aspirated fluid.
  • the non-pressure compensated (non-steady state) dispensed volume represented by line 910 is substantially smaller than the target dispense volume of 100 nL (line 914) since the system pressure at start-up is substantially lower than the desired steady state and/or predetermined pressure.
  • the non-pressure compensated dispense volume (line 910) can be lower by a factor of about ten compared to the target dispense volume (line 914). Moreover, even after 23 dispenses (see Figure 8) the dispensed volume (line 910) is still below the target volume (line 914).
  • one or more pressure sensors 50 may be included to monitor the system pressure.
  • the pressure measurements as provided by one or more pressure sensors 50 can also be used to provide diagnostic information about various fluid and flow parameters of the hydraulic system.
  • the pressure sensors 50 can be placed at the drop-on-demand valve 20 ( Figure 3) and/or at appropriate positions intermediate the syringe pump 22 ( Figure 1) and the dispenser 12 ( Figure 1), such as on the feedline 23, as illustrated in Figure 1.
  • nozzle pressure drop or total input pressure, Ps ⁇ n can be calculated from the following:
  • Ps ⁇ n the nozzle pressure drop
  • Ps ⁇ n the nozzle pressure drop
  • An estimate of the steady state pressure can also be obtained by estimating the nozzle capillary and orifice flow resistances by utilizing pressure measurements from the sensor(s) 50 ( Figures 1 and 3) during dispensing.
  • the capillary flow resistance and the orifice flow resistance can be estimated by making two measurements of the system pressure at two flow rates during steady state dispensing from the following:
  • Q is the low flow rate
  • Q h is the high flow rate
  • P is the pressure measurement at Q
  • P h is the pressure measurement at Q h
  • Rc est is the estimate of the capillary flow resistance
  • Ro est is the estimate of the orifice flow resistance.
  • the two pressure measurements, P, and P h can be made during steady state on-line dispensing by modulating the flow rate about the operating point by a small amount, for example, about ⁇ 5%.
  • a calibration mode can be used off-line to make the pressure measurements.
  • the above semi-empirical estimates of the capillary flow resistance, Rc_est, and the orifice flow resistance, Ro est permit the density and viscosity of the fluid to be estimated by using:
  • p est is the estimated fluid density and ⁇ est is the estimated viscosity.
  • transient pressure measurements utilizing the pressure sensor(s) 50 can be used to estimate the nozzle capillary and orifice flow resistances. This approach is generally accurate only when the initial pressure is within 30-50% of the steady state value because a linearized approximation of the differential equations is used.
  • the linearized pressure equations for an initial pressure of P, at the time that pulsed dispensing operation begins and decays to the steady state value of P ss can be approximated by:
  • P(t) is the instantaneous pressure as a function of time t
  • a is the system time constant
  • F valve is the open- close frequency of the drop-on-demand-valve 20 (Figure 3)
  • T v is the valve open time/valve pulse width of the drop-on- demand-valve 20 ( Figure 3)
  • C is the elastic capacitance
  • CL, ⁇ is the flow rate as provided by the syringe pump 22 ( Figure 1) which is operated by the stepper motor 26 ( Figure 1)
  • Q ⁇ 02Ite is the flow rate through the nozzle 38 ( Figure 3).
  • the elastic capacitance, C can be estimated from pressure and volume changes with the valve 20 ( Figure 3) closed, as is discussed above.
  • P is the measured initial pressure prior to dispensing
  • P ss is the measured steady state pressure after a substantially long time
  • P is the measured pressure during decay at time t.
  • These pressures can be measured using the pressure sensor(s) 50 ( Figures 1 and 3).
  • the pressure P can be measured at several different times and the results averaged to reduce noise.
  • estimates of the nozzle capillary flow resistance, Rc est, and nozzle orifice flow resistance, Ro est can be obtained.
  • These estimates of the capillary flow resistance, Rc est, and the orifice flow resistance, Ro_est can be used in conjunction with equations (29), (30) and (31) to obtain an estimate of the nozzle pressure drop, Ps,ute, which can be estimated as a steady state pressure.
  • the apparatus or system 10 may be used for a wide variety of modes such as dot dispensing, continuous dispensing and printing of micro-arrays, among other applications.
  • the operation of the aspirate-dispense system 10 ( Figure 1) may be monitored and controlled by a suitable automated control system. Additionally, the control system may be interfaced with any robot arms and/or X, X-Y or X-Y-Z movable platforms used in conjunction with the aspirate-dispense system 10, source 29, target 30 and waste receptacle to facilitate maneuverability of the various components of the system and its associated elements.

