US20110034758A1 - Cartridge For A Biological Sample - Google Patents

Cartridge For A Biological Sample Download PDF

Info

Publication number
US20110034758A1
US20110034758A1 US12/739,309 US73930908A US2011034758A1 US 20110034758 A1 US20110034758 A1 US 20110034758A1 US 73930908 A US73930908 A US 73930908A US 2011034758 A1 US2011034758 A1 US 2011034758A1
Authority
US
United States
Prior art keywords
sample
assay
cell
chamber
sperm
Prior art date
Legal status (The legal status 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 status listed.)
Abandoned
Application number
US12/739,309
Inventor
Vered Shany
Isaac Tavori
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lotus Bio (Nymphaea) Ltd
Original Assignee
Lotus Bio (Nymphaea) Ltd
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 Lotus Bio (Nymphaea) Ltd filed Critical Lotus Bio (Nymphaea) Ltd
Priority to US12/739,309 priority Critical patent/US20110034758A1/en
Assigned to LOTUS BIO (NYMPHAEA) LTD reassignment LOTUS BIO (NYMPHAEA) LTD ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SHANY, VERED, TAVORI, ISAAC
Publication of US20110034758A1 publication Critical patent/US20110034758A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B10/0045Devices for taking samples of body liquids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0681Filter
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502753Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00Heating or cooling apparatus; Heat insulating devices
    • B01L7/52Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples

