The present invention relates to a device to detect and measure biological targets in a biological sample. The device can determine one or more values for one or more measurable characteristics of a sample.
The Comprehensive Metabolic Panel (CMP) is a broad screening tool for various medical problems (e.g. diabetes, liver disease, kidney disease, etc.) or verification tool for a subject's health. Current methods of performing CMP screening involves a series of blood tests, laboratory tests, screenings, protein monitoring, electrolyte detection, and other tests to individually check liver function, glucose levels, calcium concentrations, and other such subject profiling. CMP tests and other tests to measure the presence of a biological substance (e.g. urea, glucose, sodium, electrolytes, etc.) are time consuming, burdensome, costly, labor intensive, inefficient and lacking specificity, and often dependent on patient compliance, and are often conducted in a laboratory at a location separate from the location where the subject resides. Additionally, the accuracy of current tests are questionable. For instance, measuring glucose levels with a glucometer can result in a ±20% error range, which is a real concern for many health care practitioners. Such errors are due in part to the change in hemocrit values resulting from the pathological condition of a patient. These patient tests play an important role in the detection and diagnosis of health ailments, but there is a need to overcome the issues with current diagnostic tests.
The following presents a simplified summary of the disclosure in order to provide a basic understanding of some aspects of the disclosure. This summary is not an extensive overview of the disclosure. It is intended to neither identify key or critical elements of the disclosure nor delineate any scope particular embodiments of the disclosure, or any scope of the claims. Its sole purpose is to present some concepts of the disclosure in a simplified form as a prelude to the more detailed description that is presented later
In accordance with one or more embodiments and corresponding disclosure, various non-limiting aspects are described in connection with a nanotechnology-enabled point of care device. In accordance with a non-limiting embodiment, in an aspect, a device is provided in connection with a cartridge component that stores nanomaterial labels paired to biological materials in N wells, whereby each well stores one or more nanomaterial labels paired to one or more biological materials; wherein N is an integer; a dispenser component that dispenses a biological sample into each respective well; an excitation component that emits energy from an excitation source to excite the nanomaterial label in the absence of the biological sample and excites the nanomaterial label in the presence of the biological sample; a detection component that detects a relative change in energy emitted from the nanomaterial label paired to the biological material in the absence of the biological sample as compared to the energy emitted from the nonmaterial label paired to a biological material in the presence of a biological target present in the biological sample; an analysis component that analyzes data related to the change in energy emitted from the nanomaterial label paired to the biological material as compared to a standard curve for the energy emitted from the nanomaterial label paired to a the biological material in the presence of various concentration levels of the biological target; a generation component that generates a medical diagnostic report based in part on the analyzed data; and a display component that displays the medical diagnostic report to a device user.
The disclosure further discloses a method, comprising using a processor to execute computer executable instructions stored in a memory to perform the following acts: storing nanomaterial labels paired to biological materials in N wells, whereby each well stores one or more nanomaterial labels paired to one or more biological materials; wherein N is an integer; dispensing a biological sample into each respective well; emitting energy from an excitation source to excite the nanomaterial label in the absence of the biological sample and excites the nanomaterial label in the presence of the biological sample; detecting a relative change in energy emitted from the nanomaterial label paired to the biological material in the absence of the biological sample as compared to the energy emitted from the nanomaterial label paired to a biological material in the presence of a biological target present in the biological sample; analyzing data related to the change in energy emitted from the nanomaterial label paired to the biological material as compared to a standard curve for the energy emitted from the nanomaterial label paired to a the biological material in the presence of various concentration levels of the biological target; generating a medical diagnostic report based in part on the analyzed data; displaying the medical diagnostic report to a device user.
The following description and the annexed drawings set forth certain illustrative aspects of the disclosure. These aspects are indicative, however, of but a few of the various ways in which the principles of the disclosure may be employed. Other advantages and novel features of the disclosure will become apparent from the following detailed description of the disclosure when considered in conjunction with the drawings.
The innovation is now described with reference to the drawings, wherein like reference numerals are used to refer to like elements throughout. In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of this innovation. It may be evident, however, that the innovation can be practiced without these specific details. In other instances, well-known structures and components are shown in block diagram form in order to facilitate describing the innovation.
By way of introduction, the subject matter disclosed in this disclosure relates to a point of care device to detect and measure biological targets in a biological sample. The point of care device offers the ability to measure a variety of medical screening tests including, but not limited to, a comprehensive metabolic panel of a subject simultaneously at a patient's bedside. The bedside analysis of this clinical information eliminates the need for time consuming and labor intensive laboratory tests while allowing a physician to have sometimes critical medical information about a patient immediately.
The device utilizes the advanced technologies of quantum dots to measure numerous biological targets and concentrations of such targets in a biological sample, such as blood simultaneously. Previously, multiple blood tests and screening tests (e.g. BMP/electrolytes, arterial blood gas, alveolar gas, calcium, magnesium, potassium, renal tests, urinalysis, protein, liver function tests, etc.) would have to be performed separately to determine the concentration of lipids, electrolytes, and other such biological substances in a subject. Quantum dots are luminescent semiconductor nanoparticles which emit light when activated by an energy source such as UV light. A great advantage of quantum dots are its use in multiplexing applications whereby each quantum emission wavelength can be detected by a reader, such as a UV spectrophotometer, as a unique spectral signature.
In an embodiment, multi-leg luminescent nanoparticles are useful for multiplexing applications in that by adjusting the leg width, leg length, number of legs, or base size; several unique multi-leg luminescent nanoparticles can be synthesized, each comprising a unique spectral signature. By utilizing multiplexing features, the device can associate a unique spectral signature with the presence of a unique biological target in order to detect several biological targets in a single given biological sample simultaneously and in a nominal amount of time (e.g. minutes rather than hours or days).
Referring now to the drawings, with reference initially to
In an embodiment, point of care device 100 employs a cartridge component 110, a dispenser component 120, an excitation component 130, a detection component 140, an analysis component 150, a generation component 160, and a display component 170. Cartridge component 110 stores nanomaterial labels paired to biological materials in N wells, whereby each well stores one or more nanomaterial labels paired to one or more biological materials; wherein N is an integer. Dispenser component 120 dispenses a biological sample into each respective well. Excitation component 130 emits energy from an excitation source to excite the nanomaterial label in the absence of the biological sample and excites the nanomaterial label in the presence of the biological sample.
Detection component 140 detects a relative change in energy emitted from the nanomaterial label paired to the biological material in the absence of the biological sample as compared to the energy emitted from the nanomaterial label paired to a biological material in the presence of a biological target present in the biological sample. Analysis component 150 analyzes data related to the change in energy emitted from the nanomaterial label paired to the biological material as compared to a standard curve for the energy emitted from the nanomaterial label paired to a the biological material in the presence of various concentration levels of the biological target. Generation component 160 generates a medical diagnostic report based in part on the analyzed data. Display component 170 displays the medical diagnostic report to a device user.
