Integrated modular unit including an analyte concentrator-microreactor device connected to a cartridge-cassette
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
G01N-027/00
B01L-003/00
B01L-009/00
G01N-033/53
G01N-033/543
출원번호
US-0487451
(2012-06-04)
등록번호
US-8703061
(2014-04-22)
발명자
/ 주소
Guzman, Norberto A.
출원인 / 주소
Princeton Biochemicals, Inc.
대리인 / 주소
Porzio, Bromberg & Newman, P.C.
인용정보
피인용 횟수 :
10인용 특허 :
0
초록▼
The present invention relates to an immunoaffinity device for capturing one or more analytes present at high or low concentrations in simple or complex matrices. The device is designed as an integrated modular unit and connected to capillary electrophoresis or liquid chromatography for the isolation
The present invention relates to an immunoaffinity device for capturing one or more analytes present at high or low concentrations in simple or complex matrices. The device is designed as an integrated modular unit and connected to capillary electrophoresis or liquid chromatography for the isolation, enrichment, separation and identification of polymeric macromolecules, primarily protein biomarkers. The integrated modular unit includes an analyte-concentrator-microreaction device connected to a modified cartridge-cassette.
대표청구항▼
1. An integrated modular unit, comprising: a modular analyte concentrator-microreactor (ACM) device attached to a support;a transport capillary or passage connected to the analyte concentrator-microreactor (ACM) device;a separation capillary or passage connected to the analyte concentrator-microreac
1. An integrated modular unit, comprising: a modular analyte concentrator-microreactor (ACM) device attached to a support;a transport capillary or passage connected to the analyte concentrator-microreactor (ACM) device;a separation capillary or passage connected to the analyte concentrator-microreactor (ACM) device;the analyte concentrator-microreactor (ACM) device having inlet and outlet ends connected to the transport capillary or passage;the analyte concentrator-microreactor (ACM) device having inlet and outlet ends connected to the separation capillary or passage;the analyte concentrator-microreactor (ACM) device having an internal passage or channel with a staggered configuration which includes an elongated concentration area;the elongated concentration area of the analyte concentrator-microreactor (ACM) device serving as an intersection region where the transport capillary or passage and the separation capillary or passage connect at two separate and distant points to form an analyte concentrator-microreactor area;the elongated concentration area of the analyte concentrator-microreactor (ACM) device providing a place of shelter for received microstructures or a matrix assembly;one or more affinity ligands can be immobilized to the microstructures or the matrix assembly localized within the elongated concentration area of the analyte concentrator-microreactor (ACM) device for generating a concentration space where concentration of one or more analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart from a sample introduced into the transport capillary or passage occurs and/or for generating a microreaction space where microreaction of the one or more analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart from a sample introduced into the transport capillary or passage occurs;alternatively the one or more affinity ligands can be immobilized directly to an internal wall of a cavity or channel forming the elongated concentration area of the analyte concentrator-microreactor (ACM) device without the need of the microstructures or the matrix assembly;controlling means for independently controlling flow of the sample or buffers in the transport capillary or passage and past the analyte concentrator-microreactor (ACM) device and conveyed by electromigration, electro-osmotic flow, mechanical pressure or a combination of electro-osmotic flow and mechanical pressure to an outlet end of the transport capillary or passage, and for separately and independently controlling flow of a separation buffer supply, eluting buffer supply or cleaning buffer supply through the separation capillary or passage and past the analyte concentrator-microreactor (ACM) device and conveyed by electromigration, electro-osmotic flow, mechanical pressure or a combination of electro-osmotic flow and mechanical pressure to an outlet end of the separation capillary or passage; andan interchangeable cartridge-cassette detachably connected by couplers to the inlet and outlet ends of the separation capillary or passage,wherein the inlet and outlet ends of the separation capillary or passage connected to the analyte concentrator-microreactor (ACM) device form part of a continuous capillary piece creating an integrated affinity capture-separation and/or microreaction-separation cartridge-cassette modular unit and a detection system can be positioned in operation with a monitoring area of the separation capillary or passage;wherein the modular analyte concentrator-microreactor (ACM) device can capture, isolate, concentrate and separate analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart bound to and released from the analyte concentrator-microreactor (ACM) device by alternating fluid communication of the separation buffer supply and then the eluting buffer supply and delivering the released analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart to the detection system of a capillary electrophoresis instrument or other analytical separation instrument separately, independently and sequentially by electromigration, electro-osmotic flow, mechanical pressure or a combination of electro-osmotic flow and mechanical pressure within the separation capillary or passage. 