Massachusetts Institute of Technology

Affinity Biosensors, LLC

Dana-farber-cancer Institute Inc.

Scott R Manalis

Thomas P Burg

Selim Olcum

Kenneth Babcock

Michel Godin

Philip Dextras

Sungmin Son

Yao-Chung Weng

Andrea Kristine Bryan

Joseph M Jacobson

William H Grover

Thomas Burg

Saul Griffith

Robert J Kimmerling

Nathan Cermak

Alexander K Shalek

Subra Suresh

Mark L Stevens

Steven Charles Wasserman

Brent Ridley

Jungchul Lee

Ken Babcock

Mark Murakami

Francisco Feijó Delgado

Andrew Navia

Nicholas L Calistri

Sangwon Byun

Shijie Nigel Chou

Amneet Gulati

Vivian C Hecht

Joon Ho Kang

David Weinstock

Peter Winter

Jennyfer Galvez-Reyes

Described in exemplary embodiments herein are methods, compositions, and kits for diagnosing, prognosing, monitoring, treating and/or preventing a hemopoietic malignancy and/or relapse thereof in a subject. In some embodiments, the methods can include determining an average cellular mass of cells in a sample from the subject and/or detecting one or more molecular signatures in one or more of the cells. In some embodiments, treatment includes administering one or more BCR-ABL tyrosine kinase inhibitors or a pharmaceutical formulation thereof, one or more pre-BCR signaling pathway inhibitors or a pharmaceutical formulation thereof, one or more p38 MAPK inhibitors or a pharmaceutical formulation thereof; or any combination thereof.

Methods and compositions for predicting and preventing relapse of acute lymphoblastic leukemia

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. In certain embodiments, the systems and methods comprise determining a node deviation due to a single particle (or node deviations for a plurality of particles).

Systems and methods for measuring properties of particles

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).

Systems, articles, and methods for flowing particles

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.

Simultaneous oscillation and frequency tracking of multiple resonances via digitally implemented phase-locked loop array

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.

Hydrodynamic trap array

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.

Method for measuring bacterial growth and antibiotic resistance using suspended microchannel resonators

The method and apparatus of the present invention detects changes in cell biomechanics caused by any of a variety of diseases and conditions. In one embodiment, the method and apparatus of the invention detect infection of red blood cells. In one embodiment, the invention is a method and apparatus comprising a microfluidic channel with a constriction, for trapping infected red blood cells while allowing healthy red blood cells to deform and pass through the channel. In another embodiment, the invention comprises a suspended microchannel resonator for detecting and counting red blood cells at the constriction of the microfluidic channel.

Method and apparatus for high throughput diagnosis of diseased cells with microchannel devices

Serial suspended microchannel resonator sensor array. The array includes a plurality of resonator cantilevers in fluid communication with one another and a plurality of delay channels in fluid communication with, and disposed between, the resonator cantilevers. An object introduced into the array will flow in one direction and be measured by each of the cantilevers in turn after a selected delay in the delay channels.

Serial arrays of suspended microchannel resonators

Method for measuring a target particle property. A suspended microchannel resonator is calibrated to determine the relationship between a detected mass and a resonance frequency shift of the resonator. The target particle is suspended in a fluid and introduced into the resonator, and the resonator frequency shift due to the particle is measured. Target particle mass is calculated from the resonator frequency shift, the target particle density, and the fluid density. A target particle property such as size or volume is determined from the calculated target particle mass.

Method and apparatus for measuring particle characteristics through mass detection

Methods and apparatus for improving measurements of particle or cell characteristics, such as mass, in Suspended 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.

Method and apparatus for trapping single particles in microfluidic channels

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.

Flow cytometry methods and immunodiagnostics with mass sensitive readout

Method for determining buoyant mass and deformability of a cell. The method includes introducing the cell into a suspended microchannel resonator that includes a constriction near a distal location in the resonator. A first frequency shift in the resonator is monitored as a cell moves to the distal location in the resonator, the first frequency shift being related to the buoyant mass of the cell. Transit time of the cell through the constriction is measured by monitoring a second frequency shift as a result of a change in cell location as it passes through the constriction, whereby deformability is determined from the measured buoyant mass and transit time.

Apparatus and method for measuring buoyant mass and deformability of single cells

Methods and apparatus for improving measurements of particle or cell characteristics, such as mass, in Suspended Microchannel Resonators (SMR's). Apparatus include in particular designs for trapping particles in SMR's for extended measurement periods and for changing the fluid properties within the SMR during the extended periods. Methods include techniques to provide for cell growth over time and over time in response to changing fluid properties to aid in determining parameters such as drug resistance and drug susceptibility.

Method and apparatus for extended time and varying environment measurements of single particles in microfluidic channels

Measurements of the mass and surface charge of microparticles are employed in the characterization of many types of colloidal dispersions. The suspended microchannel resonator (SMR) is capable of measuring individual particle masses with femtogram resolution. The high sensitivity of the SMR resonance frequency to changes in particle position in the SMR channel is employed to determine the electrophoretic mobility of discrete particles in an applied electric field. When an oscillating electric field is applied to the suspended microchannel, the transient resonance frequency shift corresponding to a particle transit can be analyzed to extract both the buoyant mass and electrophoretic mobility of each particle. These parameters, together with the mean particle density, can be used to compute the size, absolute mass, and surface charge of discrete particles.

Method and apparatus for integrated measurement of the mass and surface charge of discrete microparticles using a suspended microchannel resonator

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.

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Cambridge, MA, United States of America

Scott R Manalis