In an aspect, cartridge component 110 stores nanomaterial labels paired to biological materials in N wells, whereby each well stores one or more nanomaterial labels paired to one or more biological materials; wherein N is an integer. A nanomaterial label is a luminescent nanoparticle ranging in size from 0.001 nm to 999.99 nm capable of pairing to a biological material and a biological target. Furthermore, a nanomaterial label comprises the ability to exhibit a change in absorption of energy (e.g. electromagnetic radiation, ultraviolet light, particle beam, and other such energy sources) and able to emit a unique spectral signature represented as a narrow emission wavelength band. Additionally, the nanomaterial label is a luminescent nanoparticle capable of excitement from an energy source (e.g. electromagnetic radiation, ultraviolet light, particle beam, etc.).
The nanomaterial label can be a quantum dot such as a spherical quantum dot, tetrapod quantum dot, quantum dot heterostructure, multi-leg luminescent nanomaterial, multi-branched luminescent nanomaterial, snowflake-shaped quantum dot, teardrop-shaped quantum dot, disk-shaped quantum dot, cube-shaped quantum dot, or star-shaped quantum dot. In an aspect, the nanomaterial label can be a multi-leg luminescent nanoparticle (“MLN”). An MLN comprises a base and one or more legs protruding from the base.
In an aspect, a base describes the component of the MLN from which one or more legs extend. In an aspect, a one or more leg describes one or more protrusions from the base of the MLN. Each MLN has ‘x’ legs extending from a base material whereby “n” in an integer. In an aspect, the addition of each new leg, allows the MLN to be detected by a reader (e.g. UV spectrophotometer, flow cytometer, etc.) as a new spectral signature that is different and identifiable from any MLN that lacks the same number of legs. For instance, and MLN whereby x=3 comprises three legs extending from the base, however an MLN whereby x=5 comprises five legs extending from the base. The MLN whereby x=3 has a unique spectral signature than the MLN whereby n=5. Furthermore, the unique spectral signature allows for each respective MLN to be identified individually by detection due to the differentiability of the spectral signature from other spectral signatures.
In an aspect, each leg comprises a leg length and a leg width, each of which can be respectively adjusted for each MLN. A leg length describes the distance from the centroid of the MLN to the tip end point of a leg whereby the leg length is a length greater than or equal to 0.001 nm and less than or equal to 999.999 nm. Each MLN leg has a leg width which is the distance from the centroid of the MLN to the side point of a leg whereby the leg width is a length greater than or equal to 0.001 nm and less than or equal to 999.999 nm. Each leg length and each leg width can be adjusted to a distance greater than or equal to 0.001 nm and less than or equal to 999.99 nm and each leg on a particular MLN can be of different leg length or leg width whereby each unique leg width and each unique leg length respectively present a unique spectral signature on a reader.
Furthermore, in an aspect, an MLN has a base length which is the distance from the centroid of the MLN to the base edge wherein the distance from the centroid to the base edge can be greater than or equal to 0.001 and less than or equal to 999.999 nm in distance and can be adjusted for each unique MLN. Additionally, in an aspect, an MLN comprises a base edge which is the point where each leg junctures with the base. Each leg can extend from a different base edge point thereby allowing for multiple base edges regions for each MLN.
In another aspect, each MLN may comprise legs of different leg lengths, legs of the same length or a mixture of legs of the same length, legs of different leg length, legs of the same leg width's, legs of different leg width's, MLN's of different base lengths, or MLN's of different base edge's. Each combination of leg length, leg width, base length or number of legs characterizing a respective MLN allows for the synthesis of numerous MLN's, each with a different spectral signature output thereby resulting in an detection of several uniquely identifiable MLN's. This simultaneous identification of several unique MLN's allows for multiplexing in the point of care device whereby multiple biological targets can be labeled by unique MLN's (e.g. an MLN with a unique spectral signature) and detected. Furthermore, several MLN features (number of legs, leg length, leg width, base length, etc.) can be adjusted to allow for hundreds (and in some cases thousands) of unique MLN to respectively identify hundreds of unique biological targets simultaneously.
The quantum dot, such as an MLN, can be water-soluble (e.g. synthesized to be hydrophilic), have one or more pairing moieties on the external surface to provide surface chemistries, and surface physiochemical properties enabling the quantum dot to pair to biological materials or biological targets. A pairing moiety can be any one or more of a thiol, F127COOH, alkyl group, propyl group, N-(3-aminopropyl)-3-mercapto-benzamide, 3-aminopropyl-trimethoxysilane, 3-mercaptopropyltrimethoxysilane, 3-maleimidopropyl-trimethoxysilane, or 3-hydrazidopropyl-trimethoxysilane, diacetylenes, acrylates, acrylamides, vinyl, and styryl. In an aspect, the pairing moiety is any one of a thiol moiety, F127COOH, alkyl group, propyl group, N-(3-aminopropyl)-3-mercapto-benzamide, 3-aminopropyl-trimethoxysilane, 3-mercaptopropyltrimethoxysilane, 3-maleimidopropyl-trimethoxysilane, or 3-hydrazidopropyl-trimethoxysilane, diacetylenes, acrylates, acrylamides, vinyl, styryl, or other such functional group. In another aspect, pairing moieties can be chemical groups, or any combination of chemical groups, including, but not limited to, amino groups, carboxyl groups, azide groups, alkyne groups, hydrazine groups, aldehyde groups, aminooxy groups, ketone groups, maleimide groups, thiol groups, or other such chemical groups. Furthermore, pairing moieties can be diacetylenes, acrylamides, vinyl, styryl, silicon oxide, boron oxide, phosphorous oxide, silicates, borates and phosphates.
A biological material is at least one of a: antibody, nucleic acid, polysaccharide, protein, drug, monoclonal antibody, antigen, polyclonal antibody, and other such biological material. Furthermore, a biological target at least one of a cell, protein, polysaccharide, drug, monoclonal antibody, polyclonal antibody antigen receptor, biological marker, peptide, protein. In an instance, the cartridge component 110 stores nanomaterial labels paired to biological materials in N wells, wherein N is an integer. The cartridge component 110 can be any solid support comprising rows of holes bored into the solid support to a specific depth, so as not to breach one side of the solid support. Each hole is known as a well and as such each well stores a nanomaterial label paired to biological materials. For instance, if N=100, there are 100 wells in the solid support is stored nanomaterial labels paired to biological materials.
The wells can be arranged in any order, such as ten rows of wells with ten wells in each row or even five rows of wells with twenty wells in each row. The wells can be organized in a symmetrical fashion or in no random order. An example of a cartridge component 110 is a microwell array, which can comprise over one million wells in some instances. Each well can act as an individual test environment whereby numerous simultaneous reactions can take place simultaneously.
In an embodiment, the floor of each well hole can hold mobile or immobilized biological materials (e.g. antibody, small molecule, liposome, protein, aptamer, toxin, peptide, growth factor, etc.). The biological materials can then be paired to a nanomaterial label (e.g. tetrapod quantum dot) by bio-conjugation, functionalization or bonding (e.g. coating the quantum dot with hydrophobic ligands which are linked to carboxylic acid) or bond (e.g. covalent, ionic, or hydrogen bonding, Van der Waals' forces, magnetics, or mechanical bonding) which are all well known in the art. For instance, in order to detect glucose in a subject's blood sample a well floor can hold immobilized glucose oxidase (“GOD”) (in an instance the GOD can be freely mobile too) whereby the GOD is paired to a CdSe tetrapod quantum dot. In another instance, a second well can hold a tetrapod quantum dot encapsulated with a sodium selective polymer matrix (e.g. sodium ionophore X conjugated with chromoinophore), which can change color based on the exchange of sodium ions (e.g. from sodium present in the biological sample, such as blood) that contact the sodium selective polymer matrix tetrapod quantum dot. Each well can store a different biological material paired to a unique nanomaterial label to perform a different test (e.g. glucose detection, sodium detection, etc.) whereby even all tests in a comprehensive metabolic panel can be performed simultaneously.
