Abstract: Systems and methods for measuring the properties (e.g., mechanical properties) of particles such as biological entities, in a fluidic channel(s) are generally provided. In some embodiments, the systems and methods comprise measuring an acoustic scattering of single particles. For example, a single particle (e.g., a biological entity) may be flowed in a suspended fluidic channel (e.g., a suspended microfluidic channel) and the fluidic channel is oscillated at or near a (mechanical) resonant frequency (e.g., at a second or higher bending mode) of the suspended fluidic channel. In some cases, an acoustic scattering signal (e.g., the change in resonant frequency of the fluidic channel as the particle flows along a longitudinal axis of the channel) may correspond to a property (e.g., a mechanical property, a cross-linking density, a transport rate of small molecules into/out of the particle) of the particle.

Abstract: Systems and methods for flowing particles, such as biological entities, in a fluidic channel(s) are generally provided. In some cases, the systems described herein are designed such that a single particle may be isolated from a plurality of particles and flowed into a fluidic channel (e.g., a microfluidic channel) and/or collected e.g., on fluidically isolated surfaces. For example, the single particle may be present in a plurality of particles of relatively high density and the single particle is flowed into a fluidic channel, such that it is separated from the plurality of particles. The particles may be spaced within a fluidic channel so that individual particles may be measured/observed over time. In certain embodiments, the particle may be a biological entity. Such article and methods may be useful, for example, for isolating single cells into individual wells of multi-well cell culture dishes (e.g., for single-cell analysis).

Abstract: Aspects of the application relate to methods and systems for evaluating treatment response by measuring treatment-induced changes at the single cell level. The disclosure provides methods for isolating single cells that are primary cancer cells, including primary cancer cells from solid tumors, and detecting in minutes to hours from their removal from the body the response of such cells to anti-cancer agents such as radiation, small molecules, biologies, DNA damaging agents and the like.

Abstract: Systems and methods for flowing particles, such as biological entities, in a fluidic channel(s) are generally provided. In some cases, the systems described herein are designed such that a single particle may be isolated from a plurality of particles and flowed into a fluidic channel (e.g., a microfluidic channel) and/or collected e.g., on fluidically isolated surfaces. For example, the single particle may be present in a plurality of particles of relatively high density and the single particle is flowed into a fluidic channel, such that it is separated from the plurality of particles. The particles may be spaced within a fluidic channel so that individual particles may be measured/observed over time. In certain embodiments, the particle may be a biological entity. Such article and methods may be useful, for example, for isolating single cells into individual wells of multi-well cell culture dishes (e.g., for single-cell analysis).

Abstract: Systems and Methods for controlling one or more mechanical resonators and determining information from resonant shift of the resonator(s) behavior, including at least one mechanical resonator, an excitation element for driving the resonator(s), a sensor for monitoring the motion of the resonator(s), at least one phase locked loop (PLL) in feedback between the excitation and monitoring elements, wherein each PLL is configured to operate at or near a different resonant mode of the resonator(s), and a processor for determining information from PLL internal signals indicative of a resonator frequency shift.

Abstract: Systems and methods for measuring the properties (e.g., mechanical properties) of particles such as biological entities, in a fluidic channel(s) are generally provided. In some embodiments, the systems and methods comprise measuring an acoustic scattering of single particles. For example, a single particle (e.g., a biological entity) may be flowed in a suspended fluidic channel (e.g., a suspended microfluidic channel) and the fluidic channel is oscillated at or near a (mechanical) resonant frequency (e.g., at a second or higher bending mode) of the suspended fluidic channel. In some cases, an acoustic scattering signal (e.g., the change in resonant frequency of the fluidic channel as the particle flows along a longitudinal axis of the channel) may correspond to a property (e.g., a mechanical property, a cross-linking density, a transport rate of small molecules into/out of the particle) of the particle.

Abstract: Systems and methods for measuring the properties (e.g., masses, weights, densities, etc.) of particles, such as biological entities, in a fluidic channel are generally provided. In some embodiments, the systems and methods comprise a plurality of suspended microchannel resonators (SMRs) configured to operate simultaneously. A particle or a plurality of particles may be dissolved or suspended in a fluid, whereby the fluid is flowed through an inlet (e.g., an inlet channel) that is fluidically connected in parallel and in fluid communication with at least one SMR (e.g. at least one SMR, at least two SMRs, at least four SMRs, at least 8, at least 16 SMRs). Fluid containing a particle or particles may flow into the plurality of SMRs, which may oscillate at a certain frequency (e.g., a resonance frequency). As particles pass through the SMR(s), the mass of particle may cause a change in the resonance frequency, the change in frequency which may be read out via embedded piezoresistors.

Abstract: A method of rapid functional analysis of cells is provided. A body fluid sample is introduced into a reservoir of a measurement instrument. A living cell is loaded directly from the body fluid sample into a channel of the measurement instrument in the absence of long-term cell culturing, cell passaging, and application of long-term drug pressure to cells. A functional biomarker of the living cells is measured while the living cell flows through the channel. The functional biomarker measured may be mass accumulation rate (MAR) or mass change. The measurement instrument may be a suspended microchannel resonator (SMR).

Abstract: Patient samples are monitored to detect minimal residual disease (MRD) post successful cancer treatment. Upon detection of MRD, functional assays can be performed on living cancer cells from the patient to evaluate possibly effective therapies along with subsequent genomic or other more destructive assays to provide additional efficacy information using a single sample. An effective treatment against the MRD can be identified and selected for the patient. The patient can be monitored and the process repeated until MRD can no longer be detected.

