Our research can be divided into the following topics. Click below to learn more.
Digital Microfluidic Theory and Improvements
"Digital microfluidics" is a term used to describe the fluid-handling technique in which discrete liquid droplets are manipulated electromechanically across an array of electrodes coated with a hydrophobic insulator. For new users, we recently developed an open-source digital microfluidic control system, called DropBot (see the DropBot archive for schematics, downloads, instructions, and more). Additionally, we have written several review articles describing digital microfluidics (see articles in Science, ABC, Adv. Mat., COCB, or ARAC), and have worked to develop a variety of method improvements, tackling issues including biofouling, device geometry limitations, electronic control systems, and reliable dispensing. Papers describing our efforts in these areas are listed below.
- Le, N.H.; Sathishkumar, N.; Salari, A.; Manning, R.; Meyer, R.E.; Kan, C.W.; Wiener, A.D.; Rossotti, M.A.; Decombe, S.; Campos, R.P.S.d.; Chamberlain, M.D.; Tanha, J.; Pollock, N.R.; Duffy, D.C.; Wheeler, A.R. " A Compartmentalization-Free Microfluidic Digital Assay for Detecting Picogram Levels of Protein Analytes" Lab Chip 2025, 25, 2862-2873. Supporting Info. Video 1.
- Ho, M.; Au, A.; Flick, R.; Vuong, T.V.; Sklavounos, A.A.; Swyer, I.; Yip, C.M.; Wheeler, A.R. "Antifouling Properties of Pluronic and Tetronic Surfactants in Digital Microfluidics" ACS Appl. Mater. Interfaces, 2023, 15, 6326−6337. Supporting Info, Movie.
- von der Ecken, S.; Sklavounos, A.A.; Wheeler, A.R. "Vertical Addressing of 1-Plate Electrodes for Digital Microfluidics" Adv. Mater. Tech., 2022, 7, 2101251. Supplementary: Info, Movie, Zip file
- Swyer, I.; Fobel, R.; Wheeler, A.R. "Velocity Saturation in Digital Microfluidics" Langmuir 2019, 35, 5342-5352. Supplementary: Info, Movie 1, Movie 2, Movie 3.
- Dixon, C.; Ng, A.H.C.; Fobel, R.; Miltenburg, M.B.; Wheeler, A.R. "An Inkjet Printed, Roll-Coated Digital Microfluidic Device for Inexpensive, Miniaturized Diagnostic Assays" Lab on a Chip, 2016, 16, 4560-4568. Supporting info. Supporting video.
- Sarvothaman, M.K.; Kim, K.S.; Seale, B.; Brodersen, P.M.; Walker, G.C.; Wheeler, A.R. "Dynamic Fluoroalkyl Polyethylene Glycol Co-Polymers: A New Strategy for Reducing Protein Adhesion in Lab-on-a-Chip Devices" Adv. Func. Mater., 2015, 25, 506-515. Supporting info.
- Fobel, R.; Kirby, A.E.; Ng, A.H.C.; Farnood, R.R.; Wheeler, A.R. "Paper Microfluidics Goes Digital" Adv. Mat. 2014, 26, 2838-2843. Supporting info.
- Fobel, R.; Fobel, C.; Wheeler, A.R. "Dropbot: An Open-Source Digital Microfluidic Control System with Precise Control of Electrostatic Driving Force and Instantaneous Drop Velocity Measurement" Appl. Phys. Lett. 2013, 102, 193513. Supporting info.
- Eydelnant, I.A.; Uddayasankar, U.; Li, B.; Liao, M.W.; Wheeler, A.R. "Virtual Microwells for Digital Microfluidic Reagent Dispensing and Cell Culture" Lab on a Chip 2012, 12, 750-757.
- Au, S.H.; Kumar, P.; Wheeler, A.R. "A New Angle on Pluronic Additives: Advancing Droplets and Understanding in Digital Microfluidics" Langmuir 2011, 27, 8586-8594. Suppl. File 1.
- Shih, S.C.C.; Fobel, R.; Kumar, P.; Wheeler, A.R. "A Feedback Control System for High-Fidelity Digital Microfluidics" Lab Chip, 2011, 11, 535-540. Suppl. File 1, Suppl. File 2.