A comprehensive metabolic panel is a group of chemical tests performed on a subject, often using the subject's blood. In an aspect, the point of care device 100 can test for levels of albumin, alkaline phosphates (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), calcium, chloride, bicarbonate, magnesium, carbon dioxide (CO2), creatinine, glucose, potassium, sodium, total bilirubin, total protein, amylase, bilirubin, calcium, cholesterol, HDL cholesterol, LDL cholesterol, Cortisol, creatine kinase, creatanine kinase, estriol, ferritin, follicle-stimulating hormone, pH gas, PCo2 gas, Po2 gas, growth hormone-arginine stimulation, immunoglobulins, IgA, IgE, IgG, IgM, Iron, Lactate dehydrogenase, Luteinizing hormone, osmolality, parathyroid hormone, phosphatase (alkaline), Prolactin (hPRL), albumin, globulin, thyroid-stimulating hormone, thyroidal iodine uptake, thyroxine, triglycerides, triiodothyronine, triiodothyronine resin uptake, urea nitrogen, ureic acid.
Furthermore, in an aspect, the point of care device 100 also can test for hematologic indicators including but not limited to Bleeding time, CD4+ T-lymphocyte count, erythrocyte, erythrocyte sedimentation rate (Westergreen), Hematocrit, Hemoglobin A1C, Hemoglobin-blood, Hemoglobin-plasma, Leukocyte count and differential, leukocyte count, neutrophils-segmented, neutrophils-banded, eosinophils, basophils, lymphocytes, monocytes, mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), partial thromboplastin time, platelet count, prothrombin time, reticulocyte count, thrombin time, volume, plasma, red cell.
Additionally, in an aspect, the point of care device 100 can also test for cerebrospinal indicators including but not limited to cell count, chloride, gamma globulin, glucose, pressure, proteins. This device may also test for cerebrospinal indicators including but not limited to chloride, urine, calcium, chloride, creatinine clearance, estriol total, 17-hydroxycorticosteroids, 17-Ketosteroids total, osmolality, oxalate, potassium, proteins total, sodium, uric acid, body mass index (BMI). This device may also test for sexually transmitted diseases including but not limited to chlamydia, gonorrhea, herpes I, herpes II, hepatitis A, hepatitis B, hepatitis C, syphilis, HIV-1, HIV-II, human papilloma virus. In an aspect, the point of care device 100 can also test for other bacterial and viral infectious diseases including, but not limited to, influenza, Ebola, hantavirus, or staph aureus.
Additionally, in an aspect, the point of care device 100 can also test for cerebrospinal indicators including but not limited to anthrax, plague, small pox, malaria, influenza. This device may detect urinary tract infections including but not limited to Escherichia coli, straphylococcus saprophyticus, klebsiella, enterococci, ureaplasma urealyticum, mycoplasma hominis, proteus mirabilis. This device may also test for pyelonephritis, klebsiella, P. mirabilis, citrobacter, candida albicans, pseudomonas, aeruginosa, enterobacter, serratia, gram-positive organisms and S. saprophyticus.
In an aspect, a dispenser component 120 dispenses a biological sample into each respective well. The dispenser component 120 is a containment object, which stores a biological sample of a subject. The dispenser component 120 interlocks with the cartridge component 110 whereby the dispenser component can equally dispense and distribute the stored biological sample into each respective well of the cartridge component 110. In an aspect, the dispenser component 120 has one or more valves capable of opening and closing to dispense the biological sample into the wells. Each valve can be controlled individually or in unity to open or close. For instance, the valve associated with well 1 can be opened to distribute a sample of blood into the well whereas the valve associated with well 2 can remain closed so as not to dispense any blood into well 2. Furthermore, in an aspect, dispenser component 120 can comprise an injection opening whereby a biological sample can be injected into the containment chamber of the dispenser component 120 wherein the biological samples is stored until dispensed.
In an aspect, excitation component 130 emits energy from an excitation source to excite the nanomaterial label in the absence of the biological sample and excites the nanomaterial label in the presence of the biological sample. An excitation source is an energy source from which releases energy directed at the nanomaterial label for absorption. The nanomaterial label can be excited over a broad bandwidth, yet emits energy in a narrow band, which is uniquely identifiable by a detection component 140. The excitation component 130 can comprise an excitation source that emits electromagnetic radiation over a range of wavelengths such as x-ray, ultraviolet, visible, infrared, and any waves within that spectrum range. In another embodiment, excitation component 130 can comprise an excitation source that is a particle beam, such as an electron beam.
Nanomaterial labels are capable of excitation from an excitation source that emits electromagnetic radiation of a broad bandwidth allowing for simultaneous excitation of all nanomaterial labels in all the cartridge component 110 wells thereby enabling a single excitation source to excite several unique nanomaterial labels at the same time. Although, the excitation source emits at the same broad bandwidth, each unique nanomaterial label in each respective well will emit electromagnetic radiation at different frequencies, thus the detection component 140 is capable of detecting several different nanomaterial labels associated with the presence of several biological targets.
For instance, if well 1 stores glucose oxidase and a multi-leg luminescent nanomaterial comprising two legs paired to GOD and well 2 stores a multi-leg luminescent nanomaterial comprising three legs encapsulated by a sodium selective polymer matrix, both well 1 and well 2 will be exposed to the same electromagnetic radiation frequency but well 1 can emit radiation at a different frequency as the frequency of radiation emitted from well 2. Furthermore, detection component 140 can detect the change in the emission intensity exhibited from the two leg multi-leg luminescent nanomaterial in well 1 and the change in emission intensity from the three-leg multi-leg luminescent nanomaterial in well 2 in order to detect glucose in well 1 and sodium in well 2 from the same biological sample. In another aspect, the excitation component 130 emits energy from an excitation source to excite the nanomaterial label in the absence of the biological sample, that is, prior to the introduction of biological sample such as blood to the wells.
The emission wavelength of the nanomaterial label detected by the detection component 140 in the absence of the biological sample serves as a first emission metric detection component captures. The emission wavelength of the nanomaterial label detected by the detection component 140 in the presence of the biological sample and thus the presence of a biological target serves as a second emission metric detection component captures. The change in emission of radiation from the nanomaterial label between the first emission metric and the second emission metric is detected by the detection component 140 and further analysis component 150 analyzes the difference in metrics to determine the presence of a biological target (e.g. glucose, sodium) and the levels of concentrations of the biological targets present in the biological sample (e.g. blood, serum, urine, saliva, etc.). In an aspect, excitation component 140 can excite numerous (e.g. hundreds) nanomaterial labels simultaneously in order for detection component to detect numerous (e.g. hundreds) of biological targets simultaneously.
