Adam White is a postdoctoral research fellow in the department of Genetics, jointly supervised by Polly Fordyce and Stephen Quake. He is also the director of the Stanford Microfluidics Foundry. His research focuses on the development of spectrally encoded beads for multiplexed biological assays. Adam received his PhD in Genome Science and Technology from the University of British Columbia for developing integrated microfluidic devices for high-throughput single cell reverse transcription quantitative PCR.
Honors & Awards
Postdoctoral Fellowship, Natural Sciences and Engineering Research Council of Canada (NSERC) (2017 - 2018)
Jump Start Award for Excellence in Research, Stanford University (2016)
Alexander Graham Bell Canada Graduate Scholarship – Doctoral, Natural Sciences and Engineering Research Council of Canada (NSERC) (2012)
Four-Year Fellowship, University of British Columbia (2010)
Paul Geyer Graduate Award in Biomedical Engineering, University of British Columbia (2009)
Junior Research Trainee, Michael Smith Foundation for Health (2008)
Dean of Science Scholarship, University of British Columbia (2006)
Undergraduate Scholar Program Scholarship, University of British Columbia (2001)
Doctor of Philosophy, University of British Columbia (2015)
Postdoc, Stanford University, Genetics (2016)
PhD, University of British Columbia, Genome Science and Technology (2016)
MASc, University of British Columbia, Biomedical Engineering (2010)
BSc, University of British Columbia, Physics (2007)
Polly Fordyce, Postdoctoral Faculty Sponsor
- Outstanding Reviewers for Lab on a Chip in 2017 LAB ON A CHIP 2018; 18 (10): 1398
Highly multiplexed single-cell quantitative PCR
2018; 13 (1): e0191601
We present a microfluidic device for rapid gene expression profiling in single cells using multiplexed quantitative polymerase chain reaction (qPCR). This device integrates all processing steps, including cell isolation and lysis, complementary DNA synthesis, pre-amplification, sample splitting, and measurement in twenty separate qPCR reactions. Each of these steps is performed in parallel on up to 200 single cells per run. Experiments performed on dilutions of purified RNA establish assay linearity over a dynamic range of at least 104, a qPCR precision of 15%, and detection sensitivity down to a single cDNA molecule. We demonstrate the application of our device for rapid profiling of microRNA expression in single cells. Measurements performed on a panel of twenty miRNAs in two types of cells revealed clear cell-to-cell heterogeneity, with evidence of spontaneous differentiation manifested as distinct expression signatures. Highly multiplexed microfluidic RT-qPCR fills a gap in current capabilities for single-cell analysis, providing a rapid and cost-effective approach for profiling panels of marker genes, thereby complementing single-cell genomics methods that are best suited for global analysis and discovery. We expect this approach to enable new studies requiring fast, cost-effective, and precise measurements across hundreds of single cells.
View details for PubMedID 29377915
Multi-step Variable Height Photolithography for Valved Multilayer Microfluidic Devices.
Journal of visualized experiments : JoVE
Microfluidic systems have enabled powerful new approaches to high-throughput biochemical and biological analysis. However, there remains a barrier to entry for non-specialists who would benefit greatly from the ability to develop their own microfluidic devices to address research questions. Particularly lacking has been the open dissemination of protocols related to photolithography, a key step in the development of a replica mold for the manufacture of polydimethylsiloxane (PDMS) devices. While the fabrication of single height silicon masters has been explored extensively in literature, fabrication steps for more complicated photolithography features necessary for many interesting device functionalities (such as feature rounding to make valve structures, multi-height single-mold patterning, or high aspect ratio definition) are often not explicitly outlined. Here, we provide a complete protocol for making multilayer microfluidic devices with valves and complex multi-height geometries, tunable for any application. These fabrication procedures are presented in the context of a microfluidic hydrogel bead synthesizer and demonstrate the production of droplets containing polyethylene glycol (PEG diacrylate) and a photoinitiator that can be polymerized into solid beads. This protocol and accompanying discussion provide a foundation of design principles and fabrication methods that enables development of a wide variety of microfluidic devices. The details included here should allow non-specialists to design and fabricate novel devices, thereby bringing a host of recently developed technologies to their most exciting applications in biological laboratories.
