Directed-flow assay device
12 claims: 3 independent, 9 dependent
- 1REIVINDICAÇÕES 1. Dispositivo de teste de fluxo direcionado para detecção quantitativa de analitos alvo em uma amostra, o referido dispositivo caracterizado pelo fato de que compreende:um membro de suporte de teste tendo uma primeira e uma segunda extremidade, uma membrana de porosidade analítica montado adjacente e geralmente paralela com o referido membro de suporte, a referida membrana analítico tendo uma primeira e uma segunda extremidade e pelo menos uma região de captura intermediária à primeira e à segunda extremidade, a referida pelo menos uma região de captura sendo configurada para capturar analitos marcados que se movem da primeira extremidade da referida membrana analítica em direção à referida segunda extremidade da referida membrana;uma porta de recepção de amostra em uma extremidade do referido membro de suporte para introdução no referido dispositivo da amostra a ser analisada, a referida porta de recebimento da amostra constituída por: uma camada de canal posicionada acima do referido material de vedação, a camada de canal compreendendo uma abertura e um canal, a referida abertura fornecendo comunicação de fluido com o referido canal, e o referido canal fornecendo comunicação fluido com a referida membrana porosa analítica;um material hidrofílico posicionados ao longo da referida camada de canal, o referido material hidrofílico tendo uma abertura no mesmo correspondendo à referida na referida camada de canal, e um elemento de gaxeta posicionado acima do referido material hidrofílico e tendo uma abertura no mesmo para permitir a entrada de fluido na porta, a referida gaxeta proporcionando uma vedação de fluido para o dispositivo de teste.
- 2Dispositivo, de acordo com a reivindicação 1, caracterizado pelo fato de que compreende uma membrana protetora que cobre a referida membrana analítica do lado oposto ao referido membro de suporte, a referida membrana protetora sendo opticamente não-transparente. caracterizado pelo fato de que inclui ainda uma região de controle na referida membrana porosa para coleta de conjugados que passaram pela região de captura para mostrar que a referida tira de teste foi utilizada.
- 35. Dispositivo, de acordo com a reivindicação 4, caracterizado pelo fato de que ainda compreende pelo menos uma área de calibração magnética impressa na referida membrana protetora.
- 46. Dispositivo, de acordo com a reivindicação 1, caracterizado pelo fato de que ainda compreende um material para vedação de fluido entre o referido membro de suporte de teste e a referida camada de canal.
- 57. Aparelho de análise para detecção quantitativa analitos alvo em uma amostra, o referido aparelho caracterizado pelo fato de que compreende:uma tira de teste que compreende: um membro de suporte de teste tendo uma primeira e uma segunda extremidade, uma membrana de porosidade analítica montado adjacente e geralmente paralela com o referido membro de suporte, a referida membrana analítico tendo uma primeira e uma segunda extremidade e pelo menos uma região de captura intermediária à primeira e à segunda extremidade, a referida pelo menos uma região de captura sendo configurada para capturar analitos marcados que se movem da primeira extremidade da referida membrana analítica em direção à referida segunda extremidade da referida membrana analítica;uma porta de recepção de amostra em uma extremidade do referido membro de suporte para introdução no dispositivo da amostra a ser analisada, a referida referido porta de recebimento da amostra constituída por: uma camada de canal posicionada acima do referido material de vedação, a camada de canal compreendendo uma abertura um canal, a referida abertura fornecendo comunicação de fluido com o referido canal, e o referido canal fornecendo comunicação fluido com a referida membrana porosa analítica;um material hidrofílico posicionados ao longo da referida camada de canal, o referido material hidrofílico tendo uma abertura no mesmo correspondendo à referida na referida camada de canal, e um elemento de gaxeta posicionado acima do referido material hidrofílico e tendo uma abertura no mesmo para permitir a entrada de fluido na porta, uma porção de carcaça inferior para suporte do membro de suporte, a referida carcaça geralmente configurada em formato de C;e uma porção de carcaça superior geralmente complementar à configuração da referida carcaça inferior, a referida carcaça inferior se ajustando acima da referida carcaça inferior de tal modo que a referida tira de teste atravessa a abertura em formato de C, a referida gaxeta proporcionando uma vedação de fluido entre a referida porta de recebimento de amostra e a referida carcaça.
- 68. Aparelho, de acordo com a reivindicação 7, caracterizado pelo fato de que ainda compreende uma membrana protetora cobrindo a referida membrana analítica do lado oposto ao referido membro de suporte, a referida membrana protetora sendo opticamente não-transparente.