- Abdelgawad, M., Park, P.; Wheeler, A.R. "Optimization of Device Geometry in Single-Plate Digital Microfluidics" J. App. Phys. 2009, 105, 094506.
- Yang, H.; Luk, V.N.; Abdelgawad, M.; Barbulovic-Nad, I.; Wheeler, A.R. "A World-to-Chip Interface for Digital Microfluidics" Anal. Chem., 2009, 81, 1061-1067.
- Luk, V.N.; Mo, G.C.; Wheeler, A.R. "Pluronic Additives: A Solution to Sticky Problems in Digital Microfluidics" Langmuir 2008, 24, 6382-6389. Supporting Info
- Abdelgawad M.; Freire S.; Yang H.; Wheeler A. R. "All-Terrain Droplet Actuation" Lab Chip 2008, 8, 672-677. Supporting Info
Optoelectronic Tweezers
"Optoelectronic Tweezers" (OET) is a manipulation tool that is related to digital microfluidics (DMF). In both techniques, electric potentials are applied to a series of electrodes to allow for the manipulation of fluids and particles. A key difference is – in conventional DMF, the electrodes are permanent, while in OET, the electrodes are ‘virtual’ – that is, ‘virtual electrodes’ are defined by the projection of light onto an unpatterned photoconductive material. In effect, this allows for the generation of electrodes with arbitrary size and position, that can be moved in time by projecting a series of moving light patterns onto the device. Papers describing our work with OET are listed below, and a short movie illustrating our OET-driven microrobot can be viewed here. For more on OET, see our recent review article in Chemical Society Reviews.
- Li, G.; Xu, B.; Wang, X.; Yu, J.; Zhang, Y.; Fu, R.; Yang, F.; Gu, H.; Huang, Y.; Chen, Y.; Zhang, Y.; Wang, Z.; Shen, G.; Wang, Y.; Xie, H.; Wheeler, A.R.; Li, J.; Zhang, S. " Crossing the Dimensional Divide with Optoelectronic Tweezers: Multicomponent Light-Driven Micromachines with Motion Transfer in Three Dimensions" Adv. Mater. 2025, 37, 2417742. Supporting Info. Movie 1. Movie 2. Movie 3. Movie 4. Movie 5. Movie 6. Movie 7. Movie 8.
- Chen, X.; Chen, X.; Elsayed, M.; Edwards, H.; Liu, J.; Peng, Y.; Zhang, H.P.; Zhang, S.; Wei Wang; Wheeler, A.R. "Steering Micromotors via Reprogrammable Optoelectronic Paths" ACS Nano 2023, 17, 5894-5904. Supporting Info,Movie 1,Movie 2,Movie 3,Movie 4,Movie 5
- Mennillo, L.; Bendkowski, C.; Elsayed, M.; Edwards, H.; Zhang, S.; Pawar, V.; Wheeler, A.R.; Stoyanov, D.; Shaw, M. "Adaptive Autonomous Navigation of Multiple Optoelectronic Microrobots in Dynamic Environments" IEEE Robot. Autom. Lett., 2022, 7, 11102-11109.
- Zhang, S.; Elsayed, M.; Peng, R.; Chen, Y.; Zhang, Y.; Neale, S.L.; Wheeler, A.R "Influence of Light Pattern Thickness on the Manipulation of Dielectric Microparticles by Optoelectronic Tweezers" Photonics Research 2022, 10, 550-556. Supplementary Movie.
- Zhang, S.; Li, W.; Elsayed, M.; Peng, J.; Chen, Y.; Zhang, Y.; Zhang, Y.; Shayegannia, M.; Dou, W.; Wang, T.; Sun, Y.; Kherani, N.P.; Neale, S.L.; Wheeler, A.R. "Integrated Assembly and Photopreservation of Topographical Micropatterns" Small , 2021, 17, 2103702. Supporting info, Supporting video
- Zhang, S.; Elsayed, M.; Peng, R.; Chen, Y.; Zhang, Y.; Peng, J.; Li, W.; Chamberlain, M.D.; Nikitina, A.; Yu, S.; Liu, X.; Neale, S.L.; Wheeler, A.R. "Reconfigurable Multi-Component Micromachines Driven by Optoelectronic Tweezers" Nature Comm. , 2021, 12, 5349. Supporting info, Supporting video
- Zhang, S.; Zhai, Y.; Peng, R.; Shayegannia, M.; Flood, A.G.; Qu, J.; Liu, X.; Kherani, N.P.; Wheeler, A.R. "Assembly of Topographical Micropatterns with Optoelectronic Tweezers" Adv. Optical Mater. 2019, 7(20), 1900669. Supplementary: Info, Movie.
