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Transmission Raman Spectroscopy
Transmission Raman spectroscopy (TRS) is a variant of Raman spectroscopy which is advantageous in probing bulk content of diffusely scattering samples. Although it was demonstrated in the early days of Raman spectroscopy it was not exploited in practical settings until much later, probably due to limitations of technology at the time. It was rediscovered in 2006, where the authors showed that it was capable of allowing Raman spectroscopy through many millimetres of tabletted or powdered samples. In addition, this research has also identified several highly beneficial analytical properties of this approach, including the ability to probe bulk content of powders and tissue in the absence of subsampling and to reject Raman and fluorescence components originating from the surface of the sample. Theory Transmission Raman is possible because light scatters through turbid materials that do not significantly absorb or block the light. By a similar mechanism to spatially offset Raman spectr ...
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Raman Spectroscopy
Raman spectroscopy () (named after Indian physicist C. V. Raman) is a spectroscopic technique typically used to determine vibrational modes of molecules, although rotational and other low-frequency modes of systems may also be observed. Raman spectroscopy is commonly used in chemistry to provide a structural fingerprint by which molecules can be identified. Raman spectroscopy relies upon inelastic scattering of photons, known as Raman scattering. A source of monochromatic light, usually from a laser in the visible, near infrared, or near ultraviolet range is used, although X-rays can also be used. The laser light interacts with molecular vibrations, phonons or other excitations in the system, resulting in the energy of the laser photons being shifted up or down. The shift in energy gives information about the vibrational modes in the system. Infrared spectroscopy typically yields similar yet complementary information. Typically, a sample is illuminated with a laser beam. Electr ...
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Near Infrared
Infrared (IR), sometimes called infrared light, is electromagnetic radiation (EMR) with wavelengths longer than those of visible light. It is therefore invisible to the human eye. IR is generally understood to encompass wavelengths from around 1 millimeter (300 GHz) to the nominal red edge of the visible spectrum, around 700  nanometers (430  THz). Longer IR wavelengths (30 μm-100 μm) are sometimes included as part of the terahertz radiation range. Almost all black-body radiation from objects near room temperature is at infrared wavelengths. As a form of electromagnetic radiation, IR propagates energy and momentum, exerts radiation pressure, and has properties corresponding to both those of a wave and of a particle, the photon. It was long known that fires emit invisible heat; in 1681 the pioneering experimenter Edme Mariotte showed that glass, though transparent to sunlight, obstructed radiant heat. In 1800 the astronomer Sir William Herschel discovered ...
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Raman Microscope
The Raman microscope is a laser-based microscopic device used to perform Raman spectroscopy.''Microscopical techniques in the use of the molecular optics laser examiner Raman microprobe'', by M. E. Andersen, R. Z. Muggli, Analytical Chemistry, 1981, 53 (12), pp 1772–177/ref> The term MOLE (molecular optics laser examiner) is used to refer to the Raman-based microprobe. The technique used is named after C. V. Raman, who discovered the scattering properties in liquids. Configuration The Raman microscope begins with a standard optical microscope, and adds an excitation laser, laser rejection filters, a spectrometer or monochromator, and an optical sensitive detector such as a charge-coupled device (CCD), or photomultiplier tube, (PMT). Traditionally Raman microscopy was used to measure the Raman spectrum of a point on a sample, more recently the technique has been extended to implement Raman spectroscopy for direct chemical imaging over the whole field of view on a 3D sample. Im ...
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Micrometres
The micrometre (American and British English spelling differences#-re, -er, international spelling as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer (American and British English spelling differences#-re, -er, American spelling), also commonly known as a micron, is a unit of length in the International System of Units (SI) equalling (SI standard prefix "micro-" = ); that is, one millionth of a metre (or one thousandth of a millimetre, , or about ). The nearest smaller common SI unit is the nanometre, equivalent to one thousandth of a micrometre, one millionth of a millimetre or one billionth of a metre (). The micrometre is a common unit of measurement for wavelengths of infrared radiation as well as sizes of biological cell (biology), cells and bacteria, and for grading wool by the diameter of the fibres. The width of a single human hair ranges from approximately 20 to . The longest human chromosome, chromosome 1 (human), chromosome ...
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Process Analytical Technology
Process analytical technology (PAT) has been defined by the United States Food and Drug Administration (FDA) as a mechanism to design, analyze, and control pharmaceutical manufacturing processes through the measurement of critical process parameters (CPP) which affect the critical quality attributes (CQA). The concept actually aims at understanding the processes by defining their CPPs, and accordingly monitoring them in a timely manner (preferably in-line or on-line) and thus being more efficient in testing while at the same time reducing over-processing, enhancing consistency and minimizing rejects. The FDA has outlined a regulatory framework for PAT implementation. With this framework – according to Hinz – the FDA tries to motivate the pharmaceutical industry to improve the production process. Because of the tight regulatory requirements and the long development time for a new drug, the production technology is "frozen" at the time of conducting phase-2 clinical trials. Ge ...