2. The integrated modular unit of claim 1 wherein the microstructures or matrix assembly have a surface or a wall having a surface to which one or more affinity ligands are immobilized. 3. The integrated modular unit of claim 2 wherein the matrix assembly includes a plurality of microstructures. 4. The integrated modular unit of claim 2 wherein the matrix assembly is free-floating, and the analyte concentrator-microreactor area retains the free-floating matrix assembly by pressure-resistant porous end walls or frits disposed at the corresponding connecting points of the inlet and outlet ends of the analyte concentrator-microreactor (ACM) device and the transport passage and the separation passage. 5. The integrated modular unit of claim 2 wherein the matrix assembly includes a fixed architecture defined by beaded microstructures interconnected to each other and to the inner wall of the cavity or channel forming the analyte concentrator-microreactor area of the analyte concentrator-microreactor (ACM) device. 6. The integrated modular unit of claim 2 wherein the matrix assembly includes sol-gel or monoliths which are supports having a single, continuous piece of porous materials, nanoparticles and/or nanocomposites. 7. The integrated modular unit of claim 2 wherein the affinity ligands immobilized to the surface of the microstructures or surface of the inner wall of the cavity or channel forming the analyte concentrator-microreactor area of the analyte concentrator-microreactor (ACM) device are immobilized by physicochemical interactions or by covalent chemical interactions. 8. The integrated modular unit of claim 1 wherein the affinity ligands immobilized to the surface of the microstructures or the matrix assembly or the surface of the inner wall of the cavity or channel forming the analyte concentrator-microreactor area of the analyte concentrator-microreactor (ACM) device include biological and non-biological affinity ligands, selected from intact polyclonal or monoclonal antibodies, single-chain antibodies, antibody fragments, antigens, protein A, protein G, protein A/G, protein L, lectins, glycoproteins, glycolipids, enzymes, substrates, cofactors, coenzymes, drugs, vitamins, hormones, proteins, viruses, cells, subcellular structures, cell components, prions, receptors, membranes, DNA, RNA, aptamers, dyes, ions, metal-containing moieties, organometallic moieties, recombinant ligands, and synthetic ligands. 9. The integrated modular unit of claim 1 wherein the analytes of interest and/or their respective modified and/or altered corresponding counterpart include biological and non-biological analytes present in simple and complex matrices, selected from intact antibodies, antibody fragments, antigens, protein A, protein G, lectins, glycoproteins, glycolipids, enzymes, substrates, cofactors, coenzymes, drugs, vitamins, hormones, proteins, viruses, circulating and non-circulating cells, cell components, prions, bacterial cells, receptors, membranes, DNA, RNA, ions, metal-containing moieties, organometallic moieties, synthetic ligands, metabolites, and various altered or modified molecular entities. 10. The integrated modular unit of claim 1 wherein the at least one or more affinity ligands immobilized to the surface of the microstructures or matrix assembly or surface of the inner wall of the cavity or channel forming the analyte concentrator-microreactor area of the analyte concentrator-microreactor (ACM) device is capable of performing a reversible affinity capture reaction with the one or more analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart present in a simple or complex sample. 11. The integrated modular unit of claim 1 wherein at least one or more affinity ligands immobilized to the surface of the microstructures or surface of the inner wall of the cavity or channel forming the analyte concentrator-microreactor area of the analyte concentrator-microreactor (ACM) device is capable of performing one chemical or biochemical reaction with the one or more analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart present in a simple or complex sample. 12. The integrated modular unit of claim 11 wherein the at least one chemical or biochemical reaction includes peptide synthesis, nucleic acid synthesis, or an enzymatic reaction. 