Choi K.; Boyaci 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. Journ. of Chromatog. A. 2016, 1444 , 1-7. 10.1016/j.chroma.2016.03.029

Choi et al. (2018) successfully introduced a method to couple solid-phase microextraction (SPME) with HPLC-MS using digital microfluidics (DMF). This method was applied to the quantification of pg/mL-level free steroid hormones in urine.

De Campos R.P.S.; Rackus D.G.; Shih R.; Zhao C.; Liu X.; Wheeler A.R. "plug-n-Play" Sensing with Digital Microfluidics. Anal. Chem. 2019, 91 (3), 2506-2515. 10.1021/acs.analchem.8b05375

De Campos et al. (2019) introduced a solution to the "flexibility gap" between fluidic operations in digital microfluidics and embedded sensors: "plug-n-play DMF" (PnP-DMF). Proof of concept:PnP-DMF using commercial biosensors for glucose and β-ketone, a custom paperbased electrochemical sensor for lactate, and a generic screen-printed electroanalytical cell.

Rackus D.G.; De Campos R.P.S.; 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 Chip. 2017, 17 (13), 2272-2280. 10.1039/c7lc00440k

Rackus et al. (2017) describe a new technique termed pre-concentration by liquid intake by paper (P-CLIP) that addresses this mismatch, allowing digital microfluidics to interface with volumes on the order of hundreds of microliters. They successfully demonstrated its utility with a magnetic bead-based immunoassay of a malaria biomarker.

Swyer I.; Von der Ecken S.; Wu 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 (4), 641-653. 10.1039/C8LC01214H

Swyer et al. (2019) introduced a two-plate DMF strategy used to interface small-volume samples (<5 uL) with NMR microcoils, allowing for the determination of reaction-product diffusion coefficients as well as quantitative monitoring of reactive intermediates.

Alias A.B.; Huang H.-Y.; Wang Y.-W.; Lin K.-T.; Lu P.-J.; Wu T.-H.; Jiang P.-S.; Chen C.-A.; Yao D.-J. DNA Sequencing from Subcritical Concentration of Cell-Free DNA Extracted from Electrowetting-on-Dielectric Platform. Micromachines. 2022, 13 (4). 10.3390/mi13040507

Alias et al. (2022) used DMF for extracting femtogram quantities of cell-free DNA (cf-DNA) form 1 uL of KSOM mouse embryo culture medium using the DropBot platform. This will pave a new path towards the lab-on-a-chip (LOC) concept.

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. Nat. Comms. 2020, 11 (1). 10.1038/s41467-020-19394-5

Lamanna et al. (2020) introduced DMF Isolation of Single Cells for -Omics (DISCO), which combines DMF, laser cell lysis, and AI-driven image processing to collect the contents of single cells from heterogeneous populations. The results confirm the utility of DISCO for sequencing at levels that are equivalent to or enhanved relative to the state of the art.

Leipert J.; Tholey A. Miniaturized sample preparation on a digital microfluidics device for sensitive bottom-up microproteomics of mammalian cells using magnetic beads and mass spectrometry-compatible surfactants. Lab Chip.2019, 19 (20), 3490-3498. 10.1039/c9lc00715f

Leipert & Tholey (2019) developed protocols for bottom-up LC-MS based proteomics sample preparation for as little as 100 mammalian cells on a DMF device to overcome previously unfeasible proteome analysis of samples prepared on-chip. This demostrated the first sample preparation workflow for proteomics on a DMF chip, allowing the sensitive analysis of limited biological material.

Li B.B.; Scott E.Y.; Dean Chamberlain M.; Duong B.T.V.; Zhang S.; Done S.J.; Wheeler A.R. Cell invasion in digital microfluidic microgel systems. Sci. Adv. 2020, 6 (29). 10.1126/sciadv.aba9589

Li et al. (2020) introduced the Cell Invasion in Digital Microfluidic Microgel Systems (CIMMS) with a breast cancer model, which bridges the gap between microfluidic methods in which cells invade into free space and those in which cells invade into hydrogels.

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 (2), 313-325. 10.1039/d1lc00854d

Li, Scott, Olafsen, Matthews & Wheeler (2022) used a 3D invasion assay called cell invasion in digital microfluidic microgel systems (CIMMS) to perform cell culture and staining for studying the effect of AHR expression on invasion.

Liu Y.; Jeraldo P.; Mendes-Soares H.; Masters T.; Asangba A.E.; Nelson H.; Patel R.; Chia N.; Walther-Antonio M. Amplification of Femtograms of Bacterial DNA within 3 h Using a Digital Microfluidics Platform for MinION Sequencing. ACS Omega. 2021, 6 (39), 25642-25651. 10.1021/acsomega.1c03683

Liu et al. (2021) developed a DMF system for rapid whole genome amplification using as low as 10 fg of C. glutamicum DNA within 2 h and to identify the target bacterium within 30 min for rapid MinION sequencing. This approach can be used to identify microbes with minute amounts of genetic material in samples depleted of human cells within 3 h.

