Hi LLC

Massachusetts Institute of Technology

Harvard College

Adam H Marblestone

Jamu Alford

Changhuei Yang

Edward Stuart Boyden

Daniel Sobek

Fei Chen

Roarke W Horstmeyer

Yuecheng Shen

Paul Warren Tillberg

Shahar Alon

Samuel Gordon Rodriques

George M Church

Evan R Daugharthy

Michael Henninger

Ivo Vellekoop

Christian T Wentz

Haowen Ruan

Asmamaw T Wassie

Mark Andrew Skylar-Scott

Ruixuan Gao

Haojiang Zhou

Andrew C Payne

Daniel Oran

Brian S Robinson

Ashutosh Chaturvedi

Shoh Asano

Anubhav Sinha

Brian Robinson

An optical measurement system comprising an optical source configured for delivering sample light in an anatomical structure, such that the sample light is scattered by the anatomical structure, resulting in physiological-encoded signal light that exits the anatomical structure, an optical detector configured for detecting the physiological-encoded signal light, and a processor configured for acquiring a TOF profile derived from the physiological-encoded signal light, the initial TOF profile having an initial contrast-to-noise ratio (CNR) between a plurality of states of a physiological activity in the anatomical structure. The processor is further configured for applying one or more weighting functions to the initial TOF profile to generate a weighted TOF profile having a subsequent CNR greater than the initial CNR between the plurality of states of the physiological activity. The processor is further configured for processing the weighted TOF profile, and identifying one of the plurality of states of the physiological activity.

Time-of-flight optical measurement and decoding of fast-optical signals

The invention, in part, includes methods of single molecule protein sequencing that include using weak binding spectra in the amino acid identification.

Single molecule peptide sequencing methods

In a non-invasive optical detection system and method, sample light is delivered into a scattering medium. A first portion of the sample light passing through a volume of interest exits the scattering medium as signal light, and a second portion of the sample light passing through a volume of non-interest exits the scattering medium as background light that is combined with the signal light to create a sample light pattern. Reference light is combined with the sample light pattern to create an interference light pattern having a holographic beat component. Ultrasound is emitted into the volume of non-interest in a manner that decorrelates the background light of the sample light pattern from the holographic beat component. The holographic beat component is detected during the measurement period. An optical parameter of the volume of interest is determined based on the detected holographic beat component.

Non-invasive optical detection system and method

An optical source sweeps a source light over an optical wavelength range. An interferometer splits the source light into sample light and reference light, delivers the sample light into an anatomical structure, such that the sample light is scattered by the anatomical structure, resulting in physiological-encoded signal light that exits the anatomical structure, and combines the signal light and the reference light into an interference light pattern having an array of spatial components and a plurality of oscillation frequency components. An optical detector array detects intensity values of the array of spatial components. A processor derives an array of intensity values of each oscillation frequency component from the detected spatial component intensity value array, reduces each derived oscillation frequency component intensity value array to a single frequency component intensity value, and determines a depth of a physiological event in the anatomical structure based on the reduced frequency component intensity values.

Non-invasive optical detection system and method of multiple-scattered light with swept source illumination

Disclosed herein are devices and methods for modifying a conventional imager to have functional features similar to that of a lock-in camera. Optical mask devices are configured to be coupled to conventional imager sensors and the configuration of the mask devices can be adjusted to acquire image data in rapid succession. One variation of an optical mask device comprises a substrate comprising a pattern of light-blocking and light-transmitting regions and an attachment structure for coupling the optical mask device to the imager. The substrate is configured to adjust the position of the light-blocking regions and light-transmitting regions relative to the light-sensing region of the imager based on a set of one or more predetermined substrate configurations. In some variations, the mask device and/or the imager sensor may be mechanically moved relative to each other based on the set of one or more predetermined substrate configurations.

