KR20090051030A - Particle sensitive/radiation sensitive devices - Google Patents

Abstract

Modifications to the injection molded cruciform polyurethane sheet 402 having four arms 403 containing eyelets 404 for attaching the sheet 402 to the aperture making device via a pin 405. An apparatus 401 is provided for manufacturing possible openings. The device 401 is a sharp probe 407 connected to the mechanical actuator 408 and an elastomeric support component connected to the mechanical actuator 410 and opposite the sharp probe 407 on the opposite side of the sheet 402. 409). The elastomer support component 409 comprises a stainless steel metal rod having a cavity 411 filled with electrolyte fluid 413. The mechanical actuator 408 is set to allow precise mechanical operation of the sharp probe 407 to and fro perpendicular to the face of the seat 402. Similarly, the mechanical actuator 410 is set to allow a precise mechanical actuation of the elastomeric support component 409 by reciprocating perpendicular to the face of the seat 402. To each actuator 408 and 410 is connected an actuator controller 414 which in turn is connected to and controlled by the computer 15. Both the sharp probe 407 and the elastomer support component 409 are connected to a voltage clamping current signal detector 416. During manufacture of the openings, the elastomeric support component 409 is used to adjust the degree of elastic recoil of the sheet 402 and is adjusted to one or more predetermined positions one or more times. Mechanical conditioning can be achieved before, during or after the preparation of the resin.

Description

Particle sensitive / radiation sensitive devices

The present invention generally relates to particle sensitive or radiation sensitive devices comprising an adjustable elastomeric material containing adjustable elastomeric apertures, and to methods of making such adjustable elastomeric apertures and to detecting, measuring or A method of using such an adjustable elastomeric opening for controlling.

The detection, measurement or control of matter and / or radiation is an essential theme in the natural world and the invention world. However, materials and radiation can only be dissipated thermodynamically so that the boundaries of vessels, membranes and conduits provide a means of confining and containing material and / or radiation. The boundary that limits the dissipation of a substance and / or radiation is referred to as substantially impervious, impermeable or opaque. An opening is a passage through an impermeable, opaque or opaque medium that enables passage of material and / or radiation from one side of the boundary to the other. Thus, the openings can be used to detect, measure or control the substance and / or radiation because the path of passage of the substance and / or radiation is created and the mechanism for observing them is well known.

Charged moving particles can form currents and openings can be used to measure or control the charged particles. Electrical observation of the electrical path of ions through an opening filled with electrolyte was first disclosed in US 2656508 for use as a particle detection device called a Coulter counter, which described two substantially separate electrically conductive ionic fluid reservoirs. Include. The two reservoirs are separated from each other by a substantially electrically insulating barrier and there is an opening through which the particles of approximately size can pass and move between the reservoirs. The electrodes located in each reservoir provide a means for applying a voltage difference or voltage between the electrodes to generate a current of ions through the opening. Thus, particles that are temporarily occluded in the opening can be detected by monitoring electrical signals in a technique called resistive pulse sensing. Temporary and partial occlusion of the opening by particles of approximate size results in blockades of ion flow that can be characterized by a change in the current amplitude and the measurement of the duration of blockage occurrence. These parameters can be related to the hydrodynamic geometry and physical properties of the openings and occluded particles and can be used for quantitative analysis together with containment frequencies (Bayley et al., “Resistive Pulse Sensing-From Microbes to Molecules” Chem. Rev. , 100, 2575-2594, 2000). Particles that do not fit in the opening tend to cause blockage, while particles smaller than 2% of the opening volume generate a blockage signal that is too small to be differentiated from the background electrical noise of the ion current flow. The coulter counter detects various particle diameters ranging from 400 nm to 1 mm using discrete numbers of solid state openings ranging from 20 μm to 2 mm in diameter (Bayley et al., “Resistive Pulse Sensing-From Microbes to Molecules ”Chem. Rev., 100, 2575-2594, 2000). Coulter type analysis of molecular scale particles is accomplished using molecular scale openings of biological origin. Examples of such openings are ion channels and membrane pores used by living cells to move molecules from one side of the lipid membrane to another (Bayley et al., “Resistive Pulse Sensing-From Microbes to Molecules ”Chem. Rev., 100, 2575-2594, 2000). One example is a toxin pore called alpha-hemolysin secreted by the bacterium Staphylococcus aureus , which associates from a water soluble monomer to a membrane bound heptamer, opening a ˜2.0 nm diameter opening in a lipid membrane. To form. The application of alpha-hemolysin pores to coulter type nucleic acid particle analysis has been published (Kasianowicz et al., “Characterization of individual polynucleotide molecules using a membrane channel” PNAS, 93, 13770-13773, 1996). It has been shown that an electric field applied across the aperture can promote single-stranded nucleic acid molecules through the alpha-hemolysin opening, one by one, embedded in the lipid membrane. Since the diameter of the opening can only accept a single strand of nucleic acid macromolecules (macromolecule), the macromolecules must cross the opening individually as linear chains. The detected resistance pulse of each macromolecule can be used to measure the nucleic acid fragment length in proportion to the length of the macromolecule.

Nanometer scale openings can be made from naturally occurring biological nanopores, as well as inorganic nanotubes (Fan et al. “DNA translocation in inorganic nanotubes”, Nano Letters, 5, 1633-1637, 2005). And from solid state materials such as track-etched polymer films (Mara et al., “An asymmetric polymer nanopore for single molecule detection”, Nano Letters, 4, 497-501, 2004) or in solid state materials. From silicon pipettes derived from thin-walled quartz capillaries (Karhanek et al., “Single DNA molecule detection using nanopipettes and nanoparticles”, Nano Letters, 5, 403-407, 2005). From lithographically sculpted pores (Li et al., “DNA molecules and configurations in a solid-state nanopore microscope”, Nature Materials, 2, 611-615, 2003), and carbon nanotubes Ito et al., “Si multaneous determination of the size and surface charge of individual nanoparticles using a carbon nanotube-based Coulter counter ”, Analytical Chemistry, 75. 2399-2406, 2003). Fixed or static geometric openings and mechanisms for observing them are known, but only a few are adjustable geometries.

A method of regulating an effective opening geometry by controlling the degree of registry between fixed geometric objects has been disclosed. GB2208611 discloses the use of openings made in two parallel polymeric film sheets, where effective adjustment of the opening size is made by controlling the degree of registry between the openings in the parallel sheet. US6706203 and US2003 / 0080042 disclose adjustable nanopores, nanotomes and nanonotweezers comprising two sliding solid state crystals or ceramic window openings that overlap to create a single small opening, wherein the effective Adjustment of the opening geometry is made by controlling the degree of registry between the windows. Piezoelectric operation is used to achieve mechanical operation on the nanometer scale, operating in dimensions of 1 to 10 nanometers. In US4853618, a coulter type particle analysis device having openings of various sizes is disclosed, wherein the opening geometry is a precisely controlled insertion of an insert inserted into a static opening, thus partial occlusion of the static opening geometry and an effective opening geometry. Controlled by regulation.

