WO2009101395A1 - Particle separation apparatus and methods - Google Patents

Particle separation apparatus and methods Download PDF

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Publication number
WO2009101395A1
WO2009101395A1 PCT/GB2009/000373 GB2009000373W WO2009101395A1 WO 2009101395 A1 WO2009101395 A1 WO 2009101395A1 GB 2009000373 W GB2009000373 W GB 2009000373W WO 2009101395 A1 WO2009101395 A1 WO 2009101395A1
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WO
WIPO (PCT)
Prior art keywords
substrate
sample
syringe
particle
container
Prior art date
Application number
PCT/GB2009/000373
Other languages
French (fr)
Inventor
Darren Lee Forrest
Original Assignee
Optima Design Services Limited
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 Optima Design Services Limited filed Critical Optima Design Services Limited
Publication of WO2009101395A1 publication Critical patent/WO2009101395A1/en

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/2813—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label

Definitions

  • This invention relates to particle separation apparatus and methods, in particular for cell separation technology such as is described in WO02/078906 of Cellect Technologies Corp et ⁇ l.
  • WO02/078906 describes separating a target particle from a fluid containing a target particle or particles and other particles, by applying the fluid to a photosensitive substrate and photosensitising the substrate in the vicinity of target particles causing them to attach to metal, e.g. silver grains produced locally to the target particles when the substrate is photographically developed.
  • ⁇ particles that can be separated using these methods and apparatus are mentioned living cells, sub-cellular components and organelles and other macromolecules or molecular complexes or aggregates of biological origin. This may be carried out as a method for diagnosis of a medical condition, and, in particular, for identifying cancer cells.
  • One method disclosed in WO02/078906 involves identifying a particle, or, in particular, a cell, from a population based on microscopic examination, which may be done by eye or using computer-based pattern recognition.
  • the position on a photosensitive layer on, say, a microscope slide, of an identified cell is noted, and the photosensitive layer is sensitized in the immediate vicinity of the identified cell by a beam, for example from a laser, targeted at the position of the cell.
  • Non-targeted cells do not have adjacent metal grains, and do not attach to the slide, and can be washed off.
  • the attached cells can be subsequently recovered.
  • Another method disclosed in WO02/078906, with which this invention is particularly concerned involves labelling target particles selectively with a photophoric probe that can be activated to emit light. The method then involves applying the sample to a photosensitive substrate and activating the photophoric probe to emit light which photosensitises the substrate and, on development, forms metal, particularly silver, grains to which the labelled cells will attach, leaving the others free to be washed off.
  • the apparatus for carrying out this latter method disclosed in WO02/078906 comprises a vessel or container, for holding the liquid in which the sample cells or other particles are suspended, such as a Petri dish, a flask, a bottle or any other kind of container, and such other equipment such as incubators and centrifuges, such as may typically be to hand in a laboratory in which the procedure is carried out - in other words, no special equipment is envisaged.
  • the cells or other particles are allowed to settle out of suspension on a photosensitive layer at the bottom of the containing vessel, or may be encouraged so to do as by centrifugation or by an applied electric field.
  • the present invention is based on the recognition that the procedure for separating particles disclosed in WO02/078906, particularly that embodiment of the procedure that involves the attachment of a photophoric label to target cells, could form the basis of a routine test for cancer or other medical conditions that are indicated by particular cells or other particles, such, for example as a routine screening operation carried out on a population and which involves large numbers of samples.
  • the present invention provides methods and apparatus for particle separation that facilitate the routine performance of such screening or other tests without requiring the availability of equipment that may be found as a matter of course in clinical and other laboratories, but which will not be generally available in doctors' surgeries or to doctors on their rounds or to clinical technicians engaged in mass screening.
  • the term 'particle' as used hereinafter includes cells, living or dead, and all other particles falling within the ambit of the disclosure of WO02/078906.
  • the invention comprises, in one aspect, apparatus for particle separation comprising: a support for a photosensitive substrate, and a photosensitive substrate removably supported on the support; a liquid delivery system adapted:
  • the liquid delivery system may comprise a syringe arrangement, which may comprise a syringe and a syringe-penetrable cover for the substrate.
  • the sample spreader may be adapted to spread the sample so as to limit the sample depth on the substrate to the dimensions of a single particle under investigation, whereby to assure proximity of a photophor labelled particle to the sensitised substrate surface.
  • the spreader may comprise a member adapted to cover and be spaced a predetermined distance from the substrate, whereby to cause a liquid sample on the substrate to spread out into a one particle deep layer.
  • the predetermined distance may be determined by a hollow shim having a depth of one particle.
  • different hollow shims may be provided for different particle sizes.
  • the syringe arrangement and spreader may be adapted to act together.
  • the container may comprise a spigot into which the syringe is inserted first to penetrate the substrate cover to deliver the sample to the substrate, the spigot carrying the spreader and being resiliently loaded to hold the spreader away from the substrate and to move towards the substrate under pressure applied through the syringe to spread the sample, then to retract.
  • the processing fluid delivery system may comprise preloaded capsule means operable to deliver fluids to the spread sample and may comprise capsule means holding a photophor activator, a photographic emulsion developer, a fixer and a wash, as may be necessary to process the sample.
