Abstract: The invention provides devices and methods for linked multimodal measurements of individual particles using a mass sensor and an additional sensor.

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: The invention provides methods for assessing immune system function and status based on cellular analysis. Methods of the present invention involve obtaining mass properties of immune cells collected in a tissue or body fluid sample from a subject. Such mass properties may include the mass of one or more immune cells and/or changes in mass of such immune cells over a period of time. Such data is then used for determining a status of the subject's immune response, and subsequent diagnosis and treatment of an infection or immunological disease or dysfunction.

Abstract: The present invention includes methods and systems for assessing a cellular response to a treatment modality, such as potential drug candidate, by comparing normalized single-cell measurements of cellular properties without the need of a calibration step.

Abstract: The invention provides devices and methods for optimized cellular measurements. The method comprises introducing cellular and/or non-cellular material into a measurement device, collecting data from the cellular and/or non-cellular material, providing the data to a classifier that utilizes the data to identify cellular and/or non-cellular material, and using the identification by the classifier to optimize cellular measurements made by the measurement device.

Abstract: The invention provides devices and methods for linked multimodal measurements of individual particles using a mass sensor and an additional sensor.

Abstract: Methods of calibration are provided. A method comprises introducing a material with cell-like properties and a known mass into a sensor on a measurement instrument to generate a calibration reading and adjusting an output module of the measurement instrument until the measurement instrument calibrates to the known mass for the material.

Abstract: Methods of calibration are provided. A method comprises introducing a material with cell-like properties and a known mass into a sensor on a measurement instrument to generate a calibration reading and adjusting an output module of the measurement instrument until the measurement instrument calibrates to the known mass for the material.

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: Methods of calibration are provided. A method comprises introducing a material with cell-like properties and a known mass into a sensor on a measurement instrument to generate a calibration reading and adjusting an output module of the measurement instrument until the measurement instrument calibrates to the known mass for the material.

Abstract: In silico tools are used to determine possibly effective therapies for treating a patient's cancer based on patient, drug, and cancer information. Functional assays can be performed on living cancer cells from the patient to evaluate the possibly effective therapies along with subsequent genomic or other more destructive assays to provide additional information from a single sample. Drug, patient, cancer, and outcome information can be recorded and updated iteratively and analyzed using machine learning to identify correlations between various patient, cancer, and drug characteristics and expected outcomes and drug efficacies.

Abstract: The invention provides methods that use machine learning to discover clinical data patterns that are predictive of disease, such as cancer. Clinical data from across a population is provided as input to a machine learning system. The machine learning system discovers associations in data from a plurality of data sources obtained from a population and correlates the associations to cancer status of patients in the population. The methods may further include providing patient data from an individual and predicting, by the machine learning system, a cancer state (e.g., the presence of cancer and a determination of a stage or progression of the cancer, if present) for the individual when the patient data presents one or more of the discovered associations.

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.