An effective method of regulating opening geometry by deformation of the opening geometry itself has been disclosed. GB2337597 discloses a tapered orifice made from a piezoelectric material or such other flexible material, thereby enabling the removal of containment by adjustment of the opening geometry in which the adjustment of the orifice by the piezoelectric effect is simultaneously performed. do. This provides a method of removing blockages from coulter type particle sensors by applying ultrasonic vibrations through piezoelectric effects to the conical taper. US3395344 discloses a deformable opening comprising a flexible material (including materials such as elastic and rubber) which is used in a coulter type device using an opening made by punching a diaphragm formed from a heated stylus. The ability to deform under hydrostatic pressure or vacuum is used to enable removal of the containment or partial containment. Hydrostatic pressure or vacuum exerts a strain pressure perpendicular to the face of the perforated membrane (ie parallel to the axis of the lumen opening, but perpendicular to all other points on the membrane plane) to inflate the membrane as it deforms, thereby controlling the opening geometry to blockade. It allows the removal of water. The deformable aperture of US3395344 offers several advantages over the fixed geometric aperture of the coulter counter but lacks the ability to open precisely to a specified level to detect, measure or control particles and / or radiation.

PCT / EP2005 / 053366 discloses adjustable elastomeric apertures that can be adjusted to detect, measure or control particles and / or electromagnetic radiation. The disclosed device is most typically produced by penetration of a sheet of elastomeric material precut into a cross-shaped geometry.

The deformable opening disclosed in PCT / EP2005053366 suffers from several disadvantages and limitations.

One disadvantage is that the adjustable elastomeric openings made from deformable material of uniform cross section require the use of expensive, high accuracy adjustment devices to achieve nanometer scale adjustment of the adjustable elastomeric openings.

Another disadvantage is that (i) the use of a deformable sheet of material that must be cut into a shape suitable for placement provides waste components in the form of extra cut material, and (ii) the sheet material is most typically anisotropic tensile stress ( and (iii) sheets of deformable material require a complex assembly process to be employed to create structures of varying thickness, and therefore within a certain tolerance range. It is manufactured to have a specific thickness.

The manufacture of openings by the penetration of sharp probes is limited because the elastomeric properties of the deformable material make the openings uncontrollable because the probe penetrates the elastomeric material and subsequently the modified elastomer recoils.

Another disadvantage is that the deformation properties of the elastomeric material are severe structural changes in a phenomenon known as the Mullins effect (Mullins L. “Softening of rubber by deformation” Rubber Chem. Tech. 42, 339-362, 1969). This requires that devices and methods of receiving, mitigating and utilizing the Mullins effect in the adjustable elastomer openings be adopted.

Another disadvantage is that in the case of adjustable elastomeric openings, no fluid handling capability has been developed for analyzing particles suspended in the fluid, and such fluid handling capability is required to facilitate fluid phase particle analysis.

Accordingly, it is desirable to develop new types of improved adjustable elastomeric apertures in which mechanically simple and adjustable elastomeric apertures are readily manufactured and specified for the purpose of detecting, measuring or controlling particles and / or radiation across multiple scales. Do.

It is an object of the present invention to provide an adjustable elastomeric opening that is readily manufactured from inexpensive materials. The present invention generally relates to particle sensitive or radiation sensitive devices incorporating an adjustable elastomeric material containing an adjustable elastomeric opening and to a method of making such adjustable elastomeric openings, and to detecting, measuring or controlling particles and / or radiation. It relates to the use of such adjustable elastomeric openings for the purpose.

According to one aspect of the invention, an adjustable elastomeric material containing an elastomeric partition wall suitable for forming an opening that penetrates to provide a path to particles and / or radiation, and the path provided by the opening by adjusting the partition wall portion A particle sensitive and / or radiation sensitive device is provided that includes adjusting means for changing one or more parameters of the.

In one preferred embodiment of the invention, the partition comprises a membrane portion of the material having a thickness greater than or less than the surrounding portion of the material, wherein the perimeter of the material is advantageously a well It is in the form of an elevated rim enclosing the membrane portion to form a well.

It is also preferred that one or more holes extend through the portion of the material that does not contain the partition wall to provide a fluid path through the material prior to penetration of the partition wall. The hole or each hole may be surrounded by an elevated rim that seals the hole to form a well surrounding the hole.

Advantageously the adjusting means can be detachably attached to the adjustable elastomeric material to adjust the partition wall to change one or more parameters of the path provided by the opening.

According to another aspect of the invention, an apparatus for producing a deformable opening in a deformable material, the device forcibly penetrating the deformable material to form a space in the deformable material through which the deformable A probe that allows a continuous path to extend from one side of the material to the other, and an elastomer that supports the deformable material to provide mechanical resistance in the opposite direction of the force exerted by the probe to penetrate the deformable material An apparatus is provided that includes a support component.

The non-penetrating blank membrane of the adjustable elastomeric material is formed from an elastomeric material selected from, but not limited to, the following groups: polymers; Natural and synthetic rubbers; Elastomeric materials; Natural polymers, proteins, polypeptides, polysaccharides; plastic; Doped conducting plastics; Hydrocarbon plastics; Perfluorocarbon plastics; Latex materials; Thermoplastic deformable materials; Thermoplastic polyurethane (ether and ester) deformable materials; Olefinic deformable materials including polypropylene, polyethylene, cyclic olefins; Styrenic deformable materials; Polyamide-based deformable materials; Polyester-based deformable materials; Nitrile-based deformable materials; Ethylene chloride copolymer crosslinked alloys; Silicone deformable materials; Semiconductor materials; Silicates; silicon; Doped silicon; metal; Or metal alloys; Piezoelectric materials, and piezoelectric ceramics. The deformable opening can also be defined by a composite deformable material made from a combination of one or more such materials.

The non-penetrating sclera of the adjustable elastomeric material is formed in three dimensions by a process selected from, but not limited to, the following groups: molding, injection molding; Blow molding; Compression molding; Extrusion injection molding; Embossing; Hot embossing; Stamping; casting; etching; Lithography; Photolithography; Carving; Cutting; milling; Ion milling; Polymerization; Epitaxial growth; Or any combination of the processes described above.

The non-penetrating sclera of tunable material can be any general three-dimensional geometry selected from, but not limited to, the following: cubic geometry; Rhombic geometry; Orthorhombic geometry; Planar geometry; Asymmetric planar geometry; Symmetric planar geometry; Planar geometry with two axes of symmetry; Planar geometry with three axes of symmetry; Symmetric planar geometry with four axes of symmetry; Symmetric planar geometry with five axes of symmetry; Geometry of various cross-sectional thicknesses; Planar geometry of varying cross-sectional thickness.

The non-penetrating sclera of the adjustable material can be of any general size, wherein at least one of the three-dimensional spatial dimensions of the non-penetrating sclera of the adjustable elastomeric material is less than 100 mm, or optionally less than 10 mm, or Optionally less than 1 mm, or alternatively less than 0.1 mm.

The non-penetrating sclera of adjustable material has a structural feature that makes it easy to attach to the instrumentation. The structural feature is selected from, but is not limited to, the following: holes; Eyelets; Hookes; Lugs; Ridges; Or articles embedded in an elastomeric material selected from, but not limited to: a ring; hook; pin; Rod, or any combination of the features described above.

The non-penetrating sclera of the adjustable material has a structural feature that can facilitate controlled control of the adjustable elastomeric material. The structural feature is selected from, but is not limited to, the following: holes; Ridge; Rims; ring; wall; tube; Wells; Reservoir; Defined cross-sectional area; Articles embedded in an elastomeric material selected from, but not limited to, the layer region, or the following group: fibers; ceramic; Complex or any combination of the features described above.

The non-penetrating sclera of adjustable material has a structural feature that can facilitate fluid handling. The structural feature is selected from, but is not limited to, the following: holes; Rim; wall; tube; Wells; Reservoir; Or articles embedded in an elastomeric material selected from, but not limited to, the following groups: tubes; connector; Wells; Reservoir; Ridge, or any combination of the features described above.

