WO2007115378A1

WO2007115378A1 - Microfluidic package housing

Info

Publication number: WO2007115378A1
Application number: PCT/AU2007/000480
Authority: WO
Inventors: Andrew Paul Campitelli; Sebastiaan Garst; Jason Paul Hayes; John Edward Mccormack; Matthias Schuenemann; Matthew Daniel Solomon
Original assignee: Minifab Australia Pty Ltd
Current assignee: Minifab Australia Pty Ltd
Priority date: 2006-04-11
Filing date: 2007-04-11
Publication date: 2007-10-18
Anticipated expiration: 2008-10-11

Abstract

A microfluidic package (10) is disclosed. The package has a pair of matching casing members (12, 14) at least one of which includes a featured interior surface (16) facing an opposing interior surface (18) of the other casing member (12), the interior surfaces (16, 18) being arranged to channel a fluid. There are alignment means (26) connected to one of the casing members (14) and being configured to align the opposing interior surfaces (12, 14) of the casing members (12, 14).

Description

Microfluidic package housing

FIELD OF THE INVENTION

The present invention relates broadly to microfluidic packaging.

BACKGROUND OF THE INVENTION

Microfluidic packages allow the handling of gases, vapours or liquids in volumes and flow rates that range from several microlitres per second to a few picolitres per process. Active and passive microstructures control the flow and mixing of the fluids to produce physical, chemical, biochemical and microbiological reactions in a rapid, cost effective manner. Applications of microfluidics include automation and decentralisation of highly manual laboratory processes such as blood gas analysis, pathogen detection, cardiac marker detection, cancer marker detection, virus detection, genetic analysis, chemical and pharmaceutical synthesis, environmental analysis, pathogen detection, medical diagnostics (such as blood gas analysis, cardiac marker detection, cancer marker detection, virus selection), clinical pathology, genomics and proteomics.

Conventionally, microfluidic devices are realised by bonding several superimposed layers of micro structured polymer films together. The bonding process usually involves either an auxiliary material such as adhesives or solvents, leading to the risk of involuntarily blocking channels and microfluidic structures and/or accidentally exposing biological fluids to materials that are not biocompatible, or exposes the device components to elevated temperatures or elevated pressures or a combination thereof, risking deterioration or denaturisation of biological material and reagents stored on the device, such as enzymes, immobilised DNA or immobilised antibodies. Many bonding processes cannot bond preferred materials such as polydimethylsiloxane (PDMS) with cyclic olefin copolymer (COC) or polycarbonate (PC). Integrating off the shelf non-polymer components can also be difficult for established bonding processes.

SUMMARY OF THE INVENTION

According to one aspect of the invention there is provided a microfluidic package comprising: a pair of matching casing members at least one of which includes a featured interior surface facing an opposing interior surface of the other casing member, the interior surfaces each being arranged to channel a fluid; and alignment means connected to at least one of the casing members and being configured to align the opposing interior surfaces of the casing members.

Preferably the alignment means include one or more flange means attached to one of the casing members, each of the one or more flange means being arranged to contactably receive an edge of the other casing member. More preferably one of the flange means includes projecting alignment pins or notches that mate with corresponding alignment notches or pins formed in the other of the casing members.

Preferably the casing members include interlocking means designed to interlock with one another. More preferably, the interlocking means include a tongue-in-groove arrangement, at least part of which are formed in the flange means. Even more preferably the interlocking means include snap lock means, at least part of which are formed in the flange means. Alternatively the interlocking means includes the flange means which forms an interference fit with the other casing member.

Preferably the featured interior surface includes one or more fluid channels in the form of one or more grooves. More preferably at least one of the grooves includes an enlarged region forming a recess adapted to receive a reagent pack or reactive chamber. Even more preferably the recess intersects more than one fluid channel. Still more preferably one of the grooves includes a serpentine section arranged to mix the fluid.

Preferably at least one of the casing members includes an aperture formed therethrough for transporting fluid to and/or away from the featured interior surface.

Preferably one of the casing members if adapted to receive a microfluidic insert in fluid communication with the featured interior surface. More preferably one of the casing members is adapted to receive a sensor, actuator, signal processor, or communication insert in communication with the featured interior surface. Even more preferably the one of the casing members has a depression arranged to receive the insert in communication with the featured interior surface. Still more preferably one of the casing members has a cut-out for external access to the insert. Alternatively, a spacer layer received by the flange means locates the insert relative to the interior surface.