- Zhang, S.; Li, W.; Elsayed, M.; Tian, P.; Clark, A.W.; Wheeler, A.R.; Neale, S.L. "Size-scaling effects for microparticles and cells manipulated by optoelectronic tweezers" Optics Letters, 2019, 44 (17), 4171-4174. Supplementary: Movie 1, Movie 2, Movie 3.
- Zhang, S.; Scott, E.Y.; Singh, J.; Chen, Y.; Zhang, Y.; Elsayed, M.; Chamberlain, M.D.; Shakiba, N.; Adams, K.; Yu, S.; Morshead, C.M.; Zandstra, P.W.; Wheeler, A.R. "The optoelectronic microrobot: A versatile toolbox for micromanipulation" Proceedings of the National Academy of Science, U.S.A. 2019, 116 (30), 14823-14828. Supporting Info, Supplementary Movies.
- Zhang, S.; Shakiba, N.; Chen, Y.; Zhang, Y.; Tian, P.; Singh, J.; Chamberlain, M.D.; Satkauskas, M.; Flood, A.G.; Kherani, N.P.; Yu, S.; Zandstra, P.W.; Wheeler, A.R. "Patterned Optoelectronic Tweezers: A New Scheme for Selecting, Moving, and Storing Dielectric Particles and Cells" Small, 2018, 45, 1803342. Supplementary: Info, Movie 1, Movie 2, Movie 3, Movie 4, Movie 5, Movie 6.
- Zhang, S.; Nikitina, A.; Chen, Y.; Zhang, Y.; Liu, L.; Flood, A.G.; Juvert, J.; Chamberlain, M.D.; Kherani, N.P.; Neale, S.L.; Wheeler, A.R. "Escape from an optoelectronic tweezer trap: experimental results and simulations" Optics Express, 2018, 26, 5300-5309. Supplementary: Movie 1, Movie 2; Movie 3; Movie 4.
Digital Microfluidics for Cell Culture and Analysis
In vitro cell culture and analysis is omnipresent in modern biology labs, but this comes at a cost, with world-wide activities requiring an annual expenditure of billions of dollars and hundreds of thousands of laboratory hours. Our group was the first to explore the compatibility of digital microfluidics with mammalian cell culture to automate the process and reduce reagent consumption; papers in this area are listed below. For more, see our recent review paper describing the use of DMF for cell culture and analysis.
- Lant, J.T.; Frasheri, J.; Kwon, T.; Tsang, C.M.N.; Li, B.B.; Decombe, S.; Sklavounos, A.A.; Akbari, S.; Wheeler, A.R. "A Multimodal Digital Microfluidic Testing Platform for Antibody-Producing Cell Lines" Lab Chip 2024, 24, 5398 - 5412. Supporting Info. Movie.
- Casasbuenas, D.L.; Kortebi, I; Gora, C.; Scott, E.Y.; Gomes, C.; Oliviera Jr., M.S.; Sharma, T.; Daniele, E.; Gibbs, R.; Yuzwa, S.A.; Gilbert, E.A.; Küry, P.; Wheeler, A.R.; Lévesque, M.; Faiz, M. "The laminar position, morphology, and gene expression profiles of cortical astrocytes are influenced by tume of birth from ventricular/subventricular progenitors " Glia 2024, 1-14. Supporting Figures. Movie. Supporting Data 1. Supporting Data 2.
- Scott, E.Y.; Safarian, N.; Casasbuenas, D.L.; Dryden, M.D.M.; Tockovska, T.; Ali, S.; Peng, J.; Daniele, E.; Lim, I.N.X.; Bang, K.A.; Tripathy, S.; Yuzwa, S.A.; Wheeler, A.R.; Faiz, M. "Integrating Single-Cell and Spatially Resolved Transcriptomic Strategies to Survey the Astrocyte Response to Stroke in Male Mice" Nature Comm. 2024, 15, 1584. Supporting Info.Supporting Data.