The non-penetrating sclera of adjustable material has a structural feature that can facilitate fluid handling that contributes to docking with an external hardware fluid handling device. The structural feature is selected from, but is not limited to, the following: holes; Rim; wall; tube; Wells; Reservoir; Or articles embedded in an elastomeric material selected from, but not limited to, the following groups: tubes; connector; Wells; Reservoir; Ridge, or any combination of the features described above.

The non-penetrating sclera of adjustable material has surface features that can facilitate fluid handling. The surface feature is selected from, but is not limited to, the following groups: surface treatment to make the adjustable elastomeric material hydrophobic; Surface treatments that make the adjustable elastomeric material hydrophilic; Surface treatments that make the adjustable elastomeric material oleophilic; Surface treatment that makes the adjustable elastomeric material electrostatically charged; Surface treatments that make the adjustable elastomeric material electrostatically neutral, or any combination of the features described above.

According to another aspect of the invention, one in the non-penetrating sclera of the adjustable elastomeric material, comprising a mechanism for penetrating the non-penetrating sclera of the adjustable elastomeric material with a sharp probe and means for measuring one or more parameters of the penetration process. A method for producing the above opening is provided. Penetration of the non-penetrating sclera of the adjustable elastomeric material uses one or more pointed and sharp probes. Sharp probes can be manufactured by grinding and polishing processes, molding processes, extrusion processes, electrochemical etching processes or lithographic processes. The probe may be a type or scanning probe microscope probe or a scanning tunneling microscope probe or an atomic force microscope probe with a sharp tip or defined shape cutting tool. The probe may be heated or cooled in view of the deformable material and is pushed through the deformable material to cut or separate or melt the fabric of the deformable material, or rotate or move the hole to It is possible to create openings in the deformable material by drilling out or otherwise by a combination of the methods described above.

The probe is detected by a probe detection mechanism as soon as it emerges from the opposite surface of the adjustable material. Probe detection mechanisms are selected from, but are not limited to, the following groups: optical detection; Electrical detection; Electrical detection by measured capacity change; Electrical detection by measured current changes; Electrical detection by measured tunneling current changes; Electrical detection by measured electrical resistance change; Detection by measured mechanical resistance; Elastic recoil detection, or any combination of the above mechanisms.

According to another aspect of the present invention, an elastomer adjustable by a mechanical control method comprising a mechanism for adjusting the non-penetrating sclera of the adjustable elastomeric material and means for measuring one or more parameters of the non-penetrating sclera of the adjustable elastomeric material A device is provided for preconditioning unpenetrated sclera of material. The measured parameters of the non-penetrating sclera of the adjustable elastomeric material are selected from, but are not limited to, the following groups: optical detection; Optical detection by polarization method; Electrical detection; Electrical detection by measured capacity change; Electrical detection by measured current changes; Electrical detection by measured tunneling current changes; Electrical detection by measured ion current changes; Electrical detection by measured electrical resistance change; Detection by measured mechanical resistance change; Detection by changes in measured mechanical stress; Detection by measured mechanical strain, or any combination of the parameters described above.

The elastic recoil of the adjustable elastomeric material following the emergence of a sharp probe from the opposite surface of the adjustable elastomeric material provides a mechanical elastomeric support component to the adjustable elastomeric material to provide a sharp probe from the opposite surface of the adjustable elastomeric material. By providing mechanical resistance in the opposite direction of the force exerted by the sharp probe before, during and after emergence, it is substantially mitigated. The mechanical elastomer support component is selected from, but is not limited to, fluids; Electrolyte fluids; solid; Metal solids; Metal electrodes; A metal electrode containing a cavity; A metal electrode containing a cavity filled with a fluid; A metal electrode containing a cavity filled with an electrolyte fluid; A gold electrode containing a cavity filled with an electrolyte fluid; Gel matrix; Gel matrix containing the electrolyte, or any combination of the features described above.

The cavity of the mechanical elastomeric support component may be of any size, but in fact the degree of deformation of the elastomeric material by the force exerted by the sharp probe before, during and after the emergence of the sharp probe from the opposing surface of the adjustable elastomeric material. In order to mitigate as much as possible, it is preferred to have approximately the same dimensions as the sharp probe. At least one of the three-dimensional spatial dimensions of the cavity is less than 1000 μm, or optionally less than 100 μm, or optionally less than 10 μm, or optionally less than 1 μm, or optionally less than 0.1 μm.

The cavity of the mechanical elastomer support component is any shape selected from, but not limited to, the following groups: notches; Single notch; Intersecting notches; Depressions; Tunnels or holes. The cavities of the mechanical elastomer support component may include discharge machining; milling; Ion milling; Drilling, penetration; Indenting; Indentation with Sharp Probes: Indentation of gold billets with sharp probes, or any combination of the methods described above.

The mechanical elastomer support component may be heated or cooled to heat or cool the adjustable elastomeric material. Heating or cooling may be accomplished by a method selected from, but not limited to, conductive heating and / or cooling; Convective heating and / or cooling; Heating and / or cooling by Peltier devices, or any combination of the methods described above.

The mechanical elastomer support component is located in the opening manufacturing device on the opposite side of the adjustable elastomeric material from the sharp probe side to prevent substantial deformation of the adjustable elastomeric material during penetration of the adjustable elastomeric material by the sharp probe. The position of the mechanical elastomeric support component may be at any general position that is preferably adjustable and is selected from, but not limited to: less than 1 mm, or optionally less than 100 μm, or optionally less than 10 μm, Or optionally less than 1 μm, or optionally less than 0.1 μm; Or less than 0.1 μm with strain applied by selective contact; Or less than 1 μm in strain applied in contact; Or less than 10 μm in strain applied by selective contact; Or less than 100 μm in strain applied by selective contact; Or less than 1 mm in a strain applied in selective contact; Or less than 10 mm in strain applied by selective contact.

According to another aspect of the present invention, there is provided a method for preparing a non-penetrating sclera of an adjustable elastomeric material; Providing one or more openings in the non-penetrating sclera of the adjustable elastomeric material, comprising providing a device for penetrating the non-penetrating sclera of the adjustable elastomeric material with a sharp probe and means for measuring one or more parameters of the penetration process. A method is provided for doing this. The measured parameters of the penetrating process are selected from, but not limited to, the following groups: optical detection; Optical detection by polarization; Electrical detection; Electrical detection by measured capacity change; Electrical detection by measured current; Electrical detection by measured tunneling current changes; Electrical detection by measured ion current changes; Electrical detection by measured electrical resistance change; Detection by measured mechanical resistance change; Detection by changes in measured mechanical stress; Detection by measured mechanical strain, or any combination of the parameters described above.

In accordance with another aspect of the present invention, a method is provided that uses one or more measured through parameters recorded during an opening manufacturing process to determine the quality of the openings formed thereby and their usefulness. The measured penetration parameters are selected from, but are not limited to, the following groups: optical detection; Optical detection by polarization; Electrical detection; Electrical detection by measured capacity change; Electrical detection by measured current; Electrical detection by measured tunneling current changes; Electrical detection by measured ion current changes; Electrical detection by measured electrical resistance change; Detection by measured mechanical resistance change; Detection by changes in measured mechanical stress; Detection by measured mechanical strain, or any combination of the parameters described above.

In accordance with another aspect of the present invention, a method of using one or more measured parameters of an adjustable elastomeric opening is provided to determine the quality of the formed opening and thereby its usefulness. The measured parameters are selected from, but are not limited to, the following groups: optical parameters; Optical polarization parameters; Optical diffraction parameters; Electrical parameters; Electric capacity; electric current; Tunneling current; Ion current; Electrical conductivity; Electrical resistance; Electrical membrane resistance; Electrical access resistance; Current rectification; Mechanical resistance; Mechanical stress; Mechanical strain, or any combination of the parameters described above.