- 79. Aparelho, de acordo com a reivindicação 8, caracterizado pelo fato de que a referida membrana protetora é formada integralmente com a referida membrana porosa.
- 810. Aparelho, de acordo com a reivindicação 7, caracterizado pelo fato de que inclui ainda uma região de controle na referida membrana porosa para coleta de conjugados que passaram a referida região de captura para mostrar que a referida tira teste foi utilizada.
- 911. Aparelho, de acordo com a reivindicação 10, caracterizado pelo fato de que compreende ainda pelo menos uma área de calibração magnética impressa na referida membrana protetora.
- 1012. Aparelho, de acordo com a reivindicação 7, caracterizado pelo fato de que a referida porção de carcaça inferior habitação é moldada e configurada para deixar cair no referido membro de suporte e membrana com a porta de recebimento de amostra.
- 1113. Aparelho, de acordo com a reivindicação 7, caracterizado pelo fato de que compreende um material de vedação de fluido entre o referido membro de suporte de teste e a referida camada de canal.
- 1214. Método para a detecção quantitativa de analitos alvo em uma amostra por meio de um imuno-ensaio de fluxo direcionado, um ensaio de receptor, um ensaio celular, ou um ensaio molecular, o método caracterizado pelo fato de que compreende:acoplamento de partículas superparamagnéticas com a referida amostra, as partículas superparamagnéticas sendo tratadas para ligarem-se com o analito alvo na amostra, o referido acoplamento produzindo um conjugado;aplicar o conjugado a uma extremidade de uma membrana porosa de uma tira de teste por meio de uma porta de recebimento de amostra que está localizada na tira de teste, a tira de teste tendo uma região de captura;capturar os conjugados na região de captura da membrana porosa à medida que os conjugados se movem através da membrana porosa por ação capilar;e ler a quantidade de analitos marcados na região de 5 captura por meio de um dispositivo leitor de ensaio magnético. 1/4
Independent claims12
112 paragraphs in 1 section, as filed
(54) Title: FLOW TEST DEVICE (57) Summary:
DIRECTED (30) Unionist Priority: 6/13/2006 us 11 / 452,725 (73) Owner (s): Quantum Design, Inc.
(72) Inventor (s): Herbert S. Chow, Ronald T. Laborde (74) Attorney (s): Di Blasi, Parente, Vaz and Dias & Al (86) International Order: pct US2OO7OO82O4 de
29/03/2007 (87) International Publication: wo 2007 / 145697de
21/12/2007
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Invention Patent Descriptive Report for: DIRECTED FLOW TEST DEVICE.
Technical Field
The present invention relates generally to immunoassays, receptor-based, cellular and molecular assays, and the liquid delivery devices that incorporate them. More specifically, it refers to an analysis assay or test device containing a liquid distribution element and may contain reagents for detecting an analyte of interest. Prior Art
Various chromatographic and microfluidic immunoassay techniques have been available for some time. For example, immune-based latex agglutination tests for the detection of a factor associated with rheumatoid arthritis have been used since 1956 (Singer et al., Am. J. Med. Chem. 22: 888-892 (1956)). The tests that can be performed with such chromatographic and fluid systems often involve immunoassays, which depend on the specific interaction between an antigen and a corresponding antibody. Immunoassays, therefore, have gained consideration as an important and convenient means of testing for the presence or quantity, or both, of molecules of clinical importance.
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Among the many analytical systems used for the detection of analytes, particularly those of biological interest, are fluid and chromatographic test systems. Among the analytes frequently tested with such systems are the following: (1) hormones, such as human chorionic gonadotropin (hCG), which is often tested as a marker of human pregnancy, (2) antigens, particularly specific antigens for bacteria, viruses, protozoa and pathogens, such such as streptococci, hepatitis viruses, and giardia, (3) antibodies, particularly antibodies induced, as a result of infection with pathogens, such as bacteria or viruses, such as HTV, and (4) other proteins, such as hemoglobin, often assayed in fecal occult blood determinations, an early indicator of gastrointestinal disorders, such as colon cancer, (5) enzymes, such as aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, glutamate dehydrogenase, frequently tested as indicators of physiological function and tissue damage; (6) drugs, both therapeutic drugs, such as antibiotics, tranquilizers, anticonvulsants and illegal drugs of abuse, such as cocaine, marijuana, heroin; and (7) vitamins and (8) the nucleic acid material.
