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Researchers Submit Patent Application, "Device to Detect Analytes in a Biological Sample", for Approval

May 28, 2014



By a News Reporter-Staff News Editor at Electronics Newsweekly -- From Washington, D.C., VerticalNews journalists report that a patent application by the inventor MELPIGNANO, Patrizia (Moruzzo, IT), filed on January 13, 2014, was made available online on May 15, 2014.

The patent's assignee is Or-el Organska Elektronika D.o.o.

News editors obtained the following quote from the background information supplied by the inventors: "Miniaturized devices to detect analytes in biological samples are known, comprising a light source and a system containing the sample.

"For example, the international patent application WO-A-2005/103652 describes a miniaturized device that comprises a light source consisting of an OLED (Organic Light Emitting Diode) system, diffraction filters to direct the light emitted by the light source toward the sample to be analyzed, and other diffraction layers suitable to direct the light emitted by the sample to the detection system. The device described in the application WO-A-2005/103652 provides that the wavelengths of the light emitted by the light source are selected so as to transmit to the sample only the wavelengths concerned in stressing the sample, where said selection is made through the creation of vertical cavities inside the OLED layer.

"Another state-of-the art device is described in the international patent application WO-A-2007/097572 which provides not only a light source consisting of a LED (Light Emitting Diode) system but also a layer of material intended to form a stable link with the sample to be analyzed directly applied on the light source. The layer essentially consists of a surface functionalized by means of suitable linker molecules able to fix the analyte molecules stably. The wavelengths of the light emitted by the light source are controlled using a system known as quantum dot.

"Another miniaturized device for detecting an analyte in a biological sample is described in the international patent application WO-A-03/060461, which describes in general terms a device comprising a light source, a first system of filters for transmitting the light to the sample and a detector system able to detect the light emitted by the sample, where the light emitted by the sample is directed to the detector system through a second system of filters.

"Moreover, the international patent application WO-A-2007/054710 describes a device comprising an OLED source for the emission of light necessary to excite the sample contained in a microfluid system and a detector system located in direct contact with the microfluid system. The device described therein provides that the micro-channels that make up the microfluid system consist of polydimethylsiloxane doped with suitable coloring agents, the function of which is to absorb the wavelengths of light emitted by the OLED source which could interfere with the analysis of the sample and are therefore able to transmit to the sample only the light wavelengths useful to carry out the analysis.

"The US patent application US-A-2003/035755 describes a device that has an OLED-type light source on which a microfluid device is positioned, able to contain the sample to be analyzed, and also comprises, in succession, a layer of lenses to focus the light emitted by the sample, a layer defined as pinhole layer and another filter followed by the detector system. The layer of lenses, the pinhole layer and the other filter are components suitable to focus and filter the light emitted by the sample to be analyzed so as to eliminate the wavelengths that could interfere with the analysis.

"The international patent application WO-A-2007/107947 describes a micro-electronic device to detect an analyte in a sample, characterized by the presence of heating electrodes and field electrodes. The function of the latter is to induce the movement/flow of the sample inside the device. The heating electrodes are intended to heat the sample and can be coupled with Peltier cells in order to effect thermal cycles of heating and cooling so as to conduct the relative analysis.

"The US patent application US 2002/095073, which defines the closest state of the art to the present invention, describes a wide range of bio-chips in which the biological probes are disposed on a transparent substrate, such as glass or plastic, and in which the latter can possibly be inserted in a microfluid circuit for the circulation of the biological fluid examined.

"This document describes the possible use of an OLED or LED source under the micro-array of probes deposited on the same slide. The document has problems concerning the sensitivity of detection inasmuch as, since the intensity of an OLED or LED source can be from 100,000 to 1,000 times higher than the intensity emitted by a possible marker, such as for example a fluorophore, this makes it impossible to detect the latter without the appropriate use of particular optical devices, which are not described in US'073.

"Although miniaturized devices to detect an analyte in a biological sample have already been described and marketed, there is a continuing need to develop devices that allow to conduct analyses that are increasingly sensitive and specific by operators who are not specialized, that is, not belonging to analysis laboratories, but by medics at the so-called 'points of care', where the analysis must be carried out in real time, in the presence of the patient.

"Purpose of the present invention is to provide an improved device that allows to conduct analyses of this type with optimized reaction conditions in order to increase the sensitivity and specificity of the analysis, and also to reduce the times needed to carry out the analysis. In particular, the purpose of the present invention is to perfect a miniaturized device that allows a simultaneous analysis relating to the presence of several pathogens in the biological sample analyzed.