According to another aspect of the present invention, a method of microscopic examination of an adjustable elastomeric opening is provided to determine the quality of the formed opening and thereby its usefulness. Microscopic irradiation methods are selected from, but are not limited to, the following groups: optical microscopes; Polarizing microscope; Confocal microscopy; Scanning confocal microscopy; Probe microscope; Scanning probe microscope; Atomic force microscopy; Scanning electrochemical microscopy, electron microscopy, scanning electron microscopy or transmission electron microscopy.

According to another aspect of the present invention, there is provided a method for providing a non-penetrating sclera of an adjustable elastomeric material, a device for adjusting a non-penetrating sclera of an adjustable elastomeric material and one or more parameters of the non-penetrating sclera of the adjustable elastomeric material. A method is provided for preconditioning a non-penetrating sclera of adjustable elastomeric material prior to opening manufacture, including providing a means for measuring. Preconditioning is selected from, but is not limited to: preconditioning by curing; Preconditioning by chemical curing; Preconditioning by thermal curing; Preconditioning by curing with electromagnetic radiation; compression; Seal; kidney; Preconditioning by mechanical control selected from, but not limited to, groups of bending or twisting; Preconditioning by mechanical control of zero or more cycles; Preconditioning by mechanical adjustment of at least one cycle until mechanical equilibrium is reached; Or any combination of the features described above. The measured parameters of the non-penetrating sclera of the adjustable elastomeric material are selected from, but are not limited to, the following groups: optical detection; Optical detection by polarization; Electrical detection; Electrical detection by measured capacity change; Electrical detection by measured current; Electrical detection by measured tunneling current changes; Electrical detection by measured ion current changes; Electrical detection by measured electrical resistance change; Detection by measured mechanical resistance change; Detection by changes in measured mechanical stress; Detection by measured mechanical strain, or any combination of the parameters described above.

According to another aspect of the invention, an adjustment is made by mechanical adjustment, comprising a device for adjusting the adjustable elastomeric opening and means for measuring the adjustable elastomeric opening and / or one or more parameters of the adjustable elastomeric material from which the opening is made. An apparatus is provided for conditioning an adjustable elastomer opening of a possible elastomeric material. The adjustable elastomeric openings and / or the measured parameters of the adjustable elastomeric material from which the openings are made are selected from the following groups: optical detection; Optical detection by polarization; Electrical detection; Electrical detection by measured capacity change; Electrical detection by measured current; Electrical detection by measured tunneling current changes; Electrical detection by measured ion current changes; Electrical detection by measured electrical resistance change; Detection by measured mechanical resistance change; Detection by changes in measured mechanical stress; Detection by measured mechanical strain, or any combination of the parameters described above.

According to another aspect of the invention, there is provided a method of providing an adjustable elastomer opening; A method is provided for conditioning an adjustable elastomeric opening of an adjustable elastomeric material, comprising an apparatus for adjusting the adjustable elastomeric opening and a means for measuring one or more parameters of the adjustable elastomeric opening. Conditioning is selected from, but is not limited to, the following groups: Conditioning by curing; Conditioning by chemical curing; Conditioning by heat cure; Conditioning by curing with electromagnetic radiation; compression; Seal; kidney; Conditioning by mechanical control selected from, but not limited to, groups of bending or twisting; Conditioning by mechanical control of zero or more cycles; Conditioning by mechanical control of one or more cycles until mechanical equilibrium is reached; Or any combination of the features described above. The measured parameter of the adjustable elastomeric opening of the adjustable elastomeric material is selected from, but is not limited to, the following groups: optical detection; Optical detection by polarization; Electrical detection; Electrical detection by measured capacity change; Electrical detection by measured current; Electrical detection by measured tunneling current changes; Electrical detection by measured ion current changes; Electrical detection by measured electrical resistance change; Detection by measured mechanical resistance change; Detection by changes in measured mechanical stress; Detection by measured mechanical strain, or any combination of the parameters described above.

According to another aspect of the invention, an adjustable elastomeric opening made in an adjustable elastomeric material; A device for adjusting the adjustable elastomeric opening by a mechanical control method of the adjustable elastomeric material from which the opening is made and means for measuring the adjustable elastomeric opening and / or one or more parameters of the adjustable elastomeric material from which the opening is made. A device is provided for detecting, measuring or controlling particles and / or radiation.

According to another aspect of the present invention, there is provided a method of controlling an elastomeric material comprising an adjustable elastomeric opening that routes for particles and / or radiation; Adjusting the adjustable elastomeric material to adjust the adjustable elastomeric opening to a predetermined geometry and / or size by varying one or more parameters of the path defined by the adjustable elastomeric opening; And causing the detected, measured or controlled particles or radiation to enter the adjustable elastomer openings. A method of detecting, measuring or controlling particles and / or radiation is provided.

In the operation of the apparatus and method used for the detection and / or measurement and / or control of the flux of the substance and / or radiation according to the invention, the control of the adjustment of the adjustable elastomer opening includes, but is not limited to: Can be made based on a parameter selected from the group: a flow of particles across the adjustable elastomeric opening, flow of atomic particles across the adjustable elastomeric opening; Flow of molecular particles across the adjustable elastomeric opening; Flow of ionic particles across the adjustable elastomeric opening; Flow of ionic particles in solution across the adjustable elastomeric opening; Flow of current across the adjustable elastomeric opening, flow of tunneling current across the adjustable elastomeric opening; And flow of electromagnetic radiation across the adjustable elastomeric opening. The measurable parameters of the adjustable elastomeric material from which the adjustable elastomeric opening is made may be selected from the group including, but not limited to: dose; resistance; conductivity; Opacity; transparency; Length; width; Height; volume; Thermal conductivity; And dielectric properties. The adjustable parameter associated with the actuation mechanism through which the adjustable elastomeric opening is adjusted can be selected from the group including, but not limited to: dose; conductivity; Actuator displacement; Actuator position; Stepper motor position; inductance; Motor coil inductance; Resistance and motor coil resistance.

In order that the present invention may be more fully understood, preferred embodiments of the present invention will now be described, by way of example, with reference to the accompanying drawings, in which:

1A and 1B show the adjustable diaphragm used in the preferred embodiment;

2a and 2b show a diaphragm with an actuator in a preferred embodiment, and FIGS. 3a and 3b show the actuator in different positions;

FIG. 4A shows diagrammatically a preferred opening manufacturing apparatus, and FIG. 4B is a graph of the recorded opening manufacturing case;

5 is a scanning confocal microscope image of the adjustable aperture produced by this device;

6 shows diagrammatically an opening arrangement in a preferred embodiment;

7-10 are graphs that can be used to characterize the performance of the adjustable aperture in a preferred embodiment; And

FIG. 11 is a green flow chart illustrating one possible mode of operation of the preferred embodiment of FIGS. 2A & 2B, 3A & 3B, 4A and 6.

