Microfluidic chip device for optical force measurements and cell imaging using microfluidic chip configuration and dynamics
Inventors
Hart, Sean • Hebert, Colin • Field, Christopher • Krishnan, Shweta
Assignees
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Publication Number
US-11561164-B2
Publication Date
2023-01-24
Expiration Date
Abstract
A microfluidic chip configuration wherein injection occurs in an upwards vertical direction, and fluid vessels are located below the chip in order to minimize particle settling before and at the analysis portion of the chip's channels. The input and fluid flow up through the bottom of the chip, in one aspect using a manifold, which avoids orthogonal re-orientation of fluid dynamics. The contents of the vial are located below the chip and pumped upwards and vertically directly into the first channel of the chip. A long channel extends from the bottom of the chip to near the top of the chip. Then the channel takes a short horizontal turn that nearly negates any influence of cell settling due to gravity and zero flow velocity at the walls. The fluid is pumped up to a horizontal analysis portion that is the highest channel/fluidic point in the chip and thus close to the top of the chip, which results in clearer imaging. A laser may also suspend cells or particles in this channel during analysis which prevents them from settling.
Core Innovation
The invention provides a method for analyzing one or more cells or particles using a substrate comprising a plurality of channels configured to transport the cells or particles. A collimated light source is used that is capable of interacting with the cells or particles during analysis, and the analyzing comprises optical and hydrodynamic force-based measurements.
The channel arrangement includes a first channel disposed vertically upwards with respect to gravity, a second channel horizontally within the substrate, a third channel vertically upwards with respect to gravity, and a fourth channel disposed horizontally within the substrate. The plurality of channels provide a path for movement of the one or more cells or particles through the substrate from the first channel to the second channel to the third channel to the fourth channel.
The cells or particles are injected into the first vertically oriented channel through a bottom horizontal planar surface having an opening to the first channel, configured to maintain directional and volumetric continuity with the first channel. The disclosure further supports optical interrogation and imaging configurations, force-based interrogation using laser optical-force alignment/suspension or force-based trapping, and post-analysis sorting enabling optical force and/or pressure-related separation.
Claims Coverage
The independent claim is clm-00001. It is supported by dependent claims adding seven inventive features related to channel-based transport and sorting, detector modalities, therapy-relevant analysis, and measurable properties or force-related metrics.
Vertically and horizontally arranged multi-channel path for upward transport
A plurality of channels includes a first channel disposed vertically upwards with respect to gravity, a second channel horizontally within the substrate in operable communication with the first channel, a third channel disposed vertically upwards with respect to gravity in operable communication with the second channel, and a fourth channel horizontally in operable communication with the third channel, providing a path through the substrate from the first channel to the second channel to the third channel to the fourth channel.
Bottom horizontal planar surface injection into the upward first channel with continuity
The one or more cells or particles are injected into the first channel disposed vertically within the substrate through a bottom horizontal planar surface having an opening to the first channel, to maintain directional and volumetric continuity with the first channel.
Optical and hydrodynamic force-based measurements using a collimated light source
The analyzing comprises optical and hydrodynamic force-based measurements using a collimated light source capable of interacting with the one or more cells or particles.
Sorting via a channel that splits into channels or wells
The method includes a fifth channel that splits into two or more channels or wells to sort one or more cells or particles.
Selectable imaging and spectroscopy detector modalities
The method further defines an imaging device selected from specified imaging and spectroscopy detector types including bright field imager, light scatter detector, fluorescent detectors, CCD camera, CMOS camera, photodiodes and arrays, spectrometer, photomultiplier tube or tube array, chemiluminescent and bioluminescent detectors, and Raman spectroscopy detection systems including SERS, CARS, and CSRS.
Cell therapy relevant analysis of efficacy, quality, and activation state
The method includes determining cell efficacy, quality, and activation state for cell-based therapy, assessing cell quality for efficacy assays, and evaluating the effects of a chemical, bacteria, virus, antimicrobial, or antiviral on a specific cell population.
Determining physical, optical, and labeling-related properties and metrics
Analyzing includes determining one or more physical or optical and labeling-related properties or metrics including morphology-related parameters, refractive index/birefringence, intrinsic fluorescence and various label fluorescence types, a differential retention metric, and a gradient force metric along with angular orientation and rotation metrics.
Across the independent claim and its dependents, the core inventive coverage is the vertically upwards and horizontally arranged channel path with upward injection through a bottom horizontal planar surface opening for directional and volumetric continuity, combined with optical and hydrodynamic force-based measurements using a collimated light source, with further refinements for sorting, selectable detector modalities, therapy-relevant efficacy/activation analysis, and specified physical, optical, labeling-related, and force-related metrics.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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