Devices and methods to convert conventional imagers into lock-in cameras

The present invention enables three-dimensional nanofabrication by isotropic shrinking of patterned hydrogels. A hydrogel is first expanded, the rate of expansion being controlled by the concentration of the crosslinker. The hydrogel is then infused with a reactive group and patterned in three dimensions using a photon beam through a limited-diffraction microscope. Functional particles or materials are then deposited on the pattern. The hydrogel is then shrunk and cleaved from the pattern.

Three-dimensional nanofabrication by patterning of hydrogels

A non-invasive optical detection system and method are provided. Sample light is delivered into a target volume of interest, whereby the sample light is scattered by the target volume of interest, resulting in a sample light pattern that exits the anatomical structure. Reference light is combined with the sample light pattern to generate at least one interference light pattern, each of which may have a time varying interference component that integrates to a first value in the absence of the physiological event, and that integrates to a second greater value in the presence of the physiological event. Intensities of spatial components of each interference light pattern are detected during a measurement period. A function of the detected spatial component intensities of the interference light pattern(s) is analyzed, and a presence of the physiological event in the target volume of interest is determined based on the analysis.

Non-invasive optical detection systems and methods in highly scattering medium

An optical detection method and system are provided. Sample light is delivered into an anatomical structure having a target voxel, whereby a portion of the sample light passing through the target voxel is scattered by the anatomical structure as signal light, and another portion of the sample light not passing through the target voxel is scattered by the anatomical structure as background light that is combined with the signal light to create a sample light pattern. The sample light pattern and the reference light having an M number of different phases are concurrently combined to respectively generate an M number of interference light patterns. The M number of interference light patterns are detected. M pluralities of values representative of spatial components of the respective M number of interference light patterns are generated, and a physiologically-dependent optical parameter of the target voxel is determined based on the M pluralities of values.

System and method for simultaneously detecting phase modulated optical signals

The present invention relates to a method for amplifying at least one target RNA in a fixed and, optionally, expanded biological sample. In an embodiment of the invention, the method comprises incubating the fixed biological sample with a pair of polynucleotides complementary to non-overlapping and proximal sequences of a target RNA, wherein the polynucleotide pair hybridizes to the target RNA; ligating the polynucleotide pair using a ligase; and amplifying the ligation product. The invention further provides methods for detecting and optionally quantifying and/or sequencing the amplification product. As the method comprises hybridizing polynucleotide pairs to a target RNA in a fixed biological sample, the target RNA can be hybridized in situ.

Multiplexed signal amplified FISH via splinted ligation amplification and sequencing

Described herein are systems and methods for noninvasive functional brain imaging using low-coherence interferometry (e.g., for the purpose of creating a brain computer interface with higher spatiotemporal resolution). One variation of a system and method comprises optical interference components and techniques using a lock-in camera. The system comprises a light source and a processor configured to rapidly phase-shift the reference light beam across a pre-selected set of phase shifts or offsets, to store a set of interference patterns associated with each of these pre-selected phase shifts, and to process these stored interference patterns to compute an estimate of the number of photons traveling between a light source and the lock-in camera detector for which the path length falls within a user-defined path length range.

Systems and methods for quasi-ballistic photon optical coherence tomography in diffusive scattering media using a lock-in camera detector

The invention provides in situ nucleic acid sequencing to be conducted in biological specimens that have been physically expanded. The invention leverages the techniques for expansion microscopy (ExM) to provide new methods for in situ sequencing of nucleic acids as well as new methods for fluorescent in situ sequencing (FISSEQ) in a new process referred to herein as 'expansion sequencing' (ExSEQ).

In situ nucleic acid sequencing of expanded biological samples

A non-invasive system and method. Sample light is delivered into an anatomical structure, such that a portion of the sample light passes through a target voxel comprising brain matter in the head and is scattered by the head as signal light. The signal light is detected, changes in the level of water concentration or relative water concentration of the target voxel are detected based on the detected signal light, and a level of neural activity is determined within the target voxel based on the determined changes level of the water concentration or relative water concentration of the target voxel.

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Medford, MA, United States of America

Adam H Marblestone