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Such chromatographic systems are often used by doctors and medical technicians for a quick in-office diagnosis. They are, therefore, commonly referred to as point of care (POC) devices. These tests can also be used for therapeutic monitoring of a variety of conditions and disorders. They are also increasingly used by patients themselves at home for monitoring such conditions and diseases, scientists for use in field tests for transgenic crops and environmental contaminants; soldiers in a field battle to detect biological warfare weapon conditions, and emergency veterinary technicians where rapid testing is crucial.
The chromatographic and fluid techniques used in conjunction with most common immunoassays involve the principle of immunochromatography. In general, this technique uses a particle tag or indicator that has been linked to a specific immunostaining for the molecule to be tested. The tag and antibody / antigen together are referred to as a conjugate, which is then mixed with a sample. If the analyte molecule is present in the sample, the conjugate specifically binds to the molecule. The label aspect provides a detectable indication that the molecule to be tested is present. The specific reactions that are employed vary with the nature of the molecule to be tested and the sample to be tested. Such determinations are easily made according to the molecule of interest.
Immunochromatographic and fluidic assays fall into two main categories: intercalated and competitive, according to the nature of the antigen antibody complex to detect and the sequence of reactions necessary to produce this complex. In the case of antigen detection, intercalated immunochromatographic procedures call for mixing the sample that may contain the analyte to be tested with antibodies to the analyte. These antibodies are mobile and are typically attached to a marker or reagent, such as dyed latex, a colloidal metal sol, or a radioisotope. This mixture is then applied to a capture chromatography medium. This zone or immobilized for the chromatograph can look like a stick. When the complex of the molecule to be tested and the labeled antibody reaches the zone of the antibodies immobilized on the chromatographic support, binding occurs, and the bound labeled antibodies are located in the zone. This indicates the presence of the analyte band-containing molecule a banding or capture zone that contains interest in the form of antibodies
The middle is a rehearsal strip. This technique can be used to obtain qualitative results. Examples of interleaved immunoassays performed on test strips are described in U.S. patents 4,168,146 to Grubb et al, 4366241 to Tom et al, 6017767 and 5998220 to Chandler,. . And 4,305,924 to Piasio et al.
In competitive or indirect immunoassays, the immobilized component is typically present in controlled quantities and the mobile component is present in unknown quantities. The unknown amount of moving component is supplemented with a known amount of the same component that has been labeled by adding a measurable component that does not interfere with its reactive immunochemical properties. The tag may consist of a radioisotope, a chromophore, a particle, a fluorophore, or an enzyme. The amount of labeled material immunochemically bound to the solid phase will depend on the amount of unlabeled component in solution competing for the same binding sites. The more the unknown component present, the less the amount of marked component attached. How can such a determination be made in relation.
Chromatographic assays based on enzyme gained use in addition to immuno chromatographic tests. These
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Enzyme-based assays involve an enzymatically catalyzed reaction, rather than an antigen-antibody reaction. The frequency-catalyzed enzymatic reaction generates a detectable product.
Although useful, currently available chromatography techniques using test strips have a number of drawbacks. Some examples, for example, faecal samples, contain particles that can obscure or color the pores of the chromatographic medium, making it difficult to detect the labeling reagents. Blood, for example, obviously contains cells and color components that obscure color generation in the test, and therefore makes it difficult, if not impossible, to read. Blood cells also tend to clog the middle pores. Wet chromatographic medium is also sometimes difficult to read because of specular reflection from the chromatography medium. There are several other drawbacks to chromatographic techniques, including physical properties of lateral flow, frontal movement of the fluid along the range and intensity of color generation and location.
<td colspan="2">The preparation</td><td colspan="2">sample and generation</td><td>in</td><td>waste is</td>
<td>responsible</td><td>per</td><td>others</td><td>problems with</td><td>the</td><td>devices</td>
<td>currently</td><td colspan="2">available</td><td>and techniques</td><td>in</td><td>fluids and</td>
immunochromatography. The increased prevalence of diseases transmitted by infected blood and blood fractions, such as HIV and hepatitis, has only exacerbated these concerns. The available forms of side flow devices have a large part of their components, which are used only for mechanical support of the chromatographic membrane, and are not sealed. Therefore, disposal is a concern, expensive, and possibly dangerous due to the presumed biohazards
Precautions must be taken so that workers, or people who may inadvertently come into contact with waste, do not become contaminated
A common aspect of known devices, particularly in lateral flow technology and microfluidic systems, is that the test is read visually, that is, by means of one or more optically readable lines on a test strip held in a carrier or through windows, on the device, which can have multiple configurations. As briefly mentioned above, there are several limitations or disadvantages to the known optically detected assays. Because they are optical, changes in the surface only (typically coloring) can be detected. In addition, these tests are only appropriate when the sample solution is colorless. In addition, the target analytes may be in the sample solution, but of such a low concentration that only relatively few are captured in the assay capture zone.
