Uncategorized – Lab on a Chip Blog

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Lab on a Chip thematic collection on droplet-based single cell sequencing

03 May 2019

Lab on a Chipis delighted to share with you our Thematic Collection ondroplet-based single-cell sequencing.

Thedroplet-based single-cell sequencingfield is advancing very rapidly.Large numbers of studies are underway to collect and explore the new information that is now accessible with single-cell RNA-seq.Improvements to the microfluidics are also advancing rapidly.This collection of papers and reviews focusses on the between the technological advancements and high impact applications of droplet-based single-cell sequencing.

This topical and exciting collection is collated by Thought leader Dave Weitz and theLab on a ChipEditorial Board.The collection is introduced in aperspective on single cell sequencingby the Thought leader Dave Weitz,and in two editorials,one on "InDrops and Drop-seq" by Allon Klein and Evan Macosko and one on "an engineer and business person's perspective" by businessman and engineer Mark Gilligan.

Read the full collection at: http://rsc.li/drop-sc-seq

Below is a selection of content highlights featured in the collection.In addition,all papers are free to read until 31^stMay*

Perspective

Droplet-based single cell RNAseq tools: a practical guide

Robert Salomon,David Gallego-Ortega,et al.

Critical Review

Finding a helix in a haystack: nucleic acid cytometry with droplet microfluidics

Iain C.Clark and Adam R.Abate

Paper

High throughput gene expression profiling of yeast colonies with microgel-culture Drop-seq

Leqian Liu,Adam R.Abate,et al.

Paper

Simplified Drop-seq workflow with minimized bead loss using a bead capture and processing microfluidic chip

Marjan Biočanin,Bart Deplancke,et al.

Lab on a Chipis the leading journal publishing significant and original work related to miniaturisation,at the micro- and nano-scale,of interest to a multidisciplinary readership with an Journal Impact Factor of 5.995**.The journal is guided by Editor-in-Chief Abraham (Abe) Lee (University of California,Irvine) who is supported by our team ofAssociate Editors(Yoon-Kyoung Cho,Petra Dittrich,Hang Lu,Jianhua Qin,Manabu Tokeshi,Joel Voldman and Aaron Wheeler).

We hope you enjoy reading the papers within this Thematic Collection and we welcome future submissions on droplet-based single-cell sequencing.

Dolomite/Lab on a ChipPioneers of Miniaturization Lectureship–deadline approaching-nominate a colleague now!

Organ-on a-chip systems- translating concept into practice thematic collection–Submit now

Organ-,body- and disease-on-a-chip thematic collection–Read now

Personalised medicine:liquid biopsy–Read now

Lab on a Chip Emerging Investigator Series–Apply now

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Lab on a Chip thematic collection on personalised medicine-liquid biopsy

03 May 2019

Lab on a Chipis delighted to share with you our Thematic Collection onpersonalised medicine-liquid biopsy.

This collection of papers and reviews focusses on the interface between the technological advancements and high impact applications of liquid biopsy technologies.This collection is collated by Thought Leaders Mehmet Toner and Stefanie Jeffrey and theLab on a ChipEditorial Board and is introduced in an Editorial by the Thought Leaders onLiquid biopsy: a perspective for probing blood for cancer.

Read the full collection at: http://rsc.li/liquid-biopsy

Below is a selection of content highlights featured in the collection.In addition,all papers are free to read until 31^stMay*

Tutorial Review

Cancer diagnosis: from tumor to liquid biopsy and beyond

Ramanathan Vaidyanathan,Chwee Teck Lim,et al.

Critical Review

Circulating tumor DNA and liquid biopsy: opportunities,challenges,and recent advances in detection technologies

Lena Gorgannezhad,Nam-Trung Nguyen,Muhammad J.A.Shiddikyet al.

Paper

Dynamic CTC phenotypes in metastatic prostate cancer models visualized using magnetic ranking cytometry

Leyla Kermanshah,Shana O.Kelleyet al.

Paper

An ultrasensitive test for profiling circulating tumor DNA using integrated comprehensive droplet digital detection

Chen-Yin Ou,Timothy J.Abram,Weian Zhaoet al.

Paper

Cancer marker-free enrichment and direct mutation detection in rare cancer cells by combining multi-property isolation and microfluidic concentration

Soo Hyeon Kim,Teruo Fujiiet al.

Paper

Urine-based liquid biopsy: non-invasive and sensitive AR-V7 detection in urinary EVs from patients with prostate cancer

Hyun-Kyung Woo,Hong Koo Ha,Yoon-Kyoung Choet al.

We hope you enjoy reading the papers within this Thematic Collection!

Keep up to date withLab on a Chipthroughout the year bysigning upfor free table of contents alerts and monthly e-newsletters.

Dolomite/Lab on a ChipPioneers of Miniaturization Lectureship–deadline approaching-nominate a colleague now!