- Li, B.B.; Scott, E.Y.; Olafsen, N.E.; Matthews, J.; Wheeler, A.R. "Analysis of the Effects of Aryl Hydrocarbon Receptor Expression on Cancer Cell Invasion via Three-Dimensional Microfluidic Invasion Assays" Lab Chip 2022, 22, 313–325. Supporting Info.
- Sklavounos, A.A.; Nemr, C.R.; Kelley, S.O.; Wheeler, A.R. "Bacterial Classification and Antibiotic Susceptibility Testing on an Integrated Microfluidic Platform" Lab Chip 2021, 21, 4208 - 4222. Supporting Info.
- Lamanna, J.; Scott, E.Y.; Edwards, H.S.; Chamberlain, M.D.; Dryden, M.D.M.; Peng, J.; Mair, B.; Lee, A.; Chan, C.; Sklavounos, A.A.; Heffernan, A.; Abbas, F.; Lam, C.; Olson, M.E.; Moffat, J.; Wheeler, A.R. "Digital Microfluidic Isolation of Single Cells for -Omics" Nature Comm., 2020, 11, 5632. Supplementary: Info, Movie 1, Movie 2.
- Li, B.B.; Scott, E.Y.; Chamberlain, M.D.; Duong, B.T.V.; Zhang, S.; Done, S.J.; Wheeler, A.R. "Cell Invasion in Digital Microfluidic Microgel Systems" Science Advances. 2020, 6, eaba9589. Supporting Info.
- Yu, Y.; Campos, R.P.S.d.; Hong, S.; Kraste, D.L.; Sadanand, S.; Leung, Y.; Wheeler, A.R. "A Microfluidic Platform for Continuous Monitoring of Dopamine Homeostasis in Dopaminergic Cells" Microsyst. Nanoeng. 2019, 5, 10. Supporting info.
- Yu, Y.; Shamsi, M.H.; Krastev, D.L.; Dryden, M.D.M.; Leung, Y.; Wheeler, A.R. "A Microfluidic Method for Dopamine Uptake Measurements in Dopaminergic Neurons" Lab Chip 2016, 16, 543-552. Supporting info.
- Ng, A.H.C.; Chamberlain, M.D.; Situ, H.; Lee, V.; Wheeler, A.R. "Digital microfluidic immunocytochemistry in single cells" Nat. Commun., 2015, 6, 7513. Supplementary: Info, Movie 1, Movie 2, Movie 3, Movie 4.
- Au, S.H.; Chamberlain, M.D.; Mahesh, S.; Sefton, M.V.; Wheeler, A.R. "Hepatic organoids for microfluidic drug screening" Lab on a Chip, 2014, 14, 3290-3299. Supporting info.
- Shih, S.C.C.; Mufti, N.S.; Chamberlain, M.D.; Kim, J.; Wheeler, A.R. "A droplet-based screen for wavelength-dependent lipid production in algae" Energy & Environmental Science, 2014, 7, 2366-2375. Supporting info, Supporting video.
- Eydelnant, I.A.; Li, B.B.; Wheeler, A.R. "Microgels on-Demand" Nat. Commun. 2014, 5, 3355. Supplementary: Figures, Movie 1, Movie 2.
- Au, S.H.; Fobel, R.; Desai, S.P.; Voldman, J.; Wheeler, A.R. "Cellular bias on the microscale: probing the effects of digital microfluidic actuation on mammalian cell health, fitness and phenotype" Integr. Biol. 2013, 5, 1014. Supporting info.
- Shih, S.C.C.; Barbulovic-Nad, I.; Yang, X.; Fobel, R.; Wheeler, A.R. "Digital Microfluidics with Impedance Sensing for Integrated Cell Culture and Analysis" Biosens. Bioelectron. 2013, 42, 314–320. Supporting info
- Bogojevic, D.; Chamberlain, M.D.; Barbulovic-Nad, I.; Wheeler, A.R. "A Digital Microfluidic Method for Multiplexed Cell-Based Apoptosis Assays" Lab Chip 2012, 12, 627-634.
- Srigunapalan, S.; Eydelnant I.A.; Simmons, C.A.; Wheeler, A.R. "A Digital Microfluidic Platform for Primary Cell Culture and Analysis" Lab Chip 2012, 12, 369-375.