This can provide a faded or even non-optically detectable reading, and a false negative reading can result.
Quantitative assessments are only an estimate based on the color intensity of the detection line. Since the prior art tests are optical reading, they are subject to contamination by exposure to light and caused degradation. Therefore, they have a limited archival life.
Typically one end of the test is exposed to the sample, usually a fluid of some kind, being tested for the specific target analytes of interest. The fluid migrates through a capillary or chromatography medium whereby the substance to be analyzed with the respective label is captured and immobilized, while the rest of the fluid is absorbed in a medium at the distal end of the test. Examples of optically readable side flow devices and methods are disclosed in US patents 5,591,645; 5,798,273; 5,622,871; 5,602,040; 5,714,389;
5,879,951; 4,632,901; and 5,958,790
Many current devices also have a member of the sample liquid application in direct fluid communication with the test strip. Typically, this member is made from one. absorbent material that can be contained within the device itself, or protrude from the device to be more easily introduced with the liquid sample. The absorbent liquid sample member tries to control the flow rate of the fluid through the device. The concern is that if the liquid sample is applied directly to the test strip, the strip can easily be flooded and the test rendered ineffective. In addition, the application member is usually made from a different material than the test strip itself, due to the relatively large amount of liquid that is expected to manage.
Others have tried to control the flow rate of the fluid to the test strip by test formats using capillaries. Examples of capillary tests can be found in US patents 4883760 and 5474902. However, these are not of a size suitable for use in care point situations.
Biological systems other than lateral flow immunoassays have employed magnetic particles or microspheres, which can be more specifically referred to as polymer beads impregnated with iron oxide. These spheres bind with the target analytes in the sample to be tested and are then normally isolated or magnetically separated. Once the isolation has occurred, further tests can be carried out, including observing particular images, optically either directly or through a camera. Examples of such systems can be found in US patents 3,981,776: 5,395,498: 5,476,796: 5,817,526: and 5,922,284.
Another device for the detection of target molecules in a liquid phase is presented in US patent 5,981,297, where magnetizable particles are used and the output of the magnetic field sensors indicates the presence and concentration of target molecules in the sample to be tested .
Other examples that magnetically detect using physical forces are disclosed in US patents
5.445.970;
5,981,297 and 5,925,573. However, in these devices, the magnet requires relatively high energy, because the space in which the test is placed must be large enough to accommodate the relatively thick test device.
It would therefore be advantageous to have a test device in which the fluid sample is applied in such a way that it avoids the problems of prior art devices, which has a detection region providing reproducible, standardized and reliable results and which is also archival. for storage over time. The present invention satisfies these needs and provides related advantages.
Invention Description
The present invention relates generally to immunoassays, cellular and molecule-based assays. More specifically, it refers to directed flow assays that have a sample receiving port separated by a micro-analytical channel from the membrane. In preferred embodiments,
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how tests use superparamagnetic particles
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bound complex marked particles
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captured
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zones
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predetermined regions
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test strip and the presence and quantity of labeled analytes are then detectable by magnetic means.
It is also contemplated that, in some embodiments, analytes can be detected by routine optical means, for example. The specific reagents and conjugates required for optical detection have been used for many years and are well known.
In one embodiment, the device has a test support element having a first end and a second end and an analytical porous membrane mounted adjacent and generally parallel with the support member. The analysis membrane has a first end and a
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second end, and at least one intermediate capture region from the first and second ends, where at least one capture region is configured to capture the motion-labeled analytes from the first end of the analysis membrane to the second end of the a analysis membrane.