View details for DOI 10.3791/55276
View details for PubMedID 28190039
High-Throughput Microfluidic Single-Cell Digital Polymerase Chain Reaction
2013; 85 (15): 7182–90
Here we present an integrated microfluidic device for the high-throughput digital polymerase chain reaction (dPCR) analysis of single cells. This device allows for the parallel processing of single cells and executes all steps of analysis, including cell capture, washing, lysis, reverse transcription, and dPCR analysis. The cDNA from each single cell is distributed into a dedicated dPCR array consisting of 1020 chambers, each having a volume of 25 pL, using surface-tension-based sample partitioning. The high density of this dPCR format (118,900 chambers/cm(2)) allows the analysis of 200 single cells per run, for a total of 204,000 PCR reactions using a device footprint of 10 cm(2). Experiments using RNA dilutions show this device achieves shot-noise-limited performance in quantifying single molecules, with a dynamic range of 10(4). We performed over 1200 single-cell measurements, demonstrating the use of this platform in the absolute quantification of both high- and low-abundance mRNA transcripts, as well as micro-RNAs that are not easily measured using alternative hybridization methods. We further apply the specificity and sensitivity of single-cell dPCR to performing measurements of RNA editing events in single cells. High-throughput dPCR provides a new tool in the arsenal of single-cell analysis methods, with a unique combination of speed, precision, sensitivity, and specificity. We anticipate this approach will enable new studies where high-performance single-cell measurements are essential, including the analysis of transcriptional noise, allelic imbalance, and RNA processing.
View details for DOI 10.1021/ac400896j
View details for Web of Science ID 000323014000031
View details for PubMedID 23819473
Microfluidic single cell analysis: from promise to practice.
Current opinion in chemical biology
2012; 16 (3-4): 381–90
Methods for single-cell analysis are critical to revealing cell-to-cell variability in biological systems, especially in cases where relevant minority cell populations can be obscured by population-averaged measurements. However, to date single cell studies have been limited by the cost and throughput required to examine large numbers of cells and the difficulties associated with analyzing small amounts of starting material. Microfluidic approaches are well suited to resolving these issues by providing increased senstitivity, economy of scale, and automation. After many years of development microfluidic systems are now finding traction in a variety of single-cell analytics including gene expression measurements, protein analysis, signaling response, and growth dynamics. With newly developed tools now being applied in fields ranging from human haplotyping and drug discovery to stem cell and cancer research, the long-heralded promise of microfluidic single cell analysis is now finally being realized.
View details for PubMedID 22525493
High-throughput analysis of single hematopoietic stem cell proliferation in microfluidic cell culture arrays.
2011; 8 (7): 581–86
Heterogeneity in cell populations poses a major obstacle to understanding complex biological processes. Here we present a microfluidic platform containing thousands of nanoliter-scale chambers suitable for live-cell imaging studies of clonal cultures of nonadherent cells with precise control of the conditions, capabilities for in situ immunostaining and recovery of viable cells. We show that this platform mimics conventional cultures in reproducing the responses of various types of primitive mouse hematopoietic cells with retention of their functional properties, as demonstrated by subsequent in vitro and in vivo (transplantation) assays of recovered cells. The automated medium exchange of this system made it possible to define when Steel factor stimulation is first required by adult hematopoietic stem cells in vitro as the point of exit from quiescence. This technology will offer many new avenues to interrogate otherwise inaccessible mechanisms governing mammalian cell growth and fate decisions.
View details for PubMedID 21602799
High-throughput microfluidic single-cell RT-qPCR.
Proceedings of the National Academy of Sciences of the United States of America
2011; 108 (34): 13999–4004
A long-sought milestone in microfluidics research has been the development of integrated technology for scalable analysis of transcription in single cells. Here we present a fully integrated microfluidic device capable of performing high-precision RT-qPCR measurements of gene expression from hundreds of single cells per run. Our device executes all steps of single-cell processing, including cell capture, cell lysis, reverse transcription, and quantitative PCR. In addition to higher throughput and reduced cost, we show that nanoliter volume processing reduced measurement noise, increased sensitivity, and provided single nucleotide specificity. We apply this technology to 3,300 single-cell measurements of (i) miRNA expression in K562 cells, (ii) coregulation of a miRNA and one of its target transcripts during differentiation in embryonic stem cells, and (iii) single nucleotide variant detection in primary lobular breast cancer cells. The core functionality established here provides the foundation from which a variety of on-chip single-cell transcription analyses will be developed.
View details for PubMedID 21808033
View details for PubMedCentralID PMC3161570