"The Applicant has devised, tested and embodied the present invention to overcome the shortcomings of the state of the art and to obtain these and other purposes and advantages."

As a supplement to the background information on this patent application, VerticalNews correspondents also obtained the inventor's summary information for this patent application: "The present invention is set forth and characterized in the independent claim, while the dependent claims describe other characteristics of the invention or variants to the main inventive idea.

"In accordance with the above purpose, a device to detect at least an analyte in a biological sample according to the present invention comprises a transparent substrate, made of glass or plastic material or similar, having a first surface or surface which is lower during use, to which a light source is applied, preferably but not exclusively consisting of an OLED system

"The transparent substrate comprises a second surface, or surface which is upper during use, able to support a plurality of biological protein probes, disposed in a desired geometry, to form for example a matrix or array connected to the second surface of the substrate by means of a polymer. The polymer guarantees that the probes adhere on the upper surface of the substrate thanks to the activation of a covalent link with the proteins that make up the protein probes. The polymer can be distributed on the surface either by means of immersion or dipping, or by means of another depositing procedure, which is irrelevant for the purposes of the invention. The plurality of probes will then be contained inside a microfluid system made of transparent plastic material, for example PMMA polymethyl methacrylate, and obtained for example by injection molding.

"The microfluid system is attached to the transparent substrate, which has the light source on its lower side, in a known manner, for example by means of a system with clips, and the hydraulic seal is achieved by means of an O-ring.

"The analyte to be detected may preferably consist of protein molecules, for example antigens or antibodies, or molecules of nucleic acids, for example genes or parts of genes.

"A marker element is linked to the analyte to be detected and consists, in the preferential solution of the invention, of a fluorophore, having determinate characteristics of fluorescence or phosphorescence emission, suitably coordinated to the wavelength of the incident light radiation.

"In a preferred solution of the invention, in order to maximize the detection sensitivity of the signal emitted by the fluorophore, a filter or advantageously two filters are used.

"The first filter, made on the glass or plastic support, can be used directly as a growth substrate of the OLED device, or positioned directly on the face the radiation exits from.

"In a preferred solution of the invention, the filter has a transmittance lower than 2.0*10-6 outside the wavelength, for example comprised between 400 and 550 nm, corresponding to the emission peak of the fluorophore, and a transmittance>0.6 to the peak wavelength of the source emission spectrum.

"The sample to be analyzed will be deposited directly on the face the radiation exits from, possibly contained in a microfluid system.

"In a preferred solution of the invention, the second filter, of the band-pass type, has a transmittance>0.8 in correspondence with the emission peak of the fluorophore with FWHM comprised between 20 and 40 nm and a transmittance>0.01 outside this range.

"In this way, by focusing the light source emission spectrum, thanks to the filtering system, in correspondence with the absorption peak of the marker, and by cutting sharply the emissions at frequencies above that corresponding to the absorption peak, the device according to the invention allows to maximize the detection sensitivity in that the emission of the markers (fluorophores) is optimized and is not invalidated by the relatively high light intensity emitted by the OLED source.

BRIEF DESCRIPTION OF THE DRAWINGS

"These and other characteristics of the present invention will become apparent from the following description of a preferential form of embodiment, given as a non-restrictive example with reference to the attached drawings wherein:

"FIG. 1 is a schematic vertical section of a device to detect analytes in a biological sample according to the present invention;

"FIG. 2 is a first temporal diagram of the electric feed of the device in FIG. 1;

"FIG. 3 is a second temporal diagram of the electric feed of the device in FIG. 1;

"FIG. 4 shows the absorption and emission spectrums of the marker (fluorophore) used in the device according to the present invention and associated with the OLED source;

"FIG. 5 shows the transmission spectrum of the filtering system associated with the OLED sources in order to excite the marker (fluorophore).

"To facilitate comprehension, the same reference numbers have been used, where possible, to identify common elements in the drawings that are substantially identical. It is understood that elements and characteristics of one form of embodiment can conveniently be incorporated into other forms of embodiment without further clarifications."

For additional information on this patent application, see: MELPIGNANO, Patrizia. Device to Detect Analytes in a Biological Sample. Filed January 13, 2014 and posted May 15, 2014. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=1931&p=39&f=G&l=50&d=PG01&S1=20140508.PD.&OS=PD/20140508&RS=PD/20140508

Keywords for this news article include: Electronics, Light-emitting Diode, Or-el Organska Elektronika D.o.o.

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Source: Electronics Newsweekly


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