  • the container may comprise a drain arrangement adapted to drain spent fluids away from the sample.
  • the drain arrangement may comprise a soluble plug to maintain the interior of the container sterile in storage.
  • a container may hold more than one photosensitive substrate, and may, for instance, hold eight such substrates.
  • Each substrate may comprise a glass or like material plate, like a microscope slide, and the spreader may then comprise a like plate, perhaps like a microscope slide cover slip, with a central penetrable aperture for the syringe.
  • Each substrate will then have a syringe arrangement, while a single processing fluid delivery system can be operated after all the substrates have been loaded with samples to process all samples at the same time.
  • the invention also comprises a method for separating particles having a given characteristic from a liquid sample comprising other particles comprising: processing the sample to attach an activatable photophor label to particles desired to be separated; loading the thus processed sample on to a photosensitive substrate removably supported on a support in a light tight container; spreading the sample loaded on to the substrate to a predetermined depth thereon whereby to assure proximity to the substrate of any photophor labelled particle in the sample; and processing the sample in the container to activate any photophor label on the substrate to emit light to photosensitise the substrate to produce metal grains whereby selectively to attach any labelled particle to the substrate.
  • the sample may be loaded on to the substrate from a syringe, and may be spread to the depth of a single particle, as by a spreader member adapted to cover and be spaced a predetermined distance from the substrate.
  • Multiple samples may be processed in a container having multiple substrates.
  • the samples may be loaded individually, and processed simultaneously.
  • Figure 1 is an exploded perspective view of a container comprising operative components
  • Figure 2 is an exploded diagrammatic cross section of a syringe arrangement of the container of Figure 1 ;
  • Figure 3 is a view of the arrangement of Figure 2, assembled, in a first configuration
  • Figure 4 is a view like Figure 3, in a second configuration
  • Figure 5 is a diagrammatic cross section of the container of Figure 1 ;
  • Figure 6 is a diagrammatic cross-section of a process fluid dispenser of the container of Figure 1 '
  • FIG. 1 illustrate apparatus for particle separation comprising: a support 11 for a photosensitive substrate 12, and a photosensitive substrate 12 removably supported on the support 11 ; a liquid delivery system 13 adapted:
  • a sample spreader 16 operable to define a sample depth on the substrate 12; the support 11 being enclosed in a light tight container 10.
  • the support 11 comprises a curved plate with studs 1 Ia to hold the substrates flat.
  • the 'cassette' container 10 may be provided pre-loaded with photosensitive substrates 12 as a diagnostic tool that can simply be loaded with liquid sample which can then be processed using built in features of the cassette to produce processed substrates in the form of microscope slides with particles of interest attached. The slides can then be further processed, as by microscopic visual or machine vision inspection or by freeing the captured particles for replication, chemical or biological analysis or any other appropriate processing.
  • the container 10 is light tight, at least in the sense that it blocks light to which the substrates are sensitive.
  • the liquid delivery system 13 comprises a syringe arrangement 17, comprising a syringe 18 and a syringe-penetrable cover 16 for the substrate 12.
  • the cover 16 comprises a resealing plastic plug 21 so that, when the syringe is withdrawn, the container is still light tight.
  • the cover 16 serves as a sample spreader and is adapted to spread the sample 14 so as to limit the sample depth on the substrate 12 to the dimensions of a single particle under investigation, whereby to assure proximity of a photophor labelled particle to the sensitised substrate surface.
  • the spreader 16 is adapted to cover and be spaced a predetermined distance from the substrate, whereby to cause a liquid sample on the substrate 12 to spread out into a one particle deep layer.
  • the predetermined distance is determined by a hollow shim 16a having a thickness corresponding to one particle, and the spreader is resiliently loaded, by spring 22, against the substrate 12 with the hollow shim intervening so that it is able to spread the sample to a depth of one particle.
  • the syringe arrangement 17 and spreader 16 are adapted to act together.
  • the container comprises a spigot 23 into which the syringe 18 is inserted first to penetrate the substrate cover 19 to deliver the sample to the substrate 12, the spigot 23 carrying the spreader 16 and being resiliently loaded to hold the spreader 16 away from the substrate 12 and to move towards the substrate 12 under pressure applied through the syringe 18 to spread the sample, then to retract.
  • the processing fluid delivery system comprises preloaded capsule means 24 operable to deliver fluids 15 to the spread sample and comprises capsules holding a photophor activator 15a, a photographic emulsion developer 15b, a fixer 15c and a wash 15d, as may be necessary to process the sample.
  • Each capsule means comprises a plunger 26 adapted to be depressed to puncture the bottom of the capsule and to be withdrawn to open the puncture thus formed for the release of its fluid 15
  • the container comprises a drain arrangement 25 adapted to drain spent fluids away from the sample.
  • the drain arrangement 25 comprises a soluble plug to maintain the interior of the container sterile in storage.
  • a container 10 may hold more than one photosensitive substrate, and, as illustrated, holds eight such substrates.
  • Each substrate 12 comprises a glass or like material plate, like a microscope slide, and the spreader may then comprise a like plate, perhaps like a microscope slide cover slip, with a central penetrable aperture for the syringe.
  • Each substrate will then have a syringe arrangement, while a single processing fluid delivery system can be operated after all the substrates have been loaded with samples to process all samples at the same time.
  • the photophoric labelling, its activation, and the processing of the substrates after loading with sample may be carried out as described in WO02/078906 or in any other suitable fashion.
  • the slides may be removed from the cassette container 10 by breaking a seal or other safeguard as may be desirable.

Abstract

Apparatus for particle separation comprising: a support for a photosensitive substrate, and a photosensitive substrate removably supported on the support; a liquid delivery system adapted: (a) to deliver a liquid sample on to a photosensitive substrate on the support, to be tested for the presence of particles labelled with an activatable photophoric label; (b) to deliver processing fluid to the sample to activate any labelled particle on the substrate whereby locally to sensitise the substrate and to develop the photosensitive substrate to produce metal grains where sensitised; a sample spreader operable to define a sample depth on the substrate; characterised in that the support is enclosed in a light tight container.

Description

Particle Separation Apparatus and Methods
This invention relates to particle separation apparatus and methods, in particular for cell separation technology such as is described in WO02/078906 of Cellect Technologies Corp et άl.
WO02/078906 describes separating a target particle from a fluid containing a target particle or particles and other particles, by applying the fluid to a photosensitive substrate and photosensitising the substrate in the vicinity of target particles causing them to attach to metal, e.g. silver grains produced locally to the target particles when the substrate is photographically developed.
Among particles that can be separated using these methods and apparatus are mentioned living cells, sub-cellular components and organelles and other macromolecules or molecular complexes or aggregates of biological origin. This may be carried out as a method for diagnosis of a medical condition, and, in particular, for identifying cancer cells. One method disclosed in WO02/078906 involves identifying a particle, or, in particular, a cell, from a population based on microscopic examination, which may be done by eye or using computer-based pattern recognition. The position on a photosensitive layer on, say, a microscope slide, of an identified cell is noted, and the photosensitive layer is sensitized in the immediate vicinity of the identified cell by a beam, for example from a laser, targeted at the position of the cell. Subsequently developing the photosensitive later causes the formation of silver (or other metal) grains at that position, to which the cell attaches. Non-targeted cells do not have adjacent metal grains, and do not attach to the slide, and can be washed off. The attached cells can be subsequently recovered. Another method disclosed in WO02/078906, with which this invention is particularly concerned, involves labelling target particles selectively with a photophoric probe that can be activated to emit light. The method then involves applying the sample to a photosensitive substrate and activating the photophoric probe to emit light which photosensitises the substrate and, on development, forms metal, particularly silver, grains to which the labelled cells will attach, leaving the others free to be washed off.
The apparatus for carrying out this latter method disclosed in WO02/078906 comprises a vessel or container, for holding the liquid in which the sample cells or other particles are suspended, such as a Petri dish, a flask, a bottle or any other kind of container, and such other equipment such as incubators and centrifuges, such as may typically be to hand in a laboratory in which the procedure is carried out - in other words, no special equipment is envisaged. The cells or other particles are allowed to settle out of suspension on a photosensitive layer at the bottom of the containing vessel, or may be encouraged so to do as by centrifugation or by an applied electric field. The present invention is based on the recognition that the procedure for separating particles disclosed in WO02/078906, particularly that embodiment of the procedure that involves the attachment of a photophoric label to target cells, could form the basis of a routine test for cancer or other medical conditions that are indicated by particular cells or other particles, such, for example as a routine screening operation carried out on a population and which involves large numbers of samples.
The present invention provides methods and apparatus for particle separation that facilitate the routine performance of such screening or other tests without requiring the availability of equipment that may be found as a matter of course in clinical and other laboratories, but which will not be generally available in doctors' surgeries or to doctors on their rounds or to clinical technicians engaged in mass screening. The term 'particle' as used hereinafter includes cells, living or dead, and all other particles falling within the ambit of the disclosure of WO02/078906.
The invention comprises, in one aspect, apparatus for particle separation comprising: a support for a photosensitive substrate, and a photosensitive substrate removably supported on the support; a liquid delivery system adapted:
(a) to deliver a liquid sample on to a photosensitive substrate on the support, to be tested for the presence of particles labelled with an activatable photophoric label;
(b) to deliver processing fluid to the sample to activate any labelled particle on the substrate whereby locally to sensitise the substrate and to develop the photosensitive substrate to produce metal grains where sensitised; a sample spreader operable to define a sample depth on the substrate; characterised in that the support is enclosed in a light tight container. The term 'light tight' is intended to mean substantially impenetrable to light to which the substrate is sensitive, just as a photographic dark room may be lit by red light to which photographic emulsions processed therein are not sensitive.
The liquid delivery system may comprise a syringe arrangement, which may comprise a syringe and a syringe-penetrable cover for the substrate.
The sample spreader may be adapted to spread the sample so as to limit the sample depth on the substrate to the dimensions of a single particle under investigation, whereby to assure proximity of a photophor labelled particle to the sensitised substrate surface. The spreader may comprise a member adapted to cover and be spaced a predetermined distance from the substrate, whereby to cause a liquid sample on the substrate to spread out into a one particle deep layer. The predetermined distance may be determined by a hollow shim having a depth of one particle. Clearly, different hollow shims may be provided for different particle sizes.
The syringe arrangement and spreader may be adapted to act together. The container may comprise a spigot into which the syringe is inserted first to penetrate the substrate cover to deliver the sample to the substrate, the spigot carrying the spreader and being resiliently loaded to hold the spreader away from the substrate and to move towards the substrate under pressure applied through the syringe to spread the sample, then to retract.
The processing fluid delivery system may comprise preloaded capsule means operable to deliver fluids to the spread sample and may comprise capsule means holding a photophor activator, a photographic emulsion developer, a fixer and a wash, as may be necessary to process the sample.
The container may comprise a drain arrangement adapted to drain spent fluids away from the sample. The drain arrangement may comprise a soluble plug to maintain the interior of the container sterile in storage. A container may hold more than one photosensitive substrate, and may, for instance, hold eight such substrates. Each substrate may comprise a glass or like material plate, like a microscope slide, and the spreader may then comprise a like plate, perhaps like a microscope slide cover slip, with a central penetrable aperture for the syringe. Each substrate will then have a syringe arrangement, while a single processing fluid delivery system can be operated after all the substrates have been loaded with samples to process all samples at the same time.
The invention also comprises a method for separating particles having a given characteristic from a liquid sample comprising other particles comprising: processing the sample to attach an activatable photophor label to particles desired to be separated; loading the thus processed sample on to a photosensitive substrate removably supported on a support in a light tight container; spreading the sample loaded on to the substrate to a predetermined depth thereon whereby to assure proximity to the substrate of any photophor labelled particle in the sample; and processing the sample in the container to activate any photophor label on the substrate to emit light to photosensitise the substrate to produce metal grains whereby selectively to attach any labelled particle to the substrate. The sample may be loaded on to the substrate from a syringe, and may be spread to the depth of a single particle, as by a spreader member adapted to cover and be spaced a predetermined distance from the substrate.
Multiple samples may be processed in a container having multiple substrates. The samples may be loaded individually, and processed simultaneously.
One embodiment of apparatus and a method for separating particles according to the invention will now be described with reference to the accompanying drawings, in which:
Figure 1 is an exploded perspective view of a container comprising operative components;
Figure 2 is an exploded diagrammatic cross section of a syringe arrangement of the container of Figure 1 ;
Figure 3 is a view of the arrangement of Figure 2, assembled, in a first configuration;
Figure 4 is a view like Figure 3, in a second configuration;
Figure 5 is a diagrammatic cross section of the container of Figure 1 ;
Figure 6 is a diagrammatic cross-section of a process fluid dispenser of the container of Figure 1 '
The drawings illustrate apparatus for particle separation comprising: a support 11 for a photosensitive substrate 12, and a photosensitive substrate 12 removably supported on the support 11 ; a liquid delivery system 13 adapted:
(a) to deliver a liquid sample 14 on to a photosensitive substrate 12 on the support 11 to be tested for the presence of particles labelled with an activatable photophoric label;
(b) to deliver processing fluid 15 to the sample to activate any labelled particle on the substrate 12 whereby locally to sensitise the substrate and to develop the photosensitive substrate to produce metal grains where sensitised;
a sample spreader 16 operable to define a sample depth on the substrate 12; the support 11 being enclosed in a light tight container 10. The support 11 comprises a curved plate with studs 1 Ia to hold the substrates flat.
The 'cassette' container 10 may be provided pre-loaded with photosensitive substrates 12 as a diagnostic tool that can simply be loaded with liquid sample which can then be processed using built in features of the cassette to produce processed substrates in the form of microscope slides with particles of interest attached. The slides can then be further processed, as by microscopic visual or machine vision inspection or by freeing the captured particles for replication, chemical or biological analysis or any other appropriate processing. The container 10 is light tight, at least in the sense that it blocks light to which the substrates are sensitive.
The liquid delivery system 13 comprises a syringe arrangement 17, comprising a syringe 18 and a syringe-penetrable cover 16 for the substrate 12. The cover 16 comprises a resealing plastic plug 21 so that, when the syringe is withdrawn, the container is still light tight.
The cover 16 serves as a sample spreader and is adapted to spread the sample 14 so as to limit the sample depth on the substrate 12 to the dimensions of a single particle under investigation, whereby to assure proximity of a photophor labelled particle to the sensitised substrate surface. The spreader 16 is adapted to cover and be spaced a predetermined distance from the substrate, whereby to cause a liquid sample on the substrate 12 to spread out into a one particle deep layer. The predetermined distance is determined by a hollow shim 16a having a thickness corresponding to one particle, and the spreader is resiliently loaded, by spring 22, against the substrate 12 with the hollow shim intervening so that it is able to spread the sample to a depth of one particle.
The syringe arrangement 17 and spreader 16 are adapted to act together. The container comprises a spigot 23 into which the syringe 18 is inserted first to penetrate the substrate cover 19 to deliver the sample to the substrate 12, the spigot 23 carrying the spreader 16 and being resiliently loaded to hold the spreader 16 away from the substrate 12 and to move towards the substrate 12 under pressure applied through the syringe 18 to spread the sample, then to retract.
The processing fluid delivery system comprises preloaded capsule means 24 operable to deliver fluids 15 to the spread sample and comprises capsules holding a photophor activator 15a, a photographic emulsion developer 15b, a fixer 15c and a wash 15d, as may be necessary to process the sample. Each capsule means comprises a plunger 26 adapted to be depressed to puncture the bottom of the capsule and to be withdrawn to open the puncture thus formed for the release of its fluid 15
The container comprises a drain arrangement 25 adapted to drain spent fluids away from the sample. The drain arrangement 25 comprises a soluble plug to maintain the interior of the container sterile in storage.
A container 10 may hold more than one photosensitive substrate, and, as illustrated, holds eight such substrates. Each substrate 12 comprises a glass or like material plate, like a microscope slide, and the spreader may then comprise a like plate, perhaps like a microscope slide cover slip, with a central penetrable aperture for the syringe. Each substrate will then have a syringe arrangement, while a single processing fluid delivery system can be operated after all the substrates have been loaded with samples to process all samples at the same time.
The photophoric labelling, its activation, and the processing of the substrates after loading with sample may be carried out as described in WO02/078906 or in any other suitable fashion.
After processing is complete, the slides may be removed from the cassette container 10 by breaking a seal or other safeguard as may be desirable.
While novel and inventive features of the apparatus described with reference to the drawings are described in the context of a cassette-like container pre-loaded with photosensitive substrates and all necessary processing fluids, particularly adapted to carry out the particle separation operation as described in WO02/078906, features and combinations of features will have novelty and inventiveness in their own right. The use of a hollow shim to limit the depth of the sample layer on the substrate to one particle diameter may well find application in other contexts.

Claims

Claims:
1 Apparatus for particle separation comprising: a support for a photosensitive substrate, and a photosensitive substrate removably supported on the support; a liquid delivery system adapted: (a) to deliver a liquid sample on to a photosensitive substrate on the support, to be tested for the presence of particles labelled with an activatable photophoric label;
(b) to deliver processing fluid to the sample to activate any labelled particle on the substrate whereby locally to sensitise the substrate and to develop the photosensitive substrate to produce metal grains where sensitised; a sample spreader operable to define a sample depth on the substrate; characterised in that the support is enclosed in a light tight container.
2 Apparatus according to claim 1, in which the container is light tight in the sense that it is substantially impenetrable to light to which the substrate is sensitive. 3 Apparatus according to claim 1 or claim 2, in which the liquid delivery system comprises a syringe arrangement.
4 Apparatus according to claim 3, in which the syringe arrangement comprises a syringe and a syringe-penetrable cover for the substrate.
5 Apparatus according to any one of claims 1 to 4, in which the sample spreader is adapted to spread the sample so as to limit the sample depth on the substrate to the dimensions of a single particle under investigation, whereby to assure proximity of a photophor labelled particle to the sensitised substrate surface.
6 Apparatus according to claim 5, in which the spreader comprises a member adapted to cover and be spaced a predetermined distance from the substrate, whereby to cause a liquid sample on the substrate to spread out into a one particle deep layer. 7 Apparatus according to claim 5 or claim 6, in which the predetermined distance is determined by a hollow shim having a thickness corresponding to one particle.
8 Apparatus according to any one of claims 5 to 7, in which the syringe arrangement and spreader are adapted to act together. 9 Apparatus according to any one of claims 1 to 8, in which the container comprises a spigot into which the syringe is inserted first to penetrate the substrate cover to deliver the sample to the substrate, the spigot carrying the spreader and being resiliently loaded to hold the spreader away from the substrate and to move towards the substrate under pressure applied through the syringe to spread the sample, then to retract.
10 Apparatus according to any one of claims 1 to 9, in which the processing fluid delivery system comprises preloaded capsule means operable to deliver fluids to the spread sample.
11 Apparatus according to claim 10, comprising capsule means holding any one or more of a photophor activator, a photographic emulsion developer, a fixer and a wash, as may be necessary to process the sample. 12 Apparatus according to any one of claims 1 to 11, in which the container comprises a drain arrangement adapted to drain spent fluids away from the sample.
13 Apparatus according to claim 12, in which the drain arrangement comprises a soluble plug to maintain the interior of the container sterile in storage.
14 Apparatus according to any one of claims 1 to 13, in which the container is adapted to hold more than one photosensitive substrate.
15 Apparatus according to claim 14, holding eight such substrates.
16 Apparatus according to claim 15, in which each substrate comprises a glass or like material plate, like a microscope slide, and the spreader comprises a like plate, like a microscope slide cover slip, with a central penetrable aperture for the syringe. 17 Apparatus according to claim 16, in which each substrate has a syringe arrangement, while a single processing fluid delivery system is operable after all the substrates have been loaded with samples to process all samples at the same time.
18 A method for separating particles having a given characteristic from a liquid sample comprising other particles comprising: processing the sample to attach an activatable photophor label to particles desired to be separated; loading the thus processed sample on to a photosensitive substrate removably supported on a support in a light tight container;
spreading the sample loaded on to the substrate to a predetermined depth thereon whereby to assure proximity to the substrate of any photophor labelled particle in the sample; and processing the sample in the container to activate any photophor label on the substrate to emit light to photosensitise the substrate to produce metal grains whereby selectively to attach any labelled particle to the substrate. 19 A method according to claim 18, in which the sample is loaded on to the substrate from a syringe, and spread to the depth of a single particle, as by a spreader member adapted to cover and be spaced a predetermined distance from the substrate.
20 A method according to claim 18 or claim 19, in which multiple samples are processed in a container having multiple substrates.
21 A method according to claim 20, in which the samples are loaded individually, and processed simultaneously.
PCT/GB2009/000373 2008-02-12 2009-02-10 Particle separation apparatus and methods WO2009101395A1 (en)

Applications Claiming Priority (2)

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GB0802568A GB0802568D0 (en) 2008-02-12 2008-02-12 Particle separation apparatus and methods

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WO2002078906A2 (en) * 2001-03-29 2002-10-10 Cellect Technologies Corp. Methods devices and systems for sorting and separating particles
EP1318408A2 (en) * 2001-12-07 2003-06-11 Symyx Technologies, Inc. High throughput preparation and analysis of polymer blends
US20050052646A1 (en) * 2001-06-29 2005-03-10 Meso Scale Technologies, Llc. Assay plates, reader systems and methods for luminescence test measurements
US20060105350A1 (en) * 2004-11-15 2006-05-18 Eastman Kodak Company Method and system for sorting and separating particles
US20060153736A1 (en) * 2003-09-09 2006-07-13 Kalra Krishan L Sample processing system

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2543181A (en) * 1947-01-15 1951-02-27 Polaroid Corp Photographic product comprising a rupturable container carrying a photographic processing liquid
US6159686A (en) * 1992-09-14 2000-12-12 Sri International Up-converting reporters for biological and other assays
US5854075A (en) * 1995-06-07 1998-12-29 Alpha Scientific Instruments, Inc. Automatic blood film preparation method
US6191852B1 (en) * 1997-10-14 2001-02-20 Bayer Aktiengesellschaft Optical measurement system for detecting luminescence or fluorescence signals
WO2002078906A2 (en) * 2001-03-29 2002-10-10 Cellect Technologies Corp. Methods devices and systems for sorting and separating particles
US20050052646A1 (en) * 2001-06-29 2005-03-10 Meso Scale Technologies, Llc. Assay plates, reader systems and methods for luminescence test measurements
EP1318408A2 (en) * 2001-12-07 2003-06-11 Symyx Technologies, Inc. High throughput preparation and analysis of polymer blends
US20060153736A1 (en) * 2003-09-09 2006-07-13 Kalra Krishan L Sample processing system
US20060105350A1 (en) * 2004-11-15 2006-05-18 Eastman Kodak Company Method and system for sorting and separating particles

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