Keith J. Morton

Deterministic hydrodynamics : Taking blood apart

We show the fractionation of whole blood components and isolation of blood plasma with no dilution by using a continuous-flow deterministic array that separates blood components by their hydrodynamic size, independent of their mass. We use the technology we developed of deterministic arrays which separate white blood cells, red blood cells, and platelets from blood plasma at flow velocities of 1,000 μm/sec and volume rates up to 1 μl/min. We verified by flow cytometry that an array using focused injection removed 100% of the lymphocytes and monocytes from the main red blood cell and platelet stream. Using a second design, we demonstrated the separation of blood plasma from the blood cells (white, red, and platelets) with virtually no dilution of the plasma and no cellular contamination of the plasma.

Sub-10 nm self-enclosed self-limited nanofluidic channel arrays.

We report a new method to fabricate self-enclosed optically transparent nanofluidic channel arrays with sub-10 nm channel width over large areas. Our method involves patterning nanoscale Si trenches using nanoimprint lithography (NIL), sealing the trenches into enclosed channels by ultrafast laser pulse melting and shrinking the channel sizes by self-limiting thermal oxidation. We demonstrate that 100 nm wide Si trenches can be sealed and shrunk to 9 nm wide and that lambda-phage DNA molecules can be effectively stretched by the channels.

Hydrodynamic metamaterials: Microfabricated arrays to steer, refract, and focus streams of biomaterials

We show that it is possible to direct particles entrained in a fluid along trajectories much like rays of light in classical optics. A microstructured, asymmetric post array forms the core hydrodynamic element and is used as a building block to construct microfluidic metamaterials and to demonstrate refractive, focusing, and dispersive pathways for flowing beads and cells. The core element is based on the concept of deterministic lateral displacement where particles choose different paths through the asymmetric array based on their size: Particles larger than a critical size are displaced laterally at each row by a post and move along the asymmetric axis at an angle to the flow, while smaller particles move along streamline paths. We create compound elements with complex particle handling modes by tiling this core element using multiple transformation operations; we show that particle trajectories can be bent at an interface between two elements and that particles can be focused into hydrodynamic jets by using a single inlet port. Although particles propagate through these elements in a way that strongly resembles light rays propagating through optical elements, there are unique differences in the paths of our particles as compared with photons. The unusual aspects of these modular, microfluidic metamaterials form a rich design toolkit for mixing, separating, and analyzing cells and functional beads on-chip.

Tunable Liquid Crystal-Resonant Grating Filter Fabricated by Nanoimprint Lithography

We demonstrate a tunable filter consisting of a subwavelength resonant grating filter cladded by a liquid crystal cell. The resonant wavelength of the grating filter is tuned by electrically varying the refractive index of the liquid crystal. A tuning range of around 20 nm has been achieved.

All-thermoplastic nanoplasmonic microfluidic device for transmission SPR biosensing

Early and accurate disease diagnosis still remains a major challenge in clinical settings. Biomarkers could potentially provide useful tools for the detection and monitoring of disease progression, treatment safety and efficacy. Recent years have witnessed prodigious advancement in biosensor development with research directed towards rapid, real-time, label-free and sensitive biomarker detection. Among emerging techniques, nanoplasmonic biosensors pose tremendous potential to accelerate clinical diagnosis with real-time multiplexed analysis, rapid and miniaturized assays, low sample consumption and high sensitivity. In order to translate these technologies from the proof-of-principle concept level to point of care clinical diagnosis, integrated, portable devices having small footprint cartridges that house low-cost disposable consumables are sought. Towards this goal, we developed an all-polymeric nanoplasmonic microfluidic (NMF) transmission surface plasmon resonance (SPR) biosensor. The device was fabricated in thermoplastics using a simple, single step and cost-effective hot embossing technique amenable to mass production. The novel 3D hierarchical mold fabrication process enabled monolithic integration of blazed nanogratings within the detection chambers of a multichannel microfluidic system. Consequently, a single hard thermoplastic bottom substrate comprising plasmonic and fluidic features allowed integration of active fluidic elements, such as pneumatic valves, in the top soft thermoplastic cover, increasing device functionality. A simple and compact transmission-based optical setup was employed with multiplexed end-point or dual-channel kinetic detection capability which did not require stringent angular accuracy. The sensitivity, specificity and reproducibility of the transmission SPR biosensor was demonstrated through label-free immunodetection of soluble cell-surface glycoprotein sCD44 at clinically relevant picomolar to nanomolar concentrations.

