High-density microfluidic chips contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large scale integration (LSI). A component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. These integrated microfluidic networks can be used to construct a variety of highly complex microfluidic devices, for example the microfluidic analog of a comparator array, and a microfluidic memory storage device resembling electronic random access memories.

https://science.sciencemag.org/content/sci/298/5593/580.full.pdf

Microfluidic large scale integration

The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and/or detection of particles, such as cells and/or beads. The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and/or analysis of particles, such as cells, viruses, organelles, beads, and/or vesicles. The invention also provides microfluidic mechanisms for carrying out these manipulations and analyses. These mechanisms may enable controlled input, movement/positioning, retention/localization, treatment, measurement, release, and/or output of particles. Furthermore, these mechanisms may be combined in any suitable order and/or employed for any suitable number of times within a system. Accordingly, these combinations may allow particles to be sorted, cultured, mixed, treated, and/or assayed, among others, as single particles, mixed groups of particles, arrays of particles, heterogeneous particle sets, and/or homogeneous particle sets, among others, in series and/or in parallel. In addition, these combinations may enable microfluidic systems to be reused. Furthermore, these combinations may allow the response of particles to treatment to be measured on a shorter time scale than was previously possible. Therefore, systems of the invention may allow a broad range of cell and particle assays, such as drug screens, cell characterizations, research studies, and/or clinical analyses, among others, to be scaled down to microfluidic size. Such scaled-down assays may use less sample and reagent, may be less labor intensive, and/or may be more informative than comparable macrofluidic assays.

Microfluidic particle-analysis systems

In vitro and in vivo model systems to study microbial biofilm formation

Luminescence test measurements are conducted using an assay module having integrated electrodes with a reader apparatus adapted to receive assay modules, induce luminescence, preferably electrode induced luminescence, in the wells or assay regions of the assay modules and measure the induced luminescence.

Assay plates, reader systems and methods for luminescence test measurements

Using a simple two step fabrication process substrates with a large and uniform Raman enhancement, based on flexible free standing nanopillars can be manufactured over large areas using readily available silicon processing equipment.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.201103496

Large Area Fabrication of Leaning Silicon Nanopillars for Surface Enhanced Raman Spectroscopy

Real-time chemical imaging of bacterial activities can facilitate a comprehensive understanding of the dynamics of biofilm structures and functions. Synchrotron-radiation-based Fourier transform infrared (SR-FTIR) spectromicroscopy can yield high spatial resolution and label-free vibrational signatures of chemical bonds in biomolecules, but the abundance of water in biofilms has hindered SR-FTIR's sensitivity in investigating bacterial activity. We developed a simple open-channel microfluidic system that can circumvent the water-absorption barrier for chemical imaging of the developmental dynamics of bacterial biofilms with a spatial resolution of several micrometers. This system maintains a 10 microm thick laminar-flow-through biofilm system that minimizes both the imaging volume in liquid and the signal interference from geometry-induced fringing. Here we demonstrate the ability of the open-channel microfluidic platform to maintain the functionality of living cells while enabling high-quality SR-FTIR measurements. We include several applications that show how microbes in biofilms adapt to their immediate environments. The ability to directly monitor and map bacterial changes in biofilms can yield significant insight into a wide range of microbial systems, especially when coupled to more sophisticated microfluidic platforms.

Real-Time Chemical Imaging of Bacterial Activity in Biofilms Using Open-Channel Microfluidics and Synchrotron FTIR Spectromicroscopy

Surface enhanced Raman spectroscopy (SERS) has been increasingly utilized as an analytical technique with significant chemical and biological applications (Qian et al 2008 Nat. Biotechnol. 26 83; Fujita et al 2009 J. Biomed. Opt. 14 024038; Chou et al 2008 Nano Lett.8 1729; Culha et al 2003 Anal. Chem. 75 6196; Willets K A 2009 Anal. Bioanal. Chem. 394 85; Han et al 2009 Anal. Bioanal. Chem. 394 1719; Sha et al 2008 J. Am. Chem. Soc. 130 17214). However, production of a robust, homogeneous and large-area SERS substrate with the same ultrahigh sensitivity and reproducibility still remains an important issue. Here, we describe a large-area ultrahigh-uniformity tapered silver nanopillar array made by laser interference lithography on the entire surface of a 6 inch wafer. Also presented is the rigorous optical characterization method of the tapered nanopillar substrate to accurately quantify the Raman enhancement factor, uniformity and repeatability. An average homogeneous enhancement factor of close to 108 was obtained for benzenethiol adsorbed on a silver-coated nanopillar substrate.

/pdf/rigorous-surface-enhanced-raman-spectral-characterization-of-2epi25u67y.pdf

Rigorous surface enhanced Raman spectral characterization of large-area high-uniformity silver-coated tapered silica nanopillar arrays.

Manipulation of DNA molecules in solution has become an essential aspect of genetic analyses used for biomedical assays, the identification of hazardous bacterial agents, and in decoding the human genome Currently, most of the steps involved in preparing a DNA sample for analysis are performed manually and are time, labor, and equipment intensive These steps include extraction of the DNA from spores or cells, separation of the DNA from other particles and molecules in the solution (eg dust, smoke, cell/spore debris, and proteins), and separation of the DNA itself into strands of specific lengths Dielectrophoresis (DEP), a phenomenon whereby polarizable particles move in response to a gradient in electric field, can be used to manipulate and separate DNA in an automated fashion, considerably reducing the time and expense involved in DNA analyses, as well as allowing for the miniaturization of DNA analysis instruments These applications include direct transport of DNA, trapping of DNA to allow for its separation from other particles or molecules in the solution, and the separation of DNA into strands of varying lengths

Microfluidic DNA sample preparation method and device

Methods for fabricating nanoscale array structures suitable for surface enhanced Raman scattering, structures thus obtained, and methods to characterize the nanoscale array structures suitable for surface enhanced Raman scattering. Nanoscale array structures may comprise nanotrees, nanorecesses and tapered nanopillars.

Nanoscale array structures suitable for surface enhanced raman scattering and methods related thereto

Systems and methods for separating particles and/or toxins from a sample fluid. A method according to one embodiment comprises simultaneously passing a sample fluid and a buffer fluid through a chamber such that a fluidic interface is formed between the sample fluid and the buffer fluid as the fluids pass through the chambers the sample fluid having particles of interest therein; applying a force to the fluids for urging the particles of interest to pass through the interface into the buffer fluid; and substantially separating the buffer fluid from the sample fluid.

Robin Miles

Papers

Real-Time Chemical Imaging of Bacterial Activity in Biofilms Using Open-Channel Microfluidics and Synchrotron FTIR Spectromicroscopy

Rigorous surface enhanced Raman spectral characterization of large-area high-uniformity silver-coated tapered silica nanopillar arrays.

Microfluidic DNA sample preparation method and device

Nanoscale array structures suitable for surface enhanced raman scattering and methods related thereto

Systems and Methods for Separating Particles and/or Substances from a Sample Fluid