Definitions

  • Embodiments of the disclosure relate to a cartridge for a biologic sample.
  • Biological samples such as semen, vaginal secretions, vaginal cells, blood, urine, saliva, lymph and the like, are commonly tested at the field, with portable apparatuses, tools or disposable diagnostics, or in laboratories.
  • Laboratory work including field work, often requires taking a portion of the sample, processing it in various ways using laboratory operations and finally assessing a result.
  • Laboratory medicine commonly includes anatomic pathology histopathology, cytopathology, microscopy, clinical microbiology, bacteriology, virology, parasitology, immunology, mycology, clinical biochemistry instrumental analysis, enzymology, toxicology, endocrinology and hematology.
  • An automated analyzer is often defined as a medical laboratory instrument designed to rapidly measure different chemicals and other characteristics in a samples, with minimal human assistance.
  • the automation of laboratory testing does not usually remove the need for human expertise (as some results must still be evaluated by medical technologists and other qualified clinical laboratory professionals, and sometimes manual processing is required), but it does ease concerns about error reduction, staffing concerns and safety.
  • a sealed removable cartridge adapted for insertion into an assay device and adapted to contain a biologic sample
  • the cartridge comprising: two or more assay locations adapted to facilitate, within said cartridge, two or more assays of said biologic sample; and an actuator interface adapted to interface with an actuator of said assay device, to transport said biologic sample towards at least one of said assay locations.
  • said biologic sample is selected from a group which includes: a semen sample, a vaginal secretion sample, a vaginal cell sample, a blood sample, a urine sample, a saliva sample, a lymph sample and/or any combination thereof.
  • said two or more assays are selected from a group which includes: a sperm concentration assay, a semen pH assay, a leukocyte threshold assay, a sperm motility assay, a sperm morphology assay, a semen volume assay, a viscosity assay, a turbidity assay, and/or any combination thereof.
  • said at least one of said assays is adapted to facilitate diagnosis of at least one sexually transmitted disease (STD) selected from a group which includes: syphilis, gonorrhea, candida, human papiloma virus (HPV), mycoplasma, ureaplasma, human immunodeficiency virus (HIV), Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas, Hepatitis C and/or any combination thereof.
  • STD sexually transmitted disease
  • a housing of said cartridge is substantially rigid.
  • a housing of said cartridge is substantially flexible.
  • said cartridge further comprises a cell separation system, comprising: a first chamber adapted to contain at least a portion of said semen sample; and a second chamber adapted to receive motile cells upon introduction of a separation-enabling agent into said first chamber.
  • a cell separation system comprising: a first chamber adapted to contain at least a portion of said semen sample; and a second chamber adapted to receive motile cells upon introduction of a separation-enabling agent into said first chamber.
  • said cell separation system is adapted to assess motility of sperm cells.
  • said cell separation system is adapted to isolate motile sperm of said semen sample for a usage selected from a group consisting of: intra uterine insemination (IUI), vaginal insemination, and in-vitro fertilization (IVF).
  • IUI intra uterine insemination
  • IVF in-vitro fertilization
  • the cartridge is further adapted to manipulate said biologic sample using at least one manipulation technique selected from a group which includes: homogenization, liquefaction, deposition on a reagent-loaded pad, mixing with a reagent, deposition on an antibody-loaded pad, incubation, separation, migration, sedimentation and/or any combination thereof
  • a method for using a sealed removable cartridge for performing two or more assays comprising: inserting the cartridge into a compartment of an assay device; inserting a biologic sample into the cartridge; and activating the assay device to facilitate, within the cartridge, two or more assays of the biologic sample.
  • the method further comprises operating an actuator of the assay device for interfacing with the cartridge and for transporting the biologic sample towards at least two assay locations where the two or more assays are facilitated.
  • the biologic sample is selected from a group which includes: a semen sample, a vaginal secretion sample, a vaginal cell sample, a blood sample, a urine sample, a saliva sample, a lymph sample and/or any combination thereof.
  • the two or more assays are selected from a group which includes: a sperm concentration assay, a semen pH assay, a leukocyte threshold assay, a sperm motility assay, a sperm morphology assay, a semen volume assay and/or any combination thereof
  • At least one of the assays is adapted to facilitate diagnosis of at least one STD selected from a group which includes: syphilis, gonorrhea, candida, HPV, mycoplasma, ureaplasma, HIV, Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas, Hepatitis C and/or any combination thereof.
  • the method further comprises operating a computerized control of the assay device for performing at least one action selected from a group which includes: facilitate at least one of the assays, receive a reading from said at least one sensor of the assay device, compute a result of at least one of the assays, compute a combined measure of results of two or more of the assays, compute a predicted optimal fertilization date and/or any combination thereof.
  • the method further comprises operating a cell separation system of the cartridge, the operating comprising: depositing at least a portion of the semen sample in a first chamber of the cell separation system; introducing a separation-enabling agent into the first chamber, to facilitate swimming of motile cell into a second chamber of the cell separation system.
  • the method further comprises collecting the motile cells from the second chamber.
  • the collecting of the motile cells comprises collecting of motile sperm, for a usage selected from a group which includes: IUI, vaginal insemination, IVF and/or any combination thereof.
  • the method further comprises assessing motility of cells based on a relative amount of motile cells in the second chamber.
  • a cell separation system comprising: a first chamber adapted to contain at least a portion of said semen sample; and a second chamber adapted to receive motile cells upon introduction of a separation-enabling agent into said first chamber.
  • the system is further adapted to assess motility of sperm cells.
  • the system is further adapted to isolate motile sperm of said semen sample for a usage selected from a group which includes: intra uterine insemination (IUI), vaginal insemination, in-vitro fertilization (IVF) and/or any combination thereof.
  • IUI intra uterine insemination
  • IVF in-vitro fertilization
  • the system is enclosed within a sealed cartridge adapted for insertion into an assay device.
  • a method for operating a cell separation system comprising: depositing at least a portion of the semen sample in a first chamber of the cell separation system; introducing a separation-enabling agent into the first chamber, to facilitate swimming of motile cells into a second chamber of the cell separation system.
  • the method further comprises collecting the motile cells from the second chamber.
  • the collecting of the motile cells comprises collecting of motile sperm, for a usage selected from a group consisting of: IUI, vaginal insemination, and IVF.
  • the method further comprises assessing motility of cells based on a relative amount of motile cells in the second chamber.
  • FIG. 1A shows an exploded view of a sealed, removable cartridge
  • FIG. 1B shows a perspective view of a main body of a sealed, removable cartridge
  • FIG. 1C shows a perspective view of another sealed, removable cartridge
  • FIG. 2 shows an exploded view of an assay device
  • FIG. 3A shows a cross-sectional view of a cell separation system
  • FIG. 3B shows a top view of a cell separation system
  • FIG. 4A shows a perspective view of an assay device
  • FIG. 4B shows a perspective view of a receptacle
  • FIG. 4C shows a cross-sectional view of an assay device.
  • the assay device in conjunction with the cartridge, may be used for assessing, by way of at least one assay, one or more parameters pertaining to the biologic sample. Additionally or alternatively, the assay device may be used for treating the biologic sample, such as, in the case of a semen sample, preparing it for intra uterine insemination (IUI), vaginal insemination, and/or in-vitro fertilization (IVF).
  • IUI intra uterine insemination
  • IVF in-vitro fertilization
  • the biologic sample may be, for example, a semen sample, a vaginal secretion sample, a biologic cell sample, cervical mucus, a blood sample, a urine sample, a saliva sample, a lymph sample, or any other sample of biologic matter collected from a human or any other animal.
  • the cartridge may be substantially sealed, so that its biologic contents do not come in direct contact with the assay device and therefore no substantial contamination of the assay device and/or its immediate surroundings is caused.
  • the sealed cartridge may, however, include an input port through which the biologic sample is fed, and/or an exhaust for discarding excess pressure—but both features may be configured in such a way that no substantial contamination is caused
  • the assay device may interface with the cartridge using an actuator adapted to transport the biologic sample within the cartridge, towards one or more locations within the cartridge referred to as assay port(s) and/or treatment port(s), where the biologic sample is assessed and/or treated, respectively.
  • the cartridge may be removed from the assay device and discarded.
  • the cartridge may be stored (such as in cooled or cryogenic storage), along with its contents, for future testing, analysis and/or treatment of the sample.
  • the cartridge may be configured such that only a part of it, containing portion of sample or the treated sample, is removed and stored for further testing, analysis and/or treatment.
  • the assay device may be relatively easy to operate and its operation may require no special laboratory training, so that a nurse, a physician, or any other caregiver may operates it in what is often referred to as a “point of care—a clinic, a medical institution or the like. Furthermore, the assay device may still be operated at the field, such as with portable apparatuses, tools or disposable diagnostics or in a laboratory.
  • an assay device adapted to receive a receptacle, such as a condom or any sample collection cup, containing a reproductive system sample such as semen, a vaginal secretion, any type of cell found in the vagina, cervical mucus and/or the like.
  • a reproductive system sample such as semen, a vaginal secretion, any type of cell found in the vagina, cervical mucus and/or the like.
  • the assay device may be used for assessing, using at least one assay, one or more parameters pertaining to the semen sample and/or for treating the sperm sample.
  • the assay device may include an extraction mechanism for extracting the semen sample from the receptacle and for transporting the semen sample towards one or more assay locations where the semen sample is assessed.
  • the assay device may further include a result indicator, such as a color-changeable pad, for conveying the assessment results to its user.
  • a result indicator such as a color-changeable pad
  • the user is the reproductive system sample provider, and, accordingly, the assay device may be adapted for use by a non-medically trained person.
  • the assay device may be therefore offered to consumers either as a prescription medical device or as an over-the-counter (OTC) non-prescription device.
  • OTC over-the-counter
  • An additional aspect of some embodiments relates to the sealed, removable cartridge itself, which may be adapted for use in conjunction with an assay device or as a standalone solution.
  • the cartridge may be essentially rigid or essentially flexible, and may include an actuator interface for interfacing with an external means of pressure creation, so as to transport the biologic sample towards one or more assay and/or treatment ports.
  • the means of pressure difference creation may be a part of the assay device.
  • the actuator may be an essentially flexible area of the cartridge, which may be pressed, optionally manually, to transport the sample.
  • a further aspect of some embodiments relates to a cell separation system.
  • a cell separation system When used with sperm cells, it is adapted to assess motility of sperm cells and/or to isolate motile sperm cells of the semen sample for intra uterine insemination (IUI), vaginal insemination, or in-vitro fertilization (IVF) purposes.
  • the cell separation system may also be used for separating other types of motile cells from immotile cells.
  • the cell separation system may include a first chamber adapted to contain at least a portion of a semen sample, and a second chamber adapted to receive motile cells upon introduction of a separation-enabling agent into the first chamber.
  • the separation-enabling agent may be a gas, a liquid, a gel and/or any other suitable substance.
  • the first chamber may include an enriched population of immotile cells while the second chamber may include an enriched population of motile cells.
  • the cell separation system is optionally enclosed within the cartridge which is, in turn, adapted for insertion into the assay device.
  • the cell separation system may be used as a standalone device, separate from the cartridge and assay device discussed above.
  • FIG. 1A shows an exploded view of an exemplary sealed, removable cartridge 100 (hereinafter “cartridge”), in accordance with an embodiment.
  • Cartridge 100 may include a main body 102 , a top cover 104 and optionally a base 106 .
  • Main body 102 is also shown, from a perspective view, in FIG. 1B .
  • Main body 102 may be shaped as a rectangular box, a cylinder a flexible pouch and/or the like.
  • At least one of main body 102 , top cover 104 and base 106 may be essentially rigid, optionally made of a rigid material such as a polymer, a metal, glass or the like; alternatively, the at least one of main body 102 , top cover 104 and/or base 106 may be made of a combination of rigid materials or of a combination of at least one rigid material and at least one flexible material.
  • Main body 102 may include an inlet 108 a for insertion of a biologic sample into cartridge 100 .
  • a matching hole 108 b may exist in top cover 104 , to allow for a connection of a sample cup (not shown) to cartridge 100 .
  • the sample cup may have a tip adapted to be inserted, at least partially, into hole 108 b and into inlet 108 a, for supplying the biologic sample, while maintaining overall sealing as discussed above.
  • the inserted biologic sample may be transported inside cartridge 100 by virtue of at least one vacuum conduit, such as conduits 110 .
  • Conduits 110 may include internal tubing not visible in this figure.
  • Conduits 110 when containing fluid, may be in contact with at least one actuator interface, such as actuator interfaces 112 a - b .
  • Actuator interfaces 112 a - b may be shaped as a niche (optionally arched) in main body 102 .
  • At least one external actuator interfacing with actuator interfaces 112 a - b , may provide conduits 110 with positive or negative gas pressure, so that the biologic sample is pushed or pulled along the conduits.
  • the actuator may be a peristaltic pump adapted to apply peristaltic pressure on a flexible pipe 114 which is in fluid contact with conduits 110 .
  • Flexible pipe 114 may be secured in place using, for example, two holders 116 . Since there is optionally no fluid contact with the outside environment, by virtue of the peristaltic pump which operates externally on flexible pipe 114 , the interfacing with the actuator does not cause contamination of the environment outside cartridge 100 .
  • any positive displacement system such as a syringe or a micropipette may be used.
  • electromagnetic fields may induce transportation of the sample or part of the sample using, for example, electrophoresis.
  • an electron enriched material such as a salt gradient may be used.
  • another actuator interface may be an essentially flexible portion of cartridge 100 and/or its internal tubes, adapted for manual squeezing in order to transport the biologic sample.
  • a set of filters 118 may be positioned in between the edge of conduits 110 and an elevation 120 of base 106 .
  • a filter 122 may be positioned in between a volume compartment 124 and another elevation 126 of base 106 .
  • Filters 122 and 118 may, by virtue of a suitably small pore size, provide ventilation to cartridge 100 , while preventing leakage of hazardous materials to the environment.
  • Cartridge 100 may include two or more assay locations adapted to facilitate, within the cartridge, two or more assays of the biologic sample.
  • the term “assay location”, as referred to herein, may refer to any site within cartridge 100 adapted to act on the biologic sample and/or to analyze (or enable analysis by an external sensor of an assay device) at least one parameter pertaining to the sample.
  • the two or more assay locations may be selected from the following: at least one result pad such as two result pads 128 ; at least one pH and/or leukocytes test 132 ; at least one morphology assay 134 ; at least one reagent location, such as five reagent locations 136 ; at least one homogenizer, such as two homogenizers 138 ; at least one cell separation system 140 ; and at least one free volume compartment 124 .
  • the assay location may be adapted to perform assays such as: Acrosom reaction assay, with or without calcium ionophore; a 23187 ARIC test and progesterone; bio active recombinant human ZP3 or active synthetic ZP3 peptides or analogues; adding reagent (for example 7-amino-actinomycin-D) to identify necrotic cells (SYTO 16) and reading results at 610 nm to 670 nm hence detecting apoptosis; Sanger sequencing; microplate assay; Polymerase Chain Reaction (PCR); probe-based hybridization assay; Processor Aided Motility count (CASA); Peroxidase; Zinc at 560 nm; Fructose at 470 nm; glucosidase at 405 nm; heavy metals assay; hormones such as Progesterone, Testosterone, and Estrogen; Antigen and/or cancer markers such as PSA, trace elements, carbohydrates proteo
  • the assay location may perform its assay at least partially by manipulating the biologic sample.
  • the assay location may utilize one or more of the following sample manipulation techniques: homogenization, liquefaction, mixing with a reagent, mixing with an antibody, deposition on a reagent-loaded pad, deposition on an antibody-loaded pad, concentration assessment, incubation, separation, migration, sedimentation viscosity assessment, turbidity, and the like.
