There are many user environments, the fields of medical research and pharmaceutical development being examples, where it is necessary to accurately acquire fluid samples and where also often desirable to measure optical characteristics of the acquired fluid samples. Such optical characteristics include, for example, the ability of a sample to absorb light. The acquired samples have volumes that may be as small as a few nanoliters. In the measurement of optical characteristics, and especially when the samples have small volumes, it is highly desirable, and sometimes necessary, that the largest measurement amplitude be obtained. In many instances, the largest measurement amplitude is obtained when the sample is centered with respect to the optical path of the beam of electromagnetic radiation provided by the optical instrument. For instance, when the optical instrument is a spectrophotometer, the integrated signal value is substantially maximized when the sample is centered in the spectrophotometer's optical path.
There is a need for methods and systems that automatically position the sample in the optical path of an optical measuring system in order to maximize the measurement amplitude.
One embodiment of the method of this invention for positioning an assembly in an optical device includes the steps of positioning the assembly off center with respect to an optical path of a beam of electromagnetic radiation provided by the optical device, measuring an optical property utilizing the optical device, and translating the assembly, in a direction substantially transverse to the optical path, to another position. The steps of measuring the optical property and of translating the assembly are repeated until a desired position is determined, where a substantial maximum of the measured optical property is obtained at the desired position. The assembly is then positioned substantially at the desired position.
One embodiment of the system of this invention includes a vessel holding element capable of holding a vessel in a predetermined position with respect to a beam of electromagnetic radiation, and optical subsystem capable of providing the beam of electromagnetic radiation, a positioning subsystem capable of repeatably positioning the vessel holding element, where the vessel holding element is positioned in a direction transverse to the beam of electromagnetic radiation, and a component capable of determining a position at which a substantial maximum of the measured optical property can be obtained.
In one embodiment, the component capable of determining the position at which the vessel is substantially centered includes one or more processors and one of more computer usable media. The computer usable media has computer readable code embodied therein, where the computer readable code is capable of causing the one or more processors to execute an embodiment of the method of this invention.
For a better understanding of the present invention, reference is made to the accompanying drawings and detailed description and its scope will be pointed out in the appended claims.
Before describing the present invention in detail, it is to be understood that this invention is not limited to specific apparatuses, method steps, or equipment, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. Methods described herein may be carried out in any order of the recited steps that is logically possible. Furthermore, where a range of values is provided, it is understood that every intervening value, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the invention. Also, it is contemplated that any optional feature of the inventive embodiments and aspects described herein may be set forth and claimed independently, or in combination with any one or more of the features described herein, or may be specifically excluded.
Unless defined otherwise below, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Still, certain terms are defined herein for the sake of clarity.
The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates, which may need to be independently confirmed. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited.
It must be noted that, as used in this specification and the appended claims, the singular forms “a”, “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a biopolymer” includes more than one biopolymer, and the like.
It will also be appreciated that throughout the present application, that words such as “upper”, “lower” are used in a relative sense only.
The term “assessing” and “evaluating” are used interchangeably to refer to any form of measurement, and includes determining if an element is present or not. The terms “determining,” “measuring,” and “assessing,” and “assaying” are used interchangeably and include both quantitative and qualitative determinations. Assessing may be relative or absolute. “Assessing the presence of” includes determining the amount of something present, as well as determining whether it is present or absent.
The term “using” has its conventional meaning, and, as such, means employing, e.g. putting into service, a method or composition to attain an end.
An embodiment 10 of the method of this invention for positioning an assembly in an optical device, where the assembly includes a sample, is shown in
Another embodiment 100 of the method of this invention is shown in
It should be noted that, in one embodiment, this invention not being limited only to this embodiment, a determination as to whether a relative maximum has been approximately obtained or a relative maximum appears to lie between two measurements can be made by comparing subsequent measurements and the determining whether the rate of change of the measured values and goals from increasing (positive) to decreasing (negative), or vice versa.