13. The integrated modular unit of claim 1 wherein the analyte concentrator-microreactor area of the analyte concentrator-microreactor (ACM) device has an encapsulated cellular and/or subcellular structure. 14. The integrated modular unit of claim 12 wherein the encapsulated cellular or subcellular structure is adapted to perform metabolic studies. 15. The integrated modular unit of claim 1 wherein the analyte concentrator-microreactor area of the analyte concentrator-microreactor (ACM) device has an encapsulated cellular receptor. 16. The integrated modular unit of claim 15 wherein the encapsulated cellular receptor is adapted to perform bioactivity studies. 17. The integrated modular unit of claim 1 wherein the analyte concentrator-microreactor (ACM) device has an acoustic micromixing system. 18. The integrated modular unit of claim 1 wherein the analyte concentrator-microreactor (ACM) device has a microwave pulse system. 19. The integrated modular unit of claim 1 wherein the analyte concentrator-microreactor (ACM) device has a temperature control system. 20. The integrated modular unit of claim 1 wherein the analyte concentrator-microreactor (ACM) device has connecting points to the transport passage and separation passage that are easy to assemble and tightly connected or hermetically sealed. 21. The integrated modular unit of claim 1 wherein the analyte concentrator-microreactor (ACM) device has a fluid controlling system composed of micro-valves operated manually or by electronic-controlled circuitry. 22. The integrated modular unit of claim 1 wherein the controlling means controls the operation of a cleaning buffer fluid means for introducing a cleaning buffer, optimization buffer fluid means for introducing an optimization buffer, sample fluid means for introducing a sample fluid, and washing buffer fluid means for introducing a washing buffer fluid through the transport capillary or passage. 23. The integrated modular unit of claim 22 wherein the controlling means controls the operation of the cleaning buffer fluid means, the optimization buffer fluid means, separation buffer fluid means for introducing the separation buffer supply, and a plug of the eluting buffer supply for introducing the plug of elution buffer supply followed by the separation buffer supply introduced through the separation capillary or passage. 24. The integrated modular unit of claim 1 wherein the analytical separation instrument to which the integrated modular unit, is connected to form an integrated microreaction and/or affinity-capture, desorption or elution, derivatization or tagging, separation, detection, quantification, identification and characterization unit is a capillary electrophoresis instrument in conventional or microchip-microfluidic format, a low-pressure liquid chromatography instrument, a high-performance liquid chromatography instrument, a ultra-pres sure high-performance liquid chromatography instrument, a nano high-performance liquid chromatography instrument, a gas chromatography instrument, or a modified version of these instruments. 25. The integrated modular unit of claim 1 wherein the integrated modular unit formed utilizes one or more detectors of on-line and/or off-line detector types, including ultraviolet, fluorescence, laser-induced fluorescence, mass spectrometer, nuclear magnetic resonance, circular dichroism, electrochemical, conductivity, and radioactive. 26. The integrated modular unit of claim 1 wherein the separation capillary or passage is filled with an electrical conductive fluid that preserves the integrity of the immobilized affinity ligands. 27. The integrated modular unit of claim 1 wherein the separation capillary or passage is filled with a gel matrix containing an electrical conductive fluid that preserves the integrity of the immobilized affinity ligands. 28. The integrated modular unit of claim 23 wherein the plug of an elution buffer or solution contains an organic solvent, a chaotropic agent, a high salt buffer, a low pH buffer, a high pH buffer, a detergent, or a combination of them and/or a chromophoric substance. 29. The integrated modular unit of claim 1 wherein the analyte concentrator-microreactor (ACM) device is color-coded to represent the presence of specific affinity ligands and/or a particular functionality, wherein it is used for the determination of a certain number of analyte biomarkers associated to the diagnosis and/or prognosis of a particular disease or toxic state, and/or to identify the normality-abnormality of a certain organ, tissue, cluster cells, or circulating cell. 30. The integrated modular unit of claim 1 wherein if separation of analytes occurs by capillary electrophoresis, the separation can be carried out by one or more or a combination of any modes of capillary electrophoresis. 