University of Toronto

Other

Dh Technologies Development Pte. Ltd.

Miroculus Inc.

Sci-bots Inc.

Tecan Trading Ag

Aaron Ray Wheeler

Mais Jehan Jebrail

Irena Barbulovic-Nad

Hao Yang

Mohamed Abdelgawad

Ryan Fobel

Robert Fredric Joseph Casper

Julian Lucas Lamanna

Noha Ahmed Mousa

Chang Liu

John Lawrence Campbell

Yves LeBlanc

Alphonsus Hon-Chung Ng

Jared M Mudrik

Steve Chao-Chung Shih

Shuailong Zhang

Michael W L Watson

Kihwan Choi

Man Ho Stephen Ho

Michael Dean Chamberlain

Michael David Murdoch Dryden

Christopher Alvin Dixon

Mohamed Omar Abdelgawad

Christian Fobel

Darius George Rackus

Andrea Kirby

Mohtashim Shamsi

Yue Yu

Man Ho Ho

Alphonsus Hon-Ghung Ng

Robert Fredric Casper

Michael Wl Watson

Irena Barbulovuic-Nad

A system for identifying and targeting individual cells within a cell population for selective extraction of cellular content. The system includes a digital microfluidic device having at least one hydrophilic site for receiving cells, an imaging system including a stage for receiving the digital microfluidic device and an imaging module for identifying at least one targeted cell among the cells at the at least one hydrophilic site and a pulsed laser source for lysing the targeted cell to produce a lysate. A control system controls the pulsed laser source, the imaging system and the digital microfluidic device and is programmed for coordinating steps of i) moving droplets on the digital microfluidic device, ii) selecting the targeted cell to be lysed located at the hydrophilic site, iii) illuminating the selected targeted cell by the pulsed laser source to lyse the selected targeted cell to produce lysate, and iv) collecting the lysate.

System for identifying and targeting individual cells within a heterogeneous population for selective extraction of cellular content

Disclosed herein are two related techniques for digital microfluidic (DMF) processing of liquids that rely on electrostatic actuation of fluid through a strip of solid, porous media. In the first technique, droplets in a DMF device containing particles of different sizes are driven through a solid porous medium, allowing for filtering, concentration, and recovery of the particles into droplets on the basis of size. In the second technique, an aliquot of liquid media is loaded directly onto a solid porous medium, where it is wicked into a DMF device, such that the filtrate can be collected into droplets. Both techniques may be useful for generating plasma from whole blood on a DMF device, an operation that will have far-reaching implications for diagnostic applications of digital microfluidics.

Methods for the filtration of small-volume heterogeneous suspensions in a digital microfluidic device

Disclosed herein is a surfactant additive, ethylenediamine tetrakis(ethoxylate-block-propoxylate) tetrol with 16 ethylene oxide repeat units and 18 propylene oxide repeat units (known by its trade name as Tetronic 90R4) used as a droplet-additive, or to coat DMF driving electrode surfaces which dramatically improves the capability to work with high-protein-content liquids (e.g., whole blood) on digital microfluidic chips. This surfactant prevents protein adsorption and fouling of DMF electrode surfaces to an extent that was heretofore impossible. Specifically, this surfactant allows for the manipulation of droplets of undiluted whole blood for &#x3e;1 hour per electrode (&#x3e;1 50 times better than what is possible for any known additive). This improvement in handling high protein content media will revolutionize blood-based diagnostics on digital microfluidic platforms.

Surfactant additives for digital microfluidic devices for high protein content droplets transport

Methods are provided for the preparation of a sample using a digital microfluidic platform and the optional subsequent mass analysis of an extracted analyte. A sample is dried, optionally on a solid phase support, and contacted with digital microfluidic array. An analyte present within the dried sample is extracted into an extraction solvent by electrically addressing the digital microfluidic array to transport a droplet of extraction solvent to the dried sample spot. The extracted sample may be dried and subsequently processed on the digital micro fluidic array for derivatization. The digital microfluidic device may further include an integrated microfluidic channel having an output aperture, and the method may further include contacting a droplet containing extracted analyte with the microfluidic channel and applying a suitable electric field for generating nano-electrospray, thereby enabling the device to be directly interacted with a mass analysis device.