- Au, S.H.; Shih, S.C.C.; Wheeler, A.R. "Integrated Microbioreactor for Culture and Analysis of Bacteria, Algae and Yeast" Biomed. Microdev., 2011, 13, 41-50.
- Barbulovic-Nad, I.; Au, S.; Wheeler, A.R. "A Microfluidic Platform for Complete Mammalian Cell Culture" Lab Chip 2010, 10, 1536-1542. Supporting Info
- Barbulovic-Nad, I.; Yang, H.; Park, P.S.; Wheeler, A.R. "Digital Microfluidics for Cell-Based Assays" Lab Chip 2008, 8, 519-526.
Digital Microfluidics for Clinical Applications
Many applications in the clinical laboratory require the use of complex, heterogeneous samples such as ~mm-sized tissue sections or dried blood spots (DBSs) on filter paper. Digital microfluidics confers unique advantages for such applications, such as the capacity to work with meso-scale reagent volumes (nL – µL), and compatibility with solid samples (i.e., no chance of clogging). We have recently begun to exploit these properties to develop integrated “sample-to-answer” systems for clinical analysis. Papers in this area are listed below.
- Sathishkumar, N.; Valenzuela, J.G.C.; Le, N.H.; Yong, A.K.C.; Rossotti, M.A.; Dahmer, J.; Sklavounos, A.A.; Plante, M.; Brassard, D.; Malic, L.; Moraitis, A.N.; Biga, R.; Idrissi, I.E.; Tanha, J.; Labrecque, J.; Veres, T.; Wheeler, A.R. "A Combined Digital Microfluidic Test for Assessing Infection and Immunity Status for Viral Disease in Saliva" Lab Chip 2025, 25, 3197-3207. Supporting Info. Movie 1.
- Ho, M.; Sathishkumar, N.; Sklavounos, A.A.; Sun, J.; Yang, I.; Nichols, K.P.; Wheeler, A.R. "Digital Microfluidics with Distance-Based Detection – a New Approach for Nucleic Acid Diagnostics" Lab Chip 2024, 24, 63-73. Supporting Info.
- Knipes, A.K.; Summers, A.; Sklavounos, A.A.; Lamanna, J.; de Campos, R.P.S.; Narahari, T.; Dixon, C.; Fobel, R.; Ndjakani, Y.D.; Lubula, L.; Magazani, A.; Muyembe, J.J.; Lay, Y.; Pukuta, E.; Waku-Kouomou, D.; Hao, L.; Kayembe, J.K.; Fobel, C.; Dahmer, J.; Lee, A.; Ho, M.; Valenzuela, J.G.C.; Rackus, D.G.; Shih, R.; Seale, B.; Chang, A.; Paluku, G.; Rota, P.A.; Wheeler, A.R.; Scobie, H.M. "Use of a Rapid Digital Microfluidics-Powered Immunoassay for Assessing Measles and Rubella Infection and Immunity in Outbreak Settings in the Democratic Republic of the Congo" PLOS One, 2022, 17, e0278749. Supporting Info.
- Narahari, T.; Dahmer, J.; Sklavounos, A.; Kim, T.; Satkauskas, M.; Clotea, I.; Ho, M.; Lamanna, J.; Dixon, C.; Rackus, D.G.; Silva, S.J.R.d.; Pena, L.; Pardee, K.; Wheeler, A.R. "Portable Sample Processing for Molecular Assays: Application to Zika Virus Diagnostics" Lab Chip 2022, 22, 1748-1763. Supporting Info.
- Sklavounos, A.A.; Lamanna, J.; Modi, D.; Gupta, S.; Mariakakis, A.; Callum, J.; Wheeler, A.R. "Digital Microfluidic Hemagglutination Assays for Blood Typing, Donor Compatibility Testing, and Hematocrit Analysis" Clin. Chem. 2021, 67, 1699–1708. Supplementary: Info, Movie.
- Dixon, C.; Lamanna, J.; Wheeler, A.R. "Direct loading of blood for plasma separation and diagnostic assays on a digital microfluidic device" Lab on a Chip. 2020, 20, 1845-1855. Supplementary: Info, Movie.
