MXPA99001146A - Analytical system and method - Google Patents

Abstract

An analytical or preparatory system comprises as a base unit (12), an adapter (14), and a substrate (16). The adapter (14) is attached to an attachment region on the base unit (12), and the substrate (16) is attached to an attachment region on the adapter (14). The adapter (14) permits the base unit (12) to be interfaced with a wide variety of different substrates (16) to perform chemical and biological analytical analyses and preparatory procedures.

Description

SYSTEM. AND ANALYTICAL METHOD BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates generally to systems and methods for performing chemical and biological analyzes. More particularly, the present invention relates to the design and use of an analyzer system which employs analytical substrates evaluated in a base unit, wherein an adapter is used as an interconnection between the substrate and the base unit. Numerous systems and instruments are available to perform chemical, clinical and environmental analyzes of chemical and biological specimens. Conventional systems may employ a variety of detection devices to verify a chemical or physical change that is related to the composition or other characteristics of the specimen being tested. Such instruments include spectrophotometers, fluorometers, light detectors, radioactive meters, magnetometers, galvanometers, reflectometers, ultrasonic detectors, temperature detectors, pressure detectors, eflometers, electrophoretic detectors, PCR systems, LCR systems and the like. Such instruments are often combined with electronic support systems, such as microprocessors, timers, video display devices, LCD screens, input devices, output devices and the like, in an independent analyzer. Such analyzers can be adapted to receive a sample directly, but more usually, they will be designed to receive a sample placed on a substrate receiving the sample, such as a rod, cuvette, analytical rotor or the like. Usually, the substrate receiving the sample will be made for a single use (ie, that will be disposable), and the analyzer will include circuits, optical devices, devices to manipulate the sample and other structures necessary to perform the test on the substrate . As a result, it is intended that most analyzers work with only one type of substrate receiving the sample and that they are not easily adaptable for use with other substrates. Recently, a new class of sample receiving substrates has been developed, known as "micro-fluid systems". Microfluidic substrates have networks of chambers connected by channels which have such scalar dimensions, wherein at least one dimension is usually between 0.1 μm and 500 μm. Such microfluidic substrates can be manufactured using photolithographic techniques. similar to those used in the semiconductor industry, and the resulting devices can be used to perform a variety of sophisticated chemical and biological analytical techniques. Microfluidic analytical technology has numerous advantages, including the ability to use very small sample sizes, typically in the order of nanoliters. Substrates can be produced at a relatively low cost, and can be given formats to perform numerous specific analytical operations, including mixing, distribution, valving, reactions, and detections. Due to the variety of analytical techniques and potentially complex sample flow patterns that can be incorporated into particular micro-fluidic test substrates, significant demands can be placed on the analytical units that support the test substrates. The analytical units not only have to manage the direction and timing of the flow through the network of channels and reservoirs on the substrate, but they also have to provide one or more physical interactions with the samples at locations distributed around the substrate, including the heating, cooling, exposure to light or other radiation, detection of light or other emissions, measurement of electrical / electrochemical signals, pH, and the like. The management of flow control can also comprise a variety of interactions, including applications with a particular pattern of voltage, current, or energy to the substrate (for electrokinetic flow control), or the application of pressure, acoustic energy, or other interventions mechanical to otherwise induce the flow. It can be seen in this way that a virtually infinite number of specific test formats can be incorporated into the microfluidic test substrates. Due to such variety and complexity, many if not most of the test substrates will require analyzers configured specifically to perform a particular test. In fact, it is possible that particular test substrates employ more than one analyzer to perform different tests. The need to provide a dedicated analyzer for each substrate and test, however, will significantly reduce the flexibility and cost advantages of microfluidic systems. Therefore, it would be desirable to provide improved analytical systems and methods which overcome or substantially mitigate at least some of the problems discussed above. In particular, it would be desirable to provide analytical systems that include base analytical units, which can support a number of different microfilm or test substrates having substantially different flow patterns, chemical properties and other analytical characteristics. It would be particularly desirable to provide analytical systems where the cost of modifying a base analytical unit to perform different tests on different test substrates is significantly reduced. 2. Description of the Background Art Microfluidic devices for analyzing samples are described in the following patents and published patent applications: U.S. Patent Nos. 5,498,392; 5,486,335; and 5,304,487; and WO 96/04547. An analytical system having an analytical module which is connected to an expansion vessel of a computer for general purposes is described in WO 95/02189. A sample typically present on an analytical rotor or other sample holder may be placed in the receptacle and the computer used for the control analysis of the sample in the module. Chemical analysis systems are described in U.S. Patent Nos. 5,510,082; 5,501,838; 5,489,414; 5,443,790; 5,344,326; 5,344,349; 5,270,006; 5,219,526; 5,049,359; 5,030,418; and 4,919,887; published European applications EP 299 521 and EP 6 031; and Japanese applications published JP 3-101752; JP 3-094158; and JP 49-77693. The description of the present application relates to the following co-pending applications, the entire description of which is incorporated herein by reference, application no. 60/015498 (provisional), filed in TAbril 16, 1996; request no. 08 / 671,987, filed June 28, 1996; request no. 08 / 671,986, filed June 28, 1996; request no. 08 / 678,436, filed July 3, 1996; and the request does not. 08 / 683,080, filed on July 16, 1996.