Method of processing dried samples using digital microfluidic device

Disclosed herein is a method and system for concentrating analyte from large sample solutions using a combination of magnetic microparticles on a digital microfluidic device using virtual channels. Virtual channels are produced by applying voltages to a series of driving electrodes of the DMF that connect a reservoir of solution situated just outside of the DMF device to a fluid exit location. The magnetic microparticles are first exposed to a liquid sample containing the analyte whereupon analytes are bound by analyte specific receptors on the microparticles. By flowing these solutions of magnetic particles through virtual channels in DMF device, large volumes can be processed, regardless of the total capacity of the DMF. Engaging a magnet underneath the DMF device while a suspension of magnetic microparticles is flowed through the virtual channel causes the microparticles to become immobilized and the supernatant solution is removed. The isolated magnetic microparticles can then be resuspended in a much smaller volume and further processed on the DMF device for whatever application, thereby significantly increasing the concentration of the analytes in the small droplets compared to the original liquid solution.

DMF method and system for concentrating analyte from large volumes into smaller volumes using magnetic microparticles

The present disclosure discloses a multi-droplet sensing and actuation system, for use in a digital microfluidic chip operation wherein a linearly independent alternating current signal is applied to each discrete actuation electrode thus encoding the electrode's identity. The combined measured impedance signal from multiple channels is then processed to decode an impedance measurement for the volume between each discrete actuation electrode and its corresponding conductive counter electrode region, where the sensed impedance is inversely proportional to an amount of liquid within the volume.

Multiplexed droplet actuation and sensing in digital microfluidics

A patterned optoelectronic tweezers (p-OET) device is provided. The p-OET device includes a top and a bottom electrode arranged in a parallel spaced apart relationship. A patterned photoconductor layer is provided on the bottom electrode, and forms a pattern comprising at least one raised region where the bottom electrode is coated by a photoconductor material and at least one hollow region where the bottom electrode is exposed. The pattern includes one or more boundaries between the raised and hollow regions. In some implementations, the boundaries of the patterned photoconductive layer define a permanent trap feature.

Patterned optoelectronic tweezers

Methods and systems for processing fluids utilizing a digital microfluidic device and transferring droplets from the digital microfluidic device to a downstream analyzer are described herein. Methods and systems in accordance with the present teachings can allow for the withdrawal of fluid from a digital microfluidic device, and can in some aspects enable the integration of a digital microfluidic device as a direct, in-line sample processing platform from which a droplet can be transferred to a downstream analyzer.

Fluid transfer from digital microfluidic device

Methods are provided for the preparation of a sample using a digital microfluidic platform and the optional subsequent mass analysis of an extracted analyte. A sample is dried, optionally on a solid phase support, and contacted with digital microfluidic array. An analyte present within the dried sample is extracted into an extraction solvent by electrically addressing the digital microfluidic array to transport a droplet of extraction solvent to the dried sample spot. The extracted sample may be dried and subsequently processed on the digital microfluidic array for derivatization. The digital microfluidic device may further include an integrated microfluidic channel having an output aperture, and the method may further include contacting a droplet containing extracted analyte with the microfluidic channel and applying a suitable electric field for generating nano-electrospray, thereby enabling the device to be directly interfaced with a mass analysis device.

Methods and devices for liquid-liquid extraction using digital microfluidic arrays are provided. A polar droplet is transported to a separation region containing a substantially non-polar solvent, where non-polar impurities may be extracted from the polar droplet while maintaining a distinct phase separation. In a preferred embodiment, biological samples containing hormones are dried on a digital microfluidic array, lysed by a lysing solvent, dried, subsequently dissolved in a polar solvent, and further purified in a separation step in which droplets are transported through a volume of non-polar solvent. The method disclosed herein provides the distinct advantage of an automated sample preparation method that is capable of extracting hormones from low sample volumes with high precision and recovery.