- Ng, A.H.C.; Fobel, R.; Fobel, C.; Lamanna, J.; Rackus, D.G.; Summers, A.; Dixon, C.; Dryden, M.D.M.; Lam, C.; Ho, M.; Mufti, N.S.; Lee, V.; Asri, M.A.M.; Sykes, E.A.; Chamberlain, D.; Joseph, R.; Ope, M.; Scobie, H.M.; Knipes, A.; Rota, P.A.; Marano, N.; Chege, P.M.; Njuguna, M.; Nzunza, R.; Kisangau, N.; Kiogora, J.; Karuingi, M.; Burton, J.W.; Borus, P.; Lam, E.; Wheeler, A.R."A Digital Microfluidic System for Serological Immunoassays in Remote Settings" Sci. Trans. Med. 2018, 10, eaar6076. Supplementary Materials.
- Abdulwahab, S.; Ng, A.H.C.; Chamberlain, M.D.; Ahmado, H.; Behan, L.-A.; Gomaa, H.; Casper, R.F.; Wheeler, A.R. "Towards a Personalized Approach to Aromatase Inhibitor Therapy: A Digital Microfluidic Platform for Rapid Analysis of Estradiol in Core-Needle-Biopsies" Lab on a Chip, 2017, 17, 1594-1602.
- Ng, A.H.C.; Lee, M.; Choi, K.; Fischer, A.T.; Robinson, J.M.; Wheeler, A.R. "A Digital Microfluidic Platform for the Detection of Rubella Infection and Immunity: A Proof of Concept" Clin. Chem., 2015, 61, 420-429. Supporting info. Supporting video.
- Kim, J.; Abdulwahab, S.; Choi, K.; Lafreniere, N.M.; Mudrik, J.M.; Gomaa, H.; Ahmado, H.; Behan, L.-A.; Casper, R.F.; Wheeler, A.R. "A Microfluidic Technique for Quantification of Steroids in Core Needle Biopsies" Analytical Chemistry, 2015, 87, 4688-4695. Supporting info.
- Kirby, A.E.; Lafrenière, N.M.; Seale, B.; Hendricks, P.I.; Cooks, R.G.; Wheeler, A.R. "Analysis on the Go: Quantitation of Drugs of Abuse in Dried Urine with Digital Microfluidics and Miniature Mass Spectrometry" Analytical Chemistry, 2014, 86, 6121-6129. Supporting video.
- Lafrenière, N.M.; Shih, S.C.C.; Abu-Rabie, P.; Jebrail, M.J.; Spooner, N.; Wheeler, A.R. "Multiplexed extraction and quantitative analysis of pharmaceuticals from DBS samples using digital microfluidics" Bioanalysis 2014, 6, 307-318.
- Shih, S.C.C.; Yang, H.; Jebrail, M.J.; Fobel, R.; McIntosh, N.; Al-Dirbashi, O.Y.; Chakraborty, P.; Wheeler, A.R. "Dried Blood Spot Analysis by Digital Microfluidics Coupled to Nanoelectrospray Ionization Mass Spectrometry" Analytical Chemistry 2012, 84, 3731-3738.
- Jebrail, M.J.; Yang, H.; Mudrik, J.M.; Lafreniere, N.M.; McRoberts, C.; Al-Dirbashi, O.Y.; Fisher, L.; Chakraborty, P.; Wheeler, A.R. "A Digital Microfluidic Method for Dried Blood Spot Analysis" Lab on a Chip 2011, 11, 3218-3224. Supporting info.
- Mousa, N.A.; Jebrail, M.J.; Yang, H.; Abdegawad, M.; Metalnikov, P.; Chen, J.; Wheeler, A.R.; Casper, R.F. "Droplet-Scale Estrogen Assays in Breast Tissue, Blood, and Serum" Sci. Trans. Med., 2009, 1, 1ra2. Supporting Info
Digital Extraction Techniques
Most real-world chemical analysis applications begin with a complex sample that contains a mixture of many constituents (e.g., serum, pond water, cell lysate, etc.). Complex samples are often impossible to analyze without extraction (or "cleanup") to simplify the sample. Digital microfluidics is proving to be a powerful technology for extraction, which can include non-specific methods (e.g., reversed-phase solid extraction or liquid-liquid extraction) and specific methods (e.g., using immunospecificity to isolate desirable analytes). Papers describing our efforts in this area are listed below.