The devices here also preferably have a sample receiving port, preferably connected via a channel, or in fluid communication with, the test strip itself. In these embodiments, a sample application member, or a sample pad, is not strictly necessary. The sample receiving port is appropriately sized and constructed to hold a desired amount of liquid and is in direct fluid communication with the test strip. The port receiving the sample is at one end of the support member for introducing the sample to be analyzed for said device. The sample receiving door has a fluid sealing material, and a channel layer positioned adjacent to the sealing material. The channel layer has an opening in it and also a channel, such that the opening provides fluid communication with the channel, and such that the channel provides fluid communication with the analytical porous membrane. A hydrophilic material is positioned on the channel layer and has an opening corresponding to the opening of the channel layer. A sealing element is positioned over the hydrophilic material and has an opening in it to allow fluid to enter the door. The gasket provides a seal between the test and any surrounding casing.
Additional embodiments of the present invention may have a protective membrane that covers the analytical membrane on the side opposite the support element. The protective membrane can be optically non-transparent. In other embodiments, the protective membrane is integrally formed with the porous membrane. Alternatively, the protective membrane can be formed according to a surface treatment of the porous membrane.
Additional embodiments of the present invention may have a control region on the porous membrane for collecting magnetic conjugates that have passed the capture region to show that the test strip has been used. In additional embodiments, at least one magnetic calibration area can be printed on the protective membrane. The calibration area can be in the form of a line, or even a single point, among others.
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Preferred embodiments of the invention have a lower body portion for supporting the support member. This housing will preferably be C-shaped, although many other forms are contemplated here, provided that access by a reading device to the test strip is provided. The upper shell portion may also be present in these embodiments. This upper housing portion preferably has a complementary configuration to the lower housing portion and fits over the lower body portion such that the immunoassay test strip passes through the opening of, or in the arms of, the shape of Ç.
The invention further provides several methods that employ the devices described herein. For example, a method for conducting quantitative lateral flow immunoassay detection of target analytes in a sample is provided. The method involves coupling superparamagnetic conjugate particles configured to bind with a desired target analyte in the sample. The analyte and superparamagnetic particle complex is applied to one end of the test
<td>It is delivered</td><td>for</td><td>the membrane</td><td>porous</td><td>of a</td><td>strip</td><td>of test</td><td>in</td>
<td colspan="2">lateral flow,</td><td>through</td><td>of a</td><td>door</td><td>in</td><td>reception</td><td>in</td>
<td>sample.</td><td>The</td><td>complex</td><td>in</td><td>analyte</td><td>and</td><td colspan="2">particles</td>
superparamagnetic cells move through the porous membrane by capillary action. Then, the quantity of labeled analytes in the capture region is read by means of a magnetic test reader device.
The present invention has improved sensitivity over known side flow devices. It provides a very fast analytical measurement (within a few minutes). There are many advantages of using magnetic particles over known colored particles or other prior art optical indicators. These include quantitative linearity of magnetic detection in relation to the amount of magnetic material present in a wide range, by means of at least four orders of magnitude. Time stability is also superior because the magnetic particles are stable, thus allowing the developed test to be archived and retested as necessary. In addition, magnetic particles are generally inert to biological systems and the environment. So, - they not only remain stable, they are environmentally and biologically safe. Other magnetic particles are already in widespread use with other technologies across the diagnostic industry so that they are readily available. Other benefits of magnetic detection are that once the particles are
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* superparamagneticas, they are magnetic only when exposed to a magnetic field. This allows them to be manipulated freely in solution, without aggregation.
Another significant advantage over prior art optical side flow devices is that, with the present invention, the total amount of substances to be analyzed in the test strip capture region is measured as a single mass in a volumetric measurement. The permeability of the magnetic field is such that any analyte contained within the detector's active region will be measured. This contrasts with optical detection techniques, where only analyte interactions reported on or very close to the strip surface are detectable. In the present invention, the intensity of the magnetic signal increases directly with the mass of iron involved, unrelated to its proximity to the strip surface. This inherent linearity of magnetic detection contributes to an increase in sensitivity, precision and dynamic range. In addition, superparamagnetic particles are physically similar to colloidal gold, with respect to size, and can be easily adapted for a wide range of lateral flow tests. Note that colloidal gold, as well as fluorescent latex particles, are typically used in the optically detected prior art immunological assays.
In most lateral flow devices, usually at one end of the porous membrane is the sample introduction area. This is conventionally done from a sample block and a conjugate block. In the prior art, the conjugate pad is the source of freely moving colored particles, typically colloidal solutions of colloidal gold gold, or fluorescent latex particles. In various embodiments of the present invention, there is no absorbent zone or conjugate pad. Moving particles are the superparamagnetic particles that mark the target analytes from the sample to be introduced through the fluid channel. In preferred embodiments of the present invention, the sample is mixed with the superparamagnetic particles before the sample is applied to the device, or at the same time. Several functional advantages exist with this configuration. For example, the kinetics of the reaction of particles in solution ensures that the reaction is faster, provides more complete incubation, and extends to completion. On the other hand, when the reaction proceeds from a wavefront of a porous membrane, the reaction tends to be
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slower and there is a possibility that it will not reach an end sooner, or at all.
