Agency for Science, Technology and Research

National University of Singapore

Massachusetts Institute of Technology

Nanyang Technological University

Hanry Yu

Kam W Leong

Hwa Liang Leo

Ser-Mien Chia

Andrew C A Wan

Wanxin Sun

Yi-chin Toh

Feng Wen

Zhilian Yue

Yi Chin Toh

Shuoyu Xu

Jackie Yi-Ru Ying

Jun Li

Peter T C So

Jing Zhang

Karl Schumacher

Yang Yu

Daekeun Kim

Yuet Mei Khong

Shufang Zhang

Shyi-Herng Kan

Chi Zhang

Vijay Raj Singh

Shyi Herng Kan

Susanne San San Ng

Hai Ting Ho

San San Susanne Ng

Rongbin Han

Danny Van Noort

Lei Xia

Yanan Du

Colin J R Sheppard

Jagath Rajapakse

Heejin Choi

Yan Seng Elijah Yew

Jiangwa Xing

Yuting He

Dean Tai

Farah Tasnim

Derek Phan

Jackie Y Ying

San San Suzanne Ng

There is provided a method of assessing fibrosis in a tissue sample. The method includes: obtaining a stained image of a stained tissue sample, the stained tissue sample being stained in relation to collagen therein; producing a plurality of different types of collagen images based on the stained image, the plurality of different types of collagen images corresponding to a plurality of different types of collagen, respectively; determining a plurality of different types of collagen parameters based on the plurality of different types of collagen images using a deep neural network; and determining a degree of fibrosis in the stained tissue sample based on the plurality of different types of collagen parameters. The plurality of different types of collagen comprises portal collagen, fibrillary collagen and septal collagen. The different types of collagen images are produced by determining if the collagen satisfies a predetermined size condition or a predetermined distance condition with respect to a boundary of the portal tracts and central veins.

Method and system for assessing fibrosis in a tissue sample

Disclosed are methods of differentiating stem cells in order to obtain hepatocyte-like cells, the method comprising the steps of a) subjecting definitive endoderm to at least one epigenetic modulator to obtain hepatoblasts and b) subjecting the hepatoblasts to at least one stem cell differentiation pathway inhibitor to obtain hepatocyte-like cells; wherein steps a) and b) do not comprise the use of a growth factor. In one preferred embodiment, the epigenetic modulator may be sodium butyrate and/or DMSO and the stem cell differentiation pathway inhibitor may be SB431542 and/or DMSO. Also disclosed are hepatocyte-like cells obtained from the method and uses of these cells such as drug screening.

Differentiation of hepatocyte-like cells from stem cells

A method for determining a stage of fibrosis in a liver is disclosed. The method comprises the steps of: (1a) obtaining input data relating to the liver, the input data being generated using a second harmonic generation based imaging system; (1b) identifying a plurality of morphological features of the liver from the input data relating to the liver; (1c) generating a plurality of measurements based on the identified plurality of morphological features; and (1d) determining the stage of fibrosis in the liver based, on the generated plurality of measurements.

Method and system for determining a stage of fibrosis in a liver

A method and system of in vitro developmental toxicity testing comprising the steps of micropatterning an extracellular matrix; growing embryonic stem cells on the micropatterned extracellular matrix in the presence of mesoendodermal induction and testing for change of the geometrical mesoendoderm structure in the presence or absence of a test compound wherein (1) a decrease in mesoendodermal differentiation and/or (2) a change in morphology of the geometrical mesoendoderm structure in the presence of the test compound compared to cells in the absence of the test compound indicates that the test compound is a developmental toxic agent.

Method and system for in vitro developmental toxicity testing

An imaging system is provided that includes a pulsed light source providing pulsed light and is applicable to both microscopes and endoscopes. One or more optical elements with certain dispersive properties are positioned to receive the pulsed light and apply selective dispersive properties to shift the focal plane according to the user and to produce two photon (2p) wide field uniform illumination and 2p wide field structured illumination for the purpose of improving the optical axial resolution and rejection of background signal. An imaging element receives the signal arising from the 2p wide field uniform illumination and 2p wide field structured illumination and produces a respective 3D resolved image of a sample.

High sensitivity temporal focusing widefield multiphoton endoscope capable of deep imaging

A method for assessing fibrosis in a tissue is proposed. The method uses a test image which is an image of the tissue and comprises identifying, from the test image, a portal collagen area, a septal collagen area and a fibrillar collagen area respectively comprising pixels representing portal collagen, septal collagen and fibrillar collagen of the tissue, obtaining quantitative values of one or more features for each identified area based on characteristics of the identified area in the test image and assessing fibrosis using the quantitative values obtained for all the identified areas.

Method and system for assessing fibrosis in a tissue

The invention provides a surface, wherein said surface comprises (i) a polymer substrate and (ii) sugar groups and peptide groups coupled to said substrate suitable for culturing hepatocytes.

Bioactive surface for hepatocyte-based applications

The invention relates to an apparatus () for culturing anchorage-dependent cells. The apparatus () comprises a housing () with an inlet () and an outlet (), and a plurality of culture plates () removably stacked within the housing (). The housing () has a circumferential wall (), a base () and a top wall (). The base () comprises the inlet () and the top wall () comprises the outlet (). The circumferential wall () of the housing () defines a longitudinal axis thereof, as well as an inner cross section perpendicular to the longitudinal axis. Shape and dimensions of the inner cross section are essentially uniform along the longitudinal axis. The culture plates () are arranged at least essentially parallel to each other. Each plate () is mounted and sealed to the circumferential wall () of the housing (). Plates () are arranged at a distance from each other. Each culture plate () has a through hole (), so that inlet () and outlet () are in fluid communication. Each through hole () is positioned at an outer end of the respective culture plate (), proximate the circumferential wall (). Through holes () of adjacent culture plates () are distally positioned in the plane of the inner cross section of the housing ().