31. The integrated modular unit of claim 1 wherein the controlling means comprises a valve system operatively associated with the transport passage and the separation capillary or passage for independently controlling the flow of the sample in the transport passage and separately and independently forming a microenvironment in the staggered concentration-microreaction of the analyte concentrator-microreactor (ACM) device to mix reagents to optimize the binding and capture of the one or more analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart. 32. The integrated modular unit of claim 31 wherein the valve system includes valves which are motor operated and remotely controlled by a processor based on a predetermined set of instructions. 33. The integrated modular unit of claim 1 wherein the valve system includes valves which are manually operated. 34. The integrated modular unit of claim 1 wherein the analyte concentrator-microreactor (ACM) device and the connected transport capillary or passage and the separation capillary or passage has a temperature control system generated by air or a dry system not involving liquid. 35. The integrated modular unit of claim 1 wherein the analyte concentrator-microreactor (ACM) device and the connected transport capillary or passage and the separation capillary or passage has a temperature control system generated by a liquid system surrounding the transport and separation passages. 36. The integrated modular unit of claim 1 wherein the transport passage and separation passage are connected to the analyte concentrator-microreactor (ACM) device through a micro-valve and connector for each single port of four entrance-exit ports respectively of the inlet and outlet ends that connect to the transport capillary or passage and the inlet and outlet ends that connect to the separation capillary or passage of the analyte concentrator-microreactor (ACM) device. 37. An integrated modular unit, comprising: a modular analyte concentrator-microreactor (ACM) device secured to a support;a transport capillary or passage connected to the analyte concentrator-microreactor (ACM) device;a separation capillary or passage connected to the analyte concentrator-microreactor (ACM) device;the analyte concentrator-microreactor (ACM) device having inlet and outlet ends connected to the transport capillary or passage;the analyte concentrator-microreactor (ACM) device having inlet and outlet ends connected to the separation capillary or passage;the analyte concentrator-microreactor (ACM) device having an internal passage or channel with a staggered configuration which includes an elongated concentration area;the elongated concentration area of the analyte concentrator-microreactor (ACM) device serving as an intersection region where the transport capillary and the separation capillary connect at two separate and distant points to form an analyte concentrator-microreactor area;the elongated concentration area of the analyte concentrator-microreactor (ACM) device providing a place of shelter for received microstructures or a matrix assembly;one or more affinity ligands can be immobilized to the microstructures or the matrix assembly localized within the elongated concentration area of the analyte concentrator-microreactor (ACM) device for generating a concentration space where concentration of one or more analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart from a sample introduced into the transport passage occurs and/or for generating a microreaction space where microreaction of the one or more analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart from a sample introduced into the transport passage occurs;alternatively the one or more affinity ligands can be immobilized directly to an internal wall of a cavity or channel forming the elongated concentration area of the analyte concentrator-microreactor (ACM) device without the need of the microstructures or the matrix assembly;controlling means for independently controlling flow of the sample or buffers in the transport capillary or passage and past the analyte concentrator-microreactor (ACM) device and conveyed by electromigration, electro-osmotic flow, mechanical pressure or a combination of electro-osmotic flow and mechanical pressure to an outlet end of the transport capillary or passage, and for separately and independently controlling flow of a separation buffer supply, eluting buffer supply or cleaning buffer supply through the separation capillary or passage and past the analyte concentrator-microreactor (ACM) device and conveyed by electromigration, electro-osmotic flow, mechanical pressure or a combination of electro-osmotic flow and mechanical pressure to an outlet end of the separation capillary or passage; anda cartridge-cassette connected to the inlet and outlet ends of the separation capillary,inlet and outlet ends of the separation capillary connected to the analyte concentrator-microreactor (ACM) device form part of a continuous capillary piece creating an integrated affinity capture-separation and/or microreaction-separation cartridge-cassette modular unit and a detection system can be positioned in