The following description is provided by way of example with reference to a preferred embodiment of the invention using polyurethane as the adjustable elastomeric material. One preferred example of polyurethane is the polyether type Elastollan® 1100 series from BASF Corporation, Wyandotte Michigan, USA. However, materials that can be used as the adjustable elastomeric material in other embodiments of the present invention include, but are not limited to: polymers; Natural and synthetic rubbers; Elastomeric materials; Natural polymers, proteins, polypeptides, polysaccharides; plastic; Doped conducting plastics; Hydrocarbon plastics; Perfluorocarbon plastics; Latex materials; Thermoplastic deformable materials; Thermoplastic polyurethane (ether and ester) deformable materials; Olefinic deformable materials including polypropylene, polyethylene, cyclic olefins; Styrenic deformable materials; Polyamide-based deformable materials; Polyester-based deformable materials; Nitrile-based deformable materials; Ethylene chloride copolymer crosslinked alloys; Silicone deformable materials; Semiconductor materials; Silicates; silicon; Doped silicon; metal; Or metal alloys; Piezoelectric materials, and piezoelectric ceramics. The deformable opening can also be defined by a composite deformable material made from a combination of one or more such materials.

In addition, the adjustable elastomer openings can be modified by surface treatment of the adjustable elastomeric material. The surface treatment can be selected from the group including, but not limited to: surface treatment to make the adjustable elastomeric material hydrophobic, surface treatment to make the adjustable elastomeric material hydrophilic, and to make the adjustable elastomeric material lipophilic. Surface treatment; A surface treatment that makes the adjustable elastomeric material electrostatically charged, a surface treatment that makes the adjustable elastomeric material electrostatically neutral, and any combination of the surface treatments described above.

1A and 1B illustrate an adjustable diaphragm in the form of a cross-shaped injection molded elastomer sheet 101 made of polyurethane comprising one or more adjustable openings made by penetration into a sheet for use in a preferred embodiment of the present invention. 100). In a non-illustrated variant embodiment, FIG. 1A shows a plan view of a diaphragm 100 having a planar cross-shaped geometry of the same size. The polyurethane sheet 101 is formed from a polyurethane having a shape by injection molding in a cavity of a suitable shape. The cross shape of the polyurethane sheet 101 comprises four identical arms 102. Eyelets 1023 penetrating the polyurethane sheet 101 are formed at the ends of each of the four arms 102. A raised circular rim 104 is formed in the center of the polyurethane sheet 101, and a partition 105, a disk of planar cross section, is formed in the center of the raised rim 104. The partition 105 is connected with the raised rim 104 by the tapering zone 106 of various cross sections. In the central region of each arm 102 is a raised rim 107 that surrounds the formed porthole 108 through the polyurethane sheet 101. In this regard, the above-described features for each arm 102 of the polyurethane sheet 101 are the same so that each arm 102 is identically arranged eyelet 103, raised rim 107 and porthole. Have 108. Actuator 204 is provided to effect deformation of diaphragm 100, as described in more detail below with reference to FIGS. 2A and 2B. The actuators 204 can move independently in the same or opposite directions or together in the same or opposite directions. FIG. 1B shows a cross section through the diaphragm 100 along the broken line A-A 109 of FIG. 1A.

2A diagrammatically shows the diaphragm 200 of FIG. 1A with each of the four arms of the polyurethane sheet 201 individually attached to the actuator 204. Eyelets 203 of polyurethane sheet 201 facilitate attachment with actuator 204 containing pins 205 that match the size and position of eyelets 203 formed in polyurethane sheet 201. The pin 205 penetrates the eyelet 203. FIG. 2B shows a cross section through the diaphragm 200 along dashed line (A-A) 209 of FIG. 2A.

3A and 3B show photos of an injection molded polyurethane sheet located on the adjusting device 302 and attached to the actuator 304 through the eyelet 303 by the actuator pin 305. 3A shows the polyurethane sheet 301 in an unregulated configuration. 3B shows an isotropic biaxially stretched polyurethane sheet 301 caused by the same opposite displacement of the actuator 304 on the opposite side connected by the four cross arms by the pin 305. The ruler 306 represents the displacement of the set of actuator pins 305 as a distance difference of about 5 millimeters (mm) between the position of FIG. 3A and the position of FIG. 3B. The sum of the isotropic biaxial displacements is therefore 10 mm per axis and is given by the symbolic representation ΔX.

4A is a simplified schematic diagram of a preferred opening making device 401 for making one or more adjustable elastomeric openings in a polyurethane sheet 402. The opening manufacturing apparatus 401 in FIG. 4A includes an injection molded polyurethane sheet 402 (shown in cross section). The arm 403 of the polyurethane sheet 402 containing the eyelet 404 easily attaches the sheet 402 to the opening manufacturing apparatus 401 via the pin 401. The sharp probe 407 is attached to the mechanical actuator 408 contained in the opening manufacturing device 401. The elastomeric support component 409 is connected to the mechanical actuator 410 of the aperture making device 401 and is positioned opposite the sharp probe 407 on the opposite side of the polyurethane sheet 402 in place of the cross partition 412. The elastomer support component 409 comprises a stainless steel metal rod having a cavity 411 filled with electrolyte fluid 413. The mechanical actuator 408 is set to allow precise mechanical operation of the sharp probe 407 by to and fro perpendicular to the polyurethane sheet 402 face in place of the cross diaphragm 412. Similarly, the mechanical actuator 410 is set to reciprocate perpendicular to the polyurethane sheet 402 plane in place of the cross diaphragm 412 to enable accurate mechanical operation of the elastomeric support component 409. An actuator controller 414 is connected to each of the actuators 408 and 410, which in turn are connected to and controlled by the computer 15. Actuators 408 and 410 may move the independently attached sharp probe 407 and / or elastomer support component 409 vertically to the polyurethane sheet 402 face and move in the direction indicated by the double arrow. The sharp probe 407 and the elastomer support component 409 are both connected to a voltage clamping current signal detector 416. One type of voltage clamp current signal detector 416 of this type is a voltage clamping amplifier (CV203BU predetermined by Molecular Devices Corporation, Sunnyvale CA, USA) connected to electrodes 407, 409 via a shielded amplifier, as shown in FIG. 4A. Axopatch 200B with amplifier). Analog current signals are obtained using an amplifier in resistive feedback mode with a 10 ㎑ low pass bessel filter digitized with Digidata 1322A (obtained from Molecular Devices Corporation) and supplied with the amplifier. The pCLAMP version 9 program is written to the computer hard disk.

The adjustment of the elastomeric support component 409 in the manufacture of the openings described above is used to control the degree of elastic recoil of the polyurethane sheet 402 in place of the cross partition 412. Elastomer support component 409 may be adjusted to any general position selected from the group including, but not limited to: less than 1 mm, or optionally less than 100 μm, or optionally less than 10 μm, or Optionally less than 1 μm, or alternatively less than 0.1 μm, or optionally less than 0.1 μm with strain applied, or less than 1 μm with strain selectively contacted, or less than 10 μm with strain selectively contacted, or Less than 100 μm with strain applied by selective contact, or less than 1 mm with strain applied by selective contact, or less than 10 mm by strain applied by selective contact. The position of the elastomeric support component 409 may be adjusted to one or more predetermined positions one or more times to achieve mechanical conditioning prior to, during or after the manufacture of the opening. The opening manufacturing method may also be switched such that the probe 407 penetrates the cross partition 412 from the back side of the cross partition.

Elastomer support component 409 and / or sharp probe 407 may also be temperature controlled.

The electrolyte fluid 413 filling the cavity 411 of the elastomer support component 409 in the manufacture of the openings as described above was filtered sterilized through a 0.22 μm Millipore filter, 1 M KCL, 10 mM Tris-HCL pH 8.0, 1 mM EDTA, 0.1 %, Triton X-100 and stored as frozen aliquots. All reagents were AR grade.

The sharp probe 407 in the manufacture of openings as described above is a conical probe made by AC electrochemical etching of polycrystalline tungsten rods (0.51 mm diameter of Midwest Tungsten Service Inc., Willowbrook IL, USA) at 4 M NaOH.