The sample, together with the labels of bound magnetic particle and target analytes, move with capillary action along the porous membrane and are captured in a predefined location called the capture region or capture zone. There may be more than one capture zone, to allow multiplexing. As used herein, the term multiplexing refers to tests for more than one type of analyte at the same time on the same test strip. Excess analytes and liquid transport continues to pass through the capture zone to the other end of the porous membrane, sometimes forming a control line or zone separate from the capture zone. An additional feature is that, typically, a wick pad is mounted at the end of the porous membrane to improve the capillarity action, leading the flow from the introduction of one side of the porous membrane across the entire length of the membrane.
In the embodiments here not using optical detection, the upper part of the porous member can be covered by another protective sheet or membrane that is not transparent. It can be completely opaque. This top sheet may also include pre-printed standards, which are used for calibration purposes, so that the auto switch can be calibrated for each test, to ensure absolute accuracy. The protective sheet cannot be a separate element in some cases, but it can only be the top surface of the membrane properly treated to function as a protective or surface sheet. BRIEF DESCRIPTION OF THE DRAWING
These and other aspects, characteristics and advantages of the present invention will be more evident after considering the following description of preferred embodiments taken in conjunction with the accompanying drawings, in which numbers
<td>of reference</td><td>equals</td><td>designate</td><td colspan="2">equal parts over</td><td>gives</td>
<td>description:</td><td></td><td></td><td></td><td></td><td></td>
<td>Figure 1</td><td>is</td><td>seen in</td><td>exploded perspective</td><td>in</td><td>one</td>
<td>device</td><td>flow</td><td>directed</td><td>test according</td><td>with</td><td>The</td>
the present invention;
Figure 2 is a side sectional view of the assembled test strip of Figure 1;
Figure 3 is a perspective view of the lower housing portion of the apparatus.
Figure 4 is a perspective view of the interior of the upper housing part of the apparatus of Fig. 1;
Figure 5 is a perspective view of the fully assembled device of the present invention.
BEST MODE FOR CARRYING OUT THE INVENTION
The following description of preferred embodiments makes reference to the accompanying drawings, which form a part of it, and which show, by way of illustration, specific embodiments of the invention. It is to be understood by specialists working in this technological field that other embodiments can be used and structural as well as procedural changes can be made without departing from the scope of the present invention.
With reference now to Figures 1-5, the directed flow tester 10 according to the present invention comprises the immunoassay of test strip 12, which has an analytical porous membrane 14 mounted adjacent to and generally parallel with the limb of support 11. Adhesive layer 13 (Figure 2) anchors the analysis membrane to the support element 11. The analysis membrane has a first end and a second end.
Superparamagnetic particles (not shown) may be present in the sample preparation on the 20 side outside the device. These particles are configured to bond with the target analytes in the sample. The membrane has an intermediate capture region for the first and second ends of the analysis membrane. The capture region usually has control and detection regions 28, shown in Figure 1. The capture region is configured to capture the motion-labeled analytes from the first end of the analysis membrane to the second end of the analysis membrane. Additional regions can be present, if desired, for example, for calibration. See, for example, the calibration strips 25 (Figures 1 and 2) on the protective membrane 24. This could also be a point, such as point 27 in Figure 5. As shown in Figure 2, it can be either a line or a point.
One aspect of the present invention is that it has the door receiving sample 30 at one end of strip 12 for introducing the sample to be analyzed. In previous devices, the port receiving the sample is usually formed by the device box, if at all. In the present invention, the sample receiving door is generally located on the strip, and is made or constructed from layers of applied material.
The sample receiving door is formed by fluid sealing material 15 on the lower part, which is positioned on the support element. Preferably, the fluid sealing material 15 is hydrophilic. The layer 18 is positioned on the fluid sealing material and has channels 16 and the opening 19 formed therein. Channel 16 extends longitudinally along the fluid strip directly into the capture region of the device. Generally, the channel is constructed of sufficient size and configuration to allow sufficient fluid flow, without fluid leaking out from the sides or exhibiting clogging or agglomeration, as would otherwise be the case with more viscous samples, such as blood. Although Figure 1 shows channel 16, being slightly narrower than opening 19, it is contemplated here that channel 16 can be the same width, or even wider than opening 19. Alternatively, channel 16 may have a greater distal opening for the sample door than its proximal width for the sample receiving door. This variation could be particularly useful in the case where coagulation or aggregation of the sample is of concern.