An embodiment 200 of the system of this invention is shown in
In one embodiment, but not limited only to this embodiment, the vessel 220 is a cuvette, a micro cuvette, a pipette, or a micro pipette. The vessel holding element 210 may be, but is not limited to, a housing holding the vessel or an element of specific design and that enables the holding of the vessel. The positioning subsystem 250 can be, but is not limited to, a stepper motor with a lead screw and means for operatively connecting the vessel holding element 210 to the lead screw (such as a nut or a slide), a linear motor, a motor and encoder system and a slide, carriage or nut, or a similar motion producing subsystem (structure) that is substantially repeatable in its positioning characteristics and means for operatively connecting the vessel holding element 210 to the motion producing structure in the positioning subsystem 250 (such a structure to attach to). The optical subsystem 230 can be, but is not limited to, a portion of (or the entire) a measurement system such as, for example, a spectrophotometer. The analysis component 260 can be, but it are limited to, a component including digital or analog electronics (or mechanical analogues) that enables the determination of the position at which a substantially relative maximum value is obtained for the measured optical property of the sample contained in the vessel 220 or at which the vessel 220 is substantially centered with respect to the beam of electromagnetic radiation. The analysis component 260 is operatively connected to the optical subsystem 230 and to the positioning subsystem 250. In one embodiment, the analysis component 260 receives measurement data for the measured optical property from the optical subsystem and receives/provides positioning data from/to the positioning subsystem 250.
One embodiment 300 of the analysis component 260 is shown in
In one instance, the computer readable code, in causing their one or more processors 310 to determine the position at which the vessel is substantially center, cause is the one or more processors to determine a position at which an approximate (also referred to as substantially) relative maximum of the optical property is obtained. In one embodiment, the position at which an approximate relative maximum of the optical property is obtained is determined by obtaining an expression for the measured values of the optical property, obtaining an approximate relative maximum of the expression and determining the position at which the approximate relative maximum of the expression is obtained.
The embodiment 300 of the analysis component 260 shown in
Embodiments of the vessel holding element 210, this invention not being limited to only these embodiments, are shown in
Bracket 14d has a top edge 18, a bottom portion 19 attached to the elongated support member 12, and two opposing and elongated bracket members 16a and 16b such as fingers, tines, or prongs. The two opposing bracket members 16a and 16b are separated by a gap 20, which provides an aperture for an optical path when the common carrier 10 is used with a spectrophotometer or similar instrument so that light can pass through the Cuvette 28. The width of the gap 20 can vary between embodiments to match the distance between the reservoirs (for example, but not limited to, wells in a microtiter plate) from which samples are loaded.
Bracket member 16a has a recess 22a formed by a concave surface 24a and a radial surface 25a. The recess 22a opens to the top edge 18 of the bracket 14d and extends toward the bottom portion 19 to the radial surface 25a. The concave surface 24a and the radial surface 25a are substantially orthogonal. Bracket member 14b has a recess 22b substantially similar to and opposing the recess 22a. The recess 22b is formed by a concave surface 24b and a radial surface (not shown). In one possible embodiment, as explained in more detail herein, the shape of the recesses 22a and 22b conform to the outer circumference of the vessel, which in the exemplary embodiment is a Cuvette 28 (shown mounted in brackets 14a and 14h).
The recesses 22a and 22b form a receptacle for holding the Cuvette 28. Additionally, the radial surface 25a of the elongated bracket member 16a and the radial surface (not shown) of the elongated bracket member 16b form a seat 26 against which the Cuvette 28 is positioned. Additionally, the distance between the seat 26 and the top edge 18 of the bracket 16d is smaller than the height of the Cuvette 28 so that when the Cuvette 28 is positioned against the seat 26, the top edge 30 of the Cuvette 28 extends at least slightly beyond the top edge 18 of the bracket 14d, which assists capillary uptake of the sample. Additionally, the distances from the elongated support member 12 to the seat 26 and from the top edge 18 to the seat 26 are substantially consistent between each of the brackets 14a-14h.
The bottom portion 19 of the bracket 14d defines a break 32 that is open to the gap 20 and extends between the sides 36 and 38 of the elongated support member 12 and has a circular cross-section with a circumference slightly larger than the width of the gap 20. The break provides a relief that makes it easier to spread the bracket members 16a and 16b so that a Cuvette 28 can be mounted in the recesses 22a and 228. An alternative embodiment does not includes the break 32, which makes the common carrier easier to mold when it is formed with a plastic, acrylic, or similar material. In this alternative embodiment the gap 20 terminates at the base portion of the bracket 14d. In another alternative embodiment, the gap 20, with out without a break 32 terminates at a midpoint between the top edge 30 and the bottom portion 19 of the bracket 14d.