BRIEF DESCRIPTION OF THE INVENTION The present invention overcomes at least some of the deficiencies described above by providing systems and analytical methods and preparations which employ an adapter for interfacing between a sample substrate and an analytical base unit. The sample substrate is usually a microfluidic substrate but could be any other sample substrate capable of receiving test specimens or starting materials to process or provide a detectable signal, wherein the base unit manages the flow of the sample, the flow of the sample. reactive, and other aspects of the analytical and / or preparative techniques carried out on the substrate. The adapter allows a single type of base unit, i.e., a base unit having a particular configuration, to interface with a large number of test and other substrates that have very different configurations and to administer numerous specific analytical and preparatory techniques on substrates with little or no reconfiguration of the base unit itself. The methods and devices will find use with the techniques, analytical and preparative. By "analytical", it is understood that the test or process has as its main objective to detect and / or quantify an analyte or analytes in a test specimen. By "preparative", it is understood that the process has as its main objective to produce one or more products from one or more starting materials or reagents. The remaining description relates mainly to analytical methods and devices, but for the most part, all the technology described will be equally useful for preparing materials for other subsequent uses. In a first aspect, the present invention provides an analytical system comprising a base unit having a junction region with an interconnection arrangement of the base including at least one interconnection component therein. An adapter that is configured to be removably ched to the junction region of the base unit and has an adapter-base interconnection arrangement which also includes an interconnect component. The adapter-base interconnection arrangement is coupled with the interconnection arrangement of the base when the adapter is ched to the base unit, and at least some of the interconnection components in each arrangement will be coupled or interconnected. The adapter further includes a binding region of the sample substrate having an adapter-substrate interconnection arrangement of sample in him. The sample adapter-substrate interconnection arrangement will usually also include at least one interconnection component (but in some cases it could act primarily to place the interconnection components on the base units relative to the interconnection components on the sample substrate) . A sample substrate is configured to removably attach to the binding region of the sample substrate of the adapter and in itself includes an interconnection array of a sample substrate which usually includes at least one interconnecting component. The interconnection components in the interconnection array of the sample substrate will be coupled with the corresponding interconnection components in the sample adapter-substrate interconnection array and / or in the interconnection arrangement of the base when the substrate is attached to the substrate. binding region of the sample substrate. Providing an adequate interconnection component in each of the interconnection arrangements, energy connections and / or signals can be made between the base unit and the sample substrate in a virtually infinite number of patterns. In some cases, the base unit will provide only power and signal connections to the adapter, while the adapter will provide a relatively complex sample adapter-substrate interconnection arrangement to manage the flow, other operating parameters, and detection on the substrate shows. In other cases, however, the interconnection arrangement of the base on the base unit may be more complex, including for example, light sources, detectors, and / or high voltage power, and the adapter will be less sophisticated, often , acting mainly to place the sample substrate in relation to the interconnection components on the base unit, channeling voltages, and allowing direct communication between the base unit and the sample substrate. Exemplary interconnecting components include electrical power sources, analog signal connectors, digital signal connectors, power transmission sources, energy emission detectors, other detectors and sensors, and the like. Sources of energy transmission can be light sources, acoustic energy sources, heat sources, cooling sources, pressure sources, and the like. Energy emission detectors include light detectors, fluorometers, UV detectors, radioactivity detectors, heat detectors (thermometers), flow detectors, and similar 1Qs. Other sensors and sensors for measuring-the pH, electrical potential, current, and the like can be provided. It should be appreciated that interconnecting components will often be provided in pairs when a component in an array is coupled or linked to a corresponding component in the coupling array to provide the power transformer, signals, or other information. however, they do not need to have such components in pairs, and often the power transmission sources or emission detectors will be provided without a corresponding interconnection component in the coupling interconnection array.The base unit, the adapter and the substrate Samples will be configured so that they can be physically joined together to form the analytical system, for example, the junction region in the base unit can be a cavity, well, slot, or other receptacle that receives the adapter, where the The dimensions of the receptacle are selected to be coupled with the adapter. ilar, the junction region on the adapter may comprise a receptacle, well, slot, or other space that is intended to receive the sample substrate and the position of the substrate appropriately in relation to the adapter or the base unit. The sample substrate will preferably employ mesoscale fluid channels and reservoirs, ie, wherein the channels have at least one dimension in the range of 0.1 μm to 500 μm, usually 1 μm to 100 μm. The present invention, however, is not limited to the particular form in which the base unit, adapter and substrate are attached and / or to the particular dimensions of the flow channels on the sample substrate. Although described as a system of three connections, it should be understood that additional components or "connections" can be used. For example, additional carriers or adapters could be used to provide additional interfaces or interconnections, such as a carrier for the sample substrate, where the carrier would be mounted inside or be attached to the adapter, which is received on the base unit. Similarly, the junction region in the base unit receiving the adapter may comprise a discrete component, which is itself removable Q is permanently fixed to the base unit. The formation of the junction region using a discrete component is advantageous since it facilitates the standardization of the system. For example, the adapter region component of the adapter could be manufactured separately, optionally in a single location, and / or in other circumstances prepared for strict specifications, both of which would help ensure that the base units incorporating such junction regions standardized are compatible with all corresponding adapters. The junction region of the standardized adapter would also be adapted to interconnect with other components of the base unit, such as heaters, cooling blocks, bolt connections and the like, thereby facilitating interconnection with those elements. Thus, systems having four or more connections fall within the scope of the present invention. In a second aspect of the present invention, the analytical system comprises a base unit and a sample substrate, as generally described above. An adapter is configured to removably attach to the junction region of the base unit and includes a junction region to removably receive the sample substrate. The adapter holds the sample substrate in a fixed position relative to the base unit and provides (i) a connection path of an interconnection component in the interconnection