operation with a monitoring area of the separation capillary;wherein the modular analyte concentrator-microreactor (ACM) device can capture, isolate, concentrate and separate analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart bound to and released from the analyte concentrator-microreactor (ACM) device by alternating fluid communication of the separation buffer supply and then the eluting buffer supply and delivering the released analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart to the detection system of a capillary electrophoresis instrument or other analytical separation instrument separately, independently and sequentially by electromigration, electro-osmotic flow, mechanical pressure or a combination of electro-osmotic flow and mechanical pressure within the separation capillary or passage; andwherein the analyte concentrator (ACM) device and the cartridge-cassette are manufactured as a single integrated entity. 38. The integrated modular unit of claim 1 wherein the support is a box. 39. The integrated modular unit of claim 37 wherein the support is a box. 40. The integrated modular unit of claim 1 further comprising an auxiliary capillary or passage coupled to the modular analyte concentrator-microreactor (ACM) device. 41. The integrated modular unit of claim 40 further comprising at least one pump connected to the auxiliary capillary passage, the at least one pump functions to generate a gradient of at least one buffer or solutions to benefit the separation of the one or more analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart. 42. The integrated modular unit of claim 37 further comprising an auxiliary capillary or passage coupled to the modular analyte concentrator-microreactor (ACM) device. 43. The integrated modular unit of claim 42 further comprising at least one pump connected to the auxiliary capillary passage, the at least one pump functions to generate a gradient of at least one buffer or solutions to benefit the separation of the one or more analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart. 44. The integrated modular unit of claim 1 further comprising an auxiliary detection system connected via a fiber optic to the separation capillary or passage and positioned downstream of the analyte concentrator-microreactor (ACM) device and upstream of the auxiliary separation capillary or passage. 45. The integrated modular unit of claim 37 further comprising an auxiliary detection system connected via a fiber optic to the separation capillary or passage and positioned downstream of the analyte concentrator-microreactor (ACM) device and upstream of the auxiliary separation capillary or passage. 46. The integrated modular unit of claim 1 wherein the support is a casing, the casing is color-coded to represent the presence of specific affinity ligands and/or a particular functionality, wherein it is used for the determination of a certain number of analyte biomarkers associated to the diagnosis and/or prognosis of a particular disease or toxic state, and/or to identify the normality-abnormality of a certain organ, tissue, cluster cells, or circulating cell. 47. The integrated modular unit of claim 37 wherein the support is a casing, the casing is color-coded to represent the presence of specific affinity ligands and/or a particular functionality, wherein the casing is used for the determination of a certain number of analyte biomarkers associated to the diagnosis and/or prognosis of a particular disease or toxic state, and/or to identify the normality-abnormality of a certain organ, tissue, cluster cells, or circulating cell. 48. An integrated modular unit, comprising: a plurality of modular analyte concentrator-microreactor (ACM) devices attached to a support;a plurality of transport capillaries or passages, each of the transport capillaries or passages being connected to one of the analyte concentrator-microreactor (ACM) devices;a separation capillary or passage connected to each of the analyte concentrator-microreactor (ACM) devices;each of the analyte concentrator-microreactor (ACM) devices having inlet and outlet ends connected to a respective one of the transport capillaries or passages;each of the analyte concentrator-microreactor (ACM) devices having inlet and outlet ends connected to the separation capillary or passage;each of the analyte concentrator-microreactor (ACM) devices having an internal passage or channel with a staggered configuration which includes an elongated concentration area;the elongated concentration area of each of the analyte concentrator-microreactor (ACM) devices serving as an intersection region where the respective one of the transport capillaries or passages and the separation capillary connect at two separate and distant points to form an analyte concentrator-microreactor area;the elongated concentration area of each of the analyte concentrator-microreactor (ACM) devices providing a place of shelter for received microstructures or a matrix assembly;one or more