In an aspect, a detection component 140 detects a relative change in energy emitted from the nanomaterial label paired to the biological material in the absence of the biological sample as compared to the energy emitted from the nanomaterial label paired to a biological material in the presence of a biological target present in the biological sample. The detection component 140 is a tool that can capture electromagnetic emissions. In an aspect, detection component 140 can detect electromagnetic radiation or light (e.g visible, infrared, ultraviolet, x-ray, gamma ray, etc.) by utilizing the photoelectric effect, whereby light is absorbed in discrete packets called photons. Furthermore, light can be absorbed or emitted only as particles with discrete chunks of energy called quanta or quantum in the plural. When light is absorbed by the nanomaterial label, for instance a quantum dot, it interacts with the quantum dots electrons causing the electrons to transition between energy states. The light is absorbed in photons packets, whereby the photons (emitted from excitation source 130) “excite” the quantum dots electrons to higher energies. The energy of each photon is determined by its wavelength (but not its intensity).
When the quantum dots absorb the photons, the quantum dots electron increases in energy by the energy of the photon and when the quantum dot emits light, the electron's energy decreases by the photon's energy. The wavelength of the photon emitted from the quantum dot in the absence of a biological target (present in a biological substance) is different from the wavelength of the photon emitted by the quantum dot in the presence of a biological target. Moreover, this change in wavelength emitted in the absence of a biological target and in the presence of a biological target is detected by the detection component 140. Furthermore, the wavelength emitted by the quantum dot in the presence of a biological target will differ based on the level or concentration of biological target present in the biological sample. For instance, if there is more glucose present in a subject's blood, the wavelength emitted by a quantum dot in the presence of more glucose is different than the wavelength emitted by the quantum dot in the presence of less glucose, which is a detectable change detection component 140 can capture.
The detection component 140 can be any of a variety of detectors that quantify the change in wavelength emissions of quantum dots, such as a spectrometer for instance. In an embodiment, the detection component 140 can measure the absorption (or the emission) of light by a quantum dot. In another embodiment the detection component 140 can measure the time-varying intensity of light, which compares the intensity of light emitted or absorbed in some cases (y-axis) vs. wavelength (x-axis) to determine the fraction of light emitted (or absorbed in the case of absorption measurement) or what is commonly referred to as an emission (absorption in some cases) spectra.
Furthermore, the dilution of the biological sample can effect the quanta of light absorbed by the quantum dots in the presence of a respective dilution. For instance, if excitation component emits an initial intensity of light at the quantum dot in the presence of a dilute sample of blood, the amount of light absorbed by the quantum dot depends on the number of molecules of a particular biological target in the blood. For a very dilute solution (e.g. low amounts of glucose), the amount of light absorbed by the quantum dot is proportional to the concentration of glucose in the blood, the length of the light's path in the blood (whereby the concentration and length of light's path define how many molecules, of glucose for example, the light encounters) and a constant of proportionality known as an extinction coefficient which describes the quantum physics of the nanomaterial labels (e.g quantum dots in this example). Thus detection component 140 can capture data related to the biological sample that can determine the concentration of a biological target in a sample. However, analysis component 150 can analyze and make sense of the data captured by detection component 140.
In an aspect, analysis component 150 analyzes data related to the change in energy emitted from the nanomaterial label paired to the biological material as compared to a standard curve for the energy emitted from the nanomaterial label paired to a the biological material in the presence of various concentration levels of the biological target. In an aspect, analysis component 150 can analyze the data associated with the change in emission from nanomaterial labels captured by detection component 150 in order to determine the presence of a biological target and the concentration of respective biological targets in a biological sample. In an aspect, analysis component 150 can make use of a standard curve to determine the presence and concentration of biological targets in a biological sample.
A standard curve is a plot of multiple samples with known measured properties, which can be compared, to unknown samples to determine measured properties of the unknown sample. The samples with known properties are the standards (and the graph is the standard curve) by which the properties of an unknown sample are compared to by analysis component 150. For instance, analysis component 150 can compare a standard curve showing the absorbance of different concentrations of protein (e.g. milligrams of protein on the x-axis versus emission (or absorbance) wavelength of a quantum dot (which can also be noted as the absorbance wavelength by the detection component 140) in the presence of respective milligrams of protein on the y-axis) to emission wavelength data from a quantum dot (with the same properties as that quantum dot used to create the standard curve) in the presence of the respective protein in a subjects unknown sample, such as blood.
Analysis component 150 can determine the concentration of protein in the subjects blood by comparing the absorbance data (or emission data in some cases, so long as the comparison is always consistent, that is comparing standard absorption data to unknown absorption data; or standard emission data to unknown emission data) for the quantum dot in the presence of the subjects blood to absorption data for a quantum dot in a standard protein concentration. Thus, analysis component 150 analyzes data related to the change in energy emitted from the nanomaterial label paired to the biological material as compared to a standard curve for the energy emitted from the nanomaterial label paired to a the biological material in the presence of various concentration levels of the biological target. In an embodiment, the analysis component 120 can employ software to compute the concentration of one or more biological targets in a biological sample.
In an aspect, generation component 160 generates a medical diagnostic report based in part on the analyzed data. In an aspect, generation component can interpret the data analyzed by analysis component 150 and interpret such information into medically relevant information, such as the actual amount of concentration of a biological target in a subjects biological sample and output the concentration levels, the presence of the biological target, and provide medical feedback such as whether the concentrations warrant physician intervention, follow-up tests, potential diagnosis, and other relevant medical information. In an aspect, a subject is any human or animal.
In another aspect, biological sample can include blood, artery scarping, a blood clot, bodily fluids, serum, plasma, urine, vaginal fluid, mucus, lymph, blood byproducts, semen, saliva, sputum, spinal fluid, lymph fluid, skin, respiratory, intestinal, and genitourinary tracts, tears, milk, blood cells, tumors, organs, ocular lens fluid, amniotic fluid, in vivo cell culture constituents and also samples of in vitro cell culture constituents.
Display component 170 displays the medical diagnostic report to a device user. In an aspect, the display component 170 presents the data from generation component 160 to a device user. The display component 170 can be a touch screen, interactive monitor, LCD screen, projector screen, or any type of mechanism for presenting information. The display component 170 can display charts, graphs, text, words, numbers, numerous colors, and other such features. Additionally, display component 170 can comprise an audio feature whereby the medical diagnostic report can be audibly communicated to a device user and include alarm functions as well as audio sounds associated with monitoring needs (such as a sound related to low levels of glucose present in a subjects blood).
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In another aspect, the point of care device 300 can centrally store medical records electronically on a shared database. The database is capable of remote access by patients and medical providers. The system then stores numerous medical records on a medical information database via a medical information server connected to a network. A plurality of medical provider computers can be connected to the network and utilize software to communicate with the medical information server. Furthermore, the device can be configured to store other information such as medical history, surgical history, hospitalization, pregnancy history, medical treatment, gynecological history, pap history, allergy treatment, immunization treatment, family history, birth control history, vital sign and statistics, patient information, or physical exam notes.