Preferably a sealing gasket is sandwiched between the featured surface and the insert. More preferably another sealing gasket is sandwiched between the insert and the opposing interior surface of the other casing member.

Preferably one or both of the casing members includes an optical window.

Preferably the casing members are integrally formed of a polymer material.

BRIEF DESCRIPTION OF THE FIGURES

In order to achieve a better understanding of the nature of the invention preferred embodiments of a microfluidic package will now be described, by way of example only, with reference to the accompanying figures in which:

figure 1 is a perspective view of one embodiment of an assembled microfluidic package according to one aspect of the invention;

figure 2 shows exploded perspective views of the embodiment shown in figure 1 ;

figure 3 shows exploded perspective views of another embodiment of a microfluidic package according to the invention;

figure 4 shows exploded perspective views of another embodiment of a microfluidic package according to the invention;

figure 5 shows exploded perspective views of another embodiment of a microfluidic package according to the invention;

figure 6 shows exploded perspective views of another embodiment of a microfluidic package according to the invention;

figure 7 shows exploded perspective views of another embodiment of a microfluidic package according to the invention; figure 8 shows exploded perspective views of another embodiment of a microfluidic package according to the invention;

figure 9 shows exploded perspective views of another embodiment of a microfluidic package according to the invention;

figure 10 shows exploded perspective views of another embodiment of a microfluidic package according to the invention;

figure 11 shows perspective views and a crossectional view of another embodiment of a microfluidic package according to the invention, including a snap lock mechanism;

figure 12 shows exploded views and a crossectional view of another embodiment of a microfluidic package according to the invention, including a slot/slider mechanism;

figure 13 shows perspective views and a crossectional view of another embodiment of a microfluidic package according to the invention, held together by an interference fit;

figure 14 shows a top view of another embodiment of a microfluidic package according to the invention, including alignment pins and notches;

figure 15 shows perspective views of another embodiment of a microfluidic package according to the invention, including a snap lock mechanism and alignment pins and notches;

figure 16 shows a crossectional view through a reagent blister or pouch piercable by pins;

figures 17 and 18 are exploded perspective views of another embodiment of a microfluidic package according to the invention including a fluidic interconnection insert;

figures 19 and 20 are top X-ray and cross-sectional views of the embodiment of a microfluidic package shown in figures 17 and 18. The sectional plane is indicated by A-A¹ in figure 19;

figure 21 is a process flow diagram for a microfluidic package according to the invention for polymerase chain reaction process for amplifying nucleic acid while detecting the amplification products in real time; figure 22 is a plan view of a disassembled microfluidic package according to the invention for polymerase chain reaction;

figure 23 is a process flow diagram for a microfluidic package according to the invention for enzymatic immunoassay reaction with optical detection;

figure 24 is a plan view of a disassembled microfluidic package according to the invention for enzymatic immunoassay reaction; and

figure 25 shows another embodiment of a microfluidic package according to the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A perspective view of one embodiment of an assembled microfluidic package, according to one aspect of the invention, is shown in figure 1, and is indicated generally by the number 10. Two different exploded perspective views of the same embodiment are shown in figure 2A and 2B. The package 10 has a pair of matching casing members 12, 14 integrally formed of a polymer material. At least one of the matching casing members 12, 14 has a featured interior surface 16 facing an opposing interior surface 18 of the other casing member 12. The interior surfaces 16, 18 have fluid channels in the form of grooves such as 20. In some embodiments of a microfluidic package only one of the surfaces 16, 18 is featured. Some of these channels may include an enlarged and/or deeper region, such as 22, forming a recess for receiving a reactive chamber in this embodiment. The reactive chamber may be, for example, a micro array of hybridised DNA or a reactive chamber for observing fluorescent signals. In the embodiment shown in figure 8, however, the enlarged region 22 intersects more than one channel and can accept a breakable reagent pack or blister 54. The reagent blister 54 may contain reagents such as enzymes, oligonucleotides, primers, antibodies, antigens, conjugates, reporter agents, blocking agents, rehydration agents, calibration fluids, rinse buffer, wash buffer, positive or negative control solutions. The reagents may also contain suspensions of nanoparticles or beads in buffer solutions such as binding buffer. Figure 16 shows a blister that is pierced by pins 120 attached to a casing member 12 when the package is squeezed. This releases the substance stored within the blister. The pins are not essential but do promote ease of blister rupture. As shown in figure 2, the channels may include a serpentine region 24 arranged to mix a fluid travelling along it. Other features may include reservoirs, pumps, valves, mixes or connectors.