4B shows a graph 417 of the current tracking 418 that is recorded for the aperture manufacturing case described above. The y-axis 419 shows the current level in pico amps (pA). X-axis 420 shows time in seconds (s). The appearance of the current trace 418 represents opening manufacture. This outline includes a period indicating the open circuit state before penetration by the recorded current value of 0 pA 421. Following the onset of penetration, a short period of raised current response 422 is recorded followed by a rapid rise 423 indicating completion of the electrical circuit. The circuit is completed by the establishment of an electrical continuity between the sharp probe 407 and the electrolyte fluid 413 contained in the cavity 411 of the elastomeric support component 409. As the probe 407 advances through the adjustable elastomeric bulkhead, the recorded current trace 418 increases to reach the set point value 424, at which point the probe 407 turns and records the recorded current trace. 418 is observed to decrease rapidly (425). Prior to the breakdown of electrical conduction between the probe 407 and the electrolyte fluid 413 shown by the reduction of the recorded current to 0 pA 427, the probe 407 retracts from the newly formed opening (not shown). Secondary spike 426 is recorded in the current trace.

Trace geometry 421-427 represents the opening manufacturing process caused by the interaction between the sharp probe 407, the cruciform bulkhead 412 and the electrolyte fluid 413 contained within the cavity 411 of the elastomer support component 409. . Sharp probe 407, cross partition 412, electrolyte fluid 413 contained within cavity 411 of elastomer support component 409, location of elastomer support component 409, temperature of probe 407, elastomer support component Changes in the temperature of 409, the temperature of the cross-shaped bulkhead 412, or any other parameter of the opening manufacturing process will appear as a change in the recorded tracking geometry 421-427. Changes in the manufactured apertures of the present invention may be correlated with the performance of the adjustable elastomeric apertures. Accordingly, tracking contour 421-427 can be used to specify the performance of the adjustable elastomeric opening. Thus, for example, the presence of a well defined stair contour 422 created by the pre-tunneling current when the probe 407 initially begins to penetrate the septum 412 may result in an opening suitable for a preferred embodiment of the present invention. The presence of shoulder contour 426 also tends to indicate an initial outflow of the electrolyte fluid 413 into the opening after the probe begins to appear from the opposite side of the septum 412, and with a particular contour 418 The presence of substantially the same level of contour 427 indicates that the opening was substantially completely resealed upon retraction of the probe 407 from the partition 412.

5 shows a scanning confocal microscope image 500 having a scale bar 501 representing 500 μm. In image 500, a portion 502 produced by the manufacture of an opening in a septum of an injection molded polyurethane article by controlled penetration of a sharp tungsten probe is surrounded by a raised mound 504. 503. Thus, the appearances 502-504 seen in the micrographic images can be used to characterize the performance of the adjustable elastomeric aperture.

6 is a simplified schematic diagram of a preferred aperture adjustment device 600 for using an adjustable elastomeric aperture in polyurethane sheet 602. In FIG. 6, the aperture adjustment device 600 includes a polyurethane sheet 602 (shown in cross section) containing a single adjustable elastomeric opening 603. The cross arm 604 containing the eyelet 605 easily attaches the polyurethane sheet 602 to the opening adjustment device 601. In order to measure the partition electrically, the opening adjustment device 601 includes an electrolyte reservoir 607 in contact with the surface of the partition. The second electrolyte reservoir 608 is formed by a rim 609 formed on the sheath plane opposite the polyurethane sheet 602. The porthole 610 of the polyurethane sheet 602 makes the electrolyte 611 in the electrolyte reservoir 607 accessible to the first Ag / AgCl electrode 612. The second Ag / AgCl electrode 613 is immersed in the electrolyte 611 in the second electrolyte reservoir 608. A voltage bias applied across the two electrodes 612 and 613 by the voltage clamping current signal detector 614 causes the generated ion current to flow through the opening 603 of the polyurethane sheet 602. Voltage clamping current signal detector 614 to be measured.

The opening adjustment device 601 is provided by an actuator 615 connected to the eyelet 605 of the polyurethane sheet 602 by a pin 617 that matches the size and position of the eyelet 605 of the polyurethane sheet 602. Contributes to adjusting the adjustable elastomer opening in operation. Actuator 615 may be actuated by one or more actuator controllers 616 connected to computer 618 or optionally manually actuated.

In the task of achieving adjustment of the adjustable elastomeric opening, the computer 618 controls the opening adjustment device 601 in dependence on the feedback received from the voltage clamping current signal detector 614. Computer 618 allows aperture adjustment algorithms to be programmed and recorded and used, and data acquisition algorithms to be programmed and recorded and used to allow fully automated and accurate operation of the adjustable elastomeric aperture.

FIG. 7 is a composite graph 700 of primary wetting of an adjustable elastomeric opening made in an injection molded polyurethane sheet polyurethane article as described above. The bottom trace 701 shows the amount of isotropic biaxial control applied to the injection molded polyurethane sheet polyurethane article as described above. The y-axis 702 is the adjustment (ΔX) in millimeters (mm) of the distance between the eyelet and the eyelet measured from the eyelet outer surface of the inside of the unregulated polyurethane article (41.5 mm) extracted from the measurement after adjustment. The x axis 703 is time in seconds (s). The upper trace 704 shows the current flow between two electrodes immersed in an electrolyte in contact with the opposite side of the injection molded cruciate partition I _m . The y axis 705 is a current measured in nano amps. x-axis 706 is time in seconds (s). The voltage bias is held at 50 Hz throughout the write and data is obtained at 50 μs sampling intervals. It can be seen from the graph 700 that the lower x-axis 703 time and the upper x-axis 706 time represent the same time course and the lower ΔX trace 701 is associated with the upper I _m trace 704. have. When ΔX increased from 0 to 5 mm and maintained at that level, graph 700 shows the lack of the observed current change in the initial current level (I _m = 0 mA) and I _m of the penetrating cross partition. At 624 s, the current trace increased abruptly and rapidly reached steady state (I _m to 4 mA). As soon as ΔX subsequently decreased to 1.8 mm, I _m returned to the initial open loop value (I _m = 0 Hz). The occurrence of electrical activity could only be detected after 624 s simultaneous exposure to electrolyte and biaxial isotropic elongation (ΔX = 5 mm). Once started, the trans-barrier ion current rapidly increased to ˜4 mA. When ΔX relaxed to ≦ 1.5 _mm , I _m fell to undetectable levels. This series of events shows that openings of this nature are effectively self-sealing. Accordingly, the traces 701 and 704 can be used to specify the performance of the adjustable elastomeric openings.

FIG. 8 is a composite graph 800 of opening and closing of adjustable elastomeric openings made in injection molded polyurethane sheets following primary wetting. The bottom trace 801 shows the amount of isotropic biaxial control applied to the injection molded polyurethane sheet. The y-axis 802 is the adjustment (ΔX) in millimeters (mm) of the distance between the eyelet and the eyelet measured from the eyelet outer surface inside the unregulated molded polyurethane sheet (41.5 mm) extracted from the measurement after adjustment. . x-axis 803 is time in seconds (s). The upper trace 804 shows the current flow between two electrodes immersed in an electrolyte in contact with the opposite side of the injection molded cruciate partition I _m . The y-axis 805 is a current measured in nano amps. x-axis 806 is time in seconds (s). It can be seen from the graph 800 that the bottom x-axis 803 time and the top x-axis 806 time represent the same time course and the bottom ΔX trace 801 is associated with the top I _m trace 804. have. The voltage bias is kept at 50 Hz during recording and data is obtained at 1000 μs sampling intervals. Graph 800 may encounter a transition zone that carefully adjusts ΔX to allow repeated observation of the occurrence and destruction of electrical conduction. Continuous stepwise increase of ΔX does not lead to a significant change in I _m initially. At the end of the transition zone (ΔX to 0.8 mm) a sudden increase in I _m (up to ˜40 mm) is observed. In contrast, in the reverse direction of regulation, I _m can gradually decrease until it can not be detected due to electrical disconnection and shows that the adjustable elastomer opening can repeatedly self-seal as soon as it relaxes. Accordingly, the traces 801 and 804 can be used to characterize the performance of the adjustable elastomeric opening.