  • the assay may be adapted to facilitate diagnosis of at least one STD.
  • STD for example, syphilis, gonorrhea, candida, human papiloma virus (HPV), mycoplasma, ureaplasma, human immunodeficiency virus (HIV), Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas, Hepatitis C and/or any other STD or infection.
  • the assay may further be adapted to facilitate diagnosis of one or more fertility factors or indicators of the tested subject, such as sperm cell concentration, semen volume, sperm cell morphology, semen pH, female secretion, sperm-cervical mucus interaction and/or the like
  • Result pads 128 may be loaded with a reagent, and when sample is delivered via tips 130 , reaction occurs and a result is shown (also referred to as classical flow-through diagnostics). Result pad 128 may be used as a strainer of the sample if reaction with reagents is performed within the homogenizer, as described below. Result pad 128 may be coupled with an antibody agent. When the sample is delivered via tips 130 , it flows on or within result pads 128 until in reaction with an antibody compound (also referred to as classical lateral flow diagnostics). For example, anti CD 59 Result pad 128 may be operable for adding a reagent to the sample already on the result pad, using a gas and/or a liquid. The gas and/or the liquid may flow onto the sample through tips 130 . Results may be read visually as color, a texture, a shape and/or the like. Results may also be read by a sensor.
  • Homogenizers 138 may be operable for homogenizing the sample prior to performing further assays and/or for mixing the sample with other reagents and/or biological components. Homogenization may be achieved via rapid movement of the sample, such as by mixing it using a rotateable or a reciprocating member. For example, triangular mixers 138 a may be used for mixing the sample.
  • Semen pH threshold and leukocytes threshold tests 132 may include an absorbent pad holder 132 a.
  • the pad may include a color-changeable reagent indicating pH level, and/or a color-changeable reagent indicating leukocyte level. Such pads are available from different manufacturers.
  • sperm cell morphology assay 134 which is shown only schematically since it is located within main body 102 , may be adapted to hold, mark, stain and/or analyze morphological characteristics of the biologic sample. For example, if the biologic sample is semen, morphology assay 134 may analyze morphological defects of the sperm cells which may degrade its fertilization potential.sperm cells morphology assay 134 may be detached from cartridge 100 and held for further diagnosis.
  • Reagent locations 136 may each include a reagent container.
  • the reagent upon contact with the biologic sample, may yield a reaction and/or a colored compound indicating existence and/or concentration of a component in the sample.
  • Other reagents such as cell support medium, labeling compounds, markers, peptide and the like, available from various companies, may also be used.
  • Cell separation system 140 may be adapted to assess motility of sperm cells or any other cells of the biologic sample. Additionally or alternatively, cell separation system 140 may be adapted to isolate motile sperm cells of the semen sample for intra uterine insemination (IUI), vaginal insemination, and/or in-vitro fertilization (IVF) purposes.
  • IUI intra uterine insemination
  • IVF in-vitro fertilization
  • Cell separation system 140 may be based upon the principle that motile cells (such as, for example, sperm cells) have swimming abilities, whereas immotile cells lack these abilities, at least to some extent. Therefore, cell separation system 140 is constructed such that motile cells move, essentially using their own swimming capabilities, to a different location, while a sediment of immotile cells is left behind.
  • motile cells such as, for example, sperm cells
  • immotile cells lack these abilities, at least to some extent. Therefore, cell separation system 140 is constructed such that motile cells move, essentially using their own swimming capabilities, to a different location, while a sediment of immotile cells is left behind.
  • FIG. 3A is a cross-sectional view and FIG. 3B is a top view.
  • Cells separation system 140 may include two chambers: a central chamber 302 shaped as a dimple in main body 102 , and a peripheral chamber 304 shaped as a shallower, circumferential depression around the central chamber.
  • a biologic sample (such as semen) 308 is deposited inside central chamber 302 , while keeping the sample's level below a rim 306 .
  • Rim 306 may be dimensioned and designed with specific surface roughness or serration in order to facilitate required surface tension capabilities for specific sample/reagent combination.
  • a separation-enabling agent 310 such as a Ringer's solution, Hartmann's solution, Saline and/or the like is then introduced into central chamber 302 and/or into peripheral chamber 304 , such that the separation-enabling agent covers both the entirety of central chamber 302 and at least a portion of peripheral chamber 304 .
  • semen sample 308 and separation-enabling agent 310 may be left for a period of optionally 15 to 60 minutes in a temperature of optionally 30-37 degrees Celsius, allowing motile cells to swim up through separation-enabling agent 310 and at least partially into peripheral chamber 304 . After the specified period, the motile cells may be collected, manually or automatically, from peripheral chamber 304 .
  • Cell separation system 140 may also be operated inversely—a sample may be deposited in peripheral chamber 304 keeping its level below rim 306 ; a separation-enabling agent may be introduced into central chamber 302 while overflowing rim 306 onto the peripheral chamber; and the components may be left to allow motile cells to swim up from the peripheral chamber into the central chamber.
  • a cell separation system such as system 140 or any other system may be constructed according to the principle that a first chamber is adapted to contain a semen sample, and a second chamber is adapted to receive motile cells upon introduction of a separation-enabling agent into the first chamber.
  • a first chamber is adapted to contain a semen sample
  • a second chamber is adapted to receive motile cells upon introduction of a separation-enabling agent into the first chamber.
  • each of central chamber 302 and peripheral chamber 304 may be the first or the second chamber.
  • Cell separation system 140 may be used to assess motility of sperm cells of the semen sample, and/or to isolate motile sperm cells of the semen sample for intra uterine insemination (IUI), vaginal insemination and/or in-vitro fertilization (IVF) purposes.
  • IUI intra uterine insemination
  • IVF in-vitro fertilization
  • free volume compartment 124 may be adapted to measure and/or to dose the volume or a portion of the volume of the biologic sample. Free volume compartment 124 may be used to hold required dose of the sample and than transfer it to the correct assay, as different assays require different volumes of sample. The volume may be manually read, such as by reading the scale at the sample surface level or by a sensor adapted for such reading.
  • FIG. 1C shows a perspective view of another exemplary sealed, removable cartridge 170 , according to an embodiment.
  • Cartridge 170 may differ from cartridge 100 ( FIGS. 1A-B ), inter alia, in its essentially flexible housing 172 .
  • Flexible housing 172 may be made of any flexible material, such as a polymer, an IV pouch, a food/liquid storage pouch, a hazardous material storage pouch, or any other pouch.
  • Internal conduits 176 may also be flexible, to enable manual or automatic squeezing of housing 172 and the conduits to transport a biologic sample within cartridge 170 , towards two or more assay locations such as assay locations 178 and 180 .
  • FIG. 2 shows an exploded view of an exemplary assay device 200 , according to an embodiment.
  • Assay device 200 may include a compartment 202 or any other cavity adapted to receive a cartridge 204 , which may be cartridge 100 of FIGS. 1A-B , cartridge 170 of FIG. 1C or any other suitable cartridge.
  • Compartment 202 is shown, for simplicity of presentation, as a space above a base 206 of assay device 200 .
  • a compartment may be a slot, a recess and/or any other cavity adapted for partial or full insertion of a cartridge.
  • Assay device 200 may further include a top cover 208 having a handle 210 .
  • Top cover 208 may be pivotally connected to base 206 , to enable opening of the top cover for insertion and removal of cartridge 204 .
  • an assay device may structured such that insertion and removal of a cartridge do not necessitate manual opening of a cover, a door or the like.
  • an assay device may include an automatically-opening door or a door which opens upon physical engagement of a cartridge.
  • an assay device may lack a cover or a door at all, so that at least a portion of a cartridge remains exposed when the cartridge is inside its compartment.
  • Assay device 200 may further include an actuator 212 adapted to interface with cartridge 204 and to provide positive and/or negative gas (such as air or any other suitable gas) pressure to the cartridge.
  • the pressure created by actuator 212 may propagate along one or more conduits within cartridge 204 , so that a biologic sample contained in the cartridge is transported along the cartridge.
  • Actuator 212 may be a pump, such as a positive displacement pump, a peristaltic pump or any other type of pump adapted to provide positive and/or negative pressure to the one or more conduits of cartridge 204 . Additionally or alternatively, a common syringe or a micropipette, manually or machine operated, may be used.
  • a different actuator may be at least one roller adapted to squeeze cartridge 204 (or a different cartridge) in order to transport the biologic sample within it.
  • Assay device 200 may include a means for reading results, or to inspect any other assay within cartridge 100 . Results may be read visually, or the device may further include one or more sensors, such as, for example, three sensors 214 . At least one of sensors 214 may be adapted to sense one or more parameters pertaining to the biologic sample in cartridge 204 , and may be positioned such that it is in sensing stance of at least one assay location of the cartridge.
  • At least one of sensors 214 may be an image sensor, namely—a camera, adapted to visually inspect at least one assay location of cartridge 204 .
  • the image sensor may sense, for instance, a color (via sensed wavelength), a texture and/or the like which exist in the at least one assay ports.
  • the color (via sensed wavelength), a texture and/or shape may be indicative of one or more parameters of the biologic sample.
  • the image sensor may be adapted to sense light at 610-670 nanometers (nm) for detecting apoptosis in the biologic sample.
  • pH may be read by pH electrode; Turbidity and viscosity sensors may be ones available on the market; a pad loaded with specific reagents also available on the market.
  • Assay device 200 may further include a processor 216 , adapted to control at least one of sensors 214 and/or to process data received from the sensors.
  • Processor 216 may be realized as any available micro processor, micro controller and/or general purpose computer.
  • processor 216 may display locally to its user results of one or more assays performed in cartridge 204 . The results may be stored for further processing, displayed in a remote location and/or transferred using communication protocols known in the industry, wired or wireless.
  • processor 216 may analyze a series of temporally-distinct semen samples of the same person, and provide the user with a prediction of an optimal date in which the person's semen may be best for fertilization.
  • processor 216 may recognize a pattern of gradually changing fertility factors (such as sperm cell concentration, sperm cell motility and/or the like) and calculate, accordingly, future fertility factors in that same tested person.
  • fertility factors such as sperm cell concentration, sperm cell motility and/or the like
  • processor 216 may recognize a pattern of gradually changing fertility factors (such as sperm cell concentration, sperm cell motility and/or the like) and calculate, accordingly, future fertility factors in that same tested person.
  • fertility factors such as sperm cell concentration, sperm cell motility and/or the like
  • Processor 216 may be further adapted to perform one or more of facilitating at least one of the assays, receiving a reading from the at least one sensor, computing a result of at least one of the assays, and/or computing a combined measure of results of two or more of the assays, hence concluding different results.
  • a combined measure may be used as a fertility index.
  • male subjects with low sperm qualities may get a higher index score by changing their way of life, avoiding oxidative stress or other methods known in prior art.
  • FIG. 4 shows a perspective view of another assay device 400 , according to an embodiment.
  • Assay device 400 may be relatively easy to operate and its operation may require no special laboratory training, so that a nurse, a physician, or any other caregiver may operate it in what is often referred to as a “point of care”—a clinic, a medical institution or the like. Furthermore, the assay device may still be operated in a laboratory.
  • Assay device 400 may include a compartment 402 adapted to receive a receptacle, such as a condom or a sample collecting cup, containing a reproduction system sample such as semen, vaginal secretions, cervical mucus, vaginally-collected cells and/or the like.
  • a receptacle such as a condom or a sample collecting cup
  • a reproduction system sample such as semen, vaginal secretions, cervical mucus, vaginally-collected cells and/or the like.
  • the receptacle is the one disclosed in applicant's PCT Published Application No. WO 2008/035333.
  • Receptacle 440 may include an elongated, flexible bag, which may have a condom-like shape with inner cavity (such as 443 ) defined by the walls of the receptacle bag ( 440 ).
  • the narrow end 442 A of the receptacle may be at least partially sealed.
  • the walls at the narrow end of the receptacle may exhibit pore sizes of less then 0.42 nm.
  • the broad end 442 B which is distally opposing the narrow end 442 A, may be open.
  • the broad, open end 442 B may further include a rim 444 that may be used for the association of the receptacle within a contraceptive, as detailed below herein.
  • Rim 444 is illustrated at a deformed state, wherein the rim is shaped into an eight form, by, for example, pinching two opposing sides of the rim towards each other.
  • the receptacle 440 may be constructed of rubber, silk, polyurethane, silicone and the like.
  • the thickness of the receptacle may vary in the range of about 5 to 1500 microns.
  • Size of receptacle 140 may vary in length and diameter. For example, length of receptacle 440 from end 442 A to end 442 B may be in the range of, about 100-200 mm.
  • diameter of rim 444 of receptacle 440 may be in the range of, about 37 to 60 millimeter.
  • Receptacle (such as 440 ) may further be associated with a male contraceptive device, such as a condom 446 .
  • Receptacle 440 may be fitted into male condom 446 , such that the receptacle is contained within the inner space of the condom.
  • Shown in FIG. 4B is a receptacle 440 fitted about two thirds of its length into a condom 446 .
  • Receptacle 440 may be secured to condom 446 by various ways.
  • rim 444 and rim 448 of condom 446 may be associated by pressing, stitching, mechanical fitting, zip-lock fit, zipper fit, fitting grooves, adhering, gluing and the like.
  • rim 444 of receptacle 440 may include perforation/grooves that may be used to fit to the upper rim, 448 of condom 446 .
  • Assay device 400 may include an extraction mechanism for extracting the reproduction system sample from the receptacle and for transporting the reproduction system sample towards one or more assay ports and/or treatment ports, where the reproduction system sample is assessed and/or treated, respectively.
  • the extraction mechanism may be embodied as a strike handle 404 pivotally attached to a main body 410 of assay device 400 , and having a protruding structure 406 matching a structure of a recess 408 in the main body.
  • the receptacle may be positioned in compartment 402 with its reproduction system sample-containing edge at recess 408 , and handle 404 may be lowered so as to squeeze the receptacle and extract at least some of its reproduction system contents.
  • the extraction mechanism may include a peristaltic pump (not shown) and/or a set of rollers adapted to induce the reproduction system sample out of the receptacle.
  • the extraction mechanism may be the receptacle itself, being elastic in nature and therefore manually squeezable by a user.
  • FIG. 4C shows a cross-sectional view of assay device 400 .
  • the volume of the reproduction system is optionally measured in a chamber 412 .
  • the extracted reproduction system may be forced, by virtue of the extraction mechanism, to a conduit 414 leading to one or more assay locations, such as assay location 416 .
  • the one or more assays are optionally those described above in regard to cartridge 100 ( FIGS. 1A-B ).
  • At least one chemical may flow to a result indicator such as a color-changeable result pad 418 , causing the pad to change color responsive to the assay result.
  • Result pad 418 may be embedded in a sliding base 420 of assay device, and the sliding base may be pivotally attached, using a hinge 422 , to main body 410 .
  • Sliding base 420 may be slid by the user when the one or more assays are complete, to reveal result pad 418 and see the result.
  • Handle 404 may include a reference color scale (not shown) for comparing the shade, shape, texture and/or the like of result pad 418 to a reference and thus providing the user with a meaningful result.
  • the reference color scale may be printed on handle 404 or attached to it as a sticker.
  • the reference color scale optionally includes literal explanation of the meaning of each color; the explanation may, additionally or alternatively, be included in product literature accompanying assay device 400 .
  • assay location 416 is a replaceable, and is adapted to be replaced by an additional assay location for facilitating an additional assay.
  • assay device 400 may be used multiple types for performing the same assay (such as an assay pertaining to fertilization potential which may have to be repeated every once in a while) or may be used each time for performing a different assay of the same semen sample or a different semen sample.
  • each of the words “comprise” “include” and “have”, and forms thereof, are not necessarily limited to members in a list with which the words may be associated.