Apparatus for culturing anchorage dependent cells

A microfluidic continuous flow device comprising a channel which comprises a first and a second area wherein the first area of the channel is a compartment which is defined by partitioning elements and the second area of the channel is a space outside the compartment; wherein through passages which are formed between the partitioning elements are dimensioned such as to retain a biological material and optionally a sustained release composition which can be comprised in the compartment within the compartment; wherein the channel has a first inlet to the compartment through which biological material can be introduced into the compartment; a second inlet for introducing a cultivation medium into a space of the channel arranged outside of the compartment, and an outlet. The present invention further refers to methods of using the devices of the present invention and kits comprising the microfluidic continuous flow devices of the present invention.

Microfluidic continuous flow device

Scaffold comprises a polymer defining macropores and comprising hydroxypropylcellulose partially substituted by a substituent comprising a self-crosslinkable group, which is crosslinked through the self-crosslinkable group. The macropores have an average pore size larger than 50 microns and are at least partially interconnected. In one method, bicontinuous emulsion comprising a continuous aqueous phase and a continuous polymer phase is formed. The polymer phase comprises hydroxypropylcellulose partially substituted by a substituent comprising a self-crosslinkable group, and is crosslinked through the self-crosslinkable group to form a polymer defining at least partially interconnected pores. In another method, phase separation is induced in a solution comprising a polymer precursor and water to form a bicontinuous emulsion comprising a continuous polymer phase and a continuous aqueous phase. The polymer precursor comprises a self-crosslinkable group and is crosslinked through the self-crosslinkable group in the emulsion to form a polymer defining at least partially interconnected macropores.

Forming porous scaffold from cellulose derivatives

The apparatus for cell or tissue culture comprises a base plate (), an intermediate face () and a top plate (). The intermediate face () is removably sandwiched between the base plate () and the top plate (). The base plate () has a circumferential wall (), a base () and a top wall (). The top wall () of the base plate () comprises a plurality of recesses () arranged in n lines, wherein n is an integer from 1 to about 25. Each line of recesses () ranges from a first recess to a last recess. Each recess has a circumferential recess wall (), which has one recess inlet and one recess outlet (). The circumferential wall () comprises a number of 2 n ports (). Each port () is coupled to a single line of recesses (). The recesses () of each line of recesses are in fluid communication with (i) each other via the recess inlets and a recess outlets () and (ii) with a first and a second port () of the 2 n ports, such that the first recess of each line of recesses is coupled to a first port and the last recess of each line of recesses is coupled to a second port. The intermediate face () has a plurality of recesses () arranged in m lines, fitted into the plurality of recesses () of the top wall () of the base plate (). m is an integer from 1 to about 25 equal to or smaller than n. The recesses () of the intermediate face () have water permeability. The top plate () is reversibly sealed to the intermediate face () and the intermediate face () is reversibly sealed to the base plate (). Thus the recesses () of the top wall () of the base plate () define culture chambers. Each culture chamber has a circumferential wall defined by the recess wall () and a removable top, which is defined by a portion of the top plate ().

Apparatus for cell or tissue culture

This invention relates to a method for the encapsulation of cells in biologic compatible three dimensional scaffolds and the use of such cells encapsulated in a scaffold. The cells are embedded in a charged polymer that is complex coacervating with an oppositely charged polymer within biologic compatible scaffolds. The polymer complex embedding the cells is forming an ultra thin membrane on the surface of the three dimensional scaffold.

Encapsulation of cells in biologic compatible scaffolds by coacervation of charged polymers

A device for imaging a tissue culture comprises a chamber for housing a tissue to be cultured and imaged. The chamber comprises a transparent window. The device also includes a platform facing the window. Micro-needles are mounted on the platform and are connected for fluid communication with a fluid source. The platform and the window are magnetically biased toward each other to press the micro-needles into a tissue sandwiched between the window and platform for injecting a fluid into the tissue. One or more spacers are placed between the platform and the window for preventing over-compression of the tissue by the platform and the window. During use, a fluid is supplied to the tissue through the needles from the fluid source and the tissue is imaged through the window of the chamber.

Imaging chamber with window and micro-needle platform magnetically biased toward each other

A microscope for optical imaging of high optical scattering coefficient biological tissue, comprising an optical excitation source for irradiating a scan area of the sample and generating optical emissions, wherein the sample has a first face facing away from the source and a second face facing the source. A two dimensional element for scanning the light over the sample; a focusing element having a numerical aperture NAi to focus the light onto the sample; a first optical condenser to collect light from the first face, the collected light comprising source transmitted light and first optical emission generated in the sample, the condenser having a NA2 larger than NAi; an optical filter to block the transmitted source light; an aperture with a size corresponding to the irradiated area of the sample, the aperture at the conjugate image position of the sample generated by the condenser; and an optical detector collecting light from the first face for detecting the first optical emission from the scan area.

SHG quantification of matrix-related tissue dynamic and disease

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Singapore, Singapore

Hanry Yu