9A is a composite graph 900 of opening and closing of adjustable elastomeric openings made in an injection molded polyurethane sheet following primary wetting. The bottom trace 901 shows the amount of isotropic biaxial control applied to the injection molded polyurethane sheet. The y-axis 902 is the adjustment (ΔX) in millimeters (mm) of the distance between the eyelet and the eyelet measured from the eyelet outer surface of the inside of the unregulated molded crosshair (41.5 mm) extracted from the measurement after adjustment. x-axis 903 is time in seconds (s). The upper trace 904 shows the current flow between the two electrodes immersed in the electrolyte in contact with the opposite side of the injection molded cruciate partition I _m . The y-axis 905 is the current measured in nanoamps. x-axis 906 is time in seconds (s). It can be seen from the graph 900 that the bottom x-axis 903 time and the top x-axis 906 time represent the same time course and the bottom ΔX trace 901 is associated with the top I _m trace 904. have. The voltage bias is kept at 50 Hz during recording and data is obtained at 1000 μs sampling intervals. Graph 900 shows the step adjustment of ΔX and the corresponding I _m response during one complete cycle of opening and closing of the opening within the practical I _m current measurement range (0 to 10 mA) of the current amplifier. The dynamic range of the openings under these conditions corresponded to ΔX ˜0.8 mm (5.3 GΩ) to ΔX ˜3.2 mm (30.5 mm). Traces 901 and 904 may be obtained one or more times and used to account for the elastomer softening Mullins effect. Such traces 901 and 904 may be obtained one or more times and used to condition the opening. Accordingly, the traces 901 and 904 can be used to characterize the performance of the adjustable elastomeric opening.

9B is a graph 907 illustrating the relationship between ΔX and I _m . Tracking 908 shows the I _m response following step adjustment of ΔX during one complete cycle of opening and closing of the opening within the practical I _m current measurement range (0 to 10 mA) of the current amplifier. The x-axis 909 controls the change in millimeters (mm) of the distance between the eyelet and the eyelet measured from the eyelet outer surface inside the unregulated molded polyurethane sheet (41.5 mm) extracted from the measurement after adjustment (ΔX). to be. The y axis 910 is a current measured in nano amps. Accordingly, tracking 908 can be used to characterize the performance of the adjustable elastomeric opening.

10 is a composite graph 1000 of adjustable elastomeric openings made in injection molded polyurethane sheets following primary wetting. DNA molecules are contained in the electrolyte. Bottom trace 1001 shows the amount of isotropic biaxial control applied to the injection molded polyurethane sheet. The y-axis 1002 is the adjustment (ΔX) in millimeters (mm) of the distance between the eyelet and the eyelet measured from the eyelet outer surface of the inside of the unregulated molded polyurethane sheet (41.5 mm) extracted from the measurement after adjustment. to be. x-axis 1003 is time in seconds (s). Tracking of the top 1004 shows the flow of current between two electrodes immersed in an electrolyte injection in contact with the other side of the molded polyurethane sheet (I _m). The y-axis 1005 is the current measured in nanoamps. x-axis 1006 is time in seconds (s). It can be seen from the graph 1000 that the bottom x-axis 1003 time and the top x-axis 1006 time represent the same time course and the bottom ΔX trace 1001 is associated with the top I _m trace 1004. have. The voltage bias is kept at 200 Hz during writing and data is obtained at 10 μs sampling intervals. Graph 1000 shows the step adjustment of ΔX and the corresponding I _m . The electrolyte reservoir on the sheath side of the septum contained pUC DNA at 2 ng / μl. Zone Ι-V marked on the current trace is depicted as a sudden baseline shift when ΔX is adjusted. Current tracking 1004 shows downward, pointed, temporary lines that did not appear prior to the addition of DNA in zones Ι, III, and V. FIG. Transient lines are typical of DNA current blockade (Mara et al., “An asymmetric polymer nanopore for single molecule detection”, Nano Letters, 4, 497-501, 2004; Karhanek et al., “Single DNA molecule detection using nanopipettes and nanoparticles ”, Nano Letters, 403-407, 2005; Li et al.,“ DNA molecules and configurations in a solid-state nanopore microscope ”, Nature Materials, 2, 611-615, 2003; Ito et al.,“ Simultaneous determination of the size and surface charge of individual nanoparticles using a carbon nanotube-based Coulter counter ”Analytical Chemistry, 75. 2399-2406, 2003), where each isolated is caused by single molecular occlusion of the opening. Areas II and IV of reduced ΔX (1.92-1.95 mm) and lower baseline I _m (2.1-2.3 mm 3) do not show this transient line, indicating that the reduction of the opening provides an entropy barrier to DNA translocation. Indicates. Graph 1000 shows that the effect was reversible because the appearance and disappearance of transient lines was observed to coincide with the increase and decrease of ΔX. Thus, regulation of the aperture provides a mechanism for controlled gating of the DNA molecule and tracking 1001 and 1004 can be used to characterize the performance of the adjustable elastomeric aperture. The electrolyte was 1M KCL, 10 mM Tris-HCL pH 8.0, 1 mM EDTA, 0.1%, Triton X-100, filter sterilized through a 0.22 μm Millipore filter and stored in a frozen aliquot. All reagents were AR grade. DNA samples were 2686 base pair plasmid pUC 19 (available from Sigma-Aldrich, St Louis, MO, USA), linearized with Sma 1 and dephosphorylated with cal intestinal phosphatase (CIP) and purified using a QIAquik spin column. Used at a concentration of 2 ng / μl.

FIG. 11 is a flow chart illustrating one exemplary general mode of operation of an embodiment of the invention described in FIGS. 2A & 2B, 3A & 3B, 4A, and 6. For each of the embodiments described in FIGS. 2A & 2B, 3A & 3B, 4A and 6, the exemplary mode of operation is to achieve mechanical equilibrium of the elastomeric material by comparing the measured parameters before and after mechanical adjustment. will be. Mechanical equilibrium indicates relaxation of the Mullins effect in the elastomeric material of the partition prior to or after the manufacture of the opening, and is achieved when the change in the measured parameter is within the specified tolerance range.

The measured parameters of the non-penetrating sclera or the pierced membrane are selected from the group including, but not limited to: optical detection, optical detection by polarization, electrical detection, electrical detection by measured capacitance change, measured Electrical detection by current change, electrical detection by measured electrical resistance change, detection by measured mechanical resistance change, detection by measured mechanical stress change, detection by measured mechanical strain change, or as described above Any combination of parameters.