Abstract

A sealed removable cartridge adapted for insertion into an assay device and adapted to contain a biologic sample, the cartridge comprising: two or more assay locations adapted to facilitate, within said cartridge, two or more assays of said biologic sample; and an actuator interface adapted to interface with an actuator of said assay device, to transport said biologic sample towards at least one of said assay locations.

Description

    FIELD OF THE DISCLOSURE
  • Embodiments of the disclosure relate to a cartridge for a biologic sample.
  • BACKGROUND
  • When diagnosing a sample, it is often required to reach a significant conclusion with respect to the sample's contents. Biological samples, such as semen, vaginal secretions, vaginal cells, blood, urine, saliva, lymph and the like, are commonly tested at the field, with portable apparatuses, tools or disposable diagnostics, or in laboratories. Laboratory work, including field work, often requires taking a portion of the sample, processing it in various ways using laboratory operations and finally assessing a result. Laboratory medicine commonly includes anatomic pathology histopathology, cytopathology, microscopy, clinical microbiology, bacteriology, virology, parasitology, immunology, mycology, clinical biochemistry instrumental analysis, enzymology, toxicology, endocrinology and hematology.
  • Over the past years, automated analyzers became more and more common in laboratories. An automated analyzer is often defined as a medical laboratory instrument designed to rapidly measure different chemicals and other characteristics in a samples, with minimal human assistance. The automation of laboratory testing does not usually remove the need for human expertise (as some results must still be evaluated by medical technologists and other qualified clinical laboratory professionals, and sometimes manual processing is required), but it does ease concerns about error reduction, staffing concerns and safety.
  • Applicant's U.S. Provisional Patent Application No. 60/981,856, filed Oct. 23, 2007, discloses a diagnostic device. This application is incorporated herein by reference in its entirety.
  • SUMMARY
  • There is provided, according to an embodiment, a sealed removable cartridge adapted for insertion into an assay device and adapted to contain a biologic sample, the cartridge comprising: two or more assay locations adapted to facilitate, within said cartridge, two or more assays of said biologic sample; and an actuator interface adapted to interface with an actuator of said assay device, to transport said biologic sample towards at least one of said assay locations.
  • In some embodiments, said biologic sample is selected from a group which includes: a semen sample, a vaginal secretion sample, a vaginal cell sample, a blood sample, a urine sample, a saliva sample, a lymph sample and/or any combination thereof.
  • In some embodiments, said two or more assays are selected from a group which includes: a sperm concentration assay, a semen pH assay, a leukocyte threshold assay, a sperm motility assay, a sperm morphology assay, a semen volume assay, a viscosity assay, a turbidity assay, and/or any combination thereof.
  • In some embodiments, said at least one of said assays is adapted to facilitate diagnosis of at least one sexually transmitted disease (STD) selected from a group which includes: syphilis, gonorrhea, candida, human papiloma virus (HPV), mycoplasma, ureaplasma, human immunodeficiency virus (HIV), Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas, Hepatitis C and/or any combination thereof.
  • In some embodiments, a housing of said cartridge is substantially rigid.
  • In some embodiments, a housing of said cartridge is substantially flexible.
  • In some embodiments, said cartridge further comprises a cell separation system, comprising: a first chamber adapted to contain at least a portion of said semen sample; and a second chamber adapted to receive motile cells upon introduction of a separation-enabling agent into said first chamber.
  • In some embodiments, said cell separation system is adapted to assess motility of sperm cells.
  • In some embodiments, said cell separation system is adapted to isolate motile sperm of said semen sample for a usage selected from a group consisting of: intra uterine insemination (IUI), vaginal insemination, and in-vitro fertilization (IVF).
  • In some embodiments, the cartridge is further adapted to manipulate said biologic sample using at least one manipulation technique selected from a group which includes: homogenization, liquefaction, deposition on a reagent-loaded pad, mixing with a reagent, deposition on an antibody-loaded pad, incubation, separation, migration, sedimentation and/or any combination thereof
  • There is further provided, according an embodiment, a method for using a sealed removable cartridge for performing two or more assays, the method comprising: inserting the cartridge into a compartment of an assay device; inserting a biologic sample into the cartridge; and activating the assay device to facilitate, within the cartridge, two or more assays of the biologic sample.
  • In some embodiments, the method further comprises operating an actuator of the assay device for interfacing with the cartridge and for transporting the biologic sample towards at least two assay locations where the two or more assays are facilitated.
  • In some embodiments, the biologic sample is selected from a group which includes: a semen sample, a vaginal secretion sample, a vaginal cell sample, a blood sample, a urine sample, a saliva sample, a lymph sample and/or any combination thereof.
  • In some embodiments, the two or more assays are selected from a group which includes: a sperm concentration assay, a semen pH assay, a leukocyte threshold assay, a sperm motility assay, a sperm morphology assay, a semen volume assay and/or any combination thereof
  • In some embodiments, at least one of the assays is adapted to facilitate diagnosis of at least one STD selected from a group which includes: syphilis, gonorrhea, candida, HPV, mycoplasma, ureaplasma, HIV, Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas, Hepatitis C and/or any combination thereof.
  • In some embodiments, the method further comprises operating a computerized control of the assay device for performing at least one action selected from a group which includes: facilitate at least one of the assays, receive a reading from said at least one sensor of the assay device, compute a result of at least one of the assays, compute a combined measure of results of two or more of the assays, compute a predicted optimal fertilization date and/or any combination thereof.
  • In some embodiments, the method further comprises operating a cell separation system of the cartridge, the operating comprising: depositing at least a portion of the semen sample in a first chamber of the cell separation system; introducing a separation-enabling agent into the first chamber, to facilitate swimming of motile cell into a second chamber of the cell separation system.
  • In some embodiments, the method further comprises collecting the motile cells from the second chamber.
  • In some embodiments, the collecting of the motile cells comprises collecting of motile sperm, for a usage selected from a group which includes: IUI, vaginal insemination, IVF and/or any combination thereof.
  • In some embodiments, the method further comprises assessing motility of cells based on a relative amount of motile cells in the second chamber.
  • There is further provided, according to an embodiment, a cell separation system, comprising: a first chamber adapted to contain at least a portion of said semen sample; and a second chamber adapted to receive motile cells upon introduction of a separation-enabling agent into said first chamber.
  • In some embodiments, the system is further adapted to assess motility of sperm cells.
  • In some embodiments, the system is further adapted to isolate motile sperm of said semen sample for a usage selected from a group which includes: intra uterine insemination (IUI), vaginal insemination, in-vitro fertilization (IVF) and/or any combination thereof.
  • In some embodiments, the system is enclosed within a sealed cartridge adapted for insertion into an assay device.
  • There is further provided, according to an embodiment, a method for operating a cell separation system, the method comprising: depositing at least a portion of the semen sample in a first chamber of the cell separation system; introducing a separation-enabling agent into the first chamber, to facilitate swimming of motile cells into a second chamber of the cell separation system.
  • In some embodiments, the method further comprises collecting the motile cells from the second chamber.
  • In some embodiments, the collecting of the motile cells comprises collecting of motile sperm, for a usage selected from a group consisting of: IUI, vaginal insemination, and IVF.
  • In some embodiments, the method further comprises assessing motility of cells based on a relative amount of motile cells in the second chamber.
  • In addition to the exemplary aspects and embodiments described above, further aspects and embodiments will become apparent by reference to the figures and by study of the following detailed description.
  • BRIEF DESCRIPTION OF THE FIGURES
  • Exemplary embodiments are illustrated in referenced figures. Dimensions of components and features shown in the figures are generally chosen for convenience and clarity of presentation and are not necessarily shown to scale. It is intended that the embodiments and figures disclosed herein are to be considered illustrative rather than restrictive. The figures are listed below.
  • FIG. 1A shows an exploded view of a sealed, removable cartridge;
  • FIG. 1B shows a perspective view of a main body of a sealed, removable cartridge;
  • FIG. 1C shows a perspective view of another sealed, removable cartridge;
  • FIG. 2 shows an exploded view of an assay device;
  • FIG. 3A shows a cross-sectional view of a cell separation system;
  • FIG. 3B shows a top view of a cell separation system;
  • FIG. 4A shows a perspective view of an assay device;
  • FIG. 4B shows a perspective view of a receptacle; and
  • FIG. 4C shows a cross-sectional view of an assay device.
  • DETAILED DESCRIPTION
  • An aspect of some embodiments related to an assay device adapted to receive a sealed, removable cartridge containing a biologic sample. The assay device, in conjunction with the cartridge, may be used for assessing, by way of at least one assay, one or more parameters pertaining to the biologic sample. Additionally or alternatively, the assay device may be used for treating the biologic sample, such as, in the case of a semen sample, preparing it for intra uterine insemination (IUI), vaginal insemination, and/or in-vitro fertilization (IVF).
  • The biologic sample may be, for example, a semen sample, a vaginal secretion sample, a biologic cell sample, cervical mucus, a blood sample, a urine sample, a saliva sample, a lymph sample, or any other sample of biologic matter collected from a human or any other animal.
  • The cartridge may be substantially sealed, so that its biologic contents do not come in direct contact with the assay device and therefore no substantial contamination of the assay device and/or its immediate surroundings is caused. The sealed cartridge may, however, include an input port through which the biologic sample is fed, and/or an exhaust for discarding excess pressure—but both features may be configured in such a way that no substantial contamination is caused
  • The assay device may interface with the cartridge using an actuator adapted to transport the biologic sample within the cartridge, towards one or more locations within the cartridge referred to as assay port(s) and/or treatment port(s), where the biologic sample is assessed and/or treated, respectively.
  • After use, the cartridge may be removed from the assay device and discarded. Alternatively, the cartridge may be stored (such as in cooled or cryogenic storage), along with its contents, for future testing, analysis and/or treatment of the sample. The cartridge may be configured such that only a part of it, containing portion of sample or the treated sample, is removed and stored for further testing, analysis and/or treatment.
  • The assay device may be relatively easy to operate and its operation may require no special laboratory training, so that a nurse, a physician, or any other caregiver may operates it in what is often referred to as a “point of care—a clinic, a medical institution or the like. Furthermore, the assay device may still be operated at the field, such as with portable apparatuses, tools or disposable diagnostics or in a laboratory.
  • Another aspect of some embodiments relates to an assay device adapted to receive a receptacle, such as a condom or any sample collection cup, containing a reproductive system sample such as semen, a vaginal secretion, any type of cell found in the vagina, cervical mucus and/or the like. In case the sample is semen, the assay device may be used for assessing, using at least one assay, one or more parameters pertaining to the semen sample and/or for treating the sperm sample.
  • The assay device may include an extraction mechanism for extracting the semen sample from the receptacle and for transporting the semen sample towards one or more assay locations where the semen sample is assessed.
  • The assay device may further include a result indicator, such as a color-changeable pad, for conveying the assessment results to its user.