In an embodiment, point of care device 300 can be utilized for glucose estimation in a subject's biological sample, which can be useful in determining conditions such as diabetes mellitus. In an embodiment, point of care device 100 utilizes quenching of fluorescence or emission spectrum's of quantum dots to determine the concentration of glucose present in a biological sample. The concentration of hydrogen peroxide (H2O2) detected in the biological sample by detection component 140 is associated with the concentration of glucose in the biological sample, wherein 1 mole of H2O2 is released from oxidation of 1 mole of glucose. A typical range of blood glucose levels from a hypoglycemic state to hyperglycemic state lies from 30 mg/dl (1.66 mM) to 360 mg/dl (20 mM). Nine quantum dot-ligand quenching systems were tested in an experiment was tested against samples along the typical blood glucose range. Each system was allowed 5 minutes of reaction time to present the sensitivity of each system in regards to glucose sensing via fluorescence quenching detection. The result was an increased quenching of the quantum dots emission wavelength with increasing concentrations of H2O2 quantified by the slope of relative fluorescence intensity (I/I0) versus H2O2 concentration, which is referred to as sensitivity.
The experiment began with conjugating each water-soluble quantum dot-pairing moiety system (also known as quantum dot ligand system) to glucose oxidase (GOD). At the start of the experiment, the concentration of three spherical quantum dots; CdSe—CdS, CdSe—ZnS and CdS—ZnS were estimated as 0.32 mg/ml, 0.26 mg/ml and 0.23 mg/ml of PBS respectively, assuming complete recovery of the quantum dots during extraction from microemulsion into the PBS phase. Briefly, 2.5 mg of EDC (1 ml of PBS, pH=7.4) were added to 5 ml of each of the nine quantum dot-ligand systems (in PBS). The samples were then gently stirred for 30 minutes. Then, 2.5 mg of NHS (1 ml of PBS, pH=7.4) were added to all the samples and again stirred for 30 minutes. 1 ml of enzyme solution (1 mg/ml of GOD in PBS) was then added to each of the samples and stirred gently for 8 hours at 4° C. The quantum dot-ligand systems were then washed thrice and then redispersed in PBS. EDC coupled NHS to carboxyl groups on the quantum dots surface, resulting in formation of NHS esters, which reacted with the amine group of GOD, to form an amide linkage. The mechanism is clearly depicted in
Next, the enzyme activity and stability of the quantum dot-ligand-GOD (QD-ligand-GOD) systems were observed. The estimation of Enzyme Activity (EA), which are the Units of GOD per mg of Quant Dots, was performed as per a method reported by Sigma-Aldrich (2010), for each of the nine QD-ligand-GOD systems. The mechanism of activity estimation is explained by equations 1 and 2 and activity is calculated as per the equation in
During characterization of the QD-ligand systems, the systems were analyzed for particle size, shape and crystallographic information in addition to the quenching effects the presence of H2O2 in the measured sample had on quantum dot fluorescence. The absorbance spectra for the nine QD-ligand systems in PBS were determined using UV-visible spectrophotometer (Nicolet Evolution 300). The band gap of QDs were determined by fitting the absorbance data to the following Equation: (σhν)2=A (hν−Eg) where, σ is molar absorption coefficient, A the proportionality and hν the photon energy. The mean size of core QD can be calculated by using the relationship between, QD band gap Eg (obtained from Equation 4), bulk band gap Eg (bulk), and mean particle diameter dp, which is expressed by Brus [54] as follows in the following Equation (A):
Where h is Planks constant, ∈ is dielectric constant of semiconductor, e the charge of electron, m*e=me.m0 and m*h=mh.m0. Here me and mh are the effective masses of electron and hole for core QD, and m0 is the mass of an electron. By using Equation (5), we estimate the mean sizes of nine QD-ligand systems. The universal constants used are m0=9.1*10-31 kg, ∈o=8.854*10-12 F/m, e=1.6*10-19 C, h=6.626*10-34 J/s. The individual constants for CdSe, CdS and ZnS are taken from the CRC handbook and complied in the table shown in
Further, the fluorescence spectra of QD-ligand and QD-ligand-GOD systems were obtained from Hitachi Fluorescence Spectrophotometer F-2500. The slit width was fixed at 10 nm for both excitation and emission windows while the excitation wavelength was kept at 420 nm.
The micrographs of the QD-ligand system were obtained with Philips Technai G2 at 120 kV. Additionally, High-Resolution Transmission Electron Microscopy (HRTEM) micrographs and the Electron Diffraction (ED) patterns were obtained from JEOL FEG-TEM at 200 kV. A drop of QD-ligand buffer dispersion was directly placed on a copper grid and dried overnight before the analysis was performed.
The experimental materials used in the synthesis, characterization, and selection of the quantum dot-ligand system included the surfactant, dioctyl sulfosuccinate sodium salt (Aerosol-OT, or AOT, 99% pure), Cadmium nitrate (LR grade), Zinc nitrate (LR grade), n-heptane (extrapure, 99%) were purchased from S.D. Fine (India) chemicals. Ammonium sulfide ((NH4)2S) (25% aqueous), Mercaptoacetic acid (97%, aqueous), Mercaptopropionic acid (99%, aqueous) and Sodium Sulfite (anhydrous) were purchased from Alfa Aesar, (U.K). N-Hydroxysuccinimide (98%) and L-Glutathione (reduced 98%) was obtained from Aldrich. Selenium powder (black, GR grade) of 99.5% purity was supplied by Kemie Labs, India. D-Glucose (minimum 99.5%), Glucose Oxidase (G2133 type VII from Aspergillus niger, 160,000 U/g solid), Peroxidase (P8375, Type VI from Horseradish, 250 Purpurogallin units/mg), Phosphate Buffered Saline tablets (P4417) and o-Dianisidine (D9143) were obtained from Sigma. N-(3-Dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride (98% (AT)) was obtained from Sigma-Aldrich. Hydrogen peroxide (50% aqueous solution) was obtained from Qualigens Fine Chemicals. All the chemicals were used without any further purification. Ultra-pure water (Milli-Q, Millipore) was used throughout the experiments.
The microemulsion synthesis of CdSe—CdS, CdSe—ZnS and CdS—ZnS coreshell QDs and their extraction in aqueous phase was performed as per an ecofriendly method recently reported by Saran and Bellare. Briefly the core-shell QDs were prepared using AOT\water\n-heptane microemulsion system at room temperature and then extracted using appropriate thiol ligand into PBS buffer as per a Post-Synthesis Stabilization (PostSS) method. Each core-shell QD was extracted using 1 M aqueous solutions of MAA and MPA and 0.5 M aqueous solution of GSH. The core-shell QDs were synthesized at water-to-surfactant molar ratio (R=10) and shell-to-core molar ratio (S=2). Finally 10 ml microemulsion of core-shell QDs was extracted to 5 ml of PBS, ultrasonicated for 60 seconds and washed three times.
Experimental Results and Discussion.
The microemulsion synthesis of ligand capped QD's offered an 80% recovery of heptane and 40% recovery of surfactant AOT. The QDs were functionalized with mercaptothiol ligands, detached from the organic phase and extracted into a stable aqueous buffer in a single step. Each of the three ligands MAA, MPA and GSH were used to extract/cap each of the three QDs; CdSe—CdS, CdSe—ZnS and CdS—ZnS.
The nine QD-ligand systems were studied with TEM, HRTEM and ED to obtain information about nanoparticle size and shape as well as crystallographic properties.
In an embodiment, point of care device 100 can detect the presence and concentrations of electrolytes, potassium, calcium and bicarbonate utilizing nanomaterial labels. In Diabetes Ketoacidosis (DKA), the estimation of serum Na+, K+, HCO3- and pH are of utmost importance as acidosis leads to derangement of ionic physiology. Due to the increase of H+ ions an efflux of the K+ ions moves into the extracellular fluid, and accordingly an influx of H+ ions into the cells also results. This leads to cellular acidosis and hyperkalemia. Also, due to the acidosis there is depletion of the bicarbonate ions. Dehydration and hyperkalemia leads to hypernatremia.