arrangement of the base to the substrate or (ii) a connection path of an interconnection component in the arrangement of the sample substrate towards the base unit. In this aspect of the present invention, the adapter can act primarily to place a sample substrate relative to the interconnection array in the base unit. For example, if the interconnection arrangement of the base unit includes a light source and / or light detector, the adapter can appropriately place the sample substrate relative to the light source / detector to effect a desired measurement. The adapter could optionally, but not necessarily, provide additional interconnection capabilities between the sample substrate and the base unit. In yet another aspect of the present invention, adapters are provided for use in combination with base units and sample substrates, as described above. The adapter comprises an adapter body having an adapter-base interconnection arrangement that includes at least one of an energy connector and a signal connector positioned to couple with the corresponding connector (s) in the interconnection arrangement of the adapter. the base when the adapter is attached to the junction region on the base unit. The adapter further includes a binding region of the sample substrate having a sample adapter-substrate interconnection arrangement that includes at least flow deflection connectors positioned to couple with the corresponding regions in the interconnection array of the sample substrate when the sample substrate is bonded to the attachment region of the adapter. Flow deflection connectors will commonly be electrodes for the control of electrokinetic flow in microfluidic substrates that are scalable and other, although they could also be components that produce acoustic, pressure or mechanical flow. The sample adapter-substrate interconnection array will often include interconnecting components in addition to the flow deflection connectors, such as radiation emission and detection components positioned to interconnect with particular regions of the sample substrates. The base unit can be autonomous, that is, it can include all digital and / or analog circuits as well as input / output interconnections that are necessary to control a test and produce test results of the system. Often, however, it will be preferable to interconnect the base unit with a computer for general or conventional purposes, where the computer can provide some or all of the control analyzes and / or reporting functions, as well as some or all of the interconnections or user interfaces. Usually, the computer will be a standard personal computer or workstation, which operates in a standard operating system, such as DOS, Windows® 95, Windows® NT, UNIX, Macintosh, and the like. The computer will be able to provide a number of standard user input devices, such as a keyboard, hard disk, floppy disk, CD player, as well as user outputs, such as screens, printers, floppy disks, writable CD outputs , and similar. The use of the computer is particularly advantageous, since it can significantly reduce the cost of the base unit and allow a meaningful update of the computer system component while using the same base unit. Despite these advantages, in some cases it may be desirable to incorporate the interconnection and digital circuits of a computer in the base unit of the present invention, which allow all the capabilities of a conventional digital computer, but with perhaps less flexibility. When the system of the present invention is controlled via digital circuits, i.e., using a separate conventional computer interconnected with the base unit or using digital control circuits incorporated within the base unit, it will usually be desirable to provide at least a portion of the instructions of operation associated with any particular adapter and / or any particular sample substrate and test format in a computer readable form; that is, in a conventional computer storage medium, such as a floppy disk, a compact disc (CD ROM), tape, flash memory, or the like. The medium will store the computer readable code indicating the desired instructions, wherein the instructions will be able to interconnect the computer (which can be a separate or integrated computer) with the base unit and control a test performed by the base unit on the sample present on the sample substrate maintained by an adapter received on the base unit. The present invention thus comprises a computer program itself in the form of a tangible medium, for example, disk, CD, tape, memory, etc., which can be used in combination with the system of the present invention. The present invention further comprises systems, which include an adapter as discussed above in combination with the tangible medium that stores the instructions described above in the computer. The present invention further comprises systems which are combinations of one or more sample substrates as set forth in a general manner above, together with a tangible means indicating the computer readable code comprising the instructions indicated above. The computer program can be provided to the user preloaded in the desired medium, usually a floppy disk or a CD ROM, or alternatively can be downloaded to the medium by the user from a central location via a network, over telephone lines, or via other means of communication and transmission available. The program will then be incorporated into the medium and will be available for use in the systems and methods of the present invention. In a still further aspect of the present invention, a method for configuring an analytical system comprises providing a base unit having a junction region that includes at least one interconnect component therein. An adapter is removably attached to the region of the base unit so that an interconnection component on the adapter is coupled with a corresponding interconnect component on the base unit. The adapter includes a binding region of the sample substrate having at least one interconnect component therein, and a sample substrate removably attaches to the binding region of the sample substrate on the adapter, so that one component of interconnection on the sample substrate is coupled with a corresponding interconnection component on the adapter. Usually, but not necessarily, the adapter removably attaches to the base unit by placing the adapter into a receptacle on the base unit, and a sample substrate removably attaches to the adapter by placing the sample substrate into a receptacle on the adapter. The sample substrate will preferably be a microfluidic device having a plurality of channels that connect to a plurality of reservoirs and that include flow deviation regions placed in one of the reservoirs and / or channels. The base unit can then direct or manage the flow of the substrate by providing flow control signals to the adapter. The flow control signals energize the regions of flow deflection on the adapter so that the corresponding flow deflection regions on the substrate are energized to control the flow through the channels and between the reservoirs. For example, flow control can be effected by electrodes that are electrically shunted onto the sample substrate to produce an electrokinetic flow control. Alternatively, the energizing step may comprise acoustically activating the flow deflection regions on the sample substrate. Usually, the adapter will include sources of electromagnetic radiation and detectors to generate and detect signals in a variety of analytical techniques. Any of the above control steps can be implemented by providing a computer-readable code to an integrated or separate computer, which controls the analytical system.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 illustrates a first embodiment of an analytical system that incorporates the features of the present invention. Figure 2 illustrates a second embodiment of an analytical system that incorporates the features of the present invention. Figure 3 is a block diagram illustrating the flow of information between the different components of the system of the present invention. Figure 4 illustrates an exemplary analytical system incorporating the system components of the present invention.

DESCRIPTION OF THE SPECIFIC MODALITIES The analytical systems according to the present invention comprise a base unit, an adapter and a sample substrate. Each of these parts of the system will be described in detail below.In general, the analytical systems will be configured to receive and analyze a wide variety of samples and specimens.For example, the samples can be biological specimens of a patient, but also can be of a wide variety of other biological, chemical, environmental and other specimens that have a component to be characterized or analyte to be detected.The analytical systems can be used to implement numerous specific analytical and / or preparative techniques, such as Chromatography, PCR, LCR, enzymatic reactions, immunological reactions, and the like, samples will usually be liquid or liquefied before being tested, and will often undergo a chemical or biological reaction before analysis.Analytical systems can provide a variety of manipulations. the sample in addition to the reactions that emic and biological, such as mixing, distribution, valving, separation, heating, cooling, detection and the like. Analytical systems may depend on numerous known detection techniques such as spectrophotometry, fluorometry, radiometry, magnetometry, galvanometry, reflectometry, ultrasonic detection, mephlometry, electrophoretic measurements, temperature measurements, pressure measurements, potentiometric measurements, amperometric measurements and the like. In the case of the following exemplary and preferred embodiments, the manipulation and detection of the sample are carried out on microfluidic substrates where the sample is manipulated between reservoirs of very small volume and channels of fiow formed in the substrate. Usually, all flow and test conditions on the substrate will be controlled through the base unit and adapter, as described in greater detail below. The base unit of the present invention will typically comprise an enclosure or frame which can be used for mounting, for example, on the floor, or on a counter, on a support, or in any other conventional form, or which can be portable or manual. The base unit will usually include at least power circuits and / or signal transmission, and will usually include the ability to process signals to assist in analyzing and / or storing the data received from the adapter as described in greater detail below. The base unit will usually also include a microprocessor to help administer both its substrate management and data collection work. Optionally, visual information display devices in the form of video monitors, alphanumeric display devices, printers, LED display devices and the like, on or in the frame, often together with data entry devices, may be provided, such as keyboards, touch-sensitive screens and the like. In exemplary embodiments, however, the base unit includes only a plug connector for interfacing with an external computer, where the computer provides the necessary input and output devices. In such cases, the base unit will often, but not necessarily, include an internal microprocessor to control or help control the internal operations of the base unit and the adapter. Alternatively, a microprocessor could be provided in the adapter, with the base unit providing only interconnection functions between the adapter and the computer. In other cases, all control functions will be managed through the separate computer with the base unit and the adapter providing only distribution and interconnection functions. Again, it should be appreciated that the availability of both the base unit and the adapter provide a very wide range of specific designs with different functions that are selectively distributed between the adapter and the base unit for particular sample and substrate designs. The base unit will include a joining region to removably secure the adapter. The junction region on the base unit has a base interconnection arrangement that includes at least one, and usually multiple, interconnection components that are intended to provide power and / or information communication with the adapter. The interconnection component (s) comprises a wide variety of devices as described in greater detail below. The joining region can be any feature or structure on the enclosure or frame of the base unit that can be removably attached to the adapter. The junction region will usually be constructed so that the adapter can be connected in a unique configuration exclusively, so that the interconnection arrangement of the base will be uniquely configured in relation to the adapter. The binding region can have a wide variety of shapes, such as receptacles, wells, grooves, trays (similar to a CD tray), or the like. Often, the junction region will define a receptacle having dimensions which correspond to the peripheral outlet dimensions of the adapter, so that the adapter can be maintained in a desired orientation relative to the base unit. Alternatively, or in addition, legs, bolts, fasteners or other attachment elements may be provided to hold the adapter on the base unit in a desired orientation. The adapter will also comprise an enclosure or frame, although the enclosure or frame will usually be significantly smaller than that of the base unit. The enclosure or frame will be adapted to be received over or in the junction region of the base unit, as discussed generally above, and will itself include a junction region to removably secure the sample substrate. The binding region on the adapter can take any of the forms discussed above for the binding region on the base unit, and it will usually be necessary for the binding region to immobilize the sample substrate in a particular orientation relative to the adapter. The adapter will include an adapter-base interconnection arrangement which meets with or engages the interconnection arrangement of the base when the adapter is mounted in the junction region on the base unit. The adapter-base interconnection array will include at least one interconnect component which is coupled with a corresponding interconnect component within the interconnect array of the base, usually to provide the power and / or signal connection between the base unit and the adapter. The interconnecting components can provide a wide variety of additional interconnections, and will be described in greater detail later. The binding region of the sample substrate will include an interconnection array of the adapter-sample substrate that is intended to be coupled with or connected to a sample substrate interconnection array on the sample substrate when the sample substrate is. a joined the union region. The substrate adapter-substrate interconnection array itself will include at least one interconnect component which can be any of the components described in greater detail below. Usually, the sample adapter-substrate interconnection arrangement will include multiple interconnect components which are either placed or. distributed in a selected pattern to be coupled with at least some corresponding interconnecting component in the sample substrate array on the sample substrate. The sample substrate can comprise any of a variety of known analytical devices or articles that are intended to receive a sample and process the sample in some manner to provide a detectable output that can be related to a characteristic of the sample, for example, the presence of an analyte, the composition or nature of a molecule present in the sample (e.g., protein or nucleic acid sequence) or the like. It is particularly intended that the present invention be used with a microfluidic mixing substrate of the type described in US Patent Nos. ,498,392; 5,486,355; 5,304,487; and the published PCT application WO 96/04547, the descriptions of which are incorporated herein by reference. Suitable microfluidic substrates are also disclosed in commonly assigned co-pending patent applications Nos. 08 / 761,987, filed on June 28, 1996, and 08 / 845,759, filed on April 25, 1997, all descriptions of which are incorporated herein by reference. reference. A particular advantage of the present invention is that the adapter can be configured to receive any of a variety of specific sample substrate configurations. In that way, the designer of the sample substrate is free to optimize the size, design, flow paths and other characteristics of the sample substrate regardless of the nature of the base unit. Within a broad latitude, the most specific design characteristics of the sample substrate can be accommodated by designing an adapter properly. Although this advantage is available, it is also possible that the sample substrate design takes into account specific characteristics and design characteristics of either or both of the base unit and the adapter. It should be appreciated that the architecture of the system employing the adapter as an interconnection between the sample substrate and the base unit provides significant design flexibility. The sample substrate will have dimensions and other features selected to allow removable attachment to the binding region, as discussed generally above. The sample substrate will further include the interconnection arrangement of the substrate which includes at least one interconnection component placed to mate with a corresponding interconnection component on the interconnection arrangement of the sample substrate-adapter on the adapter. Again, the interconnection components can comprise any of a wide variety of particular devices and elements, as discussed in more detail. Interconnecting components on the adapter and the sample substrate will generally be able to provide flow control administration of the sample and other liquid reagents present and applied to the sample substrate and will further provide interconnection of the energy and signals between the adapter and the sample substrate. As used herein and in the claims, the phrase "interconnection component." refers to any of a wide variety of discrete components or regions present in the interconnection arrangements on the base unit, adapter, or substrate, sample. The interconnecting components will generally provide electrical or other power transfer, analog or digital signal transfer, power transmission, energy emission detection and the like. The electrical connections, both of energy transfer and of signals, will generally comprise conventional connectors in the form of electrodes, pins, pins, zero insertion force (ZIF) connectors, and the like. Such electrical connections will usually require coupling connectors in two of the interconnection arrangements that are put together when the system is put together. The electrical connectors will often be present on a surface or edge of the interconnection arrangement so that the corresponding components will be coupled together when the adapter is mounted on the base unit or the substrate is mounted on the adapter. Similarly, surface or edge electrodes may be provided in the interconnection array of the sample substrate-adapter to be coupled with the corresponding surface or edge electrodes on the sample substrate. The electrodes on the sample substrate can then be connected internally in the substrate to the desired reservoirs or fluid flow channels to effect the electrokinetic flow control, as described in the patents and patent applications incorporated above. In other cases, however, it is desirable to provide interconnection components in the interconnection array of the sample substrate-adapter, which are directly in contact with the fluid to be electrokinetically controlled. For example, probes or bolts may be provided on the adapter which will penetrate the open wells or through septa on the sample substrate to allow direct contact and direct application of the electrical potential. A specific example of such connectors is shown in Figure 2 below. It is generally intended that the energy transmission sources energetically excite a region on the test substrate or provide energy to initiate the flow of fluids on the sample substrate. Energy can take a wide variety of forms, including light, such as visible light and UV light, acoustic energy, heat, cooling, pressure, mechanical energy, electrical power and the like. In the case of sample detection, the source of energy transmission may be light or other radiation that is intended to excite a species or mark to be detected. Heating / cooling may be provided to help effect or condition a particular chemical reaction. Acoustic, pressure, and mechanical energy can be provided to directly affect the flow of fluid in the channels of microfluidic sample substrates. It should be appreciated that such power transmission sources do not necessarily have corresponding interconnection components in an adjacent interconnection array. Instead, the transmission of energy will often be directed in a general manner to regions on the sample substrate where the energy will be received.

The energy emission detectors may be provided, usually on the adapter and / or the base unit, to detect the energy emitted from the sample substrate. For example, "detection reactions can result in the emission of light via fluorescence, luminescence, radiation or other energy emissions that need to be detected and / or quantified to perform a particular analysis.The appropriate detection components can be provided in the adapter and / or base unit, and the adapter positioned to properly align the substrate in the detectors A particular class of interconnecting components employed by the analytical system of the present invention are known as "flow deflection connectors." that the diversion and flow connectors identify those interconnection components which can perform the flow of fluid on the sample substrates, particularly on the microfluidic substrates that have a network of flow channels and reservoirs For the microfluidic substrates they employ the administration of the electrokinetic flow, the flow diversion devices on the adapter will usually be electrodes, probes, pins, or the like distributed within or on the interconnection array of the sample substrate-adapter to be coupled to the network of flow channels and reservoirs on the sample substrate as shown in FIG. described generally above and in the references incorporated above. The electrodes will usually have corresponding electrode terminals present within the interconnection array on the sample substrate, so that the electrode terminals can be interconnected to the corresponding electrical connectors on the interconnection arrangement of the sample substrate-adapter on the adapter ( or in rare cases on the interconnection arrangement of the base on the base unit). In other cases, as described above, the flow deflection connectors may be probes, or bolts on the adapter which are positioned to directly engage with the fluids present on or in the sample substrate. For example, an array of bolts on an articulated cover or cover may be provided on the adapter plate, so that the sample substrate may be placed on the adapter and the cover or cover subsequently closed to penetrate the bolts into the sample wells. open on the substrate. The sample wells, of course, do not need to be open and could be covered with any penetrable membrane or septum that is pierced by the bolts when the lid or cover is closed. Other flow deflection connectors include acoustic energy sources (piezoelectric transducers) placed within the sample adapter-substrate interconnection arrangement, so that they are coupled to the sample substrate at the points where the flow of the sample is to be induced. fluid through the flow channels. Other flow deflection connectors include pressure sources which can initiate the flow by pressurization, mechanical energy sources, which can perform the mechanical pumping of the liquids through the flow channels, and the like. Referring now to Figure 1, a first exemplary analytical system 10 constructed in accordance with the principles of the present invention comprises a base unit 12, an adapter 14, and a sample substrate 16. The base unit 12 includes a bolt plug 20 for coupling with a plug 22 on a lower surface of the adapter 14. A computer gate 24 is provided for coupling with conventional serial or parallel inputs on computers for general purposes, such as personal computers, work stations and the like. Usually, base 12 will include at least signal processing and conditioning components, such as analog-to-digital converters to receive analog data from the adapter 14 and convert that data to a digital form for transmission to the computer. In other cases, however, the computer can be adapted to convert analog signals directly to digital data. The base unit 12 and / or the adapter 14 could also be provided with digital-to-analog converters to control energy, flow, or any other parameters directly from the digital signals of the computer. The adapter 14 may also include internal microprocessors for additional data handling. The adapter 14 may also include a power input, for an AC current line (Alternating Current) and / or low voltage DC (Direct Current) current (which may be provided by means of a power supply in the base unit 12). ). The bolt plug 20 is usually provided for power interconnection and signal exchange between the base unit 12 and the adapter 14. Locating bolts 28 are provided on a top surface of the base 12 to engage the locating holes 30 on the adapter 14. In this way, the entire upper surface of the base unit 12 will provide the junction region for the adapter 14 while the bolt socket 20 will generally provide the interconnection arrangement of the base-adapter with the individual bolts providing the components of interconnection. A plug 22 comprises the interconnection arrangement of the adapter-base on the adapter 14. The plug 22 provides power and signal connections to the base unit 12 and the adapter further provides an optical source and the detector 34 and a heating / cooling element. 36, both of which are coupled to particular regions on the sample substrate 16, as described further below. The adapter 14 further includes an edge connector 40 which includes a number of electrodes 42 which engage the corresponding electrodes 44 on an edge of the sample substrate 16. The sample substrate 16 is removably attached to the adapter 14 by sliding the substrate between a pair of guides 46 which are formed by parallel L-shaped channels on the upper surface of the adapter 14. When the sample substrate 16 is completely inserted between the guides 46 with the electrodes 44 received in the edge connector 40, a reaction site 50 on the sample substrate 16 is aligned with the optical source of the detector 34 on the adapter 14 and a heat treatment region 52 is aligned with the heater / cooler 36 on the adapter. In this way, the optical source detector 34, the heater / cooler 36, and the edge connector 40 comprise the interconnecting components in the attachment region of the adapter 14. The sample substrate 16 comprises a plurality of sample wells. reagents 60, each of which are coupled to an electrode 44 in the interconnection array. In this way, the flow of samples on the sample substrate can be controlled through the base unit 12 and the adapter 14 to control the energy through the electrodes 42. It should be appreciated that the energy can be provided directly by the unit base 12, case in which the adapter 14 acts simply to distribute the energy. Alternatively, the base unit 12 can provide information to the adapter, and the adapter 14 generates power internally, which is distributed through the electrodes 42. In any case, the sample flow between the reservoirs and a network of flow 66, is controlled in a desired manner. A portion of the sample and mixed reagents will flow through the heating / cooling region 52, where it will be treated appropriately. Again, the amount of heat or cooling supplied by region 36, is provided and controlled by a combination of the base unit 12 and the adapter 14, where specific functions can be provided by any of those two components. An output signal resulting from one or more reactions is eventually read in the reaction region 50 by the optical source / detector 34. The output of the optical detector 34 will be passed back to the base unit 12 through the pin plug 20 and the male plug 22. The optical detector will usually produce an analog signal, and such an analog signal can be converted to digital in either the adapter 14, the base unit 12 or the external computer (not shown). A second exemplary embodiment 100 of the analytical system of the present invention is illustrated in Figure 2. The analytical system 100 includes a base unit 112, an adapter 114, and a sample substrate 116. The base unit 112 is similar in many respects to the base unit 12 of Figure 1, and includes location pins 128, a bolt plug 120, and a computer gate 124. The base unit 112, however, further comprises an optical source / detector 134. This is different of the analytical system 10, wherein the optical source / detector 34 was provided as part of the adapter 14. The adapter 114 comprises a plate 115 having an opening 117 at its center. When the adapter 114 is mounted on the base unit 112, the opening 117 will generally rest on the optical source / detector 134. The adapter 114 further includes an articulated cover cover 119, which is used to cover and position the sample substrate 116 on the top of the plate 115. When the sample substrate 116 is placed, and the hinged cover or lid 119 is closed, a plurality of probes 121 on the bottom surface of the lid or cover will penetrate the sample and reagent wells. on the sample substrate 116. The wells 160 may be completely open or may be covered by a penetrable membrane or septum. The probes 121 will thus be immersed in and in direct contact with the liquids present in the wells 160. In this way, an electrical deviation can be provided to effect the administration of the electrokinetic flow through the network of channels 166 on the substrate sample 116. Sample substrate 116 includes a "reaction zone 150, which is, usually at least partially transparent or translucent to allow light from the detector of optical source 134 to reach the fluid in the region and allow The emitted and detected light from the region 150 will pass through the opening 117 in the adapter 114, so that it can be directly coupled to the optical source / detector 134. Again, there is a difference with the analytical system 10 of Figure 1, wherein the detection is directly effected between the adapter 14 and the sample substrate 16. It should be understood that The exemplary analytical systems 10 and 100 are intended to be representative of a virtually infinite number of possible system configurations. The use of an adapter 14 or 114 allows the different energy, signal and other functions of the analytical system to be included in any of the adapter, base unit, substrate or external computer in virtually any form, so that any particular analytical technique can be supported optimally by the system. Referring now to Figure 3, a system 200 according to the present invention can be configured in a wide variety of ways. For example, a base unit 212 may comprise a single monolithic instrument containing all the control and analysis components necessary to perform an assay (in combination with the adapter 214 and the sample substrate 216), needing only to be connected to the current the line or another source of energy. The base unit 212, however, it will be connected to a general-purpose computer 220, such as a personal computer or a workstation, which provides at least a portion of the system's input / output, control, and computational functions. _220 can be connected by any conventional connectors, typically using two input gates in series or in parallel. The computer will be programmed using program 222, which can be in the form of any conventional computer media. The program will include instructions for all or a portion of the computer's functions.

For example, the program may comprise the operating system used to perform all the analyzes using the system of the present invention. Alternatively, the computer can use a conventional operating system capable of controlling functions in real time, as discussed above. The 222 system test program will usually include system instructions that are general and apply to many tests, as well as system instructions that are specific to any particular test. The instructions can be included in a single disc or other medium, or they can be included in multiple discs, which can then be combined in a desired form to perform a particular assay. Alternatively, the test program may be downloaded to the base unit and / or to a storage medium via a network, the internet, or, otherwise, as set forth above. The system program will include functions such as the assignment of the initial system values, test format, computation instructions, user / patient input instructions and the like. Thus, it can be seen that the base unit 212 and the computer 220 will generally be useful for performing many different types of tests, while the adapter 214 and the sample substrate 216 will be more specifically directed to the particular test (s). ). One type of adapter 214 may be compatible with multiple sample substrates 216 which are intended to perform two or more different assays, wherein the system test program 222 may allow adapter 214 and base unit 212 to properly interconnect with the sample substrate. 216. In the systems according to the present invention, they will thus further comprise the combination of the test equipment 222 with any adapter 214, sample substrate (s) 216, or both. That is, a user who already has a monolithic base unit 212 or a combination of base unit 212 and computer 220 can subsequently acquire the combination of the system test program 222 and the adapter 214 that is intended to operate in a test or trials. particular. By later mounting the adapter 214 on the base unit and loading the program 222 on the computer 220 / base unit 212, the system will be configured to receive sample substrates to analyze particular test specimens for the desired analyte. Alternatively, when an adapter 214 is suitable for two or more tests, the user may subsequently acquire the combination of the test program 222 and the test substrate (s) 216, which allows the pre-existing combination of the computer 220, the base unit 212 and the adapter 214_ carry out a new test. In some cases, the combination of the adapter 214, the sample substrate (s) 216 and the system test program 222 will also be provided to the user. Referring now to Figure 4, a configuration of an exemplary system 300 is illustrated. The system 300 comprises a base unit 312, an adapter 314, and a sample substrate 316. Additionally, a universal adapter 320 is provided as a discrete component for the removable or permanent assembly on the base unit 312. The universal adapter 320 defines the junction region on the base unit 312 to receive the adapter 314. The base unit 312 provides system functions, such as an optical source / detector 322 and a heating plate 324. The universal adapter 320 is mounted on the heating plate 324 on a supporting surface 326 of the base unit 312. The base unit 312 is then ready to removably receive the adapter plate (s) 314, which in turn are ready to receive the sample substrates 316. The different interconnections between the components of the The system can follow any of the patterns described above in relation to the systems of Figures 1 and 2. The use of the universal adapter 320 is advantageous, since it facilitates the standardization of the interconnection between the base unit 312 and the adapter 314. , can interconnecting a single base unit 312 (or base unit design) with an even higher range of adapters 314 using different classes or types of universal adapters, each of which may have alternative interconnection functionalities and patterns. Although the above invention has been described in some detail by way of illustration and example, for purposes of clarity of understanding, it should be obvious that certain changes and modifications may be practiced within the scope of the appended claims.

Claims (42)

1. REVINDICATORY CHAPTER Having described the invention, it is considered as a novelty and, therefore, what is contained in the following CLAIMS is claimed: 1. A system for manipulating materials, characterized in that it comprises: a base unit that has a region of union with a interconnection arrangement of the base that includes at least one interconnection component in it; an adapter configured to be removably attached to the junction region and having an adapter-base interconnection arrangement that includes at least one interconnection component placed to mate with a corresponding interconnection component in the interconnection arrangement of the base when the adapter is attached to the junction region, a binding region of the substrate, and an adapter-substrate interconnection arrangement having at least one interconnect component therein; and a substrate configured to be removably attached to the attachment region of the adapter substrate and having a substrate interconnection arrangement that includes at least one interconnection component placed to mate with a corresponding interconnection component in the interconnection array. of adapter-substrate when the substrate is attached to the binding region of the substrate.
2. 2. The analytical system according to claim 1, characterized in that the interconnection arrangement of the base includes at least one interconnection component. Selected from the group consisting of electrical power sources, analog signal connectors, digital signal connectors, power transmission sources, electrical / electrochemical signal detectors, pH detectors, and energy emission detectors. The analytical system according to claim 1, characterized in that the arrangement of the substrate-adapter includes at least one interconnection component selected from the group consisting of electrical power sources, analog signal connectors, digital signal connectors, energy transmission, pH detectors, energy emission detectors, and electrical / electrochemical signal detectors. 4. The analytical system according to claim 1, characterized in that the sources of energy transmission are selected from the group consisting of light sources, acoustic energy sources, heat sources, cooling sources, and sources of energy. Pressure. 5. The analytical system according to claim 1, characterized in that the base unit comprises a digital processor. The analytical system according to claim 1, characterized in that the interconnection arrangement of the base comprises at least electrodes of electric power placed to couple with the electric power electrodes on the adapter-base interconnection arrangement of the adapter and at least the electrodes of 10 electrical signals placed to couple with the electric signal electrodes on the adapter's base-adapter interconnection arrangement, where the power electrodes provide electrical power to the adapter and the signal electrodes provide 15 data transmission between the base unit and the adapter. 7. The analytical system in accordance with the faith | claim 1, characterized in that the junction region on the base unit comprises a receptacle formed on a surface of the base unit. 8. The analytical system according to claim 9, characterized in that the receptacle has peripheral dimensions which are coupled with the adapter. 9. The analytical system according to claim 7, characterized in that it further comprises a fastener on the base unit for securing the adapter inside the receptacle. 10. The analytical system according to claim 1, characterized in that the junction region on the base unit comprises a discrete component which is attached to the base unit. 11. The analytical system according to claim 1, characterized in that the substrate has an upper side, a lower side, and an inner region therebetween, wherein the inner region has a plurality of mesoscale channels connecting a plurality of reservoirs and wherein the flow diversion elements comprise terminals of electrodes exposed to an outer surface of the substrate and / or access points on the substrate which allow penetration of the probe. 12. The analytical system according to claim 9, characterized in that the substrate has openings on at least some of the reservoirs to allow direct penetration by probes into the interconnection arrangement of the adapter-substrate. The analytical system according to claim 11, characterized in that the interconnection arrangement of the adapter-substrate includes a multiplicity of electrodes placed on a pattern to be coupled to the electrode terminals exposed on the substrate. The analytical system according to claim 3, characterized in that the interconnection arrangement of the substrate-adapter includes at least one additional interconnection component. The analytical system according to claim 14, characterized in that the additional component comprises a source of electromagnetic radiation and wherein the substrate includes a region transparent to electromagnetic radiation, wherein the transparent region is aligned with the source when the substrate it is bonded within the region of attachment of the substrate on the adapter. 16. The analytical system according to claim 15, characterized in that it further comprises an electromagnetic radiation detector placed within the interconnection arrangement of the adapter-substrate so that it will receive the radiation emitted from the transparent region when the substrate is bound within the Union region. 17. The analytical system according to claim 1, characterized in that the junction region on the adapter comprises a receptacle formed on a surface of the adapter, the receptacle having peripheral dimensions which correspond to the external peripheral dimensions of the substrate. 18. The analytical system according to claim 17, characterized in that it further comprises a fastener on the adapter for securing the substrate within the receptacle. 19. The analytical system according to claim 1, characterized in that it further comprises a tangible medium that stores a computer-readable code comprising instructions, wherein the instructions allow a computer to interconnect with the base unit and control an assay performed by the computer. the base unit present on a substrate maintained by an adapter received on the base unit. 20. An analytical system, characterized in that it comprises: a base unit having a junction region with an interconnection arrangement of the base that includes at least one interconnection component therein; a substrate having an interconnection arrangement that includes at least one interconnection component therein; and an adapter configured to be removably attached to the junction region of the base unit and having a junction region for removably receiving the substrate, wherein the adapter holds the substrate in a fixed position relative to the unit. base and provides at least one of (i) a connection path of the interconnection component in the interconnection array of the base to the substrate or (ii) a connection path of the interconnection component in the array of the substrate to the base unit . The analytical system according to claim 20, characterized in that the adapter includes an energy distribution network, wherein the interconnection component in the interconnection arrangement of the base is a power source, and wherein the arrangement of the The substrate comprises a plurality of power connectors, which are coupled to the power distribution network in the adapter. 22. The analytical system according to claim 20, characterized by the interconnection arrangement of the base includes an energy emission detector, wherein the array of the substrate includes a power transmission region, and wherein the adapter aligns the energy emission detector with the energy transmission region, when the adapter is mounted on the junction region of the base unit and the substrate is mounted on the attachment region of the adapter. 23. An adapter to be used in combination with a base unit having a junction region with an interconnection arrangement of the base and a substrate having an interconnection arrangement of the substrate, the adapter is characterized in that it comprises: an adapter body that has an adapter-base interconnection arrangement that includes at least one of a signal power connector positioned to mate with the corresponding connectors in the interconnection arrangement of the base when the adapter is attached to the junction region on the base unit and a substrate binding region having an adapter-substrate interconnection arrangement that includes at least flow deflection connectors positioned to couple with the corresponding regions in the substrate interconnection array, when the substrate is bound in the region of the substrate. union of the adapter. The adapter according to claim 23, characterized in that the interconnection arrangement of the substrate includes at least one additional interconnection component selected from the group consisting of electric power sources, analog signal connectors, digital signal connectors, power supplies, power transmission, electrical / electrochemical signal detectors, pH detectors and energy emission detectors. The adapter according to claim 24, characterized in that the additional component comprises a source of electromagnetic radiation, and wherein the substrate includes a region transparent to electromagnetic radiation, wherein the transparent region joins the source when the substrate it is bonded within the region of the substrate on the adapter. 26. The adapter according to claim 25, characterized in that it further comprises an electromagnetic radiation detector placed within the adapter-substrate interconnection arrangement, so that it will receive the radiation emitted from the transparent region when the substrate is joined to the junction region. The adapter according to claim 23, characterized in that the junction region on the adapter comprises a receptacle formed on a surface of the adapter, the receptacle having peripheral dimensions corresponding to the external peripheral dimensions of the substrate. The adapter according to claim 27, characterized in that it further comprises a fastener on the adapter for securing the substrate inside the receptacle. 29. A system, characterized in that it comprises: an adapter according to claim 23; and a tangible means for storing a computer readable code comprising instructions, wherein the instructions allow a computer to interconnect with the base unit and control an assay performed by the base unit on a sample present on a substrate maintained by an adapter received on the base unit. 30. A system to be used in combination with a computer, a base unit having a junction region of the adapter, and an adapter, the system is characterized in that it comprises: a substrate capable of receiving a sample to be analyzed and adapted to be mounted on the adapter; and a computer readable code comprising instructions, which allow the computer to interconnect with the base unit and control an assay performed by the base unit on a sample present on the substrate maintained by an adapter received on a base unit. 31. An article of computer program to be used in combination with a computer, a base unit having a junction region of the adapter, an adapter having a binding region of the substrate, and a substrate capable of receiving a material to be processed , the article of the computer program comprises a tangible medium that stores a computer readable code comprising instructions, wherein the instructions allow a computer to interconnect to the base unit and control the process carried out by the base unit on a sample present on the computer. material of a substrate maintained by an adapter received on the base unit. 32. A method for configuring an analytical system, the method is characterized in that it comprises: providing a base unit having a junction region that includes at least one interconnection component therein; removably attaching an adapter to the junction region of the base unit, so that an interconnect component on the adapter is coupled with a corresponding interconnect component on the base unit, wherein the adapter includes a junction region of the substrate that has at least one interconnection component in it; and removably attaching a substrate to the binding region of the substrate on the adapter, so that an interconnecting component on the substrate is coupled with a corresponding interconnecting component on the adapter. 33. The method according to claim 32, characterized in that the adapter removably attaches to the base unit. Placing the adapter inside the receptacle in the base unit. 34. The method according to claim 32, characterized in that the substrate removably attaches to the adapter by placing the substrate inside a receptacle in the adapter. 35. The method of compliance with the claim 32, characterized in that the substrate has a plurality of channels connecting a plurality of reservoirs and flow deflection regions, placed in at least some of the reservoirs or channels. 36. The method of compliance with the claim 35, characterized in that it further comprises: directing the flow control signals of the base unit to the adapter; and energizing the regions of flow deflection of the adapter in response to the flow control signals, whereby the corresponding flow deflection regions on the substrate are energized to control the flow through the channels and between the reservoirs. 37. The method according to claim 36, characterized in that the energizing step comprises electrically deflecting the flow deflection regions. 38. The method according to claim 36, characterized in that the energizing step comprises acoustically actuating the regions of flow deflection. 39. The method according to claim 36, characterized in that the deviation and energization steps comprise providing readable computer instructions to a computer connected to the base unit. 40. The method of compliance with the claim 32, characterized in that the adapter further comprises at least one source of electromagnetic radiation, the method further comprising directing a control signal from the electromagnetic radiation source of the base unit to the adapter. 41. The method according to the claim 40, characterized in that the adapter further comprises an electromagnetic radiation detector, the method further comprises: a signal on the adapter in response to the radiation emitted from the substrate and directing the signal towards the base unit. 42. The method of compliance with the claim 41, characterized in that the step of generating signals and the step of directing the signals comprises providing readable computer instructions to a computer connected to the base unit.