  • Optionally, the user is the reproductive system sample provider, and, accordingly, the assay device may be adapted for use by a non-medically trained person. The assay device may be therefore offered to consumers either as a prescription medical device or as an over-the-counter (OTC) non-prescription device.
  • An additional aspect of some embodiments relates to the sealed, removable cartridge itself, which may be adapted for use in conjunction with an assay device or as a standalone solution.
  • The cartridge may be essentially rigid or essentially flexible, and may include an actuator interface for interfacing with an external means of pressure creation, so as to transport the biologic sample towards one or more assay and/or treatment ports. In case the cartridge is used with the assay device, the means of pressure difference creation may be a part of the assay device. Additionally or alternatively, the actuator may be an essentially flexible area of the cartridge, which may be pressed, optionally manually, to transport the sample.
  • A further aspect of some embodiments relates to a cell separation system. When used with sperm cells, it is adapted to assess motility of sperm cells and/or to isolate motile sperm cells of the semen sample for intra uterine insemination (IUI), vaginal insemination, or in-vitro fertilization (IVF) purposes. The cell separation system may also be used for separating other types of motile cells from immotile cells.
  • The cell separation system may include a first chamber adapted to contain at least a portion of a semen sample, and a second chamber adapted to receive motile cells upon introduction of a separation-enabling agent into the first chamber. The separation-enabling agent may be a gas, a liquid, a gel and/or any other suitable substance. After the separation, the first chamber may include an enriched population of immotile cells while the second chamber may include an enriched population of motile cells.
  • The cell separation system is optionally enclosed within the cartridge which is, in turn, adapted for insertion into the assay device. Alternatively, the cell separation system may be used as a standalone device, separate from the cartridge and assay device discussed above.
  • A Cartridge
  • Reference is now made to FIG. 1A, which shows an exploded view of an exemplary sealed, removable cartridge 100 (hereinafter “cartridge”), in accordance with an embodiment. Cartridge 100 may include a main body 102, a top cover 104 and optionally a base 106. Main body 102 is also shown, from a perspective view, in FIG. 1B. Main body 102 may be shaped as a rectangular box, a cylinder a flexible pouch and/or the like.
  • At least one of main body 102, top cover 104 and base 106 (the at least one of them may be jointly referred to as a “housing”) may be essentially rigid, optionally made of a rigid material such as a polymer, a metal, glass or the like; alternatively, the at least one of main body 102, top cover 104 and/or base 106 may be made of a combination of rigid materials or of a combination of at least one rigid material and at least one flexible material.
  • Main body 102 may include an inlet 108 a for insertion of a biologic sample into cartridge 100. A matching hole 108 b may exist in top cover 104, to allow for a connection of a sample cup (not shown) to cartridge 100. The sample cup may have a tip adapted to be inserted, at least partially, into hole 108 b and into inlet 108 a, for supplying the biologic sample, while maintaining overall sealing as discussed above.
  • The inserted biologic sample may be transported inside cartridge 100 by virtue of at least one vacuum conduit, such as conduits 110. Conduits 110 may include internal tubing not visible in this figure. Conduits 110, when containing fluid, may be in contact with at least one actuator interface, such as actuator interfaces 112 a-b. Actuator interfaces 112 a-b may be shaped as a niche (optionally arched) in main body 102.
  • At least one external actuator (not shown) interfacing with actuator interfaces 112 a-b, may provide conduits 110 with positive or negative gas pressure, so that the biologic sample is pushed or pulled along the conduits. For example, the actuator may be a peristaltic pump adapted to apply peristaltic pressure on a flexible pipe 114 which is in fluid contact with conduits 110. Flexible pipe 114 may be secured in place using, for example, two holders 116. Since there is optionally no fluid contact with the outside environment, by virtue of the peristaltic pump which operates externally on flexible pipe 114, the interfacing with the actuator does not cause contamination of the environment outside cartridge 100. For this purpose, any positive displacement system such as a syringe or a micropipette may be used. In some cases, electromagnetic fields may induce transportation of the sample or part of the sample using, for example, electrophoresis. In some cases, an electron enriched material such as a salt gradient may be used.
  • Alternatively or additionally, another actuator interface (not shown) may be an essentially flexible portion of cartridge 100 and/or its internal tubes, adapted for manual squeezing in order to transport the biologic sample.
  • A set of filters 118 may be positioned in between the edge of conduits 110 and an elevation 120 of base 106. Similarly, a filter 122 may be positioned in between a volume compartment 124 and another elevation 126 of base 106. Filters 122 and 118 may, by virtue of a suitably small pore size, provide ventilation to cartridge 100, while preventing leakage of hazardous materials to the environment.
  • Cartridge 100 may include two or more assay locations adapted to facilitate, within the cartridge, two or more assays of the biologic sample. The term “assay location”, as referred to herein, may refer to any site within cartridge 100 adapted to act on the biologic sample and/or to analyze (or enable analysis by an external sensor of an assay device) at least one parameter pertaining to the sample.
  • For example, optionally when the sample is semen, the two or more assay locations may be selected from the following: at least one result pad such as two result pads 128; at least one pH and/or leukocytes test 132; at least one morphology assay 134; at least one reagent location, such as five reagent locations 136; at least one homogenizer, such as two homogenizers 138; at least one cell separation system 140; and at least one free volume compartment 124.
  • The assay location may be adapted to perform assays such as: Acrosom reaction assay, with or without calcium ionophore; a 23187 ARIC test and progesterone; bio active recombinant human ZP3 or active synthetic ZP3 peptides or analogues; adding reagent (for example 7-amino-actinomycin-D) to identify necrotic cells (SYTO 16) and reading results at 610 nm to 670 nm hence detecting apoptosis; Sanger sequencing; microplate assay; Polymerase Chain Reaction (PCR); probe-based hybridization assay; Processor Aided Motility count (CASA); Peroxidase; Zinc at 560 nm; Fructose at 470 nm; glucosidase at 405 nm; heavy metals assay; hormones such as Progesterone, Testosterone, and Estrogen; Antigen and/or cancer markers such as PSA, trace elements, carbohydrates proteoglycans or glycoproteins, minerals blood cells, plasma sexually transmitted disease (STD) assay (such as bacteria; yeast; Candida; virus) germs; Hidukes; Cervix carcinoma assay; PAP smear, blood assay; saliva assay; urine stick assay; Immunobead assay; mixed antiglobuline reaction test (MAR test) assay; induced acrosom reaction assay; measurement of reacting oxygen assay; ROS—Oxidative stress, anti oxidants, sperm-cervical mucus interaction assay, turbidity, viscosity and/or the like in ways known in the prior art.
  • The assay location may perform its assay at least partially by manipulating the biologic sample. By way of example, the assay location may utilize one or more of the following sample manipulation techniques: homogenization, liquefaction, mixing with a reagent, mixing with an antibody, deposition on a reagent-loaded pad, deposition on an antibody-loaded pad, concentration assessment, incubation, separation, migration, sedimentation viscosity assessment, turbidity, and the like.
  • The assay may be adapted to facilitate diagnosis of at least one STD. For example, syphilis, gonorrhea, candida, human papiloma virus (HPV), mycoplasma, ureaplasma, human immunodeficiency virus (HIV), Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas, Hepatitis C and/or any other STD or infection.
  • The assay may further be adapted to facilitate diagnosis of one or more fertility factors or indicators of the tested subject, such as sperm cell concentration, semen volume, sperm cell morphology, semen pH, female secretion, sperm-cervical mucus interaction and/or the like
  • Result pads 128 may be loaded with a reagent, and when sample is delivered via tips 130, reaction occurs and a result is shown (also referred to as classical flow-through diagnostics). Result pad 128 may be used as a strainer of the sample if reaction with reagents is performed within the homogenizer, as described below. Result pad 128 may be coupled with an antibody agent. When the sample is delivered via tips 130, it flows on or within result pads 128 until in reaction with an antibody compound (also referred to as classical lateral flow diagnostics). For example, anti CD 59 Result pad 128 may be operable for adding a reagent to the sample already on the result pad, using a gas and/or a liquid. The gas and/or the liquid may flow onto the sample through tips 130. Results may be read visually as color, a texture, a shape and/or the like. Results may also be read by a sensor.
  • Homogenizers 138 may be operable for homogenizing the sample prior to performing further assays and/or for mixing the sample with other reagents and/or biological components. Homogenization may be achieved via rapid movement of the sample, such as by mixing it using a rotateable or a reciprocating member. For example, triangular mixers 138 a may be used for mixing the sample.
  • Semen pH threshold and leukocytes threshold tests 132 may include an absorbent pad holder 132 a. The pad may include a color-changeable reagent indicating pH level, and/or a color-changeable reagent indicating leukocyte level. Such pads are available from different manufacturers.
  • Sperm cell morphology assay 134, which is shown only schematically since it is located within main body 102, may be adapted to hold, mark, stain and/or analyze morphological characteristics of the biologic sample. For example, if the biologic sample is semen, morphology assay 134 may analyze morphological defects of the sperm cells which may degrade its fertilization potential. Sperm cells morphology assay 134 may be detached from cartridge 100 and held for further diagnosis.
  • Reagent locations 136 may each include a reagent container. The reagent, upon contact with the biologic sample, may yield a reaction and/or a colored compound indicating existence and/or concentration of a component in the sample. Other reagents such as cell support medium, labeling compounds, markers, peptide and the like, available from various companies, may also be used.
  • Cell separation system 140 may be adapted to assess motility of sperm cells or any other cells of the biologic sample. Additionally or alternatively, cell separation system 140 may be adapted to isolate motile sperm cells of the semen sample for intra uterine insemination (IUI), vaginal insemination, and/or in-vitro fertilization (IVF) purposes.
  • Cell separation system 140 may be based upon the principle that motile cells (such as, for example, sperm cells) have swimming abilities, whereas immotile cells lack these abilities, at least to some extent. Therefore, cell separation system 140 is constructed such that motile cells move, essentially using their own swimming capabilities, to a different location, while a sediment of immotile cells is left behind.
  • Reference is now made to FIGS. 3A and 3B, which show cell separation system 140 in more detail. FIG. 3A is a cross-sectional view and FIG. 3B is a top view. Cells separation system 140 may include two chambers: a central chamber 302 shaped as a dimple in main body 102, and a peripheral chamber 304 shaped as a shallower, circumferential depression around the central chamber.
  • In order to operate cell separation system 140, a biologic sample (such as semen) 308 is deposited inside central chamber 302, while keeping the sample's level below a rim 306. Rim 306, may be dimensioned and designed with specific surface roughness or serration in order to facilitate required surface tension capabilities for specific sample/reagent combination. A separation-enabling agent 310, such as a Ringer's solution, Hartmann's solution, Saline and/or the like is then introduced into central chamber 302 and/or into peripheral chamber 304, such that the separation-enabling agent covers both the entirety of central chamber 302 and at least a portion of peripheral chamber 304.
  • Then, semen sample 308 and separation-enabling agent 310 may be left for a period of optionally 15 to 60 minutes in a temperature of optionally 30-37 degrees Celsius, allowing motile cells to swim up through separation-enabling agent 310 and at least partially into peripheral chamber 304. After the specified period, the motile cells may be collected, manually or automatically, from peripheral chamber 304.
  • Cell separation system 140 may also be operated inversely—a sample may be deposited in peripheral chamber 304 keeping its level below rim 306; a separation-enabling agent may be introduced into central chamber 302 while overflowing rim 306 onto the peripheral chamber; and the components may be left to allow motile cells to swim up from the peripheral chamber into the central chamber.