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Chemometrics
Chemometrics is the science of extracting information from chemical systems by data-driven means. Chemometrics is inherently interdisciplinary, using methods frequently employed in core data-analytic disciplines such as multivariate statistics, applied mathematics, and computer science, in order to address problems in chemistry, biochemistry, medicine, biology and chemical engineering. In this way, it mirrors other interdisciplinary fields, such as psychometrics and econometrics. Background Chemometrics is applied to solve both descriptive and predictive problems in experimental natural sciences, especially in chemistry. In descriptive applications, properties of chemical systems are modeled with the intent of learning the underlying relationships and structure of the system (i.e., model understanding and identification). In predictive applications, properties of chemical systems are modeled with the intent of predicting new properties or behavior of interest. In both cases, ...
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Excipients
An excipient is a substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts (thus often referred to as "bulking agents", "fillers", or "diluents"), or to confer a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or enhancing solubility. Excipients can also be useful in the manufacturing process, to aid in the handling of the active substance concerns such as by facilitating powder flowability or non-stick properties, in addition to aiding ''in vitro'' stability such as prevention of denaturation or aggregation over the expected shelf life. The selection of appropriate excipients also depends upon the route of administration and the dosage form, as well as the active ingredient and other factors. A comprehensive classification system based on structure- ...
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Active Pharmaceutical Ingredient
An active ingredient is any ingredient that provides biological activity, biologically active or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the body of humans or animals. The similar terms active pharmaceutical ingredient (also abbreviated as API) and bulk active are also used in medicine, and the term active substance may be used for Natural product, natural products. Some medication products may contain more than one active ingredient. The traditional word for the active pharmaceutical agent is pharmacon or pharmakon (from el, φάρμακον, adapted from ''pharmacos'') which originally denoted a Potion, magical substance or drug. The terms active constituent or active principle are often chosen when referring to the active chemical substance, substance of interest in a plant (such as salicylic acid in willow bark or arecoline in areca nuts), because the word "ingredient" in many m ...
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Liquid Chromatography
In chemical analysis, chromatography is a laboratory technique for the Separation process, separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system (a column, a capillary tube, a plate, or a sheet) on which a material called the ''stationary phase'' is fixed. Because the different constituents of the mixture tend to have different affinities for the stationary phase and are retained for different lengths of time depending on their interactions with its surface sites, the constituents travel at different apparent velocities in the mobile fluid, causing them to separate. The separation is based on the differential partitioning between the mobile and the stationary phases. Subtle differences in a compound's partition coefficient result in differential retention on the stationary phase and thus affect the separation. Chromatography may be preparative or analytical. The pu ...
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Attenuated Total Reflectance
Attenuated total reflection (ATR) is a sampling technique used in conjunction with infrared spectroscopy which enables samples to be examined directly in the solid or liquid state without further preparation. ATR uses a property of total internal reflection resulting in an evanescent wave. A beam of infrared light is passed through the ATR crystal in such a way that it reflects at least once off the internal surface in contact with the sample. This reflection forms the evanescent wave which extends into the sample. The penetration depth into the sample is typically between 0.5 and 2 micrometres, with the exact value determined by the wavelength of light, the angle of incidence and the indices of refraction for the ATR crystal and the medium being probed. The number of reflections may be varied by varying the angle of incidence. The beam is then collected by a detector as it exits the crystal. Most modern infrared spectrometers can be converted to characterise samples via ATR by ...
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Sub-sampling (chemistry)
In analytical chemistry, sub-sampling is a procedure by which a small, representative sample is taken from a larger sample. Good sub-sampling technique becomes important when the large sample is not homogeneous. Techniques Coning and quartering Coning and quartering is a method used by analytical chemists to reduce the sample size of a powder without creating a systematic bias. The technique involves pouring the sample so that it takes on a conical shape, and then flattening it out into a cake. The cake is then divided into quarters; the two quarters which sit opposite one another are discarded, while the other two are combined and constitute the reduced sample. The same process is continued until an appropriate sample size remains. Analyses are made with respect to the sample left behind. Riffle box splitting A riffle box is a box containing a number (between 3 and 12) of "chutes" - slotted paths through which particles of the sample may slide. The sample is dropped into the ...
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Assay
An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a target entity. The measured entity is often called the analyte, the measurand, or the target of the assay. The analyte can be a drug, biochemical substance, chemical element or compound, or cell in an organism or organic sample. An assay usually aims to measure an analyte's intensive property and express it in the relevant measurement unit (e.g. molarity, density, functional activity in enzyme international units, degree of effect in comparison to a standard, etc.). If the assay involves exogenous reactants (the reagents), then their quantities are kept fixed (or in excess) so that the quantity and quality of the target are the only limiting factors. The difference in the assay outcome is used to deduce the unknown quality or quantity o ...
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