Organ-on a-chip systems- translating concept into practice thematic collection–Submit now

Organ-,body- and disease-on-a-chip thematic collection–Read now

Droplet-based single-cell sequencing–Read now

Lab on a Chip Emerging Investigator Series–Apply now

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What we know about cancer tumors

23 Jul 2018

Cancer tumors are a lot more complex than we think: besides cancer cells,supportive tissue cells,fat,and even immune cells can be found in a tumor.Combined crosstalk in between these cell groups influences the way the tumor develops or responses to drug treatment.On the other hand,the majority of what we know about cancer tumors has been acquired by studying cell ensembles.Recent strides to improve our understanding of cancer revealed that we have long been missing the stochastic interactions and rare events due to ensemble-average measurements.We can unveil how these cell groups work together and how the rare events change the fate of a tumor thanks tosingle-cell analysistechniques.

Single cells can be identified by extrinsic and intrinsic markers.Extrinsic markersare definitive of genetic and proteomic states of a cell.Flow cytometryandmass spectrometryhave been the workhorse of extrinsic marker analysis,where genetic or proteomic materials are often fluorescently labeled for detection.With these techniques,multiplexed analysisof thousands of cells can be employed simultaneously.Intrinsic markersinclude size,shape,density,optical,mechanical,and electrical properties which do not require labelling.Microfluidic techniques provide with a plethora of different functionalities to sort the cells based on intrinsic markers.Combination of both extrinsic and intrinsic data advances our understanding of how cell heterogeneity is reflected in cell-to-cell variations in tumor development and drug-response.Although many powerful methods are available for determining extrinsic markers,not many techniques can gather information about a panel of different intrinsic markers.

A recent study fromBiological Microtechnology and BioMEMS groupat MIT represents an important microfluidic approach for the development of multiparameter intrinsic cytometry tool.The approach includes several different microfluidic modules combined with microscope imaging and image processing by machine learning.Separate modules measuring cell size,deformability,and polarization can be combined and organized within the tool (Figure 1).(i) Size module detects the cell size optically in a flow through system.Cell size module is necessary to separate different cell types that can give important cues about disease state.(ii) In deformability module,cells pass through narrow channels,and their transit time defines the deformability.Cell deformability gives cues about cytoskeletal and nuclear changes associated with cancer progression.(iii) In the polarization module,dielectrophoretic force at a fixed frequency is applied on cells driven by opposing hydrodynamic forces.Cells approach coplanar electrodes with different equilibrium positions depending on their polarizability.Cell polarizability allows for distinguishing subtle changes in biological phenotypes.As a proof-of-concept work,drug-induced structural changes in cells were detected for the first time using five different intrinsic markers,including size,deformability,and polarizability at three frequencies.The authors indicate that this powerful tool can further be equipped with visual readout capabilities,such as deterministic lateral displacement array,inertial microfluidics,acoustophoresis,optical techniques.

Figure 1.Multiparameter intrinsic cytometry combines different microfluidic modules on one substrate along with cell tracking to correlate per-cell information across modules for different intrinsic properties including size,polarizability,and deformability.

To download thefull article for free*click the link below:

Multiparameter cell-tracking intrinsic cytometry for single-cell characterization
Apichitsopa,A.Jaffe,and J.Voldman
Lab Chip,2018,Lab on a Chip Recent Hot Articles
DOI:10.1039/C8LC00240A

*Article free to read until 31st August 2018

About the Webwriter

Burcu Gumuscuis a postdoctoral fellow inHerr Labat UC Berkeley in the United States.Her research interests include development of microfluidic devices for quantitative analysis of proteins from single-cells,next generation sequencing,compartmentalized organ-on-chip studies,and desalination of water on the microscale.

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Magnetic separation of circulating tumor cells…but it's not what you think

16 Nov 2017

Cancers typically originate in one organ yet can spread to distant regions of the body forming secondary tumours called metastases.This happens as cells from the primary tumour migrate into the circulatory system and then travel to other organs.These cells,which are a very rare population within the circulatory system,are termed circulating tumor cells (CTCs).Because of their role in cancer biology,they have garnered a lot of interest lately.Their detection and isolation present several analytical challenges.For one,they are the proverbial "needle in a haystack",with counts on the order of one CTC for every billion blood cells.This has traditionally led to a paradox: these rare cells are best handled in microscale systems but the world-to-chip mismatch limits microfluidic devices from rapidly processing the large (> 5 mL) samples necessary.Second,recent studies have revealed CTCs to be very heterogeneous populations,limiting the use of surface markers for labelling and capturing a broad range of CTCs.Because there is much still to learn about CTCs,there's also an interest in recovering viable CTCs for further analysis.In their recent report,Zhao et al.demonstrate a microfluidic device capable of enriching CTCs using magnetic separation.But it's not that typical magnetophoretic separations you may be familiar with!