  • Generally, a cell separation system such as system 140 or any other system may be constructed according to the principle that a first chamber is adapted to contain a semen sample, and a second chamber is adapted to receive motile cells upon introduction of a separation-enabling agent into the first chamber. In the examples given above, respectively, each of central chamber 302 and peripheral chamber 304 may be the first or the second chamber.
  • Cell separation system 140 may be used to assess motility of sperm cells of the semen sample, and/or to isolate motile sperm cells of the semen sample for intra uterine insemination (IUI), vaginal insemination and/or in-vitro fertilization (IVF) purposes.
  • Referring now back to FIGS. 1A and 1B, free volume compartment 124 may be adapted to measure and/or to dose the volume or a portion of the volume of the biologic sample. Free volume compartment 124 may be used to hold required dose of the sample and than transfer it to the correct assay, as different assays require different volumes of sample. The volume may be manually read, such as by reading the scale at the sample surface level or by a sensor adapted for such reading.
  • Reference is now made to FIG. 1C, which shows a perspective view of another exemplary sealed, removable cartridge 170, according to an embodiment. Cartridge 170 may differ from cartridge 100 (FIGS. 1A-B), inter alia, in its essentially flexible housing 172. Flexible housing 172 may be made of any flexible material, such as a polymer, an IV pouch, a food/liquid storage pouch, a hazardous material storage pouch, or any other pouch. Internal conduits 176 may also be flexible, to enable manual or automatic squeezing of housing 172 and the conduits to transport a biologic sample within cartridge 170, towards two or more assay locations such as assay locations 178 and 180.
  • An Assay Device
  • Reference is now made to FIG. 2, which shows an exploded view of an exemplary assay device 200, according to an embodiment. Assay device 200 may include a compartment 202 or any other cavity adapted to receive a cartridge 204, which may be cartridge 100 of FIGS. 1A-B, cartridge 170 of FIG. 1C or any other suitable cartridge. Compartment 202 is shown, for simplicity of presentation, as a space above a base 206 of assay device 200. In other embodiments (not shown), a compartment may be a slot, a recess and/or any other cavity adapted for partial or full insertion of a cartridge.
  • Assay device 200 may further include a top cover 208 having a handle 210. Top cover 208 may be pivotally connected to base 206, to enable opening of the top cover for insertion and removal of cartridge 204. In other embodiments (not shown), an assay device may structured such that insertion and removal of a cartridge do not necessitate manual opening of a cover, a door or the like. For example, an assay device may include an automatically-opening door or a door which opens upon physical engagement of a cartridge. Alternatively, an assay device may lack a cover or a door at all, so that at least a portion of a cartridge remains exposed when the cartridge is inside its compartment.
  • Assay device 200 may further include an actuator 212 adapted to interface with cartridge 204 and to provide positive and/or negative gas (such as air or any other suitable gas) pressure to the cartridge. The pressure created by actuator 212 may propagate along one or more conduits within cartridge 204, so that a biologic sample contained in the cartridge is transported along the cartridge. Actuator 212 may be a pump, such as a positive displacement pump, a peristaltic pump or any other type of pump adapted to provide positive and/or negative pressure to the one or more conduits of cartridge 204. Additionally or alternatively, a common syringe or a micropipette, manually or machine operated, may be used.
  • Additionally or alternatively, a different actuator (not shown) may be at least one roller adapted to squeeze cartridge 204 (or a different cartridge) in order to transport the biologic sample within it.
  • Assay device 200 may include a means for reading results, or to inspect any other assay within cartridge 100. Results may be read visually, or the device may further include one or more sensors, such as, for example, three sensors 214. At least one of sensors 214 may be adapted to sense one or more parameters pertaining to the biologic sample in cartridge 204, and may be positioned such that it is in sensing stance of at least one assay location of the cartridge.
  • For example, at least one of sensors 214 may be an image sensor, namely—a camera, adapted to visually inspect at least one assay location of cartridge 204. The image sensor may sense, for instance, a color (via sensed wavelength), a texture and/or the like which exist in the at least one assay ports. The color (via sensed wavelength), a texture and/or shape may be indicative of one or more parameters of the biologic sample. For example, the image sensor may be adapted to sense light at 610-670 nanometers (nm) for detecting apoptosis in the biologic sample. As another example, pH may be read by pH electrode; Turbidity and viscosity sensors may be ones available on the market; a pad loaded with specific reagents also available on the market.
  • Assay device 200 may further include a processor 216, adapted to control at least one of sensors 214 and/or to process data received from the sensors. Processor 216 may be realized as any available micro processor, micro controller and/or general purpose computer. For example, processor 216 may display locally to its user results of one or more assays performed in cartridge 204. The results may be stored for further processing, displayed in a remote location and/or transferred using communication protocols known in the industry, wired or wireless. As another example, if the biologic sample is a semen sample, processor 216 may analyze a series of temporally-distinct semen samples of the same person, and provide the user with a prediction of an optimal date in which the person's semen may be best for fertilization. That is, processor 216 may recognize a pattern of gradually changing fertility factors (such as sperm cell concentration, sperm cell motility and/or the like) and calculate, accordingly, future fertility factors in that same tested person. When conducting an assay of female factors, for example, estrogen and progesterone profiles, it may be possible to predict a date in which fertilization is in its best. Combining both predictions yields a better chance for successful fertilization, and an “optimal fertilization date” may be jointly determined.
  • Processor 216 may be further adapted to perform one or more of facilitating at least one of the assays, receiving a reading from the at least one sensor, computing a result of at least one of the assays, and/or computing a combined measure of results of two or more of the assays, hence concluding different results. Such a combined measure may be used as a fertility index. As an example, male subjects with low sperm qualities may get a higher index score by changing their way of life, avoiding oxidative stress or other methods known in prior art.
  • Reference is now made to FIG. 4, which shows a perspective view of another assay device 400, according to an embodiment. Assay device 400 may be relatively easy to operate and its operation may require no special laboratory training, so that a nurse, a physician, or any other caregiver may operate it in what is often referred to as a “point of care”—a clinic, a medical institution or the like. Furthermore, the assay device may still be operated in a laboratory.
  • Assay device 400 may include a compartment 402 adapted to receive a receptacle, such as a condom or a sample collecting cup, containing a reproduction system sample such as semen, vaginal secretions, cervical mucus, vaginally-collected cells and/or the like. Optionally, the receptacle is the one disclosed in applicant's PCT Published Application No. WO 2008/035333.
  • Referring now to FIG. 4B, an exemplary receptacle 440 is shown. Receptacle 440 may include an elongated, flexible bag, which may have a condom-like shape with inner cavity (such as 443) defined by the walls of the receptacle bag (440). The narrow end 442A of the receptacle may be at least partially sealed. For example, the walls at the narrow end of the receptacle may exhibit pore sizes of less then 0.42 nm. The broad end 442B, which is distally opposing the narrow end 442A, may be open. The broad, open end 442B may further include a rim 444 that may be used for the association of the receptacle within a contraceptive, as detailed below herein. Rim 444 is illustrated at a deformed state, wherein the rim is shaped into an eight form, by, for example, pinching two opposing sides of the rim towards each other. The receptacle 440 may be constructed of rubber, silk, polyurethane, silicone and the like. The thickness of the receptacle may vary in the range of about 5 to 1500 microns. Size of receptacle 140 may vary in length and diameter. For example, length of receptacle 440 from end 442A to end 442B may be in the range of, about 100-200 mm. For example, diameter of rim 444 of receptacle 440 may be in the range of, about 37 to 60 millimeter. Receptacle (such as 440) may further be associated with a male contraceptive device, such as a condom 446. Receptacle 440 may be fitted into male condom 446, such that the receptacle is contained within the inner space of the condom. Shown in FIG. 4B is a receptacle 440 fitted about two thirds of its length into a condom 446. Receptacle 440 may be secured to condom 446 by various ways. For example, rim 444 and rim 448 of condom 446 may be associated by pressing, stitching, mechanical fitting, zip-lock fit, zipper fit, fitting grooves, adhering, gluing and the like. For example, rim 444 of receptacle 440 may include perforation/grooves that may be used to fit to the upper rim, 448 of condom 446.
  • Reference is now made back to FIG. 4A. Assay device 400 may include an extraction mechanism for extracting the reproduction system sample from the receptacle and for transporting the reproduction system sample towards one or more assay ports and/or treatment ports, where the reproduction system sample is assessed and/or treated, respectively.
  • The extraction mechanism may be embodied as a strike handle 404 pivotally attached to a main body 410 of assay device 400, and having a protruding structure 406 matching a structure of a recess 408 in the main body. The receptacle may be positioned in compartment 402 with its reproduction system sample-containing edge at recess 408, and handle 404 may be lowered so as to squeeze the receptacle and extract at least some of its reproduction system contents.
  • Alternatively, the extraction mechanism may include a peristaltic pump (not shown) and/or a set of rollers adapted to induce the reproduction system sample out of the receptacle. Alternatively, the extraction mechanism may be the receptacle itself, being elastic in nature and therefore manually squeezable by a user.
  • Reference is now made to FIG. 4C, which shows a cross-sectional view of assay device 400. Before, during or after extraction of the receptacle's reproduction system contents, the volume of the reproduction system is optionally measured in a chamber 412.
  • The extracted reproduction system may be forced, by virtue of the extraction mechanism, to a conduit 414 leading to one or more assay locations, such as assay location 416. The one or more assays are optionally those described above in regard to cartridge 100 (FIGS. 1A-B).
  • When the one or more assays are complete, at least one chemical may flow to a result indicator such as a color-changeable result pad 418, causing the pad to change color responsive to the assay result. Result pad 418 may be embedded in a sliding base 420 of assay device, and the sliding base may be pivotally attached, using a hinge 422, to main body 410. Sliding base 420 may be slid by the user when the one or more assays are complete, to reveal result pad 418 and see the result.
  • Handle 404, or any other part of assay device 400, may include a reference color scale (not shown) for comparing the shade, shape, texture and/or the like of result pad 418 to a reference and thus providing the user with a meaningful result. The reference color scale may be printed on handle 404 or attached to it as a sticker. The reference color scale optionally includes literal explanation of the meaning of each color; the explanation may, additionally or alternatively, be included in product literature accompanying assay device 400.
  • Optionally, assay location 416 is a replaceable, and is adapted to be replaced by an additional assay location for facilitating an additional assay. This way, assay device 400 may be used multiple types for performing the same assay (such as an assay pertaining to fertilization potential which may have to be repeated every once in a while) or may be used each time for performing a different assay of the same semen sample or a different semen sample.
  • While a number of exemplary aspects and embodiments have been discussed above, those of skill in the art will recognize certain modifications, permutations, additions and sub-combinations thereof. It is therefore intended that the following appended claims and claims hereafter introduced be interpreted to include all such modifications, permutations, additions and sub-combinations as are within their true spirit and scope.
  • In the description and claims of the application, each of the words “comprise” “include” and “have”, and forms thereof, are not necessarily limited to members in a list with which the words may be associated.