In DKA, the pH of the blood ranges from 6.3 to 7.3. The potential clinical effects of hypernatremia, hyperkalemia and acidosis are dehydration, neural dysfunction, respiratory distress, respiratory failure, cellular death, thus it is important for a subject to estimate serum electrolytes and pH regularly. Currently, the conventional method of serum electrolyte and pH of estimation is through laboratory testing using colorimetric analysis, pH probes and certain amperometric analyzers. The major problem is the sample collection and the mode of transport. For serum electrolytes the sample has to be collected in plain blood and for pH arterial sample has to be taken and then transported in an ice bath. The transportation and laboratory reporting causes a delay in the appropriate treatment. Thus, the point of care device 100 as a detector for electrolytes and pH will provide tremendous benefits to the healthcare industry.
In an embodiment, point of care device 100 can be used to detect sodium levels in a biological sample. Dubach et al. (2007) reported the use of ion selective polymer and quantum dot for sensing sodium concentration. The ion-selective polymer is based on the traditional ion-selective optical sensors (optodes). Sodium ionophore X in conjugation with chromoionophore (a light absorbing pH indicator) formed a polymer matrix. This sodium selective polymer matrix was then used to encase quantum dots. The mechanism of sensing was based on the exchange of the sodium ions in the polymer matrix for the H+ ions thus decreasing the pH of the surrounding medium. This lead to a change in the chromoionophore color and thus indirectly determined sodium concentration. The absorption of the chromoionophore overlapped with the emission wavelengths of the encased QD. The assembly and the basis of FRET between QD and polymer are clearly shown in
The results of the sodium selective polymer matrix encased quantum dot assembly are shown in
In an embodiment, point of care device 100 can be used to detect urea in a biological sample. Urea is an important metabolite, which helps to determine the integrity of hepatic and renal physiology. A breach in the functioning of the liver or kidneys leads to the increase in the levels of urea (>60 mg %). Urea in blood is actually an indication of nitrogen levels in the blood. Usual range of urea is 7 mg % to 21 mg %. Urea is produced in the liver and is excreted by the kidneys. Thus increase in the production or the decrease in the excretion is an indication of hepatic or renal pathology, respectively. Usually the test to determine the urea levels is either a colorimetric or conductometric test. These laboratory tests are well established and require special blood sampling methods. The blood needs to be collected in an anticoagulant bulb for further evaluation, however, serum urea estimation can also be conducted. In an embodiment, point of care device 100 can be used to detect urea based on the science underlying the hydrolysis of urea into ammonia by enzyme urease. Thus, the analytical performance of these system is based on the stability of the enzyme, urease.
Huang C. P. et al. in 2006, reported the use of quantum dots for sensing urea. They used CdSe/ZnS quantum dots for the determination of urea, based on the phenomenon of fluorescence change with respect to the change in pH. When urea is hydrolyzed to ammonium ions with the help of a catalytic enzyme, urease, HCO3 ions and OH— are released and that causes the pH to increase. The results reported (
In 2008, Duong and Rhee demonstrated the application of quantum dots and sol-gel matrices in the estimation of urea. In the process they made three assemblies; QD-trapped sol-gel membranes, Urease-immobilized sol-gel membrane and Double layer consisting of QD-entrapped sol-gel membrane and Ureaseimmobilized sol-gel membrane. The quantum dots they used were mercaptopropionic acid capped CdSe—ZnS (CdSe—ZnS-MPA). The sol-gel membranes were made of 3-glycidoxytrimethoxysilane (GPTMS) and 3-aminotrimethoxysilane (APTMS). The result of the sensing ability by the three membranes is depicted in
In an embodiment, point of care device 100 can be used to detect urea in a biological sample by utilizing QD-trapped sol-gel membranes, Urease-immobilized sol-gel membrane and Double layer consisting of QD-entrapped sol-gel membrane and Urease immobilized sol-gel membrane techniques within respective wells of cartridge component 110. When a biological sample containing urea is dispersed within the respective wells, the urea can be hydrolyzed to ammonium ions with the help of a catalytic enzyme, urease. Upon the hydrolyzation of the urea into ammonium ions HCO3 ions and OH— are released and that causes the pH to increase. The detection component 140 can detect the change in wavelength emitted (via excitation of excitation component 130) from the quantum dot in the presence of the increased pH amounts. Furthermore, the analysis component 150 can compare the emission wavelength to a standard curve for emission wavelengths associated with standard concentrations of urea in order to determine the concentration of urea in the unknown sample. Generation component 160 can generate a medical diagnostic report based in part on the analyzed data and display component 170 can display the medical diagnostic report to a device user.
In an embodiment, point of care device 100 can be used to detect potassium, calcium, and bicarbonate in a biological sample. Singh et al. (2009) used a complex assembly to determine the concentration of potassium ions and calcium. They conjugated the Schiff base receptor to QD surface and demonstrated that the QD surface works as a scaffold for the organization of receptor enabling semi-selective binding to ions. The fluorescence response was found to be linear between 15-50 μM for potassium and 2-35 μM for calcium. They also demonstrated that the model could measure both potassium and calcium in solutions containing both ions. With the help of peroxide-bicarbonate system, the bicarbonate levels may be measurable. The mode of sensing can be the chemiluminescence resonance energy transfer between the peroxymonocarbonate ions and Quantum dots.
In an embodiment, point of care device 100 can be used to detect potassium, calcium, and bicarbonate. The detection component 140 can detect the change in wavelength emitted by the quantum dot in the absence of potassium and in the presence of potassium. Analysis component 150 can analyze the change in wavelength emission and compare the emission change to a standard curve of known standard concentrations of potassium. The comparison of the potassium levels from the unknown biological sample to the known standard sample can be analyzed by analysis component 150 to determine the concentration of potassium for the unknown biological sample. The device can perform the same process to detect calcium, bicarbonate in a biological sample. Each well can store a different biological material and perform a different detection test simultaneously.
In an embodiment, point of care device 100 can be used to detect pH levels of a biological sample. The possible use of quantum dots in determining the pH of a solution has been well studied by the researchers around the globe. In 2006, a quantum dot based pH probe was assembled for the brisk study of the enzyme kinetics of various reactions. Yu D. et al., used CdTe—ZnS core-shell QDs to study the reaction kinetics of hydrolysis of glycidyl butyrate by the catalyst, procine pancreatic lipase (PPL). They also compared their methodology to the existing method based on p-Nitrophenoxide (PNP). The graph showing the variation of the fluorescence with respect to the solution pH is depicted in
In 2007, a novel use of Quantum dots was floated. The use of QDs as a proton flux sensor and H9 influenza virus detector. Yun et al., used chromatophores from Rhodospirillium rubrum and labeled them with CdTe QDs stabilized by thiolglycolic acid. These QD-labeled chromatophores were then used to construct the QD virus detector. However, they too reported the variation of QD fluorescence with respect to pH change. The findings by the group are shown in
In an embodiment, the point of care device can be used to detect pH levels in a biological sample. The change in fluorescence emission of the quantum dot in the presence biological sample in the absence and presence of pH can be detected by detection component 140. Analysis component 150 can analyze the change in wavelength emission and compare the emission change to a standard curve of standard levels of pH in a known sample. The comparison of the pH levels from the unknown biological sample to the known standard sample can be analyzed by analysis component 150 to determine the concentration of pH for the unknown biological sample.