The embodiment of a microfluidic package 10 shown in figures 1 and 2 include alignment means in the form of flanges 26 connected to the lower casing member 14. The flanges 26 contactably receive a corresponding edge 28 of the other casing member 12 resulting in the alignment of the opposing interior surfaces 16, 18 of the respective casing members 12, 14. The alignment of features on the opposing interior surfaces 16, 18 may allow, for example, fluid to flow from one channel on one featured surface 16 to a channel on the other featured surface 18. Various embodiments may have 1 flange, 2, 3 (such as in figure 2), 4 (such as in figure 6) or more flanges.

Figures 14A and 14B are top views of another embodiment of a microfluidic device 10, where similar components in figures 1 and 14 are similarly labelled. In this embodiment, the flanges 26 include projecting alignment pins such as 29 that mate with corresponding alignment notches such as 30 formed in the other casing member 12. In this embodiment the alignment pins 29 and notches 30 create a unique relationship between the casing members 12, 14 preventing misassembly or misalignment.

Returning to the embodiment shown in figures 1 and 2, at least one of the casing members 12 include apertures 32 formed therethrough for transporting fluid to and/or away from the featured interior surfaces 16 or the opposing interior surface 18. The apertures may also be used to transport gases in a controlled and sequenced manner to power pneumatic pumps and/or valves.

In this embodiment, the casing members 12, 14 are adapted to receive a sensor, actuator, signal processing, communication or microfluidic insert 34 that can interact with the fluid contained in the fluid channels or is otherwise in communication with the featured interior surface. The inserts may comprise microfluidic functions such as channels, reservoirs, pumps, valves or mixes; sensor functions such as potentiometric sensing, temperature sensing, pH sensing, microspot arrays containing immobilised DNA, reaction chambers for the detection of colour changes or fluorescent events; actuator functions such as fluid transport, heating or cooling, signal processing functions, communication functions and/or power supply components such as batteries or energy harvesters. The embodiment of a microfluidic device 10 shown in figure 3 includes a depression 36 formed in the casing member 14 arranged to receive an insert 34 and thus position the insert 34 relative to the assembled casing members 12, 14. The embodiment shown in figure 4, however, includes a spacer layer 40 received by the flanges 26 and that locates the insert 34 relative to the interior surfaces 16, 18. The casing member 12 has a cut-out 38 allowing external access to the insert 34, such as, connecting electrodes to it or extracting fluid from it for example.

The embodiments of a microfluidic package shown in figures 17 and 18 include a microfluidic interconnection insert 60 which has interconnects 113,114 in the form of apertures for passing fluid and thus allowing fluid flow that is not confined along a single surface. A combination of horizontal and vertical fluid connections can be used to connect features on the opposing surfaces which are not directly opposite each other. A single design of casing member 12, 14 are usable for many differing applications by simply inserting an appropriate microfluidic insert 60.

In some embodiments of a microfluidic package 10 such as that shown in figures 5 A and 5B, sealing gaskets 42 are sandwiched between the insert 34 and the interior surfaces 16, 18 of the respective casing members 12,14. The gaskets in this embodiment has apertures 44 allowing fluid to pass therethrough.

Some embodiments of a microfluidic package 10, such as that shown in figures 6A and 6B, may include an optical window 46 which may have a transparent insert 48. In some other embodiments, the optical window is formed in a transparent casing member formed of, for example, cyclic olefin co-polymer. In this case, the window may be recessed slightly into the casing member to prevent marking. It is possible to integrate one or more lenses into the casing member.

Preferred embodiments of a microfluidic package include interlocking means designed to interlock the casing members 12, 14. Figure HA, HB, HC and HD show an embodiment 10 with interlocking means in the form of a tongues 50 formed in casing member 14 and groove 52 formed along the edge of the other casing member 12. This tongue-in-grooves arrangement forms a snap lock mechanism. The snap lock mechanism is typically designed for permanent locking, but may also be designed so that the casing members can disengage, either for ease of repair or for ease of disposal or recycling. The embodiments shown in figure 12 have long tongues 50 formed in the casing member 12 that engage long grooves 52 formed in the flange 26 of the other casing member 14. This tongue-in-groove is a sliding arrangement. The slider arrangement can be designed to be either straight for ease of dismount or wedged for permanent connection, depending on the intended use and disposal of the device. The embodiment shown in figure 6 has casing members 12 and 14 that make an interference fit to each other. The resulting clamping forces in the embodiments of figures 6, 11 and 12 are sufficient to seal all fluidic connections between the casing members and insert. Fluidic sealing may be supported by the use of sealing gaskets.