Printing of sub-20 nm wide graphene ribbon arrays using nanoimprinted graphite stamps and electrostatic force assisted bonding

Nano-graphene ribbons are promising in many electronic applications, as their bandgaps can be opened by reducing the widths, e.g. below 20 nm. However, a high-throughput method to pattern large-area nano-graphene features is still not available. Here we report a fabrication method of sub-20 nm ribbons on graphite stamps by nanoimprint lithography and a transfer-printing of the graphene ribbons to a Si wafer using electrostatic force assisted bonding. These methods provide a path for fast and high-throughput nano-graphene device production.

Nanoimprint mold fabrication and replication by room-temperature conformal chemical vapor deposition

The authors present a technique for the replication of molds for nanoimprint lithography (NIL) without solvents or etching. A thin hard amorphous silicon film is deposited onto imprinted or self-assembled polymer nanostructures by room-temperature conformal plasma-enhanced chemical vapor deposition. After attachment to another substrate and separation from the polymer original, the thin hard film forms a NIL mold that is the inverse of the polymer original. Using this technology, the authors demonstrate the replication of a 200nm pitch grating mold and sub-50-nm features over wafer-scale areas without introducing additional line edge roughness associated with conventional replication methods.

Fabrication of a 60-nm-diameter perfectly round metal-dot array over a large area on a plastic substrate using nanoimprint lithography and self-perfection by liquefaction

Typically, nanopatterning on plastic substrates has poor fidelity, poor adhesion, and low yield. Here the proposal of and the first experiment using a new fabrication method that overcomes the above obstacles and has achieved arrays of 60-nm-diameter, perfectly round metal dots over a large area on a polyethylene terephthalate (PET) substrate with high fidelity and high yield is reported. This new method is based on the use of a thin hydrogen silsesquioxane (HSQ) layer on top of PET, nanoimprint lithography, and self-perfection by liquefaction (SPEL). The HSQ layer offers excellent thermal protection to the PET substrate during SPEL, as well as good surface adhesion and etching resistance. Nanoimprinting plus a lift off created a large-area array of Cr squares (100 nm x 130 nm) on HSQ and SPEL changed each Cr square into a perfectly round Cr dot with a diameter of 60 nm, reducing the Cr footprint area by 78%. Compared to bare PET, the use of HSQ also reduced the variation in the diameter of the Cr dots from 11.3 nm (standard deviation) to 1.7 nm, an improvement of over 660%. This new technology can be scaled to much larger areas (including roll-to-roll web processing) and thus potentially has applications in various fields.

Microfluidic Integration of a Cloth-Based Hybridization Array System (CHAS) for Rapid, Colorimetric Detection of Enterohemorrhagic Escherichia coli (EHEC) Using an Articulated, Centrifugal Platform.

We describe the translation of a cloth-based hybridization array system (CHAS), a colorimetric DNA detection method that is used by food inspection laboratories for colony screening of pathogenic agents, onto a microfluidic chip format. We also introduce an articulated centrifugal platform with a novel fluid manipulation concept based on changes in the orientation of the chip with respect to the centrifugal force field to time the passage of multiple components required for the process. The platform features two movable and motorized carriers that can be reoriented on demand between 0 and 360° during stage rotation. Articulation of the chip can be used to trigger on-the-fly fluid dispensing through independently addressable siphon structures or to relocate solutions against the centrifugal force field, making them newly accessible for downstream transfer. With the microfluidic CHAS, we achieved significant reduction in the size of the cloth substrate as well as the volume of reagents and wash solutions. Both the chip design and the operational protocol were optimized to perform the entire process in a reliable, fully automated fashion. A demonstration with PCR-amplified genomic DNA confirms on-chip detection and identification of Escherichia coli O157:H7 from colony isolates in a colorimetric multiplex assay using rfbO157, fliCH7, vt1, and vt2 genes.

Nanochannels for Genomic DNA Analysis: The Long and the Short of It

This review will discuss the theory of confined polymers in nanochannels and present our experiments, which test the theory and explore use of nanochannels for genomic analysis. Genomic length DNA molecules contained in nanochannels, which are less than one persistence length in diameter, are highly elongated. Thus, nanochannels can be used to analyze genomic length DNA molecules with very high linear spatial resolution. Also, nanochannels can be used to study the position and dynamics of proteins such as transcription factors that bind to DNA with high specificity. In order to realize these goals not only must nanochannels be constructed whose radius is less than the persistence length of DNA, but it is also necessary to understand the dynamics of polymers within nanochannels and develop experimental tools to study the dynamics of polymers in such confined volumes, tools which we review here.