Digital microfluidic liquid-liquid extraction device and method of use thereof

Embodiments of the present disclosure digital microfluidic arrays that may be fabricated by a printing method, whereby digital microfluidic electrodes arrays are printed, via a printing method such as inkjet printing, onto a suitable substrate. In some embodiments, a substrate and/or ink is prepared or modified to support the printing of electrode arrays, such as via changes to the surface energy. In some embodiments, porous and/or fibrous substrates are prepared by the addition of a barrier layer, or, for example, by the addition or infiltration of a suitable material to render the surface capable of supporting printed electrodes. Various example embodiments involving hybrid devices formed by the printing of digital microfluidic arrays onto a substrate having a hydrophilic layer are disclosed.

Printed digital microfluidic devices methods of use and manufacture thereof

Devices and methods are provided for performing droplet-based solid phase processing steps on a digital microfluidic device. A solid phase material, which may be a porous solid phase material such as a porous polymer monolith is formed or located on a digital microfluidic element. The solid phase may be formed by an in-situ method in which the digital microfluidic array is actuated to transport a droplet of solid phase pre-cursor solution to a selected element on the array, and subsequently processed to form a solid phase on the array element. The integration of a solid phase material with a digital microfluidic array enables a wide range of applications including solid phase extraction and sample concentration.

Digital microfluidic devices and methods incorporating a solid phase

Devices and methods are provided for measuring, on a digital microfluidic platform, electrical signals associated with the impedance of adherent cells. In one embodiment, a sub-droplet of cell culture media containing adherent cells is passively dispensed at a pre-selected electrode location where a local hydrophilic surface region is provided, and adherent cells are attached to the local hydrophilic surface region. The cell culture media sub-droplet is replaced with a sub-droplet of a low-conductivity medium in a passive dispensing step, retaining the attached adherent cells. An AC voltage with a suitable frequency is applied between electrodes of the device and a signal associated with the impedance of the adherent cells is obtained. One of the electrodes to which the AC voltage is applied may be a dedicated sensing electrode. The local thickness of a dielectric layer coating the pre-selected electrode may be reduced to increase the detection sensitivity of the device.

Impedance-based sensing of adherent cells on a digital microfluidic device

Devices and methods for implementing cell-based assays and long-term cell culture. The device and method are based on digital microfluidics (DMF) which is used to actuate nanoliter droplets of reagents and cells on a planar array of electrodes. DMF method is suitable for assaying and culturing both cells in suspension and cells grown on surface (adherent cells). This method is advantageous for cell culture and assays due to the automated manipulation of multiple reagents in addition to reduced reagent use and analysis time. No adverse effects of actuation by DMF were observed in assays for cell viability, proliferation, and biochemistry. These results suggest that DMF has great potential as a simple yet versatile analytical tool for implementing cell-based assays and cell culture on the microscale.

Cell culture and cell assays using digital microfluidics

The present invention provides a hybrid digital and channel microfluidic device in the form of an integrated structure in which a droplet may be transported by a digital microfluidic array and transferred to a microfluidic channel. In one aspect of the invention, a hybrid device comprises a first substrate having a digital microfluidic array capable of transporting a droplet to a transfer location, and a second substrate having a microfluidic channel. The first and second substrates are affixed to form a hybrid device in which an opening in the microfluidic channel is positioned adjacent to the transfer location, so that a droplet transported to the transfer location contacts the channel opening and may enter the channel. The invention also provides methods of performing separations using a hybrid digital and channel microfluidic device and methods of assembling a hybrid digital microfluidic device.

Growing community of inventors

Toronto, Canada

Aaron Ray Wheeler