The vessel holding element 410 is formed with a resilient material so that the bracket members 16a and 16b of the bracket 14d can be spread and will naturally return to their original position. In this embodiment, the elongated bracket members 16a and 16b exert a spring force against the side of the Cuvette 28 and hold it in the receptacle formed by the recesses 22a and 22b. In one possible embodiment, the common carrier is a single piece and that is injection molded and formed with polycarbonate, acrylic, polysulphone, or another medical grade material that is resilient.
Brackets 14a-14c and 14e-14h are substantially similar to the bracket 14h. In one possible embodiment, the distance “d” between adjacent brackets 14 is about 9 mm, which corresponds to a typical distance between wells in the column of a microtiter plate. In other possible embodiments, the distance “d” is a distance other then 9 mm and matches the distance between adjacent reservoirs from which samples are loaded into the Cuvettes 28.
In one exemplary embodiment, the Cuvette 28 has an internal cavity 24 with a depth of about 4 mm and cross-sectional dimensions of about 1 mm and about 1 mm to form a capacity volume of about 4 μl. Other embodiments use cuvettes of different sizes. Although a cuvette of a particular size and structure is illustrated, other embodiments of the common carrier 10 can be used and configured for vessels (including Cuvettes in the instance shown in
When the vessel holding element is used with a spectrophotometer, one possible embodiment of the Cuvette 28 or other vessel has internal dimensions sized to be about the same size as or only slightly larger than the cross-sectional area of the light beam passed through the Cuvette 28. Any sample loaded in the Cuvette that is not in the path of the light-beam is not analyzed by the spectrophotometer.
One embodiment of the means for operatively connecting the vessel holding element 410 to the positioning subsystem 250 is shown in
Referring back to
In one possible embodiment, the base 15 is configured to be slidably inserted into a structure for operatively connecting the vessel holding element 410 to the positioning subsystem 250 that and retains the vessel holding element 410 in the automated spectrophotometer. In yet another possible embodiment, the base 15 includes indicia (not shown) indicating the location of each bracket on the vessel holding element 410. Each of the indicia is a distinctive machine-readable marking that provides a positioning guide to locate and orient the Cuvettes 28 in the automated spectrophotometer. Such indicia could be considered to be included in the positioning subsystem 250 or to be used by the positioning subsystem 250. The automated spectrophotometer indexes the vessel holding element 410 by translating the vessel holding element 410 to the correct position so that the cuvette 28 is at the desired position within the optical path of the automated spectrophotometer.
One exemplary embodiment 500 of the system of this invention is shown in
In order to better illustrate the method and system of this invention, results of an exemplary embodiment are presented herein below and shown in
In general, the techniques described above may be implemented, for example, in hardware, software, firmware, or any combination thereof. The computer implementable techniques described above may be implemented in one or more computer programs executing on a programmable computer including a processor, a storage medium readable by the processor (including, for example, volatile and non-volatile memory and/or storage elements), at least one input device, and at least one output device. Program code may be applied to data entered using the input device to perform the functions described and to generate output information. The output information may be applied to one or more output devices.
Elements and components described herein may be further divided into additional components or joined together to form fewer components for performing the same functions.
Each computer program (code) within the scope of the claims below may be implemented in any programming language, such as assembly language, machine language, a high-level procedural programming language, or an object-oriented programming language. The programming language may be a compiled or interpreted programming language.
Each computer program may be implemented in a computer program product tangibly embodied in a computer-readable storage device for execution by a computer processor. Method steps of the invention may be performed by a computer processor executing a program tangibly embodied on a computer-readable medium to perform functions of the invention by operating on input and generating output.
Common forms of computer-readable or usable media include, for example, a floppy disk, a flexible disk, hard disk, magnetic tape, or any other magnetic medium, a CDROM, any other optical medium, punched cards, paper tape, any other physical medium with patterns of holes, a RAM, a PROM, and EPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wave, or any other medium from which a computer can read.
Although the invention has been described with respect to various embodiments, it should be realized this invention is also capable of a wide variety of further and other embodiments within the spirit and scope of the appended claims.