Methods and apparatus for long read, label-free, optical nanopore long chain molecule sequencing. In general, the present disclosure describes a novel sequencing technology based on the integration of nanochannels to deliver single long-chain molecules with widely spaced (>wavelength), ˜1-nm aperture “tortuous” nanopores that slow translocation sufficiently to provide massively parallel, single base resolution using optical techniques. A novel, directed self-assembly nanofabrication scheme using simple colloidal nanoparticles is used to form the nanopore arrays atop nanochannels that unfold the long chain molecules. At the surface of the nanoparticle array, strongly localized electromagnetic fields in engineered plasmonic/polaritonic structures allow for single base resolution using optical techniques.

The invention discloses a microfluidic device for the culture, selection and/or analysis of sample organisms such as nematodes, as well as for other biological entities such as for instance animal embryos. The device features reservoirs, culture chambers and smart filtering systems allowing for the selection of specific populations/specimens of sample organisms, thus permitting long-term cultures thereof as well as phenotypic/behavioural analyses. Systems and methods for using the microfluidic device are within the present disclosure as well.

Embodiments of the present disclosure pertain to methods of utilizing force-modulated hybridization to determine the length of an analyte strand, to determine an unknown nucleic acid sequence, or to determine the binding of a nucleotide to an active agent. Additional embodiments of the present disclosure pertain to sample holder devices and methods of utilizing such devices. Further embodiments of the present disclosure pertain to detection devices.

A fluidic chip includes at least one nanochannel array, the nanochannel array including a surface having a nanofluidic area formed in the material of the surface; a microfluidic area on said surface; a gradient interface area having a gradual elevation of height linking the microfluidic area and the nanofluidic area; and a sample reservoir capable of receiving a fluid in fluid communication with the microfluidic area. In another embodiment, a fluidic chip includes at least one nanochannel array, the nanochannel array includes a surface having a nanofluidic area formed in the material of the surface; a microfluidic area on said surface; and a gradient interface area linking the microfluidic area and the nanofluidic area, where the gradient interface area comprises a plurality of gradient structures, and the lateral spacing distance between said gradient structures decreases towards said nanofluidic area; and a sample reservoir capable of receiving a fluid in fluid communication with the microfluidic area.

In an embodiment, the present disclosure pertains to a method of performing circulating tumor cell (CTC) analysis. In general, the method includes flowing a sample through a CTC microfluidic platform, deforming a CTC within the sample, measuring CTC deformation through an imprint of the deformed CTC, processing data related to the measuring, and at least one of identifying or characterizing parameters related to the data that enables at least one of detection of CTCs, enumeration of CTCs in the sample, characterization of biophysical properties, CTC cell size, CTC cell membrane deformability, stresses on CTC cell membranes, adhesion stress on CTC cells, normal stress of CTC cells, or combinations thereof. In some embodiments, the flowing includes passing the sample through at least one channel of the CTC microfluidic platform having a constricted section.

Provided herein, among other aspects, are methods and apparatuses for analyzing particles in a sample. In some aspects, the particles can be analytes, cells, nucleic acids, or proteins and can be contacted with a tag, partitioned into aliquots, detected by a ranking device, and isolated. The methods and apparatuses provided herein may include a microfluidic chip. In some aspects, the methods and apparatuses may be used to quantify rare particles in a sample, such as cancer cells and other rare cells for disease diagnosis, prognosis, or treatment.

The present invention refers to a device for the analysis of a particle comprising an analysis chamber adapted to contain a positioning fluid. A parameter of the particle suspended in the positioning fluid is detected by means of a detection and control unit. A positioning unit, during a particle analysis operation, is activated and deactivated on the basis of the detected parameter of the particle. The detection and control unit can activate the at least one positioning unit so as to generate a temporary positioning flow in the positioning fluid, such that said temporary positioning flow acts directly on the particle and drives the position of the particle so as to move it into a predefined position in the analysis chamber. The detection and control unit can also deactivate the at least one positioning unit when the particle to be analyzed is in the predefined position, such that the positioning fluid is at rest.

Constricted nanochannel devices suitable for use in analysis of macromolecular structure, including DNA sequencing, are disclosed. Also disclosed are methods for fabricating such devices and for analyzing macromolecules using such devices.

A mechanism is provided for presenting single strands of a double strand molecule to a membrane. The double strand molecule is driven to a first side of the membrane by an electric field. The membrane has a first and second nanopore spaced apart by a nanopore separation distance. The first strand of the double strand molecule is captured in the first nanopore when driven to the first side of the membrane. The second strand is captured in the second nanopore by having the nanopore separation distance between the first nanopore and the second nanopore corresponding to a strand separation distance between the first and second strands, and/or by having captured the first strand to limit diffusion of the second strand. The first and second strands respectively in the first and second nanopores are individually stretched, by the first and second strands recombining on the second side of the membrane.

System and method includes a body having a central microchannel separated by one or more porous membranes. The membranes are configured to divide the central microchannel into a two or more parallel central microchannels, wherein one or more first fluids are applied through the first central microchannel and one or more second fluids are applied through the second or more central microchannels. The surfaces of each porous membrane can be coated with cell adhesive molecules to support the attachment of cells and promote their organization into tissues on the upper and lower surface of the membrane. The pores may be large enough to only permit exchange of gases and small chemicals, or to permit migration and transchannel passage of large proteins and whole living cells. Fluid pressure, flow and channel geometry also may be varied to apply a desired mechanical force to one or both tissue layers.