Some other embodiments may have adhesively or otherwise bonded casing members and/or inserts. Still other embodiments may have externally clamped casing members.

The casing members 12, 14 and space layer 40 may be manufactured using microfabrication techniques including hot embossing, stamping, die cutting, thermoforming, injection moulding, polymerising the precursor polymers within the mould, laser cutting, micromilling or other mechanical microfabrication techniques. The sealing gaskets may be manufactured using techniques such as cast moulding, compression moulding, injection moulding, reactive injection moulding, die cutting, polymerising the precursor materials in the mould, or by microdrilling or similar mechanical microfabrication techniques.

One or all components of the microfluidic package may be coated on one or all surfaces with a barrier layer, such as parylene, in order to render the materials biocompatible and/or non-cytotoxic. Barrier layers, such as parylene, also lower the water absorption of the material, lower the water vapour permeability, and protect the material from potential harmful interaction with fluids, chemicals, agents and solvents.

The hydrophylicity of the microfluidic surfaces may be improved by surface treatment techniques such as plasma polymerisation, UV treatment, saponification, polyethylene oxide grafting, surface texturing or electrowetting.

In some embodiments, the non-specific binding of proteins or other biological materials to the microfluidic surface may be minimised by coating one or all surfaces with blocking agents such as acrylamides, polyethylene glycol, bovine serum albumin, egg albumin, whole serum, skim milk, salmon sperm DNA or herring sperm DNA.

A variety of materials can be used to manufacture embodiments of the invention. Preferably, the casing members 12, 14 are manufactured from materials selected from the group comprising cyclic olefin copolymer (COC), polycarbonate (PC), polystyrene (PS), polymethylmethacrylate (PMMA), polyethyleneterephthalate (PET), polyimide (PI), polyetherimide (PEI), polydimethylsiloxane (PDMS), acrylonitrile butadiene styrene (ABS), cellulose acetate (CA) cellulose acetate butyrate (CAB), high density polyethylene (BDPE), low density polyethylene (LDPE), polyamide (PA), polybutylene terephtalate (PBT), polyether ether ketone (PEEK), polyethylene terephtalate glycol (PETG), polymethylpentene (PMP), polyoxide methylene (POM), polypropylene (PP), polysulfone (PSU), polytetrafluoroethylene (PTFE), polyvinylchloride (PVC), polyvinylidene chloride (PVDC) or polyvinylidene fluoride (PVDF) or combinations thereof. Preferably the material selected has high strength and high dimensional stability coupled with a high coefficient of elasticity.

More preferably, the casing member 12 is manufactured from materials selected from the group comprising polycarbonate (PC), polystyrene (PS), polymethylmethacrylate (PMMA) or cyclic olefin copolymer (COC).

More preferably, the casing member 14 is manufactured from materials selected from the group comprising polycarbonate (PC), polystyrene (PS), polymethylmethacrylate

(PMMA), cyclic olefin copolymer (COC), polypropylene (PP) or acrylonitrile butadiene styrene/polycarbonate blends (ABS/PC).

Preferably, the spacer layer 40 and the inserts 56, 58, 60, 61 are manufactured from materials selected from the group comprising cyclic olefin copolymer (COC), polycarbonate (PC), polystyrene (PS), polymethylmethacrylate (PMMA), polyethyleneterephthalate (PET), polyimide (PI), polyetherimide (PEI), polydimethylsiloxane (PDMS), acrylonitrile butadiene styrene (ABS), cellulose acetate (CA), cellulose acetate butyrate (CAB), high density polyethylene (HDPE), low density polyethylene (LDPE), polyamide (PA), polybutylene terephtalate (PBT), polyether ether ketone (PEEK), polyethylene terephtalate glycol (PETG), polymethylpentene (PMP), polyoxide methylene (POM), polypropylene (PP), polysulfone (PSU), polytetrafluoroethylene (PTFE), polyvinylchloride (PVC), polyvinylidene chloride (PVDC) or polyvinylidene fluoride (PVDF) or combinations thereof.

Preferably the materials selected have low water vapour permeability and low water absorption. The required optical transparency, oxygen permeability and carbon dioxide permeability of the material depends on the process requirements.