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At 4406, point of care device emits (e.g. using excitation component 130) energy from an excitation source to excite the nanomaterial label in the absence of the biological sample and excites the nanomaterial label in the presence of the biological sample. At 4408, point of care device detects (e.g. using detection component 140) a relative change in energy emitted from the nanomaterial label paired to the biological material in the absence of the biological sample as compared to the energy emitted from the nanomaterial label paired to a biological material in the presence of a biological target present in the biological sample.
At 4410, point of care device analyzes data (e.g. using analysis component 150) related to the change in energy emitted from the nanomaterial label paired to the biological material as compared to a standard curve for the energy emitted from the nanomaterial label paired to the biological material in the presence of various concentration levels of the biological target. At 4412, point of care device generates (e.g. using a generation component 160) a medical diagnostic report based in part on the analyzed data. At 4414, point of care device displays (e.g. using display component 170) the medical diagnostic report to a device user.
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At 4506, point of care device emits (e.g. using excitation component 130) energy from an excitation source to excite the nanomaterial label in the absence of the biological sample and excites the nanomaterial label in the presence of the biological sample. At 4508, point of care device detects (e.g. using detection component 140) a relative change in energy emitted from the nanomaterial label paired to the biological material in the absence of the biological sample as compared to the energy emitted from the nanomaterial label paired to a biological material in the presence of a biological target present in the biological sample.
At 4510, point of care device analyzes data (e.g. using analysis component 150) related to the change in energy emitted from the nanomaterial label paired to the biological material as compared to a standard curve for the energy emitted from the nanomaterial label paired to the biological material in the presence of various concentration levels of the biological target. At 4512, point of care device generates (e.g. using a generation component 160) a medical diagnostic report based in part on the analyzed data. At 4514, point of care device displays (e.g. using display component 170) the medical diagnostic report to a device user. At 4516, point of care device synchronizes (e.g. using synchronization component 310) the device to a network system or another device.
The systems and processes described below can be embodied within a device via hardware, such as a single integrated circuit (IC) chip, multiple ICs, an application specific integrated circuit (ASIC), or the like. Further, the order in which some or all of the process blocks appear in each process should not be deemed limiting. Rather, it should be understood that some of the process blocks can be executed in a variety of orders, not all of which may be explicitly illustrated in this disclosure.
With reference to
The system bus 4608 can be any of several types of bus structure(s) including the memory bus or memory controller, a peripheral bus or external bus, and/or a local bus using any variety of available bus architectures including, but not limited to, Industrial Standard Architecture (ISA), Micro-Channel Architecture (MSA), Extended ISA (EISA), Intelligent Drive Electronics (IDE), VESA Local Bus (VLB), Peripheral Component Interconnect (PCI), Card Bus, Universal Serial Bus (USB), Advanced Graphics Port (AGP), Personal Computer Memory Card International Association bus (PCMCIA), Firewire (IEEE 1394), and Small Computer Systems Interface (SCSI).
The system memory 4606 includes volatile memory 4610 and non-volatile memory 4612. The basic input/output system (BIOS), containing the basic routines to transfer information between elements within the computer 4602, such as during start-up, is stored in non-volatile memory 4612. In addition, according to present innovations, codec 4605 may include at least one of an encoder or decoder, wherein the at least one of an encoder or decoder may consist of hardware, a combination of hardware and software, or software. Although, codec 4605 is depicted as a separate component, codec 4605 may be contained within non-volatile memory 4612. By way of illustration, and not limitation, non-volatile memory 4612 can include read only memory (ROM), programmable ROM (PROM), electrically programmable ROM (EPROM), electrically erasable programmable ROM (EEPROM), or flash memory. Volatile memory 4610 includes random access memory (RAM), which acts as external cache memory. According to present aspects, the volatile memory may store the write operation retry logic (not shown in
Computer 4602 may also include removable/non-removable, volatile/non-volatile computer storage medium.
It is to be appreciated that
A user enters commands or information into the computer 4602 through input device(s) 4628. Input devices 4628 include, but are not limited to, a pointing device such as a mouse, trackball, stylus, touch pad, keyboard, microphone, joystick, game pad, satellite dish, scanner, TV tuner card, digital camera, digital video camera, web camera, and the like. These and other input devices connect to the processing unit 4604 through the system bus 4608 via interface port(s) 4630. Interface port(s) 4630 include, for example, a serial port, a parallel port, a game port, and a universal serial bus (USB). Output device(s) 4636 use some of the same type of ports as input device(s) 4628. Thus, for example, a USB port may be used to provide input to computer 4602, and to output information from computer 4602 to an output device 4636. Output adapter 4634 is provided to illustrate that there are some output devices 4636 like monitors, speakers, and printers, among other output devices 4636, which require special adapters. The output adapters 4634 include, by way of illustration and not limitation, video and sound cards that provide a means of connection between the output device 4636 and the system bus 4608. It should be noted that other devices and/or systems of devices provide both input and output capabilities such as remote computer(s) 4638.
Computer 4602 can operate in a networked environment using logical connections to one or more remote computers, such as remote computer(s) 4638. The remote computer(s) 4638 can be a personal computer, a server, a router, a network PC, a workstation, a microprocessor based appliance, a peer device, a smart phone, a tablet, or other network node, and typically includes many of the elements described relative to computer 4602. For purposes of brevity, only a memory storage device 4640 is illustrated with remote computer(s) 4638. Remote computer(s) 4638 is logically connected to computer 4602 through a network interface 4642 and then connected via communication connection(s) 4646. Network interface 4642 encompasses wire and/or wireless communication networks such as local-area networks (LAN) and wide-area networks (WAN) and cellular networks. LAN technologies include Fiber Distributed Data Interface (FDDI), Copper Distributed Data Interface (CDDI), Ethernet, Token Ring and the like. WAN technologies include, but are not limited to, point-to-point links, circuit switching networks like Integrated Services Digital Networks (ISDN) and variations thereon, packet switching networks, and Digital Subscriber Lines (DSL).
Communication connection(s) 4646 refers to the hardware/software employed to connect the network interface 4642 to the bus 4608. While communication connection 4646 is shown for illustrative clarity inside computer 4602, it can also be external to computer 4602. The hardware/software necessary for connection to the network interface 4642 includes, for exemplary purposes only, internal and external technologies such as, modems including regular telephone grade modems, cable modems and DSL modems, ISDN adapters, and wired and wireless Ethernet cards, hubs, and routers.
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Communications can be facilitated via a wired (including optical fiber) and/or wireless technology. The client(s) 4702 include or are operatively connected to one or more client data store(s) 4708 that can be employed to store information local to the client(s) 4702 (e.g., associated contextual information). Similarly, the server(s) 4704 are operatively include or are operatively connected to one or more server data store(s) 4710 that can be employed to store information local to the servers 4704.