affinity ligands can be immobilized to the microstructures or the matrix assembly localized within the elongated concentration area of each of the analyte concentrator-microreactor (ACM) devices for generating a concentration space where concentration of one or more analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart from a sample introduced into the respective one of the transport capillaries or passages occurs and/or for generating a microreaction space where microreaction of the one or more analytes of interest and/or their respective modified and/or altered corresponding counterpart from a sample introduced into the respective one of the transport capillaries or passages occurs;alternatively the one or more affinity ligands can be immobilized directly to an internal wall of a cavity or channel forming the elongated concentration area of the analyte concentrator-microreactor (ACM) devices without the need of the microstructures or the matrix assembly;controlling means for independently controlling flow of the sample or buffers in each of the respective transport capillaries or passages and past each of the analyte concentrator-microreactor (ACM) devices and conveyed by electromigration, electro-osmotic flow, mechanical pressure or a combination of electro-osmotic flow and mechanical pressure to an outlet end of the respective one of the transport capillaries or passages, and for separately and independently controlling flow of a separation buffer supply, eluting buffer supply or cleaning buffer supply through the separation capillary or passage and past each of the analyte concentrator-microreactor (ACM) devices and conveyed by electromigration, electro-osmotic flow, mechanical pressure or a combination of electro-osmotic flow and mechanical pressure to an outlet end of the separation capillary or passage; andan interchangeable cartridge-cassette detachably connected by couplers to the inlet and outlet ends of the separation capillary,wherein the inlet and outlet ends of the separation capillary form part of a continuous capillary piece creating an integrated affinity capture-separation and/or microreaction-separation cartridge-cassette modular unit and a detection system can be positioned in operation with a monitoring area of the separation capillary;wherein each of the modular analyte affinity concentrator-microreactor (ACM) devices can capture, isolate, concentrate and separate analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart bound to and released from each of the analyte concentrator-microreactor (ACM) devices by alternating fluid communication of the separation buffer supply and then the eluting buffer supply and delivering the released analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart to the detection system of a capillary electrophoresis instrument or other analytical separation instrument separately, independently and sequentially by electromigration, electro-osmotic flow, mechanical pressure or a combination of electro-osmotic flow and mechanical pressure within the separation capillary or passage. 49. The integrated modular unit of claim 48 wherein each of the analyte concentrator-microreactor (ACM) devices is color-coded to represent the presence of specific affinity ligands and/or a particular functionality, wherein it is used for the determination of a certain number of analyte biomarkers associated to the diagnosis and/or prognosis of a particular disease or toxic state, and/or to identify the normality-abnormality of a certain organ, tissue, cluster cells, or circulating cell. 50. The integrated modular unit of claim 48 wherein the support is a casing, the casing is color-coded to represent the presence of specific affinity ligands and/or a particular functionality, wherein it is used for the determination of a certain number of analyte biomarkers associated to the diagnosis and/or prognosis of a particular disease or toxic state, and/or to identify the normality-abnormality of a certain organ, tissue, cluster cells, or circulating cell. 51. An integrated modular unit, comprising: a plurality of modular analyte concentrator-microreactor (ACM) devices attached to a support;a plurality of transport capillaries or passages, each of the transport capillaries or passages being connected to one of the analyte concentrator-microreactor (ACM) devices;a separation capillary or passage connected to each of the analyte concentrator-microreactor (ACM) devices;each of the analyte concentrator-microreactor (ACM) devices having inlet and outlet ends connected to a respective one of the transport capillaries or passages;each of the analyte concentrator-microreactor (ACM) devices having inlet and outlet ends connected to the separation capillary or passage;each of the analyte concentrator-microreactor (ACM) devices having an internal passage or channel with a staggered configuration which includes an elongated concentration area;the elongated concentration area of each of the analyte concentrator-microreactor (ACM) devices serving as an intersection region where the respective one of the transport capillaries or passages and the separation capillary connect at two separate and distant points to form an analyte concentrator-microreactor area;the elongated concentration area of each of the analyte concentrator-microreactor (ACM) devices providing a place of shelter for received microstructures or a matrix assembly;one or more affinity ligands can be immobilized to the microstructures or the matrix assembly localized within the elongated concentration area of each of the analyte concentrator-microreactor (ACM) devices for generating a concentration space where concentration of one or more analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart from a sample introduced into the respective one of the transport capillaries or passages occurs and/or for generating a microreaction space where microreaction of the one or more analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart from a sample introduced into the respective one of the transport capillaries or passages occurs;alternatively the one or more affinity ligands can be immobilized directly to an internal wall of a cavity or channel forming the elongated concentration area of the analyte concentrator-microreactor (ACM) devices without the need of the microstructures or the matrix assembly;controlling means for independently controlling flow of the sample or buffers in each of the respective transport capillaries or passages and past each of the analyte concentrator-microreactor (ACM) devices and conveyed by electromigration, electro-osmotic flow, mechanical pressure or a combination of electro-osmotic flow and mechanical pressure to an outlet end of the respective one of the transport capillaries or passages, and for separately and independently controlling flow of a separation buffer supply, eluting buffer supply or cleaning buffer supply through the separation capillary or passage and past each of the analyte concentrator-microreactor (ACM) devices and conveyed by electromigration, electro-osmotic flow, mechanical pressure or a combination of electro-osmotic flow and mechanical pressure to an outlet end of the separation capillary or passage; anda cartridge-cassette connected to the inlet and outlet ends of the separation capillary,wherein the inlet and outlet ends of the separation capillary form part of a continuous capillary piece creating an integrated affinity capture-separation and/or microreaction-separation cartridge-cassette modular unit and a detection system can be positioned in operation with a monitoring area of the separation capillary;wherein each of the modular analyte affinity concentrator-microreactor (ACM) devices can capture, isolate, concentrate and separate analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart bound to and released from each of the analyte concentrator-microreactor (ACM) devices by alternating fluid communication of the separation buffer supply and then the eluting buffer supply and delivering the released analytes of interest and/or their respective modified and/or altered corresponding molecular counterpart to the detection system of a capillary electrophoresis instrument or other analytical separation instrument separately, independently and sequentially by electromigration, electro-osmotic flow, mechanical pressure or a combination of electro-osmotic flow and mechanical pressure within the separation capillary or passage andwherein the analyte concentrator (ACM) devices and the cartridge-cassette are manufactured as a single integrated entity. 52. The integrated modular unit of claim 51 wherein each of the analyte concentrator-microreactor (ACM) devices is color-coded to represent the presence of specific affinity ligands and/or a particular functionality, wherein it is used for the determination of a certain number of analyte biomarkers associated to the diagnosis and/or prognosis of a particular disease or toxic state, and/or to identify the normality-abnormality of a certain organ, tissue, cluster cells, or circulating cell. 53. The integrated modular unit of claim 51 wherein the support is a casing, the casing is color-coded to represent the presence of specific affinity ligands and/or a particular functionality, wherein it is used for the determination of a certain number of analyte biomarkers associated to the diagnosis and/or prognosis of a particular disease or toxic state, and/or to identify the normality-abnormality of a certain organ, tissue, cluster cells, or circulating cell. 54. The integrated modular unit of claim 37 wherein the support is one or more supports attached to the cartridge-cassette, the one or more supports being received in a respective aperture in the analyte concentrator (ACM) device.
Goldberg, David A.; Howson, David C.; Metzger, Steven W.; Buttry, Daniel A.; Saavedra, Steven Scott, Sensitive and rapid determination of antimicrobial susceptibility.
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