- Elsayed, M.; Bodo, L.; Gaoiran, C.; Keuhnelian, P.; Dosajh, A.; Luk, V.; Schwandt, M.; French, J.L.; Ghosh, A.; Erickson, B.; Charlesworth, A.G.; Millman, J.; Wheeler, A.R. "Toward Analysis at the Point of Need: A Digital Microfluidic Approach to Processing Multi-Source Sexual Assault Samples" Advanced Science 2024, 11, 2405712. Supporting Info. Movie.
- Rackus, D.G.; P. S. de Campos, R.; Chan, C.; Karcz, M.M.; Seale, B.; Narahari, T.; Dixon, C.; Chamberlain, M.D.; Wheeler, A.R. "Pre-Concentration by Liquid Intake by Paper (P-CLIP): A New Technique for Large Volumes and Digital Microfluidics" Lab on a Chip, 2017, 17, 2272-2280. Supporting info.
- Seale, B.; Lam, C.; Rackus, D.G.; Chamberlain, M.D.; Liu, C.; Wheeler, A.R. "Digital Microfluidics for Immunoprecipitation" Analytical Chemistry, 2016, 88, 10223-10230. Supporting info.
- Choi, K.; Boyacı, E.; Kim, J.; Seale, B.; Barrera-Arbelaez, L.; Pawliszyn, J.; Wheeler, A.R. "A Digital Microfluidic Interface between Solid-Phase Microextraction and Liquid Chromatography–Mass Spectrometry" J. Chromatogr. A, 2016, 1444, 1-7. Supporting info.
- Lafreniere, N.M.; Mudrik, J.M.; Ng, A.H.C.; Seale, B.; Spooner, N.; Wheeler, A.R. "Attractive Design: An Elution Solvent Optimization Platform for Magnetic-Bead-based Fractionation Using Digital Microfluidics and Design of Experiments" Analytical Chemistry, 2015, 87, 3902-3910.
- Ng, A.H.C.; Lee, M.; Choi, K.; Fischer, A.T.; Robinson, J.M.; Wheeler, A.R. "A Digital Microfluidic Platform for the Detection of Rubella Infection and Immunity: A Proof of Concept" Clin. Chem., 2015, 61, 420-429. Supporting info. Supporting video.
- Mei, N.; Seale, B.; Ng, A.H.C.; Wheeler, A.R.; Oleschuk, R. "Digital Microfluidic Platform for Human Plasma Protein Depletion" Analytical Chemistry, 2014, 86, 8466-8472. Supporting info. Supporting video.
- Mudrik, J.M.; Dryden, M.D.M.; Lafrenière, N.M.; Wheeler, A.R. "Strong and small: strong cation-exchange solid-phase extractions using porous polymer monoliths on a digital microfluidic platform" Canadian Journal of Chemistry 2014, 92, 179-185.
- Choi, K.; Ng, A.H.C.; Fobel, R.; Chang-Yen, D.A.; Yarnell, L.E.; Pearson, E.L.; Oleksak, C.M.; Fischer, A.T.; Luoma, R.P.; Robinson, J.M.; Audet, J.; Wheeler, A.R. "Automated Digital Microfluidic Platform for Magnetic-Particle-Based Immunoassays with Optimization by Design of Experiments" Analytical Chemistry 2013, 85, 9638-9646. Supporting info.
- Ng, A.H.C.; Choi, K.; Luoma, R.P.; Robinson, J.M.; Wheeler, A.R. "Digital Microfluidic Magnetic Separation for Particle-Based Immunoassays" Analytical Chemistry 2012, 84, 8805-8812. Supporting info.
- Yang, H.; Mudrik, J.M.; Jebrail, M.J.; Wheeler, A.R. "A Digital Microfluidic Method for in Situ Formation of Porous Polymer Monoliths with Application to Solid-Phase Extraction" Anal. Chem. 2011, 83, 3824-3830.
- Miller, E.M.; Ng, A.H.C.; Uddayasankar, U.; Wheeler, A.R. "A Digital Microfluidic Approach to Heterogeneous Immunoassays" Anal. Bioanal. Chem., 2010, 399, 337-345.
