Self-contained modular analytical cartridge and programmable reagent delivery system

Abstract

A modular system for constructing a variety of self-contained analytical cartridges enabled to perform a number of symmetrical or asymmetrical tests on a single sample source within a single device. Said cartridges are embodied as a readily reversible assemblage of two or more modules that are, in turn, operable to perform one or more tasks of an analytical test as discrete articles-of-manufacture. A programmable reagent delivery system comprising one or more serialized reagent clusters having one or more wet cells (individually packaged reagents) and zero or more dry cells (calibrated spacers); wherein, said wet cells are arranged in a linear series corresponding to prescribed temporal release sequence and dry cells are interpositioned between wet cells in a manner that enables two or more test protocols having asymmetrical release sequences to be synchronized such that a single mechanism can actuate more than one test protocol simultaneously.

1 . A system of microfluidic modules, comprising:
 A plurality of coupling module-types having,
 At least a first coupling feature for receiving a next module, 
 An internal structure operable to communicate fluidically with another module-type, and/or otherwise enable one or more root-level operational protocols, 
 A cooperative overall external geometry; and, 
 Operable, in a same total number or in a different total number, to provide for more than one proper selection of modules operable to assemble into a complete cartridge having, 
 A substantially conserved overall operative external geometry, and 
 Operable to perform one or more distinct root-level operational protocol. 
   
     
     
         2 . The system of modules of  claim 1  further comprising a second coupling feature for being selectively received by an alternative module. 
     
     
         3 . The system of modules of  claim 2  wherein said internal structure of a possible module-type, namely a specimen module, is one or more chambers configured to:
 Receive a primary-input, 
 Enclose said primary-input, 
 Communicate said primary-input to a next coupling module, and 
 Provide for one or more means for externally controlling the internal pressure of said chamber; such as, ports, vents, pumps, or valves; and, 
 May further contain a mechanical and/or chemical means intended to prepare said primary-input for analysis; such as, analytical reagents, membranes, sieves, filters, or internal physical features operative with a centrifugal process. 
 
     
     
         4 . The system of modules of  claim 3  wherein said chamber further possesses an opening sealed by a pierceable barrier; such as, a self-healing stopper, through which said chamber may be evacuated of atmosphere and set under a vacuum by operable means; and whereby, said chamber is operable pull a primary-input into said chamber by forces of equalizing pressure. 
     
     
         5 . The system of modules of  claim 3  wherein said chamber is coupled to a mechanical means operable to communicate a specimen into said chamber; such as, by suction, by placement, or by capillary action. 
     
     
         6 . The system of modules of  claim 3  wherein said chamber is made to possess electrical and/or chemical sensors operable to generate an output regarding a quality of said primary-input. 
     
     
         7 . The system of modules of  claim 2  wherein said internal structure of a possible module-type, namely a reactor module, is one or more of a type of fluid control structure configured as a continuous-flow fluidic system operable to:
 Receive a primary-input transmitted from a first module, 
 Receive a compliment of secondary-inputs transmitted from one or more next modules, 
 Process said primary-input with said secondary-inputs according to said root-level operational protocol, and 
 May further be enabled to transmit a liquid signal to a next module, and may further possess a secondary-input within said structures. 
 
     
     
         8 . The system of modules of  claim 7  wherein said type of fluid control structure is a number of individual mixing chambers interconnected in operative fluid communication to provide for plural discriminate pathways of fluid communication between said chambers; and,
 Wherein at least a first pathway provides for communicating a primary-input to said mixing chambers, and 
 An operable number of secondary pathways provide for communicating a secondary-input to said mixing chamber according to a root-level, or a number of concordant subordinate-level operational protocols. 
 
     
     
         9 . The system of modules of  claim 7  wherein said type of fluid control structure is a flow cytometer comprising:
 A fluid control pathway extending into, and opening into a chamber by means of a flow aperture configured with means; such as electrodes, operative to establish an electrical field about its opening; and, 
 Wherein a quality of said primary-input is generated as an output of the effect of said inputs passage through said electrical filed as said input is made to flow through said aperture. 
 
     
     
         10 . The system of modules of  claim 7  wherein said type of fluid control structure is one or more chambers made to possess a semi-solid, or suspended solid, intermedium for processing a primary-input according to a root-level operational protocol; and may further possess means operable to establish an electrical field about such intermedium to influence the electrical qualities of a primary-input; such as, by providing for continuity in a liquid conductor, or electrodes. 
     
     
         11 . The system of modules of  claim 7  wherein said fluid control structures is a chamber made to possess an electrical and/or chemical sensor operable to generate an output regarding a quality of said primary-input. 
     
     
         12 . The system of modules of  claim 2  wherein said internal structure of a possible module-type, namely a waste module, is one or more chambers configured to:
 Receive a fluid signal transmitted from a next coupling module, 
 Contain said fluid signal with the structure of said chamber, 
 Provide for one or more means for externally controlling the internal pressure of said chamber; such as, ports, vents, pumps, or valves; and, 
 May further contain an electrical and/or chemical sensors operable to generate an output regarding a quality of a primary-input. 
 
     
     
         13 . The system of modules of  claim 2  wherein said internal structure of a possible module-type is an internal slot operable to receive and house a subassembly. 
     
     
         14 . The system of modules of  claim 13 , wherein said module-type is a reagent module and said subassembly is a reagent delivery system; and,
 Wherein said reagent delivery system is operably configured to discriminately communicate one or more compliments of a secondary-input to a next module according to a root-level, or a number of concordant subordinate-level, operational protocols; and   Whereby, said compliment of secondary-inputs is a number of individually packaged regents arranged in a temporally calibrated series defining the time dependent dispensing sequence for each reagent according a root-level or a number of concordant subordinate-level operational processes.   
     
     
         15 . The system of modules of  claim 13 , wherein said module-type is an auxiliary module and said subassembly is a type, or a combination of: a chemical, electrical, and/or light sensor, meter, filter; and/or, a photomultiplier; and/or, an electrical storage device; and/or a computational mechanism. 
     
     
         16 . The system of modules of  claim 2  wherein a said proper selection of modules further comprises an operative modular matrix that is intelligible to said selection of modules to express one or more operations distinct from said root-level operational protocol. 
     
     
         17 . The system of modules of  claim 16  wherein said operative matrix is encoded in the selection, deposition, distribution, and/or inherent properties of coupling features between: two or more modules, to or more groups of modules, or a complete modular assemblage; and
 Whereby, such coupling features may include a type or a combination of, mechanical couplings, mechanical connectors, cooperating geometries, cooperating interstices, native interfaces, interfaces manifested by a partial modular assembly, divided mechanical couplings rendered complete by a partial modular assembly, divided mechanical connections rendered complete by a partial modular assembly, the use of appliques or other visual indicators, and/or divided electrical circuits. 
 
     
     
         18 . The system of modules of  claim 17  comprising a first operation; wherein, said first order operation is expressed as a means for rendering a proper selection of modules intelligible to self-discriminate one or more aspects regarding: the selection, timing, order, and orientation of each module's assembly into a completed cartridge; and
 Whereby, such means may be a progressive process requiring the perfection of a present assembly event may manifest an operative point-of-attachment for a next assembly event, leading to a final assembly event that completes a cartridge by perfecting all point(s)-of-attachment. 
 
     
     
         19 . The system of modules of  claim 17  comprising a second order operation; wherein, said second order operation is expressed as a means for rendering select modules of a completed cartridge enabled to operate controllable aspects of the cartridge; and
 Whereby, a latent aspect of a mechanical connection providing firstly, for selective assembly may secondly, allow for one or more modules to be set in motion relative to other modules of the cartridge. 
 
     
     
         20 . The system of modules of  claim 17  comprising a third order operation; wherein, said third order operation is expressed as a means for transforming an external signal into an internal signal; that may further,
 Operate controllable aspects of the cartridge for performing a root-level operational protocol, and/or 
 Convey programmable attributes to a programmable aspect of the cartridge for performing a root-level operational protocol, and/or 
 Communicate coherent pathways for transmitting radiant energy into or out of the cartridge in a timely manner dependent upon a root-level operational protocol; and,
 Whereby, the movement of one or more modules along slide/slide-guides could: firstly, transform an linear motion having a nonlinear magnitude and duration, into an internal signal having a modulated amplitude and frequency that could be used to control the communication of secondary-inputs between modules according to a root-level operational protocol; and/or, secondly serve as a higher order programmable attribute governing a programmed reagent delivery system; and/or thirdly, timely provide for transmission pathways for radiant energy into and/or out of the cartridge by aligning one or more visual openings of a module housing over a site where a root-level operational protocol in being performed. 
 
 
     
     
         21 . The system of modules of  claim 2  wherein said root-level operational protocol is a stepwise process for combining a primary-input with a complement of secondary-inputs to generate an output regarding a quality of the primary-input, and may further accommodate a number of concordant subordinate-level protocols having distinct stepwise process and/or separate complements of secondary-inputs to generate separate outputs regarding different qualities of the primary-input; and,
 Wherein, said primary-input may be a biological specimen, and said secondary-inputs may be liquid, gas, or immobile powder reagents, and said operational protocol may be performed in a type, or a combination of a: liquid, semi-solid, suspended-solid environment. 
 
     
     
         22 . The modular system of  claim 21  wherein said complements of secondary-inputs further comprise:
 One or more individual liquid reagents individually encapsulated in separate physical containers, namely wet-cells, 
 One or more of said wet-cells arranged according to a root-level operational protocol to provide for a timed dispensing sequence, namely a serialized reagent cluster; and, 
 Wherein two or more serialized reagent clusters may be arranged in a parallel series; and, 
 Wherein a discordance between the said timed dispensing sequence between two or more serialized reagent clusters may be temporally calibrated by the interpositioning of a spacer element, namely a dry cell, to introduce a temporal delay between one or more wet-cells of said two or more serialized regent clusters so as to synchronize the temporal operation of each operational protocol when actuated by a single impetus. 
 
     
     
         23 . The system of modules of  claim 22  wherein said complement of secondary-inputs are preconfigured in operative compositions to express a temporally control dispensing sequence that may be a type, or a combination, of:
 Identical compositions; and/or, 
 Symmetrical compositions having a same number, amount, and timing; but, differing in one or more of a type; and/or, 
 Asymmetrical compositions varying in number, amount, timing, and/or type. 
 
     
     
         24 . The system of modules of  claim 21  further comprising a type, or a combination, of means for: interconnecting different types of modules, and/or controlling the communication of liquids within and between modules, and/or perform various tasks of a root-level operational protocol as the circumstances of a protocol dictate; and
 Whereby such means may be a type, or a combinations of: 
 Means capable of directing the assembly of specific modules into specific cartridge types; such as, unambiguous configurations of cooperative mechanical attachments, cooperating slide and slide-guides, clips, appliqués; 
 Means to receive, store and/or make available fluids; such as, chambers, cavities, bladders, and/or prepackaged reagent cells; 
 Means that enable the communication of a liquid within and between modules; such as, tubes, channels, or other geometric configurations of fluid control pathways that facilitate the movement and possibly separation of fluids; 
 Means to improve the interrelationship and transfer of fluids between the cooperating fluid transfer pathways of interconnected modules; such as, mechanical seals, gaskets, sterile seal barriers, or self-healing stoppers; 
 Means to improve fluid control; such as, switches, tubes, valves, choke points, diverters, piercing devices, shunts, ports, vents, gaskets, compression forms, and/or magnetized or magnetic material; 
 Means intended to prepare a sample for analysis; such as, analytical reagents, membranes, sieves, filters, or features that enable a module to undergo centrifugation; 
 Means that assist in the acquisition of data pertaining to an analytical procedure; such as, electrical, chemical, and/or light: sensors, meters, filters, photomultipliers, polarizers, or light blocking, reflective, or transparent materials, structures, or appliqués; 
 Means that further enable the operation of the device by means of an electrical current generated within or about a module or module assembly; such as, electrical circuits, electrically conductive material, or electricity storage devices, such as batteries or capacitors; 
 Means that allow module to move relative to other modules as set forth by guide paths within or about other modules; such as, plungers, select module configurations, linear actuators, slides or other types motion directing or imparting devices; 
 Means that communicate indications of proper modular assemblages; such as, the specific disposition and interrelation of one or more physical elements of cooperative mechanical attachment between cooperating modules, appliqués, or other visual elements that may further possess information as to the type of module and its operational parameters; divisions of electrical circuits disposed about cooperating modules operable to close a circuit when properly assembled and that may further enable the communication of information pertaining to the operation of a cartridge to an analytical instrument designed to operate the cartridge; and 
 Means such as the ability to vary the physical dimensions and configurations between of individual modules to meet the requirements of a specific analytical task while conforming to a standard overall dimension and mechanism-of-operation of the finished device form. 
 
     
     
         25 . The system of modules of  claim 24  further comprising a proper selection of said modules properly assembled into a complete cartridge operably equipped to perform one or more root-level operational protocols having two or more concordant subordinate-level operational protocols involving separate compliments of secondary inputs. 
     
     
         26 . The modular system of  claim 25  wherein said proper selection of modules comprises:
 One or more of a reactor module operable to receive and process a number of primary- and secondary-inputs according to a root-level operational protocol and further operable to establish fluid communication between one or more reagent modules, zero or more specimen modules, and zero or more waste modules; and, 
 One or more of a reagent module operable to contain and dispense a complement of secondary-inputs to said reactor module; and, 
 Zero or more of a specimen modules operable to contain and dispense a primary-input to said reactor module; and, 
 Zero or more of a waste module operable to receive and store processed inputs and/or input overflow from said reactor module. 
 
     
     
         27 . The modular system of  claim 26  wherein said complete cartridge encloses one or more independently controlled closed continuous-flow fluidic systems enabled by means to effect the transmission of a fluid signal along plural discriminate pathways of fluid communication; and, wherein,
 A first said pathway is enabled by a first pneumatic port operably positioned upstream of an input, and a second pneumatic port operably positioned downstream of the inputs intended destination, and further operable to couple with an external mechanical means operable to establish a pressure gradient upstream and downstream of said input thereby inducing and directing the input to flow discriminately to an intended destination; and, 
 A second said pathway is enabled by a compressive force, generated by two modules articulated against each other, to elevate the pressure upstream of an input, and said second or more pneumatic ports operable to couple with an external mechanical means to lower the internal pressure downstream of the inputs intended destination thereby inducing and directing the input to flow discriminately to an intended destination. 
 
     
     
         28 . The modular system of  claim 25  wherein said proper selection of modules comprises:
 At least one module internally operable to mix a primary-input and a secondary-input according to a root-level operational protocol, but not internally operable to provide for all secondary-inputs, or 
 At least one module operable to internally provide for a primary- or a secondary-input, but not internally operable to mix such inputs according to a root-level operational protocol, or 
 At least one module that neither provides for, nor mixes, a primary- or secondary-input according to a root-level operational protocol, but may contain waste liquids spent during the course of the operational protocol. 
 
     
     
         29 . A programmable reagent delivery system comprising:
 One or more volumes of a liquid reagent individually encapsulated in its own physical container, namely wet-cells,   Zero or more temporally calibrated spacers, namely a dry-cells, having a volume equating a measured amount of time,   A first module having an interior at least two wet-cells wide and at least one wet-cell deep, an exterior, a distal end, and a proximal end operable to couple with and transmit fluidic signals to a next module;   A compression form operable to distribute a mechanical load across one or more wet-cells while containing such cells in an operable configuration; and,   May further possess a piercing element operable to establish a fluidic connection between a wet-cell contained in said first module and a fluid control pathway of said next coupling module; and wherein,   One or more wet-cells are stacked according to a defined dispensing sequence creating a serialized reagent clusters and two or more serialized reagent clusters are arranged in a parallel series such that said dispensing sequence of each reagent cluster may be actuated by a single impetus.   
     
     
         30 . The programmable reagent delivery system of  claim 29  further comprising: One or more temporally calibrated spacers, namely a dry-cells, having a volume equating a measured amount of time; and,
 Wherein said dry cells are operably interpositioned between one or more wet-cells to introduce a temporal delay in the release sequence of two or more serialized reagent clusters so as to synchronize a temporal discordance in the dispensing sequences between reagent clusters enabling each reagent cluster to be actuated simultaneously by a single impetus. 
 
     
     
         31 . The programmable reagent delivery system of  claim 30  wherein said dry-cell may be an operable volume of a non-dispensable material encapsulated in an individual container, or an operable volume of a non-dispensable material interpositioned between one or more wet-cells when operative to communicate a programmatic time delay. 
     
     
         32 . The programmable reagent delivery system of  claim 29  further comprising means for actuating fluid communication between a first module and a next module; wherein such means may be of a type or combination of:
 The articulation of said first module into said next module, wherein said first module has a closed distal end and said articulation is operable to advance one or more enclosed wet-cells on to said piercing element, 
 Said first module having an open distal end, and enclosing one or more wet-cells contained in a compression form and wherein a force acts directly on, or by means of an intervening element, to effect a distal side of a wet-cell so as to move a proximal side of a wet-cell onto a piercing element. 
 
     
     
         33 . The programmable reagent delivery system of  claim 30  wherein said physical container further possesses one or more qualities that may be a type, or a combination of: an elastic quality operable to contain a liquid under tension; a self-sealing quality operable to be pierced through by a piercing element without significant leakage; an elastic quality operable to deform and distribute a mechanical load between a series of wet-cells without rupturing; and
 may further possess means of interconnecting two cells such as male/female connectors, or bonding surfaces; and may be made of light impenetrable material. 
 
     
     
         34 . The programmable reagent delivery system of  claim 30  wherein said piercing element may be a hollow cannula sharpened at one or more ends and operable to transmit a fluid signal through its interior, or may be a sharpened extension of a fluid control pathway provided by said next coupling module. 
     
     
         35 . A method for programming a reagent delivery system to synchronize symmetrical and/or asymmetrical reagent systems comprising:
 A. Selecting a step-wise root-level operational protocol for processing a primary-input with a compliment of secondary-inputs to generate an output that communicates a quality of the primary-input; whereby, said root-level operational protocol may further encapsulate a number of subordinate-level operational protocols having separate secondary-inputs to generate separate outputs the communicate separate qualities of the primary input; and whereby, said primary-input may be a biological specimen that is liquid, or a solid, or gas, in a liquid suspension, and said secondary-inputs may be liquid reagents,   B. Assess each operative aspects of each operational protocol:
 1. If each operational protocol is identical then, skip forward to step C, 
 2. If each operational protocol has a same overall operational time-cycle and a same total volume of secondary-inputs then, skip forward to step C, 
 3. If one said operational protocols differs in time cycle and/or a total volume of secondary-inputs and skip forward to step D; 
   C. Arranging a prescribed volume of each secondary-input(s) encapsulated in separate physical containers, namely a wet-cell, in order of a prescribed dispensing sequence to create a serialized reagent cluster for each protocol, while operably orienting two or more serialized reagent cluster in a parallel series according to the root-level operational protocol, and then continue to step E;   D. Perform the operational process prescribed in step C (see above) in addition to interpositioning one or more temporally calibrated spacer within said serialized reagent cluster according to the requirements of each protocol:
 1. If one protocol has an overall shorter operational time cycle due to a lesser total volume of secondary inputs, and/or a shorter time to yield an output, then interposition a temporally calibrated spacer:
 In a first position to delay the initiation of said protocol such that the protocol concludes later, or 
 In a last position to initiate and conclude such protocol earlier, or 
 In a first position and a last position to conclude the protocol between other protocols; and/or 
 
 2. If a protocol presents asymmetrical order of operation involving a temporal delay between the administration of two or more secondary-inputs; such as a timed incubation cycle, then
 Interposition a temporally calibrated spacer between such wet-cells to delay the dispensing cycles between said reagents, 
 
 3. And then continue to step E; 
   E. Calibrate the actuation of each serialized reagent cluster for either continuous or incremental actuation; whereby, continuous actuation provides for programming the dispensing sequence of each input in a constant or variable rate; whereas incremental actuation provides for programming the dispensing sequence to incorporate timed stops intermittently during, or between, an active dispensing event; and then communicate said operating instructions to an operative instrument, or individual, to be executed.   
     
     
         36 . A method of encoding operation within the modular matrix of a modular cartridge having three or more modules, said method comprising:
 A. Quantifying the final operative configuration of a modular cartridge,   B. Selecting an operable type of coupling element to be divided and/or distributed between two or more modules; whereby, different types of coupling can provide for selectivity during assembly and later different types of movability once assembled; and,   C. Distributing individual aspects of said element between said modules,   D. Disposing said aspects on said modules to be selective for a specific module when one or modules exist in a specific configuration; and   Whereby, useful elements may include a type, or a combination of: selective mechanical couplings between two or more modules; multipart selective mechanical connections between modules; imperfecting a part of a multi-part mechanical connection and distributing different aspects between select modules which perfect said part in a timely manner when properly assembled; cooperating geometries between two or more modules; cooperating interstices; one or more native interface(s) between two or more modules; one or more manifested interface(s) of a partial modular assembly; and/or, any one of the previous element positioned in an intentionally conflicting configuration so as to prevent an improper assemble event.   
     
     
         37 . A method for operating a modular analytical cartridge having a programmable reagent delivery system, comprising:
 A. First, induce a metered volume of specimen to flow into an intended destination by establishing a pressure gradient upstream of a specimen and downstream of an intended destination for a measured amount of time,   B. Second, induce one or more or a metered volume of reagent to flow to said intended destination by mechanically articulating one or more reagent modules according to a preprogrammed configuration of an enclosed reagent to induce a reagent container to be pierced by a piercing device in fluid communication with a pathway operable to communicate said reagent to said intended destination, while maintaining a favorable negative pressure downstream of said intended destination thereby establishing fluid communication between said reagent container and an intended destination in a manner that directs and may augment the flow of such reagents into said intended destination.   
     
     
         38 . An apparatus for operating a modular analytical cartridge having a programmable reagent delivery system, comprising:
 Means for receiving an a modular analytical cartridge; such a as a mechanical stage, or a carousel,   A pneumatic pump configured to operably couple with said cartridge by means and communicate pneumatic signals for selectively effecting the internal pressure of select modules,   A means for mechanically articulating one or more modules of said cartridge; such as a type of a linear actuator.