University of California

Jered Haun

Alan David Widgerow

Derek Banyard

Xiaolong Qiu

Elliot En-Yu Hui

Jiang Li

Hugo Salas

Janice De Jesus

David Duarte

Ahmed Zobi

Justin Stovner

Amrith Karunaratne

Erik Morgan Werner

Elliot E Hui

Elliott E Hui

Elliot Hui

Jeremy A Lombardo

Marissa Noelani Pennell

An integrated lipoaspirate processing system is disclosed for mechanically processing adipose tissue into a therapeutic material that, in some embodiments, may be directly injected into a subject. The system includes an emulsification device that is used to emulsify the lipoaspirate sample. The emulsified lipoaspirate is then filtered by a microfluidic filtration device. The filtrate of the microfluidic filtration device is then processed in a microfluidic dissociation device. The integrated platform or system helps standardize hydrodynamic processing of lipoaspirate by producing predictable and consistent shear forces and enabling automation in clinical settings. Progressive processing through multiple devices in series enables optimal recovery of regenerative cells while preventing clogging.

Integrated system for mechanical processing of lipoaspirate

A microfluidic tissue dissociation and filtration device simultaneously filters large tissue fragments and dissociates smaller aggregates into single cells, thereby improving single cell yield and purity. The device includes an inlet coupled to a first microfluidic channel at an upstream location and a first outlet at a downstream location. A first filter membrane is interposed between the first microfluidic channel and a second microfluidic channel, wherein the second microfluidic channel is in fluidic communication with the first microfluidic channel via the first filter membrane. The first filter membrane operates under a tangential flow format. A second outlet is coupled to a downstream location of the second microfluidic channel and includes a second filter membrane interposed between the second outlet and the second microfluidic channel. The dual membrane device increased single cell numbers by at least 3-fold for different tissue types.

Microfluidic filter device and method for dissociation of tissue and cell aggregates and enrichment of single cells

Provided herein are devices and methods of processing a sample that include, in several embodiments, rotating one or more microfluidic chips that are mounted on a support plate using a motor driven rotational chuck. By spinning one or more of the microfluidic chips about a common center of rotation in a controlled manner, high flow rates (and high shear forces) are imparted to the sample in a controlled manner. Each microfluidic chip can be rotated 180° on the support plate so that the sample can be run back-and-forth through the microfluidic devices. Because the support plate can be driven at relatively high RPMs, high flow rates are generated within the microfluidic chips. This increases the shear forces on the sample and also decreases the processing time involved as the sample can quickly pass through the shear-inducing features of the microfluidic chip(s).

Method and device for processing tissues and cells

A microfluidic device uses hydrodynamic shear forces on a sample to improve the speed and efficiency of tissue digestion is disclosed. The microfluidic channels are designed to apply hydrodynamic shear forces at discrete locations on tissue specimens up to 1 cm in length and 1 mm in diameter, thereby accelerating digestion through hydrodynamic shear forces and improved enzyme-tissue contact. The microfluidic digestion device can eliminate or reduce the need to mince tissue samples with a scalpel, while reducing sample processing time and preserving cell viability. Another advantage is that downstream microfluidic operations could be integrated to enable advanced cell processing and analysis capabilities. The device may be used in research and clinical settings to promote single cell-based analysis technologies, as well as to isolate primary, progenitor, and stem cells for use in the fields of tissue engineering and regenerative medicine.

Microfluidic device for the digestion of tissues into cellular suspensions

A tissue dissociation device includes an inlet coupled to a first stage having a single channel having an upstream end and a downstream end; a plurality of serially arranged intermediate stages, wherein a first intermediate stage of the plurality is fluidically coupled to the downstream end of the first stage, and wherein each subsequent intermediate stage of the plurality has an increasing number of channels (with channels of smaller dimensions); and an outlet coupled to a last stage of the intermediate stages.

Microfluidic tissue dissociation device and method

Provided herein are devices and methods of processing a sample that include, in several embodiments, rotating one or more microfluidic chips that are mounted on a support plate using a motor driven rotational chuck. By spinning one or more of the microfluidic chips about a common center of rotation in a controlled manner, high flow rates (and high shear forces) are imparted to the sample in a controlled manner. Each microfluidic chip can be rotated 180&#xb0; on the support plate so that the sample can be run back-and-forth through the microfluidic devices. Because the support plate can be driven at relatively high RPMs, high flow rates are generated within the microfluidic chips. This increases the shear forces on the sample and also decreases the processing time involved as the sample can quickly pass through the shear-inducing features of the microfluidic chip(s).

A microfluidic device uses hydrodynamic shear forces on a sample to improve the speed and efficiency of tissue digestion is disclosed. The microfluidic channels are designed to apply hydrodynamic shear forces at discrete locations on tissue specimens up to 1 cm in length and 1 mm in diameter, thereby accelerating digestion through hydrodynamic shear forces and improved enzyme-tissue contact. Experiments using animal organs show that the digestion device with hydro-mincing capabilities is superior to conventional scalpel mincing and digestion based on recovery of DNA and viable single cells. The microfluidic digestion device can eliminate or reduce the need to mince tissue samples with a scalpel, while reducing sample processing time and preserving cell viability. Another advantage is that downstream microfluidic operations could be integrated to enable advanced cell processing and analysis capabilities. The device may be used in research and clinical settings to promote single cell-based analysis technologies, as well as to isolate primary, progenitor, and stem cells for use in the fields of tissue engineering and regenerative medicine.

A method of processing a lipoaspirate sample includes mechanically processing the lipoaspirate sample to generate nanofat. The nanofat is then input into a microfluidic device comprising a plurality of serially arranged stages comprising one or more microfluidic channels having a plurality of expansion and constriction regions extending along the length of the one or more microfluidic channels, wherein each subsequent stage of the plurality has an increasing number of microfluidic channels of decreasing dimensions. The nanofat is flowed through the plurality of serially arranged stages in a plurality of cycles to generate sheared nanofat. The sheared nanofat is then collected after flowing through the plurality of serially arranged stages. The sheared nanofat may then be injected and/or applied to the subject. In an alternative embodiment, filtered or mechanically processed lipoaspirate may be run through the microfluidic device.

Growing community of inventors

Irvine, CA, United States of America

Jered Haun