Claims (24)

1-28. (canceled)
29. A cell separation system, wherein said system comprising:
a. a first chamber adapted to contain at least a portion of a cell sample; at least a portion of said sample is characterized by at least one biological or chemical characteristic; said first chamber is bounded by a rim, such that said cell sample is kept below said rim; and,
b. a second peripheral chamber; said second peripheral chamber is characterized by a circumferential depression around said first chamber; said second chamber is adapted to enable isolation of said at least a portion of said cell sample having the same biological or chemical characteristic, upon introduction of a separation-enabling agent.
30. The cell separation system according to claim 29, wherein said cell separation system is used for separating sperm cells from a semen sample; further wherein said same biological or chemical characteristic is motility of said sperm cells.
31. cell separation system according to claim 30, further adapted to assess concentration motile of sperm cells and/or isolate motile sperm cells within a semen sample for assisting fertility.
32. The cell separation system according to claim 30, wherein said rim is configured with specific surface roughness or serration to facilitate required surface tension capabilities for specific sample/reagent combination.
33. The cell separation system according to claim 30, wherein said separation-enabling agent is selected from a group consisting of Ringer's solution, Hartmann's solution, Saline, adapted to facilitate said separation of said semen sample or any cell support medium, cell washing medium, preparation medium or cell separation enabling agent.
34. The cell separation system according to claim 29, additionally comprising a reagent selected from a group consisting of selected from a group consisting of cell support medium, labeling compounds, markers, peptide, color-changeable pad; said reagent is adapted to, upon contact with said biologic sample, to yield a reaction and/or a colored compound indicating (i) existence or (ii) concentration of a component in said sample (iii) a result of said at least one assay.
35. The cell separation system according to claim 29, wherein said sample is selected from a group consisting of: a semen sample, a vaginal secretion sample, a vaginal cell sample, a blood sample, a urine sample, a saliva sample, a lymph sample or any combination thereof.
36. The cell separation system according to claim 29, adapted to enable an assay;
further wherein said assay is selected from a group consisting of: a sperm concentration assay, a semen pH assay, a leukocyte threshold assay, a sperm motility assay, a sperm morphology assay, a semen volume assay, a viscosity assay and a turbidity assay; further wherein said assays is adapted to facilitate diagnosis of at least one sexually transmitted disease (STD) selected from a group consisting of: syphilis, gonorrhea, Candida, human papiloma virus (HPV), mycoplasma, ureaplasma, human immunodeficiency virus (HIV), Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas and Hepatitis C.
37. The cell separation system according to claim 30, further adapted to isolate motile sperm of said semen sample for a usage selected from a group consisting of: intra uterine insemination (IUI), vaginal insemination, and in-vitro fertilization (IVF) and diagnosis of motile sperm cell.
38. The cell system according to claim 30, enclosed within a cartridge adapted for insertion into an assay device.
39. The cell system according to claim 38, wherein said cartridge comprising a body;
said body comprises:
(i) at least one compartment adapted to contain said at least one biologic sample; and,
(ii) at least one assay location, in which said assay of said at least one biologic sample is enabled;
b. at least one actuator adapted to interface with said cartridge to enable transportation of said biologic sample to at least one of said assay locations.
40. The cell system according to claim 39, additionally comprising a reagent selected from a group consisting of cell support medium, labeling compounds, markers, peptide, color-changeable pad; said reagent is adapted to, upon contact with said biologic sample, to yield a reaction and/or a colored compound indicating (i) existence or (ii) concentration of a component in said sample (iii) a result of said at least one assay.
41. The cell system according to claim 40, wherein said biologic sample is selected from group consisting of: a semen sample, a vaginal secretion sample, a vaginal cell sample, a blood sample, a urine sample, a saliva sample and a lymph sample or any combination thereof; further wherein said assay is selected from a group consisting of: a sperm concentration assay, a semen pH assay, a leukocyte threshold assay, a sperm motility assay, a sperm morphology assay, motile sperm cell concentration, a semen volume assay, a viscosity assay and a turbidity assay.
42. The cell system according to claim 40, wherein said assay is adapted to facilitate diagnosis of at least one sexually transmitted disease (STD) selected from a group consisting of: syphilis, gonorrhea, Candida, human papiloma virus (HPV), mycoplasma, ureaplasma, human immunodeficiency virus (HIV), Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas and Hepatitis C.
43. The cell system according to claim 40, wherein said cartridge is made of substantially rigid materials or substantially flexible materials or any combination thereof.
44. The cell system according to claim 40, wherein said actuator comprises a pump, a peristaltic pump, means of pressure difference creation, strike handle, a set of rollers, manual activation selected from a pipette, micropipette injector, syringe, any positive displacement or any combination thereof.
45. The cell system according to claim 40, further comprising a control means adapted to (i) receive a reading from at least one sensor, said sensor is in communication with said cartridge; (ii) analyze said reading; (iii) analysis readings received based upon said at least one of said assays; and (iv) output said analysis of said biological sample.
46. A method for separating cells from a biological sample, said method comprising steps of:
a. providing a cell separation system comprising: a first chamber; said first chamber is bounded by a rim; and a second peripheral chamber shallower, circumferential depression around said first chamber;
b. depositing at least a portion of said biological sample into said first chamber of said cell separation system such that said cell sample is kept below said rim; at least a portion of said sample is characterized by at least one biological or chemical characteristic;
c. introducing a separation-enabling agent into either said first chamber or said second chamber; thereby facilitating movement of said at a portion of said cell sample having the same biological or chemical characteristic into said second chamber of said cell separation system.
47. The method according to claim 46, additionally comprising at least one step selected from (i) collecting said motile cells for a usage selected from a group consisting of: IUI, vaginal insemination, and IVF and diagnosis of motile sperm cell; or (ii) assessing motility of said sperm cells based on a relative amount of motile cells in said second chamber.
48. The method according to claim 46, additionally comprising step of selecting said separation-enabling agent from a group consisting of Ringer's solution, Hartmann's solution, Saline, adapted to facilitate said separation of said semen sample, or any cell support medium, cell washing medium, preparation medium or cell separation enabling agent.
49. The method according to claim 48, additionally comprising at least one step selected from (a) providing a reagent adapted to, upon contact with said biologic sample, to yield a reaction and/or a colored compound indicating (i) existence or (ii) concentration of a component in said sample (iii) a result of said at least one assay; or (b) selecting said reagent from a group consisting of cell support medium, labeling compounds, markers, peptide, color-changeable pad or any combination thereof.
50. The method according to claim 46, additionally comprising step of selecting said sample from a group consisting of: a semen sample, a vaginal secretion sample, a vaginal cell sample, a blood sample, a urine sample, a saliva sample, a lymph sample or any combination thereof.
51. The method according to claim 46, additionally comprising at least one step selected from (a) performing an assay; further wherein said assay is selected from a group consisting of: a sperm concentration assay, a semen pH assay, a leukocyte threshold assay, a sperm motility assay, a sperm morphology assay, motile sperm concentration assay, a semen volume assay, a viscosity assay and a turbidity assay; or, (b) facilitating diagnosis of at least one sexually transmitted disease (STD) selected from a group consisting of: syphilis, gonorrhea, Candida, human papiloma virus (HPV), mycoplasma, ureaplasma, human immunodeficiency virus (HIV), Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas and Hepatitis C.
US12/739,309 2007-10-23 2008-10-23 Cartridge For A Biological Sample Abandoned US20110034758A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/739,309 US20110034758A1 (en) 2007-10-23 2008-10-23 Cartridge For A Biological Sample

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US98185607P 2007-10-23 2007-10-23
PCT/IB2008/054382 WO2009053928A2 (en) 2007-10-23 2008-10-23 Cartridge for a biological sample
US12/739,309 US20110034758A1 (en) 2007-10-23 2008-10-23 Cartridge For A Biological Sample

Publications (1)

Publication Number Publication Date
US20110034758A1 true US20110034758A1 (en) 2011-02-10

Family

ID=40580176

Family Applications (2)

Application Number Title Priority Date Filing Date
US12/739,337 Expired - Fee Related US9168028B2 (en) 2007-10-23 2008-10-23 Cartridge for a biological sample
US12/739,309 Abandoned US20110034758A1 (en) 2007-10-23 2008-10-23 Cartridge For A Biological Sample

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US12/739,337 Expired - Fee Related US9168028B2 (en) 2007-10-23 2008-10-23 Cartridge for a biological sample

Country Status (5)

Country Link
US (2) US9168028B2 (en)
EP (2) EP2212414A4 (en)
CA (2) CA2703526A1 (en)
IL (2) IL205326A0 (en)
WO (2) WO2009053927A2 (en)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140270063A1 (en) * 2013-03-15 2014-09-18 X-Ray Optical Systems, Inc. Non-homogeneous sample handling apparatus and x-ray analyzer applications thereof
US9341551B2 (en) 2012-01-10 2016-05-17 Uc-Care Ltd. Device and method for handling biological tissues
US20160169923A1 (en) * 2013-02-18 2016-06-16 Theranos, Inc. Systems and methods for multi-analysis
USD799056S1 (en) * 2015-04-24 2017-10-03 Accelerate Diagnostics, Inc. Cartridge
USD814652S1 (en) * 2016-10-14 2018-04-03 Spartan Bioscience In. Cartridge
US10012664B2 (en) 2011-09-25 2018-07-03 Theranos Ip Company, Llc Systems and methods for fluid and component handling
US10518265B2 (en) 2011-09-25 2019-12-31 Theranos Ip Company, Llc Systems and methods for fluid handling
US10557786B2 (en) 2011-01-21 2020-02-11 Theranos Ip Company, Llc Systems and methods for sample use maximization
US10634667B2 (en) 2007-10-02 2020-04-28 Theranos Ip Company, Llc Modular point-of-care devices, systems, and uses thereof
US11054432B2 (en) 2011-09-25 2021-07-06 Labrador Diagnostics Llc Systems and methods for multi-purpose analysis
US11162936B2 (en) 2011-09-13 2021-11-02 Labrador Diagnostics Llc Systems and methods for multi-analysis
USD962467S1 (en) * 2019-11-25 2022-08-30 Illumina, Inc. Flow cell device