Preferably, the sealing gaskets 42 are manufactured from polysiloxanes such as polydimethylsiloxane (PDMS), from polytetrafluoroethylene (PTFE), or thermoelastic rubbers such as Santoprene.

Preferably, the insert 34 is formed of semiconductor materials such as silicon or lithium niobate, and in some embodiments formed of glass, ceramic, or printed circuit board material.

However, the spacer layers 40 and inserts 34, 56,58, 60 and 61 may be manufactured from any suitable material, as can the casing members 12, 14 and the gaskets 42.

By way of example, figure 21 shows a process flow diagram for the detection and identification of a specific target organism (e.g. a virus, bacterium) by detecting the presence of a specific nucleic acid sequence with the help of a polymerase chain reaction (PCR).

Figure 22 shows an embodiment of a disassembled microfluidic package, according to the invention, capable of target organism identification.

The package is inserted into a suitable fluid processor, such as MiniChemLab MB 320

(MiniFab (Aust) Pty Ltd, Scoresby VIC, Australia). A sample, consisting of extracted and washed nucleic acids, a PCR master mix (e.g. a mixture of PCR buffer, MgCl₂ and deoxynucleitides dATP, dCTP, dGTP and dTTP/dUTP), an enzyme (such as Taq DNA polymerase) in a suitable buffer fluid and up to 4 sets of primers in a suitable buffer fluid are provided to the package via apertures or fluidic interfaces 104. The PCR master mix is mixed with the enzyme buffer using a fluid junction 106 and mixing/delay lines 107. In a next step, the resulting mix is again mixed with the sample using another fluid junction 106 and mixing/delay lines 107. This sample/reagent mix is split into four different subsamples, each of these subsamples is mixed with a set of primers using fluid junctions 106 and mixing/delay lines 107. The resulting four or less subsamples are then transported into reaction wells 110 and cycled through various temperatures. The repeated cycling of the sample & reagent mix through various temperatures results in an amplification of the target nucleic acids by extending sequence-specific primers yielding complimentary copies of the respective targeted nucleic acid strands. The reaction can be measured optically through an optical window 111, by real-time fluorescence detection of amplicons.

By way of example, figure 23 shows a process flow diagram for the detection of the presence of a specific substance of interest (such as proteins, hormones, cell signalling chemicals, antibodies, antigens, or cytokines) with the help of an enzyme-linked immunosorbent assay.

Figure 24 shows an embodiment of a disassembled microfluidic package, according to the invention, for enzymatic immunoassay reaction on four different samples in parallel.

Primary antibodies, which are selected for their selective binding affinity to the specific substance of interest, have been pre-immobilised into the reaction wells 110 prior to use, preferably at the manufacturing side. The remaining open binding sites in the reaction well 110 have been blocked with a blocking agent (such as bovine serum albumin 5% in a phosphate buffered saline solution), prior to use. Additionally, a substrate such as p- nitrophenylphosphate for phosphatase-conjugated secondary antibodies or o- phenylenediamine dihydrochloride for peroxidase-conjugated secondary antibodies has been pre-immobilised into some of the delay lines 107.

The package is inserted into a suitable fluid processor, such as MiniChemLab MB 320 (MiniFab (Aust) Pty Ltd, Scoresby VIC, Australia). Up to four different samples, a conjugate enzyme reporter (such as peroxidase-conjugated antibodies or phosphatase- conjugated secondary antibodies), a rinse buffer (such as phosphate buffered saline solution), and a stop solution (such as 3M NaOH for alkaline phosphatase, 2M HCl or 2M H2SO4 for peroxidase) are provided to the package via fluidic interfaces 104. Each sample is mixed with conjugate enzyme reporter via fluid junctions 106 and mixer/delay line elements 107, and then transported to the reaction well 110, where it remains for a defined amount of time. The immobilised primary antibodies capture any target substances of interest. The sample / conjugate enzyme reporter mix is then transported into a waste reservoir 112. Subsequently, the reaction well 110 is rinsed with buffer, which is also transported to the waste reservoir 112. In a next step, the immobilised substrate is rehydrated in the delay lines 107 with buffer, and then transported to the reaction well 110, where it is converted by the enzyme into a fluorescent or chromogenic signal by an enzymatically catalysed oxidation. The result can be measured through an optical window 111, by observing a change in light adsorption at a fixed wavelength in the reaction well, for example.

