NRI has been working in the areas of microfluidic and micro-conduit systems for more than a dozen years.
- Innovative distribution and transport technologies for fluidic/gas exchange,
- Micro-scale fluidic sensing and gas sensing (including analytical sensing; see Biochemical/Chemical Sensors and Sensor-Array Systems),
- Software-controlled and software-configured microfluidic and micro-conduit systems,
- Microfluidic chemistry (see first section of Chemical Processing,)
- Removable subsystems,
- Layered functional-subsystem architectures,
- Control scripting software,
- New application areas (for example Biochemical/Chemical Sensors and Sensor-Array Systems and
Next-Generation Microplate Technologies),
- Commercialization strategies.
NRI continues active R&D in each of these areas (including what NRI believes will be valuable new methods for implementation and electrical control of microfluidic valves and pumps, as well as new applications and systems; this active work is not discussed in the material provided and patent assets listed below).
The brief summarizing descriptions below are organized as:
- Microfluidic and Micro-Conduit Transport,
- Microfluidic and Micro-Conduit Systems-Level Architecture,
- Microfluidic and Micro-Conduit System Design and Emulation,
- Microfluidic and Micro-Conduit System Control and Scripting Software,
- Design for New Microfluidic System Commercialization Strategies.
1. Advanced Microfluidic and Micro-Conduit Transport
This section describes innovative NRI technologies relating to microfluidic and micro-conduit transport of fluidics, gases, slurries, gels, and other materials.
1.1 Multi-Channel Chemical Transport Bus for Microfluidic and Other Applications
This NRI technology is directed to controllable multiple-channel chemical transport bus routing and transport of fluids, gases, aerosols, slurries and other material types within a larger system such a microfluidic chemical or biochemical processor or Lab-on-a-Chip (LoC) device. It can be useful in implementing software-reconfigurable microfluidic devices. Routes through the bus can be determined by control signals and/or sequences of control signals issued under algorithmic control. Several independent flows may occur simultaneously. Techniques for limiting cross-contamination and which facilitate clearing and cleaning for future use are provided. Paths can also be designated for a single type of material, or for single one-time use. Sensors of various types can be placed at various locations along bus line segments and can be used for closed-loop control of measured flows or in clearing and/or cleaning operations. The sensors can be of one or more types such as presence sensors, flow sensors, pressure sensors, temperature sensors, conductivity sensors, optical sensors, ion sensors, and affinity sensors. At least one sensor detects the flow in an associated flow line, such that a controller uses at least one signal from the sensor to time fluid flow between the two flow ports.
The controllable multiple-channel chemical transport bus can be configured to support chemical flow durations short enough that the chemical flow at a first chemical flow port ends at a time before the chemical flow is first received at a second chemical flow port. Adaptations of Clos, Banyan, and other related multi-stage flow topology switching architectures can also be implemented using related techniques.
1.2 Controllable Nearest-Neighbor Transport Architectures for Chamber Arrays
NRI originally developed controllable 1-dimensional (row or column) and 2-dimensional (row and column) nearest-neighbor topology transport architectures as part of the simply-specified software-configured features chemical/biochemical sensor array systems (see US 13/761,142 in Biochemical/Chemical Sensors and Sensor-Array Systems) and has subsequently included in NRI’s broader fluidic transport approaches. The technology can be used in life-science microplate applications; in fact, recently Sigma-Aldrich introduced its consequential SciFlowTM 1000 microplate product line which that passively connect row-adjacent microplate wells together through capillary channels in the microplate shell with flows induced by gravity in a staircase arrangement.
1.3 Three-Dimensional Microfluidic Micro-Droplet Transport
Most of NRI’s fluidic are related technologies are conduit based. A competing technology is electrostatic transport of microdroplets using planar electrode arrays. This area is very active in academic circles and has many compelling features and capabilities. In many situations, however, it is desirable to employ a three-dimensional transport system so as to more space-efficiently, cost-efficiently, thermally-efficiently, or system-synergistically transport materials.
NRI has developed three-dimensional microfluidic micro-droplet transport technologies for transporting microdroplets in three spatial dimensions. In one implementation, microdroplet transport through inter-layer conduits between planar transport layers via electrostatic microdroplet manipulation is used. This NRI technology can be used for applications such as microdroplet-based microfluidic systems, chemical reactors, biochemical reactors, chemical analysis arrangements, biochemical analysis arrangements, and other apparatus. Additionally, the text Adaptive Cooling of Integrated Circuits Using Digital Microfludics by P. Paik, K. Chakrabarty, and V. Pamula, published by Artech House, Inc., Norwood, Me., 2007, ISBN 978-1-59693-138-1 describes an innovative planar-topology micro-droplet transport approach to cooling semiconductor systems. NRI three-dimensional microfluidic micro-droplet transport technologies can be used to advantageously extend such heat transfer approaches. For such applications, NRI three-dimensional microfluidic micro-droplet transport technologies can be implemented within an integrated circuit housing, printed circuit board, or in other configurations so as to better move waste heat among heat sources and heat sinks without undesired heat loss. Example applications include integrated circuit cooling, circuit board cooling, and heat-based energy harvesting as discussed in Semiconductor and Data Center Cooling.
2. Microfluidic and Micro-Conduit Systems-Level Architecture
This section describes innovative NRI technologies relating to systems-level architectures of microfluidic and micro-conduit systems.
2.1 Software-Reconfigurable Conduit and Reaction Chamber Microfluidic Arrangements For Lab-On-A-Chip And Miniature Chemical Processing Technologies
This NRI technology is directed to software-reconfigurable chemical process systems useful in a wide range of applications. Embodiments may include software control of internal processes, automated provisions for cleaning internal elements with solvents, provisions for clearing and drying gases, and multitasking operation. Clearing and cleaning provisions may be used to facilitate reuse of the device, or can alternatively be used for decontamination the device prior to its recycling or non-reclaimed disposal. Through use of a general architecture, a single design can be economically manufactured in large scale and readily adapted to diverse specialized applications. A family of such flexible software-reconfigurable multipurpose reusable “Lab-on-a-Chip” or “embedded chemical processor” with differing feature sets can be used to create a multi-purpose product line or standardized component that can support and enable a wide range of applications, instruments, and appliances.
2.2 Removable Replaceable Subsystem Structures for Sensor Arrays, Microplates, Microarray Systems, Chemical/Biochemical Processors and Other Applications
This NRI technology area pertains to user-removable, field-removable, and maintenance-removable microfluidics subsystem structures for use within a larger system. Some example applications include:
- Facilitated replacement for single-use applications (for testing, analysis, sample collection, etc.),
- Facilitated replacement due to expected failure rate (valve and pump membranes, sensors, etc.),
- Facilitated replacement due to expected accumulating contamination,
- Facilitated replacement due to expected use of internal consumables (reagents, catalyst, electrochemistry electrodes, etc.).
Such arrangements can also be used for fluids, gases, and fluid/gas combinations. In such designs, especially with recyclability, environmentally-aware disposal, and overall economics in mind, it makes sense to split some functional elements in the overall system so that one portion is in a removable replaceable structure and the remaining parts are in the base system that hosts the removable replaceable structure. For example:
- Fluidics-based optical sensors can be configured so that one or more of an optical sensor, optical light source, and optical elements (such as lenses, diffraction gratings, beam splitters, mirrors, etc.) are in the base system and only optically-configured fluidic passageways are in the removable replaceable structure.
- Valves and pumps can be configured so that membrane components are related optical or hydraulic are in the removable replaceable structure and mechanical-displacement actuators (such as a solenoid, stepper motor, rotating motor, linear motor, piezoelectric element), or selected actuator component (such as a solenoid coil, portion of a motor) are in the base system.
The removable replaceable structure may further include a coupling mechanism for detachably coupling the removable microfluidics structure with the removable replaceable media: this can include provisions for support and alignment, fluidic interfaces, optical interfaces, electrical interfaces, etc. Applications can include fluidics or gas-based reaction system arrays, sensor arrays, other microarray systems, chemical/biochemical processors, life-science microplates, and other applications.
2.3 Modular Layering Arrangements for Micro-Conduit Fluidics and Gas Exchange
Microfluidic and micro-conduit systems are often constructed by bonding together layers used to create elements cavities, surfaces, support, passages, and transparent optical walls with a scope of the entire system. The layers are used to create the tops, bottoms, and sides of enclosures, vessels, and conduits, and also to create structures for elements such as valves, pumps, mixing elements, and sensors that may also incorporate materials (for example elastic membranes) and elements introduced between the layers.
This NRI microfluidic and micro-conduit structuring technology uses the above manufacturing methods as well as injection modeling and other fabrication methods to create modular subsystems that in turn can themselves be stacked and (as useful or needed) can be configured to interconnect at adjoining surfaces though us of provided mating interfaces. NRI regards each stackable subsystem in this system-level construct a “modular functional layer.” Each modular functional layer can be designed to provide one or more specific functions, and can be organized, defined, and used as functional blocks. Examples of such modular functional layers can include, among others (more to be announced soon):
- “Material Transport Layers” providing one or more conduit distribution buses, NRI microfluid transport bus technologies (see Section 1.1 above), NRI’s microfluid nearest-neighbor transport technologies (see Section 1.2 above), or other transport of materials for at least one or both adjoining modular functional layers,
- “Control Layers” providing mechanical actuators, pneumatic paths, hydraulic paths, etc. for at least one or both adjoining modular functional layers,
- “Chamber Layers”/ ”Vessel Layers” providing chamber providing open volumes,
- “Passive Conduit Interconnection Layers” providing passive interconnection of conduits for at least one or both adjoining modular functional layers,
- “Sensor Layers” comprising sensing elements, etc. for at least one or both adjoining modular functional layers,
- Other types of modular functional layers (to be announced).
Accordingly, various types of modular functional layers can be defined, standardized, and manufactured. Each functional layer can have its own inputs and outputs directed to and from external apparatus (for example on one or more edges or sides of a modular functional layer, potentially using a multiple-port microfluidic, micro-conduit, electrical, optical, or mixed mode connector(s) on one or more edges of the modular functional layer, etc.). Provisions can also be provided for layer-jumping, for example using the afore-described modular functional layers edge-connections, provisions for transport through one or more modular functional layers, etc.
3. Microfluidic and Micro-Conduit System Design and Emulation
This NRI technology area pertains to software-controlled chemical process emulation systems and environments comprising individually-addressable and/or group-addressable software-controlled chemical system processing modules, software-controlled chemical system handling modules, and related components. The software-controlled modules may be designed and interconnected to emulate various fixed, configurable, and reconfigurable “Lab-on-a-Chip” (“LoC”) devices. The software-controlled modules may be designed as separate units with well-defined ports and interfaces that can be used in the construction of larger systems. These aspects may be used to design a LoC device, develop software for the operation of a LoC device, or may be used together with actual LoC devices as part of a larger system. Alternatively, the software-controlled modules may be integrated into more complex subsystems that can be used in similar or other ways, for example to implement laboratory automation features in experimental set-ups and laboratory-scale chemical production.
4. Microfluidic and Micro-Conduit System Control and Scripting Software
This NRI technology area pertains to software systems for development, control, programming, simulation, and emulation of fixed, software-configurable, software-reconfigurable, and software-controlled Lab-On-a-Chip (“LoC”) devices such as NRI technologies involving software-controlled transport and operation processes for fluidic, microfluidic, and related systems. Software development environments can feature and use authoring/editing tools, functional libraries, debuggers, modeling, and emulation tools. Configuration files can be used to specify software-defined system configurations for software-reconfigurable Lab-On-a-Chip (“LoC”) devices, models and emulation of such devices. Operation process control files can include temporal and event-driven control sequences for the operation of software-reconfigurable Lab-On-a-Chip (“LoC”) devices, models and emulation of such devices. Operation process control files can be programmed, represented, and stored as scripts. Scripts can also be used to control numerical simulations as well as physical emulations of modeled LoC devices. In some cases, an active data visualization system provides visualizations of real-time data generated by past and current simulations and emulations. Configuration files can be used as inputs for fabrication design systems to design fixed-configuration devices.
5. Design for New Microfluidic System Commercialization Strategies
Academic R&D for microfluidic systems, Lab-On-a-Chip systems, and proposed Micro Total Analysis Systems (μTAS) has been continuing for decades with very little commercial success. NRI believes the dominant impediment to mass commercial manufacture and widespread use is that each proposed device is envisioned as if it were a dedicated custom VLSI chip prior to the age of ASIC electronics. There is typically not enough market size to even justify the R&D needed for design for any one application, much less mass manufacture. A second historic impediment is that there are limited inexpensive methods for mass manufacturing, and a third historic impediment is the manufacturability of reliable microfluidic/micro-conduit valves and pumps.
The actively software-controlled NRI micro-conduit-based microfluidic technology described in Section 2.1 demonstrates that through use of a general software-operated (and software configured architecture), a single design can be economically manufactured in large scale and readily adapted to diverse specialized applications. Such a system can be thought of as a Chemical MicroprocessorTM or Biochemical MicroprocessorTM.
Accordingly, utilizing various aspects of the NRI technology based described in Sections 1-4 above, a small family of flexible software-reconfigurable multipurpose reusable “Lab-on-a-Chip” or “embedded chemical processor” with differing feature sets can be used to create a multi-purpose product line or standardized component that can support and enable an extremely wide range of applications, instruments, and appliances. Such a family of Chemical MicroprocessorTM or Biochemical MicroprocessorTM devices can be thought of as equivalent to families of computational microprocessor chips.
The result of this framework removes the market-size problem by aggregating large collections of small-market pent-up demands into enough of a value proposition to justify the R&D, manufacturing tool-up expenditure, and product support costs. This is illustrated in the figure below.
There are been increasing recent developments in the second historic impediments (limited inexpensive methods for mass manufacturing), and NRI continues its own internally-funded innovative work on the third historic impediment (reliable microfluidic/micro-conduit valve and pump manufacturability), but that market for even first-generation devices will dramatically increase R&D expenditures for radical sudden advancements in these areas.
NRI is actively seeking funding and partnership arrangements for its continued work in this area, particularly with NRI’s recent work on the reliable, inexpensive, and manufacturable microfluidic/micro-conduit valve and pump problems. At that point NRI will posses a critical center of technology for the commercialization of microfluidic, Lab-On-a-Chip systems, and long-envisioned Micro Total Analysis Systems (μTAS).
|Title||Patent Number||Application Number||Priority Dates||Text Only||Related Patents|
|General-purpose reconfigurable conduit and reaction chamber microfluidic arrangements for lab-on-chip and miniature chemical processing||10,449,540||15/499,767||11/28/2006||Text||Lab on a Chip and Microfluidics|
|Three-Dimensional Multiple-Layer Microfluidic Micro-Droplet Arrays for Chemical and Biochemical Microreactors, Miniature Bioreactors, Heat Transfer, and Other Applications||10,406,522||15/260,801||02/16/2012||Text||Microfluidic and Lab-On-A-Chip Systems|
|Software-reconfigurable conduit and reaction chamber microfluidic arrangements for lab-on-a-chip and miniature chemical processing technologies||9,636,655||13/314,170||11/28/2006||Text||Microfluidic and Lab-On-A-Chip Systems|
|Three-Dimensional Microfluidic Micro-Droplet Arrays for Electronic Integrated Circuit and Component Cooling, Energy-Harvesting, Chemical and Biochemical Microreactors, Miniature Bioreactors, and Other Applications||9,441,308||13/770,934||02/16/2012||Text||Microfluidic and Lab-On-A-Chip Systems|
|Multi-channel chemical transport bus with bus-associated sensors for microfluidic and other applications||8,812,163||13/251,288||12/4/2007||Text||Microfluidic and Lab-On-A-Chip Systems|
|Multi-Channel Chemical Transport Bus Providing Short-Duration Burst Transport Using Sensors for Microfluidic and Other Applications||8,606,414||13/251,286||12/04/2007||Text||Microfluidic and Lab-On-A-Chip Systems|
|Software-Controlled Lab-on-a-Chip Emulation||8,560,130||12/328,713||12/04/2007||Text||Microfluidic and Lab-On-A-Chip Systems|
|Software Systems for Development, Control, Programming, Simulation, and Emulation of Fixed and Reconfigurable Lab-on-a-Chip Devices||8,396,701||12/328,726Â||12/04/2007||Text||Microfluidic and Lab-On-A-Chip Systems|
|Multi-Channel Chemical Transport Bus for Microfluidic and Other Applications||8,032,258||12/328,716||12/04/2007||Text||Microfluidic and Lab-On-A-Chip Systems|
Pending Published Applications
|Title||Publication Number||Application Number||Priority Dates||Publish Date||Text Only||Related Patents|
|Software Controlled Transport and Operation Processes for Fluidic and Microfluidic Systems, Temporal and Event-Driven Control Sequence Scripting, Functional Libraries, and Script Creation Tools||2019/0073238||16/179,849||11/02/2017||Text||Microfluidic and Lab-On-A-Chip Systems|
|Valve Configurations Facilitating Clearing, Cleaning, Drying, and Burst Formation for Microfluidic Devices, Fluidic Arrangements, and Other Systems||2019/0072987||16/179,825||11/02/2017||Text||Microfluidic and Lab-On-A-Chip Systems|
|Removable fluidics structures for microarray, microplates, sensor arrays, and other removable media||2014/0274814||13/815,757||03/15/2013||09/18/14||Text||Microfluidic and Lab-On-A-Chip Systems|
|Software Systems for Development, Control, Programming, Simulation, and Emulation of Fixed and Reconfigurable Lab-On-A-Chip Devices||2013/0144586||13/757,662||12/04/2007||06/06/13||Text||Microfluidic and Lab-On-A-Chip Systems|
Pending Unpublished Applications
|Title||Application Number||Priority Dates||Related Patents|
|Functional Layer and Other Functional Modular Arrangements for Micro-Conduit Fluidics and Gas Exchange, Sensors, Illumination, and Imaging||16/502,793||07/03/2018||Microfluidic and Lab-On-A-Chip Systems|
|Removable Internally-Actuated Controlled Fluidics Structures for Interfacing with Microarray, Microplates, Sensor Arrays, and Other Removable Media||16/730,978||03/15/2013||Microfluidic and Lab-On-A-Chip Systems|
|Three-Dimensional Multiple-Layer Microfluidic Micro-Droplet Arrays with Micrifluidic Bus for Chemical and Biochemical Microreactors, Miniature Bioreactors, Heat Transfer, and Other Applications||16/565,294||02/16/2012||Microfluidic and Lab-On-A-Chip Systems|
|Multi-Channel Chemical Transport Bus with Bus-Associated Sensors for Microfluidic and Other Applications||14/335,763||12/04/2007||Microfluidic and Lab-On-A-Chip Systems|
|Distributed, Hierarchical, And Multitask Software Control of Conduit-Based Microfluidic Arrangements for Lab-On-Chip and Miniature Chemical Processing||16/659,571||11/28/2006||Microfluidic and Lab-On-A-Chip Systems|