Abstract: The invention provides methods for evaluating disease, such as cancer, by way of performing multiple assays involving single-cell analysis on live cells isolated from a sample of a patient. The data obtained from the multiple assays is analyzed and linked to thereby provide a characterization of any given cell having undergone analysis, which, in turn, allows for evaluation of the sample either known to be, or suspected of being, cancerous. A report may be generated based on the data analysis, wherein the report provides information related to the cancer evaluation, including, but not limited to, whether the sample tested positive for cancer, a determination of a stage or progression of cancer, and a customized treatment plan tailored to an individual patient's cancer diagnosis.

Abstract: The invention provides devices and methods for measuring how living cells function. The measurements can be made from tissue biopsy samples to measure functional properties of living cells from a solid tumor. After measuring a functional property of a cell, the cell remains alive and is available for other subsequent analyses. In certain aspects, the invention provides a method for measuring a cancer marker. The method includes obtaining a tissue sample comprising living cells, disaggregating the tissue sample and loading individual live cells into an input channel of a measurement instrument, and flowing the live cells through the measurement instrument to measure a functional property of the live cells.

Abstract: Systems and methods for flowing particles, such as biological entities, in a fluidic channel(s) are generally provided. In some cases, the systems described herein are designed such that a single particle may be isolated from a plurality of particles and flowed into a fluidic channel (e.g., a microfluidic channel) and/or collected e.g., on fluidically isolated surfaces. For example, the single particle may be present in a plurality of particles of relatively high density and the single particle is flowed into a fluidic channel, such that it is separated from the plurality of particles. The particles may be spaced within a fluidic channel so that individual particles may be measured/observed over time. In certain embodiments, the particle may be a biological entity. Such article and methods may be useful, for example, for isolating single cells into individual wells of multi-well cell culture dishes (e.g., for single-cell analysis).

Abstract: Systems and Methods for controlling one or more mechanical resonators and determining information from resonant shift of the resonator(s) behavior, including at least one mechanical resonator, an excitation element for driving the resonator(s), a sensor for monitoring the motion of the resonator(s), at least one phase locked loop (PLL) in feedback between the excitation and monitoring elements, wherein each PLL is configured to operate at or near a different resonant mode of the resonator(s), and a processor for determining information from PLL internal signals indicative of a resonator frequency shift.

Abstract: Hydrodynamic Trap Array. The array includes a serpentine bypassing channel including a plurality of trapping pockets disposed therein, the trapping pockets including a ramp entry portion to decrease flow velocity orthogonal to the trapping pocket to increase trapping efficiency. The relative fluid resistances of the trapping pockets and the serpentine bypassing channel are selected such that a slight majority of the flow is diverted to one of the trapping pockets. A pair of microfluidic bypass channels flank the array of traps allowing independent control of upstream and downstream pressures on each side of the array, thereby decoupling flow magnitude in the bypass channels from flow across the trapping pockets.

Abstract: Systems and Methods for controlling one or more mechanical resonators and determining information from resonant shift of the reonator(s) behavior, including at least one mechanical resonator, an excitation element for driving the resonator(s), a sensor for monitoring the motion of the resonator(s), at least one phase locked loop (PLL) in feedback between the excitation and monitoring elements, wherein each PLL is configured to operate at or near a different resonant mode of the resonator(s), and a processor for determining information from PLL internal signals indicative of a resonator frequency shift.

Abstract: Methods for improving measurements of bacterial growth, such as mass, in Suspended Microchannel Resonators (SMR's). Methods include techniques to provide for bacterial growth over time in response to changing fluid environment to aid in determining parameters such as drug resistance and drug susceptibility. In particular the methods include trapping multiple bacteria in the SMR for a time period and varying the fluid to include sequences of nutrients and antibiotics, and measuring the rate of mass change of the bacteria in response to the changes in fluid composition.

Abstract: Hydrodynamic Trap Array. the array includes a serpentine bypassing channel including a plurality of trapping pockets disposed therein, the trapping pockets including a ramp entry portion to decrease flow velocity orthogonal to the trapping pocket to increase trapping efficiency. The relative fluid resistances of the trapping pockets and the serpentine bypassing channel are selected such that a slight majority of the flow is diverted to one of the trapping pockets. A pair of microfluidic bypass channels flank the array of traps allowing independent control of upstream and downstream pressures on each side of the array, thereby decoupling flow magnitude in the bypass channels from flow across the trapping pockets.

Abstract: Mass cytometry method. In one aspect, the method includes providing a sample having at least one cell type and mixing the sample with material such as nanoparticles functionalized with affinity molecules for the at least one cell type. The sample is transported through a suspended microchannel resonator to record a mass histogram and a cell count for the at least one cell type is determined from the histogram.

Abstract: Methods and apparatus for improving measurements of particle or cell characteristics, such as mass, in Susppended Microchannel Resonators (SMR's). Apparatus include in particular designs for trapping particles in SMR's for extended measurement periods. Methods include techniques to provide differential measurements by varying the fluid density for repeated measurements on the same particle or cell.

Abstract: Methods for improving measurements of bacterial growth, such as mass, in Suspended Microchannel Resonators (SMR's). Methods include techniques to provide for bacterial growth over time in response to changing fluid environment to aid in determining parameters such as drug resistance and drug susceptibility. In particular the methods include trapping multiple bacteria in the SMR for a time period and varying the fluid to include sequences of nutrients and antibiotics, and measuring the rate of mass change of the bacteria in response to the changes in fluid composition.