Once built in layers, the sample receiving port is formed. The port provides fluid communication with the channel, and the channel provides fluid communication with the analysis membrane. The next hydrophilic material 20 is positioned on layer 18, the hydrophilic material that has an opening there corresponding to opening 19, but which covers channel 16. 0 gasket element 22 is positioned on the hydrophilic material 20 and has an opening there corresponding to opening 19 to allow fluid to enter the door. The gasket provides a fluid seal between the test and any surrounding enclosure.
In various embodiments described herein, the housing consists of a bottom portion which supports the housing 8 support member 11. As shown in Figure 3, it also preferably has side flaps 6 for the proper placement of a magnetic reading device. The bottom portion of box 8 is generally configured in the form of a C, the open side being designated by reference number 46. Figure 4 shows the bottom of the upper housing part 42. In general, it is complementary in the configuration for the lower body portion. Therefore, it is also a C-shaped configuration. The top box fits over the bottom box in such a way that the test strips 12 sweep the C-shaped opening 46, as shown in the mounting device in Figure 5 Thus, a magnetic reading device can access test strip 12 from the top and bottom surface at the same time. Figure 2 shows a side sectional view of the assembled test strip
12. The pad 26 is present at one end, as well as a protective membrane 24, which covers analytical membrane 14.
Since test strip 12 sweeps the opening 46 of the assembled housing portions, and since it is placed in the range of a magnetic reading device, it is a concern that the test strip is properly anchored within the housing, in order to avoid flexing or movement of the strip in relation to the box portions. It is also important that the relative positions of the control line, index line, and result lines are maintained. Therefore, embodiments of the present invention must grasp and tension aspects to control these effects.
Referring again to Figure 3, the bottom housing portion 8 is shown in perspective view. Although not shown in this view, test strip 12 is discarded on track 56. Preferably, the track width to accommodate the width of the strip, without connection or without unwanted lateral movement. Transverse channels 58 are present at the bottom of the rail 56. There are preferably two such transverse channels spaced at one end and a transverse channel at the other end of the rail. In addition, at one end of the rail there is an inclined transverse channel 59. These channels are configured to accommodate corresponding features on the underside of the housing part
<img file="BRPI0713636A2_D0020.tif" />
higher than 42 when assembled. Therefore, its assembly provides a tightening and tensioning aspect for the test strip.
As shown in Figure 4, the bottom side of the upper housing portion 42 has two pins 64, at one end, and one over the other end of the device. Also on one end of the tensioning device is 62. The tensioner 62 is shown with a downward sloping face and a wavy or ridged protruding edge. This edge contacts the test strip and provides an adequate degree of tension without causing the strip to deform or rupture. The configuration shown is an example and the tensioner can have other equally effective shapes.
Other features of the device are aimed at preventing the movement of the strip in relation to the magnetic field. For example, lower housing part 8 has 54 holes for receiving fixing pins in 65 upper housing portion 42. The relatively large diameter of the fixed pin hole and the jointed parts to prevent unwanted deformation or bending of the housing components, a assembled. It can also be seen in Figure 3, that the mounting holes 53 in the lower housing portion are configured to receive mounting pins 67
<img file="BRPI0713636A2_D0021.tif" />
<img file="BRPI0713636A2_D0022.tif" />
in the top box portion, preferably with a compression adjustment.
As mentioned above, figure 5 shows an embodiment of the fully assembled device. Test strip 12 is shown that measures aperture 46. Barcode area 47 on the label upper housing portion 42 provides information that the magnetic reader device uses in the assay, such as calibration and position information. It can also provide information about the nature of the particular assay, or sample to be tested.
It should be noted that, although the foregoing description generally relates to the quantitative detection of target analytes in a flow-directed immunoassay, the invention can also be used for receptor assays, cell assays or molecular assays.
Although numerous features and advantages of the present invention have been established in the previous description, together with details of the structure and function of the invention, the disclosure is for illustration only, and changes can be made in detail, especially in matters of shape, arrangement size, and of the parts, within the principles of the present invention to the fullest extent indicated by the broad general meaning of the terms in which the appended claims are expressed.