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8753290B2 (en) * 2009-03-27 2014-06-17 Intellectual Inspiration, Llc Fluid transfer system and method
RU2013145080A (en) 2011-03-09 2015-04-20 Пикселл Медикал Текнолоджиз Лтд. DISPOSABLE CARTRIDGE FOR PREPARING A Sample OF A FLUID CONTAINING A CELL FOR ANALYSIS
US9254489B2 (en) 2011-12-06 2016-02-09 Edan Diagnostics In vitro medical diagnostic device and system
EP2917362A4 (en) * 2012-11-07 2016-07-13 Sandstone Diagnostics Inc Methods and devices for processing samples and counting cells
US10197480B2 (en) 2012-11-07 2019-02-05 Sandstone Diagnostics, Inc. Methods and devices for processing samples and counting cells
USD717459S1 (en) 2012-11-12 2014-11-11 Edan Diagnostics Diagnostic device
USD706930S1 (en) 2012-11-12 2014-06-10 Edan Diagnostics Fluid cartridge
USD717438S1 (en) 2012-11-12 2014-11-11 Edan Diagnostics Fluid cartridge
CN103543185B (en) * 2012-12-06 2015-06-24 理邦(美国)诊断有限公司 Testing cartridge for an in vitro medical diagnostic device
CN103543280B (en) * 2012-12-06 2015-10-14 理邦(美国)诊断有限公司 A kind of external medical diagnosis device and system
EP2954302B1 (en) 2013-02-07 2020-08-26 Sandstone Diagnostics, Inc. Automated sample processing, fluid distribution, and sedimentation assay
FR3013839B1 (en) * 2013-11-26 2016-07-29 Inst Nat Polytechnique Toulouse DEVICE FOR TREATING A SAMPLE OF AN ACTIVE BIOLOGICAL FLUID
CN106796212A (en) * 2014-08-12 2017-05-31 新生代吉恩公司 System and method for monitoring health based on the body fluid collected
CN104914260A (en) * 2015-05-23 2015-09-16 深圳德夏生物医学工程有限公司 Portable biochemistry and special protein analyzer
EP3442706A4 (en) 2016-04-13 2020-02-19 NextGen Jane, Inc. Sample collection and preservation devices, systems and methods
US10324022B2 (en) 2016-05-11 2019-06-18 Bonraybio Co., Ltd. Analysis accuracy improvement in automated testing apparatus
US10281386B2 (en) 2016-05-11 2019-05-07 Bonraybio Co., Ltd. Automated testing apparatus
US10852290B2 (en) 2016-05-11 2020-12-01 Bonraybio Co., Ltd. Analysis accuracy improvement in automated testing apparatus
US9958665B2 (en) 2016-05-11 2018-05-01 Bonraybio Co., Ltd. Testing equipment with magnifying function
US9959621B2 (en) 2016-05-11 2018-05-01 Bonraybio Co., Ltd. Testing apparatus with dual cameras
US9958658B2 (en) 2016-05-11 2018-05-01 Bonraybio Co., Ltd. Testing equipment with magnifying function

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4294924A (en) * 1980-02-25 1981-10-13 Data Packaging Corporation Method and container for growth of anaerobic microorganisms
US5296375A (en) * 1992-05-01 1994-03-22 Trustees Of The University Of Pennsylvania Mesoscale sperm handling devices
US5686302A (en) * 1993-02-09 1997-11-11 Zech; Josef Device for removing sperm cells form seminal fluid
US20030119050A1 (en) * 1998-03-30 2003-06-26 Shafrira Shai Flow cytometer for analysis of general diagnostic factors in cells and body fluids
US7022517B1 (en) * 1999-07-16 2006-04-04 Board Of Regents, The University Of Texas System Method and apparatus for the delivery of samples to a chemical sensor array
US20060257993A1 (en) * 2004-02-27 2006-11-16 Mcdevitt John T Integration of fluids and reagents into self-contained cartridges containing sensor elements
US8535622B2 (en) * 2009-04-22 2013-09-17 Lotus Bio (Nymphaea) Ltd Sperm separation system

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA948564B (en) * 1993-11-19 1995-07-26 Bristol Myers Squibb Co Liquid separation apparatus and method
GB0003596D0 (en) * 2000-02-16 2000-04-05 Genosis Ltd Sperm separation
GB0127360D0 (en) * 2001-11-14 2002-01-09 Univ Bath Device and method for preparing particles for analysis
WO2007002579A2 (en) * 2005-06-23 2007-01-04 Bioveris Corporation Assay cartridges and methods for point of care instruments
WO2008035333A2 (en) * 2006-09-18 2008-03-27 Lotus Bio Inc. Biological fluid receptacle
US8993292B2 (en) * 2007-01-16 2015-03-31 Applied Biosystems Llc Methods and systems for differential extraction

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4294924A (en) * 1980-02-25 1981-10-13 Data Packaging Corporation Method and container for growth of anaerobic microorganisms
US5296375A (en) * 1992-05-01 1994-03-22 Trustees Of The University Of Pennsylvania Mesoscale sperm handling devices
US5686302A (en) * 1993-02-09 1997-11-11 Zech; Josef Device for removing sperm cells form seminal fluid
US20030119050A1 (en) * 1998-03-30 2003-06-26 Shafrira Shai Flow cytometer for analysis of general diagnostic factors in cells and body fluids
US7022517B1 (en) * 1999-07-16 2006-04-04 Board Of Regents, The University Of Texas System Method and apparatus for the delivery of samples to a chemical sensor array
US20060257993A1 (en) * 2004-02-27 2006-11-16 Mcdevitt John T Integration of fluids and reagents into self-contained cartridges containing sensor elements
US8535622B2 (en) * 2009-04-22 2013-09-17 Lotus Bio (Nymphaea) Ltd Sperm separation system

Cited By (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10634667B2 (en) 2007-10-02 2020-04-28 Theranos Ip Company, Llc Modular point-of-care devices, systems, and uses thereof
US11899010B2 (en) 2007-10-02 2024-02-13 Labrador Diagnostics Llc Modular point-of-care devices, systems, and uses thereof
US11199538B2 (en) 2007-10-02 2021-12-14 Labrador Diagnostics Llc Modular point-of-care devices, systems, and uses thereof
US11143647B2 (en) 2007-10-02 2021-10-12 Labrador Diagnostics, LLC Modular point-of-care devices, systems, and uses thereof
US11137391B2 (en) 2007-10-02 2021-10-05 Labrador Diagnostics Llc Modular point-of-care devices, systems, and uses thereof
US11092593B2 (en) 2007-10-02 2021-08-17 Labrador Diagnostics Llc Modular point-of-care devices, systems, and uses thereof
US10557786B2 (en) 2011-01-21 2020-02-11 Theranos Ip Company, Llc Systems and methods for sample use maximization
US10876956B2 (en) 2011-01-21 2020-12-29 Labrador Diagnostics Llc Systems and methods for sample use maximization
US11644410B2 (en) 2011-01-21 2023-05-09 Labrador Diagnostics Llc Systems and methods for sample use maximization
US11162936B2 (en) 2011-09-13 2021-11-02 Labrador Diagnostics Llc Systems and methods for multi-analysis
US9952240B2 (en) 2011-09-25 2018-04-24 Theranos Ip Company, Llc Systems and methods for multi-analysis
US11009516B2 (en) 2011-09-25 2021-05-18 Labrador Diagnostics Llc Systems and methods for multi-analysis
US10518265B2 (en) 2011-09-25 2019-12-31 Theranos Ip Company, Llc Systems and methods for fluid handling
US10534009B2 (en) 2011-09-25 2020-01-14 Theranos Ip Company, Llc Systems and methods for multi-analysis
US10012664B2 (en) 2011-09-25 2018-07-03 Theranos Ip Company, Llc Systems and methods for fluid and component handling
US10557863B2 (en) 2011-09-25 2020-02-11 Theranos Ip Company, Llc Systems and methods for multi-analysis
US10627418B2 (en) 2011-09-25 2020-04-21 Theranos Ip Company, Llc Systems and methods for multi-analysis
US10018643B2 (en) 2011-09-25 2018-07-10 Theranos Ip Company, Llc Systems and methods for multi-analysis
US10371710B2 (en) 2011-09-25 2019-08-06 Theranos Ip Company, Llc Systems and methods for fluid and component handling
US11524299B2 (en) 2011-09-25 2022-12-13 Labrador Diagnostics Llc Systems and methods for fluid handling
US11054432B2 (en) 2011-09-25 2021-07-06 Labrador Diagnostics Llc Systems and methods for multi-purpose analysis
US10383607B2 (en) 2012-01-10 2019-08-20 Uc-Care Ltd. Device and method for handling biological tissues
US9341551B2 (en) 2012-01-10 2016-05-17 Uc-Care Ltd. Device and method for handling biological tissues
US9810704B2 (en) 2013-02-18 2017-11-07 Theranos, Inc. Systems and methods for multi-analysis
US20160169923A1 (en) * 2013-02-18 2016-06-16 Theranos, Inc. Systems and methods for multi-analysis
US9360440B2 (en) * 2013-03-15 2016-06-07 X-Ray Optical Systems, Inc. Non-homogeneous sample handling apparatus and X-ray analyzer applications thereof
US20140270063A1 (en) * 2013-03-15 2014-09-18 X-Ray Optical Systems, Inc. Non-homogeneous sample handling apparatus and x-ray analyzer applications thereof
USD799056S1 (en) * 2015-04-24 2017-10-03 Accelerate Diagnostics, Inc. Cartridge
USD814652S1 (en) * 2016-10-14 2018-04-03 Spartan Bioscience In. Cartridge
USD962467S1 (en) * 2019-11-25 2022-08-30 Illumina, Inc. Flow cell device

Also Published As

Publication number Publication date
WO2009053927A3 (en) 2009-12-30
WO2009053928A2 (en) 2009-04-30
US20110086378A1 (en) 2011-04-14
EP2212414A2 (en) 2010-08-04
CA2703526A1 (en) 2009-04-30
EP2212414A4 (en) 2011-07-20
EP2210114A2 (en) 2010-07-28
WO2009053927A2 (en) 2009-04-30
EP2210114A4 (en) 2012-03-21
IL205325A0 (en) 2010-12-30
US9168028B2 (en) 2015-10-27
CA2703531A1 (en) 2009-04-30
IL205326A0 (en) 2010-12-30
WO2009053928A3 (en) 2009-12-30

Similar Documents

Publication Publication Date Title
US9168028B2 (en) Cartridge for a biological sample
US10391496B2 (en) Devices, systems, methods, and kits for receiving a swab
ES2682281T3 (en) Test cartridge with integrated transfer module
US20130331298A1 (en) Analyzer and disposable cartridge for molecular in vitro diagnostics
WO2008122908A1 (en) Method and device for gathering a fluid sample for screening purposes
US20220032295A1 (en) Devices and methods for sample preparation
US20230012231A1 (en) A method and apparatus for respiratory secretion collection and analysis
AU2023202958A1 (en) Fluid collection unit and related devices and methods
US20140294698A1 (en) Sputum trap
US5952239A (en) Cytology chamber with port to receive collection bottle and method of use
US20040184965A1 (en) Testing cup
CN116685407A (en) Developer solution vial
CN207866565U (en) A kind of integrated quantitative sampling mix reagent device
US11666906B2 (en) Parts for diagnostic devices
WO2018076231A1 (en) Tampon
KR20220119193A (en) Rapid diagnostic kit
WO2008147865A1 (en) Point of care cervical screening system
BR112016004955B1 (en) DEVICES, SYSTEMS, METHODS AND ASSEMBLIES FOR RECEIVING SWAB

Legal Events

Date Code Title Description
AS Assignment

Owner name: LOTUS BIO (NYMPHAEA) LTD, ISRAEL

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SHANY, VERED;TAVORI, ISAAC;REEL/FRAME:025167/0919

Effective date: 20101013

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION