Classifications

• • 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
  • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C1/00—Magnetic separation
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C5/00—Separating dispersed particles from liquids by electrostatic effect
  • B03C5/005—Dielectrophoresis, i.e. dielectric particles migrating towards the region of highest field strength
• • 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
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00783—Laminate assemblies, i.e. the reactor comprising a stack of plates
• • 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
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00873—Heat exchange
• • 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
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00925—Irradiation
  • B01J2219/0093—Electric or magnetic energy
• • 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
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00925—Irradiation
  • B01J2219/00932—Sonic or ultrasonic vibrations
• • 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
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00925—Irradiation
  • B01J2219/00934—Electromagnetic waves
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2400/00—Moving or stopping fluids
  • B01L2400/04—Moving fluids with specific forces or mechanical means
  • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
  • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2400/00—Moving or stopping fluids
  • B01L2400/04—Moving fluids with specific forces or mechanical means
  • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
  • B01L2400/043—Moving fluids with specific forces or mechanical means specific forces magnetic forces
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2400/00—Moving or stopping fluids
  • B01L2400/04—Moving fluids with specific forces or mechanical means
  • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
  • B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
  • B01L2400/0436—Moving fluids with specific forces or mechanical means specific forces vibrational forces acoustic forces, e.g. surface acoustic waves [SAW]
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2400/00—Moving or stopping fluids
  • B01L2400/04—Moving fluids with specific forces or mechanical means
  • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
  • B01L2400/0442—Moving fluids with specific forces or mechanical means specific forces thermal energy, e.g. vaporisation, bubble jet
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2400/00—Moving or stopping fluids
  • B01L2400/04—Moving fluids with specific forces or mechanical means
  • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
  • B01L2400/0454—Moving fluids with specific forces or mechanical means specific forces radiation pressure, optical tweezers
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2400/00—Moving or stopping fluids
  • B01L2400/04—Moving fluids with specific forces or mechanical means
  • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
  • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics

Definitions

• An array of acoustic wave sources for producing acoustic fields is fabricated on a solid, piezoelectric substrate.
• a microelecfromagnetic unit array is fabricated on a (second) substrate.
• the second substrate (for producing magnetic forces) is bound to or attached to the first piezoelectric substrate (for producing acoustic forces) to form a two-force- chip.
• Magnetic field may be generated with various approaches.
• the electromagnetic chip disclosed in the co-pending U.S. Patent Application Serial No. 09/399, 299, filed September 16, 1999, which is incorporated by reference in its entirety can be used.
• such electromagnetic chips with individually addressable microelecfromagnetic units comprise: a subsfrate; a plurality of micro-electromagnetic units on the substrate, each unit capable of inducing magnetic field upon applying electric current; means for selectively energizing any one of a plurality of units to induce a magnetic field therein.
• the electromagnetic chips further comprise a functional layer coated on the surface of the chips for immobilizing certain types of moieties or molecules.
• two substrates may be linked together in series and bound to a third substrate. These two subsfrates are structurally linked subsfrates. Again, such a step may be repeated to form combined substrates comprising more than two structurally linked subsfrates.
• the present invention is directed to a method for manipulating a moiety, which method comprises: a) introducing a moiety to be manipulated onto a chip comprising a substrate and at least two different types of built-in structures located on said substrate, wherein each of said structures is capable of, in combination of an external energy source, generating one type of physical field; and b) allowing the built-in structures of said chip, in combination of an external energy source, to exert at least two different types of physical forces on said moiety, whereby said moiety is manipulated by said physical forces.
• Cells derived from birds such as chickens, vertebrates such as fish and mammals such as mice, rats, rabbits, cats, dogs, pigs, cows, ox, sheep, goats, horses, monkeys and other non-human primates, and humans can be manipulated by the present chips, apparatuses and methods.
• Manipulatable cellular organelles include nucleus, mitochondria, chloroplasts, ribosomes, ERs, Golgi apparatuses, lysosomes, proteasomes, secretory vesicles, vacuoles or microsomes.
• Manipulatable viruses whether intact viruses or any viral stmctures, e.g., viral particles, in the virus life cycle can be derived from viruses such as Class I viruses, Class II viruses, Class III viruses, Class IV viruses, Class V viruses or Class VI viruses.
• An active chip or biochip capable of producing certain type of active forces on molecules or particles is fabricated using non-piezoelectric materials. Nevertheless, a piezoelectric transducer (a single acoustic wave source or an array of acoustic wave source) may be bound to the active biochip to form a MFC.
• Magnetic forces refer to the forces acting on a moiety, e.g., particle due to the application of a magnetic field.
• particles have to be magnetic or paramagnetic when sufficient magnetic forces are needed to manipulate particles.
• a magnetic dipole ⁇ is induced in the particle
• the optical forces are the so-called gradient-forces when a material (e.g., a microparticle) with a refractive index different from that of the surrounding medium is placed in a light gradient. As light passes through polarizable material, it induces fluctuating dipoles. These dipoles interact with the electromagnetic field gradient, resulting in a force directed towards the brighter region of the light if the material has a refractive index larger than that of the surrounding medium.
• ⁇ m is the viscosity of the medium
• C D is the drag coefficient
• Re p is the particle Reynolds number defined by
• the velocity field of a medium refers to the velocity distribution of a medium that is moving.
• the governing equation for the velocity of the medium is given by 3-7
• the MFC may incorporate an array of individually addressable heating elements. These elements are positioned or structurally arranged in certain order so that when each of or some of or all of elements are activated, temperature gradient distributions can be established to produce desired thermal convection, leading to a velocity field in the medium that is introduced into the apparatus that comprises the MFC. For example, if one heating element is activated or energized, the increase in the temperature in the medium in the neighborhood of this element will result in a local temperature gradient, leading to a thermal convection.
• the MFC may comprise multiple, interconnected heating units so that these units can be turned on or off in a synchronized order.
• the MFC may comprise only one heating element that can be energized to increase local temperature and induce thermal convection in the medium.
• the MFC may incorporate an array of individually addressable cooling elements, or a single cooling element.
• Appropriate external signal sources may be applied to these force-generation elements or structures according to required sequence and conditions so that different types of forces may be generated.
• the sequence of force generation may be as follows: acoustic elements or structures may be activated first for a specified length of time to manipulate all the particles; the magnetic elements or stmctures may then be activated for a certain length of time to manipulate magnetic particles; the DEP elements or sfructures may last be activated to manipulate particles having certain dielectric properties.
• multiple-force chips There may be many different types of embodiment of multiple-force chips, or MFC-based devices, MFC-based apparatuses and systems. In the following we describe some examples of embodiments for multiple-force chips. The descriptions may be readily extended to the MFC-based devices or the apparatus of the present invention.
• a first sub-array of units may comprise elecfromagnetic elements for producing magnetic fields
• a second sub-array of units may comprise micro-electrode elements and acoustic-force elements.
• Such binding between the two substrates 300 and 355 should be carefully done to ensure that acoustic wave can be coupled from the substrate 300 through the substrate 355 into the medium (not shown in Figure 5B).
• the methods for binding these two subsfrates together are similar to those described in the context of Figure 3B for binding the acoustic subsfrate and the dielectrophoretic-electrode containing subsfrate.
• the piezoelectric subsfrate 300 in Figure 5B can be energized by external signal source 360 through the connections on pad 462 and conductive surface 320.
• AC signals of appropriate waveforms typically sinusoidal signal, at appropriate frequencies
• mechanical vibrations are generated from the array of piezoelectric transducer sources and can be coupled into the medium (not shown in Figure 5B) through the substrate 355, producing an acoustic wave field in the medium.
• the medium may be in direct contact or in indirect contact with the substrate 355.
• the moiety in the medium will experience acoustic forces due to the acoustic field.
• the array of elecfromagnetic units 415 in Figure 5B may be energized by external current source 450 to produce a magnetic field in the medium.
• the magnetic field in the medium may exert magnetic forces on the moieties that have certain magnetic properties.
• the surface of the subsfrate 355 that has been processed to contain an array of elecfromagnetic units as shown in Figure 5B may be further coated or covered with a thin layer of functional materials.
• the medium when the medium is introduced to the apparatus comprising the subsfrate 355 (and the subsfrate 300), the medium is in indirect contact with the subsfrate 355.
• the indirect contact between the medium and the subsfrate 355 is through the layer of functional materials (and through electromagnetic units in some regions).
• the functional material layer may be used for immobilizing certain biomolecules on the surfaces of the substrate 355.
• a spiral electrode array 630 is fabricated on the dielectric layer 460. There are four, parallel, linear spiral electrode elements in the spiral array 630. Such elecfrodes can be fabricated using the methods for fabricating the interdigitated electrodes shown in Figure 3A (e.g. using photolithography with appropriate photomasks).
• the spiral elecfrode array 630 can be energized by four-phase signals (0, 90, 180 and 270 degrees for a sinusoidal or near sinusoidal waveform) supplied from a signal generator 490 through connection pads 636 to generate non-uniform, traveling wave electric fields.
• Figure 10 shows a schematic drawing of examples of three-force apparatus of the present invention, capable of producing magnetic forces, traveling wave dielectrophoretic forces and optical forces.
• the apparatus comprises a fluidic chamber, having a two-force chip, a spacer and an optical chip.
• the two-force chip capable of producing magnetic force and fraveling-wave dielecfrophoretic forces is fabricated on a subsfrate 355.
• the structure and the layout of the two-force chip in Figure 10, and methods for fabricating such a chip are similar to those of the two-force chip shown in Figure 6B.
• a spacer 850 having appropriate thickness is placed over the two-force chip.
• the spacer 850 has a channel 852 cut in the center.
• the surfaces of the three-force chips shown in Figures 11 A, 1 IB and 1 IC may be further coated with a thin layer of functional materials.
• the functional material layer may be used for immobilizing certain biomolecules on the chip surfaces.

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• Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Electrochemistry (AREA)
• General Health & Medical Sciences (AREA)
• Molecular Biology (AREA)
• Apparatus Associated With Microorganisms And Enzymes (AREA)

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• 2001
  • 2001-09-20 EP EP01973418A patent/EP1337324A2/de not_active Withdrawn
  • 2001-09-20 WO PCT/US2001/029762 patent/WO2002028523A2/en not_active Application Discontinuation
  • 2001-09-20 AU AU2001292997A patent/AU2001292997A1/en not_active Abandoned
  • 2001-09-20 CA CA002421828A patent/CA2421828A1/en not_active Abandoned

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