Abstract

L'invention concerne un procédé et un appareil permettant de réguler activement la pression hydraulique d'un système (10) d'aspiration-distribution, destiné à aspirer et distribuer des quantités précises et/ou définies d'un fluide ou d'un réactif (14). Ce procédé fournit un mécanisme de compensation de pression efficace, de manière à obtenir des pressions optimales pour l'aspiration et la distribution. Les pressions optimisées sont obtenues par une série d'opérations qui ajustent une pompe (22) à déplacement positif et une soupape (12) goutte à la demande du système d'aspiration-distribution. Ce procédé permet d'accroître, avantageusement, la vitesse du processus et de réduire la dilution et la perte de réactif (14).
PCT/US1999/003677 1998-02-20 1999-02-19 Procede d'aspiration et de distribution microfluidique WO1999042804A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU27757/99A AU2775799A (en) 1998-02-20 1999-02-19 Methods for microfluidic aspirating and dispensing

Applications Claiming Priority (4)

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US7540398P 1998-02-20 1998-02-20
US60/075,403 1998-02-20
US25312399A 1999-02-19 1999-02-19
US09/253,123 1999-02-19

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WO1999042804A3 WO1999042804A3 (fr) 1999-09-30

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EP1206967A2 (fr) * 2000-11-17 2002-05-22 Tecan Trading AG Système et méthode pour prélever et/ou distribuer des échantillons liquides
EP1231957A1 (fr) * 1999-09-14 2002-08-21 Pharmacopeia Inc. Elements de regulation du debit destines a des distributeurs de liquide
US6447723B1 (en) 2000-03-13 2002-09-10 Packard Instrument Company, Inc. Microarray spotting instruments incorporating sensors and methods of using sensors for improving performance of microarray spotting instruments
WO2002076623A1 (fr) 2001-03-27 2002-10-03 Musashi Engineering, Inc. Procede de formation de gouttelettes et dispositif de diffusion de gouttelettes a volume constant
US6537505B1 (en) 1998-02-20 2003-03-25 Bio Dot, Inc. Reagent dispensing valve
US6589791B1 (en) 1999-05-20 2003-07-08 Cartesian Technologies, Inc. State-variable control system
US6878554B1 (en) 2000-03-20 2005-04-12 Perkinelmer Las, Inc. Method and apparatus for automatic pin detection in microarray spotting instruments
EP1658894A1 (fr) 2002-02-22 2006-05-24 Biodot, Inc. Dispositif de dispersion de gouttelettes de reactif sous la surface d'un fluide au moyen d'une distribution sans contact
US7521245B1 (en) 2000-06-05 2009-04-21 Perkinelmer Las, Inc. Method for washing and drying pins in microarray spotting instruments
US7759062B2 (en) 2006-06-09 2010-07-20 Third Wave Technologies, Inc. T-structure invasive cleavage assays, consistent nucleic acid dispensing, and low level target nucleic acid detection
WO2013110474A1 (fr) * 2012-01-26 2013-08-01 Munich Metrology Gmbh Dispositif et procédé de dosage de liquides
US8920752B2 (en) 2007-01-19 2014-12-30 Biodot, Inc. Systems and methods for high speed array printing and hybridization
US9068566B2 (en) 2011-01-21 2015-06-30 Biodot, Inc. Piezoelectric dispenser with a longitudinal transducer and replaceable capillary tube

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US6926866B2 (en) 2000-11-17 2005-08-09 Tecan Trading Ag Method and device for separating samples from a liquid
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