Rather than using magnetic particles to bind to surface antigens and eventually separate out CTCs,they capitalize on a phenomenon known as "negative magnetophoresis".Cells are suspended within a uniformly magnetic medium and application of a non-uniform magnetic field results in a magnetic buoyant force.(This is akin to how negative dielectrophoresis exerts a force on particles in a non-uniform electric field.) The advantage of this method is that the "working principle applies to every non-magnetic material," according to Prof.Leidong Mao."Naturally," he thought "it could apply to CTC enrichment." However,despite previous work separating different cell populations with negative magnetophoresis,moving to CTC enrichment is not so straightforward.CTC enrichment is the most challenging separation."All previous applications in our group are with cells at high concentrations," mentioned Prof.Mao.The main challenge in developing the chip was trying to preserve the characteristics of an "ideal" CTC enrichment device;one that could process a significant amount of blood quickly,have a high recovery rate of CTCs,give reasonable purity of isolated CTCs,and retain cell integrity and viability for further analysis.

With this method,heterogeneous populations of CTCs can be enriched as selection is size dependent rather than based on expression of certain surface markers.This also avoids the costs associated with traditional magnetic labelling – typically used to label and deplete the millions of white blood cells.The device is capable of working at flow rates of 5-7 mL/hr,which is what is necessary to process an entire blood sample and can achieve high recovery rates (>90%).While the authors report purities that appear low (10-12%),they are working on improving purity.One strategy they suggest in their report is to follow the route of the iChip and combine size based separations with magnetic WBC depletion.

To read the full paper for free*,click the link below:

Label-free ferrohydrodynamic cell separation of circulating tumor cells
DOI:10.1039/C7LC00680B(Paper)Lab Chip,2017,17,3097-3111

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About the Webwriter

Darius Rackus is a postdoctoral researcher at the University of Toronto working in theWheeler Lab.His research interests are in combining sensors with digital microfluidics for healthcare applications.

*free to access until 14th December 2017

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ICAS 2017 – International Congress on Analytical 新利手机客户端Sciences

10 Jan 2017

ICAS 2017is the 5 yearly international congress organised by theChinese Chemical Society(CCS) and theInternational Union of Pure and Applied 新利手机客户端Chemistry(IUPAC).The event takes place at the Hainan International Convention and Exhibition Centre in Hainan,China between5^thand 8^thMay 2017.The theme of this year's congress is "Analytical 新利手机客户端Chemistry – From T新利手机客户端ool to Science",which will contain sessions on advanced instrumental analysis,nano新利手机客户端science and nanotechnology,biological and bioanalysis,environmental 新利手机客户端sciences,food safety,micro-analysis and microfluidic,sensors systems,mass spectrometry,separation and chromatography,spectrometry/spectroscopy,and electrochemical analysis.The Royal Society of 新利手机客户端Chemistry JournalsLab on a Chip,AnalystandAnalytical Methodsare very pleased to be supporting this event.

Visit the conferencewebsitefor further details on themes and speakers and to submit your abstract.

Important Dates:
Abstract Submission Deadline: 28^thFebruary 2017

Early Bird Registration Deadline: 31^stMarch 2017

Register now to attend and present your work!

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A new ‘on-chip' immunoassay device

22 Oct 2015

Professor Yarmash‘s lab atRutgers Universityhave developed a proof of concept microfluidic device,capable of running multiple immunoassays in parallel.The device allows 32 samples to be assayed simultaneously and multiple analytes can be tested in each sample.

As shown in the diagram below,each sample inlet has a bead trap that contains antibody-conjugated microbeads.These are commercially available,allowing virtually any analyte to be tested.The sample flows over the beads at an optimised rate,allowing the analytes to bind to their specific antibodies.A secondary antibody is added that binds to antibodies complexed to analytes,followed by a fluorescent tag that binds to the secondary antibody.然后收集微磁,placed in a 96 well plate,and analysed.

a) diagram and b) photo of the device;c) diagram of valve configuration and flow pathways during the assay;d)分析的关键步骤。

Device layout and assay principle

The authors assayed several proteins from anin vitrosupernatant and their results corroborated well with a standard benchtop immunoassay.Compared to the benchtop standard,the device has significantly reduced sample consumption as well as large reductions in microbead and detection antibody consumption.It has comparable sensitivity to the benchtop standard and has a large working range,meaning that analytes present at different concentrations in the sample can be measured simultaneously.In addition to this,it is compatible with commercial reagents and analyte concentration can be quantified.Although previously published devices have addressed some of these characteristics,this the first example where they are combined into one device.

Moving on from their proof-of-concept study,the Yarmash group hopes to develop a device capable ofin vivomeasurements.One example they give is analysis of cerebrospinal fluid in rats,an important animal model in Alzheimer's research,where immunoassays are currently limited by the small volumes available.

Todownload the full article for free*click the link below:

Development and validation of a microfluidic immunoassay capable of multiplexing parallel samples in microliter volumes
Mehdi Ghodbane,Elizabeth C.Stucky,Tim J.Maguire, Rene S.Schloss,David I.Shreiber, Jeffrey D.Zahn and Martin L.Yarmush
Lab Chip,2015,15,3211-3221
DOI: 10.1039/C5LC00398A

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About the webwriter

Claire Weston is a PhD student in theFuchter Group,atImperial College London.Her work is focused on developing novel photoswitches and photoswitchable inhibitors.

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*Access is free until 19/11/2015 through a registered RSC account – clickhereto register