26 sheets
Sheet 1 Sheet 2 Sheet 3 Sheet 4 Sheet 5 Sheet 6 Sheet 7 Sheet 8 Sheet 9 Sheet 10 Sheet 11 Sheet 12 Sheet 13 Sheet 14 Sheet 15 Sheet 16 Sheet 17 Sheet 18 Sheet 19 Sheet 20 Sheet 21 Sheet 22 Sheet 23 Sheet 24 Sheet 25 Sheet 26
21 members in 11 offices
Priority claims9
| Document | Office | Kind | Date |
|---|---|---|---|
| 11452725 | United States of America | – | |
| 45272506 | United States of America | A | |
| 45272506 | United States of America | A | |
| 2007008204 | United States of America | W | |
| 2007008204 | United States of America | W | |
| 11452725 | – | – | – |
| 2007008204 | – | – | – |
| US20060452725 | – | – | – |
| WO2007US08204 | – | – | – |
Members21
| Document | Office | Kind | |
|---|---|---|---|
| US2007287198A1 | United States of America | A1 | |
| TW200745550A | Taiwan Province of China | A | |
| CA2651958A1 | Canada | A1 | |
| WO2007145697A2 | World Intellectual Property Organization (WIPO) | A2 | |
| WO2007145697A3 | World Intellectual Property Organization (WIPO) | A3 | |
| EP2027466A2 | European Patent Office (EPO) | A2 | |
| KR20090029197A | Republic of Korea | A | |
| US7547557B2 | United States of America | B2 | |
| CN101467042A | China | A | |
| IL195077A0 | Israel | A0 | |
| JP2009540330A | Japan | A | |
| HK1132039A | Hong Kong, China | A | |
| HK1132039A1 | Hong Kong, China | A1 | |
| EP2027466A4 | European Patent Office (EPO) | A4 | |
| TWI335430B | Taiwan Province of China | B | |
| CA2651958C | Canada | C | |
| KR101096924B1 | Republic of Korea | B1 | |
| JP4918591B2 | Japan | B2 | |
| EP2027466B1 | European Patent Office (EPO) | B1 | |
| CN101467042B | China | B | |
| BRPI0713636A2This record | Brazil | A2 |
11 legal events, as the office reported them to INPADOC
Over the term
Point at a mark for the eventEvents
| Event | Code | |
|---|---|---|
| Patent application refused [chapter 9.2 patent gazette]B09B | B09B | |
| Patent application refused [chapter 9.2 patent gazette]MANTIDO O INDEFERIMENTO UMA VEZ QUE NAO FOI APRESENTADO RECURSO DENTRO DO PRAZO LEGALB09B | B09B | |
| Patent application refused [chapter 9.2 patent gazette]B09B | B09B | |
| Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]B07A | B07A | |
| Requested change of headquarter approvedB25G | B25G | |
| Grant request does not fulfill article 229-c lpi (prior consent of anvisa) [chapter 7.7 patent gazette]B07G | B07G | |
| Requested change of name of applicant approvedB25D | B25D | |
| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]B07D | B07D | |
| Request for examination: application reinstated [chapter 4.3 patent gazette]B04C | B04C | |
| Dismissal acc. art.33 of ipl - examination not requested within 36 months of filingB11A | B11A | |
| Technical and formal requirements: other requirements [chapter 6.7 patent gazette]APRESENTE NO PRAZO DE 60 (SESSENTA) DIAS A TRADUCAO COMPLETA DO PEDIDO CONFORME DETERMINA O ART. 7O DA RESOLUCAO 291/2012.B06G | B06G |
Numbers
- Publication
- PI0713636
- Publication, DOCDB
- PI0713636
- Publication, EPODOC
- BRPI0713636
- Application
- 13636
- Application, DOCDB
- PI0713636
- Application, EPODOC
- BR2007PI13636
Titles2
- Portuguese
- DISPOSITIVO DE ENSAIO DE FLUXO DIRECIONADO
- English
- DIRECTED FLOW TEST DEVICE
Classification
- CPC, 13
- G01N33/54388
- G01N30/26
- B01L3/5023
- B01L9/52
- B01L2200/026
- B01L2300/0825
- G01N33/54326
- Y10S435/81
- Y10S436/807
- Y10S436/808
- Y10S435/805
- Y10S436/81
- G01N33/53
- IPC, 1
- G01N33 53