Note that although polymerase chain reaction and enzymatic immunoassay reaction are very different processes, the casing members 12 and 14 of the respective microfluidic packages, figures 22 and 24, are identical. Only the inserts 60, 61 differ. Thus, completely different processes require only relatively minor modification of the microfluidic insert 60, 61 and none to the casing members 12, 14. This modular approach is thus highly attractive.

Now that preferred embodiments of a microfluidic package according to the invention have been described, it will be appreciated that at least some of the preferred embodiments have at least some of the following advantages:

• a complex microfluidic package can be fabricated from polymer materials, and the well developed techniques of polymer material processing utilised;

• the package can be assembled without bonding with adhesives or solvents that can damage microfluidic features or reagents, or are otherwise not biocompatible;

• the package can be assembled without applying heat to bond the package, which can denature, destroy or reduce the effectiveness of the reagents;

• materials that are difficult or impossible to bond together can be simultaneously used in the one microfluidic package;

• precise alignment of the opposing interior surfaces and thus their respective features is achieved, as is precise alignment of any inserts;

• fluid flow is not confined to a single surface, but can be directed between surfaces and the inserts. Complex three dimensional microfluidic multilayer circuits and systems can therefore be built;

• prefabricated and/or third party inserts can be used without modifications;

• an integrated package having multiple functionalities can be built; and • the packages are amenable to mass production.

It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims

1. A mi crofluidic package comprising: a pair of matching casing members at least one of which includes a featured interior surface facing an opposing interior surface of the other casing member, the interior surfaces each being arranged to channel a fluid; and alignment means connected to at least one of the casing members and being configured to align the opposing interior surfaces of the casing members.

2. A microfluidic package defined by claim 1 wherein the alignment means include one or more flange means attached to one of the casing members, each of the one or more flange means being arranged to contactably receive an edge of the other casing member.

3. A microfludic package defined by claim 2 wherein one of the flange means includes projecting alignment pins or notches that mate with corresponding alignment notches or pins formed in the other of the casing members.

4. A microfluidic package defined by any one of claims 1-3 wherein the casing members include interlocking means designed to interlock with one another.

5. A microfluidic package defined by claim 4 wherein the interlocking means include a tongue-in-groove arrangement, at least part of which are formed in the flange means.

6. A microfluidic package defined by either of claims 4 or 5 wherein the interlocking means include snap lock means, at least part of which are formed in the flange means.

7. A microfluidic package defined by claim 4 wherein the interlocking means includes the flange means which forms an interference fit with the other casing member.

8. A microfluidic package defined by any one of the claims 1-7 wherein the featured interior surface includes one or more fluid channels in the form of one or more grooves.

9. A microfluidic package defined by claim 8 wherein at least one of the grooves includes an enlarged and/or deeper region forming a recess adapted to receive a reagent pack, blister, or reactive chamber.

10. A microfluidic package defined by claim 9 wherein the recess intersects more than one fluid channel.

11. A microfluidic package defined by either of claims 9 orlO wherein one of the grooves includes a serpentine section arranged to mix the fluid.

12. A microfluidic package defined by any one of claims 1-11 wherein the casing members includes an aperture formed therethrough for transporting fluid to and/or away from the featured interior surface.

13. A microfluidic package defined by any one of claims 1-12 wherein one of the casing members is adapted to receive a microfluidic insert in fluid communication with the featured interior surface.

14. A microfluidic package defined by any one of claims 1-12 wherein one of the casing members is adapted to receive a sensor, actuator, signal processor, or communication insert in communication with the featured interior surface.

15. A microfluidic package defined by either of claims 13 or 14 wherein the casing members has a depression arranged to receive the insert in communication with the featured interior surface.

16. A microfluidic package defined by any one of claims 13-15 wherein one of the casing members has a cut-out for external access to the insert.

17. A microfluidic package defined by any one of claims 13-15 wherein a spacer layer received by the flange means locates the insert relative to the interior surface.

18. A microfluidic package defined by any one of claims 13-17 wherein a sealing gasket is sandwiched between the featured surface and the insert.

19. A microfluidic package defined by any one of claims 13-18 wherein another sealing gasket is sandwiched between the insert and the opposing interior surface of the other casing member.

20. A microfluidic package defined by any one of claims 1-19 wherein one or both of the casing members includes an optical window.

21. A microfluidic package defined by any one of claims 1-21 wherein the casing members are integrally formed of a polymer material.