In one embodiment, a client 4702 can transfer an encoded file, in accordance with the disclosed subject matter, to server 4704. Server 4704 can store the file, decode the file, or transmit the file to another client 4702. It is to be appreciated, that a client 4702 can also transfer uncompressed file to a server 4704 and server 4704 can compress the file in accordance with the disclosed subject matter. Likewise, server 4704 can encode video information and transmit the information via communication framework 4706 to one or more clients 4702.
The illustrated aspects of the disclosure may also be practiced in distributed computing environments where certain tasks are performed by remote processing devices that are linked through a communications network. In a distributed computing environment, program modules can be located in both local and remote memory storage devices.
Moreover, it is to be appreciated that various components described in this description can include electrical circuit(s) that can include components and circuitry elements of suitable value in order to implement the embodiments of the subject innovation(s). Furthermore, it can be appreciated that many of the various components can be implemented on one or more integrated circuit (IC) chips. For example, in one embodiment, a set of components can be implemented in a single IC chip. In other embodiments, one or more of respective components are fabricated or implemented on separate IC chips.
What has been described above includes examples of the embodiments of the present invention. It is, of course, not possible to describe every conceivable combination of components or methodologies for purposes of describing the claimed subject matter, but it is to be appreciated that many further combinations and permutations of the subject innovation are possible. Accordingly, the claimed subject matter is intended to embrace all such alterations, modifications, and variations that fall within the spirit and scope of the appended claims. Moreover, the above description of illustrated embodiments of the subject disclosure, including what is described in the Abstract, is not intended to be exhaustive or to limit the disclosed embodiments to the precise forms disclosed. While specific embodiments and examples are described in this disclosure for illustrative purposes, various modifications are possible that are considered within the scope of such embodiments and examples, as those skilled in the relevant art can recognize.
In particular and in regard to the various functions performed by the above described components, devices, circuits, systems and the like, the terms used to describe such components are intended to correspond, unless otherwise indicated, to any component which performs the specified function of the described component (e.g., a functional equivalent), even though not structurally equivalent to the disclosed structure, which performs the function in the disclosure illustrated exemplary aspects of the claimed subject matter. In this regard, it will also be recognized that the innovation includes a system as well as a computer-readable storage medium having computer-executable instructions for performing the acts and/or events of the various methods of the claimed subject matter.
The aforementioned systems/circuits/modules have been described with respect to interaction between several components/blocks. It can be appreciated that such systems/circuits and components/blocks can include those components or specified sub-components, some of the specified components or sub-components, and/or additional components, and according to various permutations and combinations of the foregoing. Sub-components can also be implemented as components communicatively coupled to other components rather than included within parent components (hierarchical). Additionally, it should be noted that one or more components may be combined into a single component providing aggregate functionality or divided into several separate sub-components, and any one or more middle layers, such as a management layer, may be provided to communicatively couple to such sub-components in order to provide integrated functionality. Any components described in this disclosure may also interact with one or more other components not specifically described in this disclosure but known by those of skill in the art.
In addition, while a particular feature of the subject innovation may have been disclosed with respect to only one of several implementations, such feature may be combined with one or more other features of the other implementations as may be desired and advantageous for any given or particular application. Furthermore, to the extent that the terms “includes,” “including,” “has,” “contains,” variants thereof, and other similar words are used in either the detailed description or the claims, these terms are intended to be inclusive in a manner similar to the term “comprising” as an open transition word without precluding any additional or other elements.
As used in this application, the terms “component,” “module,” “system,” or the like are generally intended to refer to a computer-related entity, either hardware (e.g., a circuit), a combination of hardware and software, software, or an entity related to an operational machine with one or more specific functionalities. For example, a component may be, but is not limited to being, a process running on a processor (e.g., digital signal processor), a processor, an object, an executable, a thread of execution, a program, and/or a computer. By way of illustration, both an application running on a controller and the controller can be a component. One or more components may reside within a process and/or thread of execution and a component may be localized on one computer and/or distributed between two or more computers. Further, a “device” can come in the form of specially designed hardware; generalized hardware made specialized by the execution of software thereon that enables the hardware to perform specific function; software stored on a computer readable storage medium; software transmitted on a computer readable transmission medium; or a combination thereof.
Moreover, the words “example” or “exemplary” are used in this disclosure to mean serving as an example, instance, or illustration. Any aspect or design described in this disclosure as “exemplary” is not necessarily to be construed as preferred or advantageous over other aspects or designs. Rather, use of the words “example” or “exemplary” is intended to present concepts in a concrete fashion. As used in this application, the term “or” is intended to mean an inclusive “or” rather than an exclusive “or”. That is, unless specified otherwise, or clear from context, “X employs A or B” is intended to mean any of the natural inclusive permutations. That is, if X employs A; X employs B; or X employs both A and B, then “X employs A or B” is satisfied under any of the foregoing instances. In addition, the articles “a” and “an” as used in this application and the appended claims should generally be construed to mean “one or more” unless specified otherwise or clear from context to be directed to a singular form.
Computing devices typically include a variety of media, which can include computer-readable storage media and/or communications media, in which these two terms are used in this description differently from one another as follows. Computer-readable storage media can be any available storage media that can be accessed by the computer, is typically of a non-transitory nature, and can include both volatile and nonvolatile media, removable and non-removable media. By way of example, and not limitation, computer-readable storage media can be implemented in connection with any method or technology for storage of information such as computer-readable instructions, program modules, structured data, or unstructured data. Computer-readable storage media can include, but are not limited to, RAM, ROM, EEPROM, flash memory or other memory technology, CD-ROM, digital versatile disk (DVD) or other optical disk storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or other tangible and/or non-transitory media which can be used to store desired information. Computer-readable storage media can be accessed by one or more local or remote computing devices, e.g., via access requests, queries or other data retrieval protocols, for a variety of operations with respect to the information stored by the medium.
On the other hand, communications media typically embody computer-readable instructions, data structures, program modules or other structured or unstructured data in a data signal that can be transitory such as a modulated data signal, e.g., a carrier wave or other transport mechanism, and includes any information delivery or transport media. The term “modulated data signal” or signals refers to a signal that has one or more of its characteristics set or changed in such a manner as to encode information in one or more signals. By way of example, and not limitation, communication media include wired media, such as a wired network or direct-wired connection, and wireless media such as acoustic, RF, infrared and other wireless media.
In view of the exemplary systems described above, methodologies that may be implemented in accordance with the described subject matter will be better appreciated with reference to the flowcharts of the various figures. For simplicity of explanation, the methodologies are depicted and described as a series of acts. However, acts in accordance with this disclosure can occur in various orders and/or concurrently, and with other acts not presented and described in this disclosure. Furthermore, not all illustrated acts may be required to implement the methodologies in accordance with certain aspects of this disclosure. In addition, those skilled in the art will understand and appreciate that the methodologies could alternatively be represented as a series of interrelated states via a state diagram or events. Additionally, it should be appreciated that the methodologies disclosed in this disclosure are capable of being stored on an article of manufacture to facilitate transporting and transferring such methodologies to computing devices. The term article of manufacture, as used in this disclosure, is intended to encompass a computer program accessible from any computer-readable device or storage media.
This application claims the benefit of U.S. Provisional Patent Application Ser. No. 61/554,145 filed Nov. 1, 2011 and titled “Point of Care Testing Device”, which is incorporated by reference herein in its entirety.
Number | Date | Country | |
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61554145 | Nov 2011 | US |