Claims (37)

An apparatus for producing a deformable opening in a deformable material, the apparatus comprising: A probe forcing the device through the deformable material to create a vacancy in the deformable material through which a continuous path extends from one side of the deformable material to the other side of the deformable material, And an elastomeric support component that supports the deformable material and provides mechanical resistance in penetration of the deformable material in a direction opposite to the force exerted by the probe. The apparatus of claim 1, wherein monitoring means are provided for monitoring one or more parameters relating to the penetration of the deformable material by the probe. The control according to claim 1 or 2, for monitoring the extent of penetration of the deformable material by the probe and in response to such monitoring controlling the adjustment of the degree of penetration of the deformable material by the probe. Means are provided. 4. The probe of claim 3 wherein said control means monitors an electrical tunneling current and / or electrical current passing through said deformable material between said probe and an electrically conductive medium on the other side of said deformable material. And monitor the extent of penetration of the deformable material by means of the device. The device according to claim 1, wherein adjustment means for adjusting the position of the support component with respect to the probe is provided. 6. The cavity of claim 1, wherein the support component comprises a cavity filled with a fluid to receive a tip of the probe upon penetration of the deformable material by the probe. 7. Device characterized in that. 7. The method of claim 1, wherein the support component is in the form of a metal electrode comprising a cavity filled with an electrolyte fluid for receiving the probe tip upon penetration of the deformable material by the probe. Featuring device 8. An apparatus according to any one of the preceding claims, wherein means for heating or cooling the support component are provided. The device of claim 1, wherein means are provided for heating or cooling the probe. A conditioning device for an adjustable elastomeric material containing an elastomeric septum portion suitable for forming an opening that penetrates and provides a path to particles and / or radiation, the apparatus comprising: Monitoring means for monitoring a parameter of the partition wall, and adjusting means for adjusting the partition wall to change one or more parameters of the path provided by the opening. The apparatus of claim 10 wherein said adjusting means comprises a probe for forcing through said deformable material to form a space in said material. 12. The apparatus of claim 11, wherein said monitoring means comprises means for measuring one or more parameters of said penetrating process during penetration of said material by said probe. 13. An apparatus according to any of claims 10, 11 or 12, wherein said monitoring means comprises optical detection means, electrical detection means and / or mechanical stress or strain detection means. 14. An apparatus according to any one of claims 10 to 13, wherein said monitoring means comprises electrical detection means for measuring a change in capacity of said material. A method of preconditioning an elastomeric material containing an elastomeric partition in front of a partition that penetrates to form an opening that provides a path for particles and / or radiation. Wherein the method comprises providing a non-penetrating membrane of adjustable elastomeric material, adjusting the non-penetrating membrane, and monitoring one or more parameters of the non-penetrating membrane. 16. The method of claim 15, wherein said preconditioning comprises preconditioning by chemical, thermal or radiation curing, or preconditioning by mechanical control. 17. The method of claim 16, wherein said preconditioning by mechanical control comprises preconditioning by a method of compression, tensioning, stretching, bending, twisting. How to feature. 18. The method of claim 16 or 17, wherein the preconditioning by mechanical adjustment comprises preconditioning by one or more mechanical conditioning cycles until mechanical equilibrium is achieved. A method of determining the suitability of an adjustable elastomeric material containing an elastomeric partition wall that forms an opening in the partition wall that provides a path to particles and / or radiation, the method comprising: Said method comprising monitoring one or more through parameters of said opening manufacturing process during penetration, and using said monitoring results to characterize the quality and usefulness of said formed aperture. 20. The method of claim 19, wherein if the monitoring result is within an acceptable range, the step of authorizing the elastomeric material for use in forming an opening that provides a path to the particles and / or radiation, and for this purpose the monitoring result is Rejecting the elastomeric material for use when out of the acceptable range. 21. The method of claim 19 or 20, wherein the recording of such monitoring results using a recording medium and the recording as an indication of the suitability of the elastomeric material capable of forming an opening providing a path to particles and / or radiation. Providing the results recorded on the medium to the recording medium. A method of determining the suitability of an opening in an adjustable elastomeric material that provides an adjustable path to particles and / or radiation, The method comprising monitoring one or more parameters of the opening, and using the monitoring results to characterize the quality and usefulness of the opening. 23. The method of claim 22, further comprising: approving the opening for use to provide a path to particles and / or radiation if such monitoring results are within an acceptable range, and wherein said monitoring results are outside said acceptable range. Rejecting the opening for the purpose of further comprising. 24. The method of claim 22 or 23, wherein the monitoring is performed by an optical microscope, a polarizing microscope, a confocal microscope, a scanning confocal microscopy, a probe microscope, a scanning probe microscope, an atomic force microscopy, scanning electrons. Microscopic examination of said opening by scanning electrochemical microscopy, electron microscopy, scanning electron microscopy or transmission electron microscopy. A recording medium for use in determining suitability of an adjustable elastomeric material containing an elastomeric partition to form openings in the partition that provide paths to particles and / or radiation, the recording medium having a path to the particles and / or radiation. A recording medium having a result recorded on the recording medium indicating suitability of the elastomeric material capable of forming an opening to provide. An adjustable elastomeric material containing an elastomeric partition wall suitable for forming an opening that penetrates to provide a path to particles and / or radiation, and for adjusting the partition wall to change one or more parameters of the path provided by the opening Particle sensitive and / or radiation sensitive device comprising control means. 27. An apparatus according to claim 26, wherein said adjusting means is suitable for changing the geometry and / or size of said opening to increase and / or decrease the diameter and / or path length of said opening. 28. An apparatus as claimed in claim 26 or 27 wherein the partition comprises a membrane portion of the material having a thickness less than a surrounding portion of the material. 29. The device of claim 28, wherein the periphery of the material is in the form of an elevated rim enclosing the membrane portion to form a well. 30. The method of any one of claims 26-29, wherein at least one hole extends through the portion of material that does not contain the partition wall to provide a fluid path through the material prior to penetration of the partition wall. Apparatus characterized in that the. 31. The device of claim 30, wherein the hole or each hole is surrounded by an elevated rim that seals the hole to form a well surrounding the hole. 32. The apparatus of any one of claims 26 to 31, wherein the adjusting means can be detachably attached to the adjustable elastomeric material to adjust the partition wall to change one or more parameters of the path provided by the opening. Apparatus characterized in that the. 33. A device according to any of claims 26 to 32, wherein said adjusting means is attachable to said adjustable elastomeric material detachably by one or more eyelets extending through said material. . 34. The device of any of claims 26 to 33, wherein the adjustable elastomeric material is in the form of a cross-shaped sheet. 35. The method according to any one of claims 26 to 34, wherein monitoring means for monitoring one or more parameters of the path provided by the opening and providing feedback to the adjustment means indicative of the monitored parameters are provided. Characterized in that the device. 36. The method of claim 26, wherein the adjustable elastomeric material is selected from the group consisting of a polymer; Natural and synthetic rubbers; Elastomeric materials; Natural polymers, proteins, polypeptides, polysaccharides; plastic; Doped conducting plastics; Hydrocarbon plastics; Perfluorocarbon plastics; Latex materials; Thermoplastic deformable materials; Thermoplastic polyurethane (ether and ester) deformable materials; Olefinic deformable materials including polypropylene, polyethylene, cyclic olefins; Styrenic deformable materials; Polyamide-based deformable materials; Polyester-based deformable materials; Nitrile-based deformable materials; Ethylene chloride copolymer crosslinked alloys; Silicone deformable materials; Semiconductor materials; Silicates; silicon; Doped silicon; Metal or metal alloy; Piezoelectric materials; And piezoelectric ceramics. 37. The device of any one of claims 26 to 36, wherein the adjustable elastomeric material is surface treated to be hydrophobic, hydrophilic, lipophilic, electrostatically charged, and / or electrostatically neutral. .

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