- Jebrail, M.; Wheeler, A.R. "A Digital Microfluidic Method for Protein Extraction by Precipitation" Anal. Chem. 2009, 81, 330-335.
Digital Chemical Reactors
Chemists have long been interested in miniaturizing chemical reactions to take advantage of favorable scaling of diffusion and heat exchange. Most efforts to miniaturize chemical reactions have relied on networks of enclosed microchannels. Such systems are not an ideal match for this application because of clogging of solid reagents and precipitates, complex plumbing issues, and material incompatibilities. Digital microfluidics represents a potential solution to these problems. We are working to develop digital liquid reactors for a variety of applications including multiplexed chemical synthesis and enzyme assays. Papers describing these efforts are listed below.
- Chan, C.; Peng, J.; Rajesh, V.; Scott, E.Y.; Sklavounos, A.A.; Faiz, M.; Wheeler, A.R. "Digital Microfluidics for Microproteomic Analysis of Minute Mammalian Tissue Samples Enabled by Photocleavable Surfactant" J. Prot. Res. 2023, 22, 3242-3253. Supporting Info, Supporting Figures, Movie.
- Peng, J.; Chan, C.; Zhang, S.; Sklavounos, A.A.; Olson, M.E.; Scott, E.Y.; Hu, Y.; Rajesh, V.; Li, B.B.; Chamberlain, M.D.; Zhang, S.; Peng, H.; Wheeler, A.R. "All-in-One Digital Microfluidcs Pipeline for Proteomic Sample Preparation and Analysis" Chemical Science 2023, 14, 2887 - 2900. Supporting Info 1, Supporting Info 2, Movie.
- Wu, B.; von der Ecken, S.; Swyer, I.; Li, C.; Jenne, A.; Vincent, F.; Schmidig, D.; Kuehn, T.; Beck, A.; Busse, F.; Stronks, H.; Soong, R.; Wheeler, A.R.; Simpson, A. "Rapid Chemical Reaction Monitoring by Digital Microfluidics-NMR: Proof of Principle Towards an Automated Synthetic Discovery Platform" Angew. Chem. Int. Ed. 2019, 58, 15372-15376. Supporting Info.
- Swyer, I.; Ecken, S.v.d.; W, B.; Jenne, A.; Soong, R.; Vincent, F.; Schmidig, D.; Frei, T.; Busse, F.; Stronks, H.J.; Simpson, A.J.; Wheeler, A.R. "Digital Microfluidics and Nuclear Magnetic Resonance Spectroscopy for in situ Diffusion Measurements and Reaction Monitoring" Lab Chip 2019, 19, 641-653. Supporting info.
- Swyer, I.; Soong, R.; Dryden, M.D.M.; Fey, M.; Maas, W.E.; Simpson, A.; Wheeler, A.R. "Interfacing Digital Microfluidics with High-Field Nuclear Magnetic Resonance Spectroscopy" Lab on a Chip, 2016, 16, 4424-4435. Supporting info.
- Kirby, A.E.; Wheeler, A.R. "Microfluidic Origami: A New Device Format for In-Line Reaction Monitoring by Nanoelectrospray Ionization Mass Spectrometry" Lab on a Chip 2013, 13, 2533-2540.
- Jebrail, M.J.; Assem, N.; Mudrik, J.M.; Dryden, M.D.M.; Lin, K.; Yudin, A.K.; Wheeler, A.R. "Combinatorial Synthesis of Peptidomimetics Using Digital Microfluidics" Journal of Flow Chemistry 2012, 2, 103-107.
- Jebrail, M.J.; Ng, A.H.C.; Rai, V.; Hili, R.; Yudin, A.K.; Wheeler, A.R. "Synchonized Synthesis of Peptide-Based Macrocycles by Digital Microfluidics" Angew. Chemie. Int. Ed., 2010, 49, 8625-8629. Supporting Info
- Luk, V.N.; Wheeler, A.R. "A Digital Microfluidic Approach to Proteomic Sample Processing" Anal. Chem. 2009, 81, 4524–4530.
- Miller, E.M.; Wheeler, A.R. "A Digital Microfluidic Approach to Homogeneous Enzyme Assays" Anal. Chem. 2008, 80, 1614-1619.