Sathyanarayanan G.; Haapala M.; Kiiski I.; Sikanen T. Digital microfluidic immobilized cytochrome P450 reactors with integrated inkjet-printed microheaters for droplet-based drug metabolism research. Anal. and Bioanal. Chem. 2018, 410 (25), 6677-6687. 10.1007/s00216-018-1280-7

Sathyanarayanan, Haapala, Kiiski & Sikanen (2018) developed and characterized DMF immobilized enzyme reactors (IMERs) for studying cytochrome P450-mediated drug metabolism in vitro on the droplet scale. The DMF devices also incorporated inexpensive microheaters for on-demand regio-specific heating of the IMERs, combined with a commercial well-plate reader for fluorescense quantification.

Yu Y.; de Campos R.P.S.; Hong S.; Krastev D.L.; Sadanand S.; Leung Y.; Wheeler A.R. A microfluidic platform for continuous monitoring of dopamine homeostasis in dopaminergic cells. Micro. and Nanoeng. 2019, 5 (1). 10.1038/s41378-019-0049-2

Yu et al. (2019) introduced an integrated microfluidic system for real-time evaluation of dopamine homeostatis in vitro and examined behavior of differentiated cells upon exposure to four dopamine transporter anti-agoists to study their pharmacokinetics. They propose this platform should be adaptable for any application that could benefit from high-temporal resolution electroanalysis combined with multi-day cell culture using small numbers of cells.

Abdulwahab S.; Ng A.H.C.; Dean Chamberlain M.; 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 Chip. 2017, 17 (9), 1594-1602. 10.1039/c7lc00170c

Abdulwahab et al. (2017) developed a novel technique powered by DMF that integrated tissue-liquid extraction and magnetic bead-based competitive immunoassay for quantification of estradiol in mg-sized core needle biopsy (CNB) tissue samples, wit a turnaround of ~40 mins.

Dixon C.; Lamanna J.; Wheeler A.R. Direct loading of blood for plasma separation and diagnostic assays on a digital microfluidic device. Lab Chip.2020, 20 (10), 1845-1855. 10.1039/d0lc00302f

Dixon, Lamanna & Wheeler (2020) used DMF to succesfully perform a blood-plasma separation with from a finger-stick blood sample and demonstrated a 21-step rubella viruse IgG immunoassay.

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 M.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. Transl. Med. 2018, 10 (438). 10.1126/scitranslmed.aar6076

Ng et al. (2018) developed a compact and portable, field-deployable, point-of-care DMF system using inexpensive inkjet-printed DMF chips that can rapidly perform magnetic-bead based ELISA immunoassays on a small volume of capillary blood for disease-specific antibodies.

Sathyanarayanan G.; Haapala M.; Sikanen T. Digital Microfluidics-Enabled Analysis of Individual Variation in Liver Cytochrome P450 Activity. Anal. Chem. 2020, 92 (21), 14693-14701. 10.1021/acs.analchem.0c03258

Sathyanarayanan, Haapala & Sikanen (2020) used DMF for rapid determination of individual alterations in hepatic cytochrom P450 (CYP) enzyme activity from human-derived liver samples. They successfully interface the DMF chip with a standard well-plate reader for fluorescent imaging, as well as integrated heating with DMF.

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 (12), 1699-1708. 10.1093/clinchem/hvab180

Sklavounos et al. (2021) developed DMF hemagglutination assays for blood typing, donor compatibility testing and hematocrit analysis , paired with a unique automated readout tool. A non-DMF-expert at a hospital trauma centre was able to successfully perform the assays.

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 (21), 4208-4222. 10.1039/d1lc00609f

Sklavounos, Nemr, Kelley & Wheeler (2021) used DMF, paired with a heating module and a machine-learning-enabled low-cost colour camera for real-time absorbance and fluorescent sample monitoring to perform automated and simultaneous bacterial classification (BC) and antibiotic susceptibility testing (AS).

Wondimu S.F.; Von Der Ecken S.; Ahrens R.; Freude W.; Guber A.E.; Koos C. Integration of digital microfluidics with whispering-gallery mode sensors for label-free detection of biomolecules. Lab Chip. 2017, 17 (10), 1740-1748. 10.1039/c6lc01556e

Wondimu et al. (2017) presented a novel multi-sensor chip comprising an array of whispering-gallery mode (WGM) micro-goblet lasers integrated into a digital microfluidic (DMF) system for label-free detection of clinical biomarkers.

Zhang Y.; Liu Y. A Digital Microfluidic Device Integrated with Electrochemical Impedance Spectroscopy for Cell-Based Immunoassay. Biosensors. 2022, 12 (50). 10.3390/bios12050330

Zhang & Liu (2022) paired an electrochemical impedence spectroscope (EIS)-based biosensor in a DMF device to quantitate human peripheral blood mononuclear cell (PBMC), which indicates a patent's immune function to various diseases and therapies.

Lu Z.; Li Y.; Qiu W.; Rogach A.L.; Nagl S. Composite Films of CsPbBr3 Perovskite Nanocrystals in a Hydrophobic Fluoropolymer for Temperature Imaging in Digital Microfluidics. ACS App. Mat. and Interfaces. 2020, 12 (17), 19805-19812. 10.1021/acsami.0c02128

Lu, Li, Qiu, Rogach & Nagl (2020) sucessfully monitored local temperatures when CsPbBr3 nanocrystal-Hyflon films immersed in aqueous solutions were incorporated into a DMF platform for high resolution thermal mapping, analyzing temperature distribution on chips.

Sathyanarayanan G.; Haapala M.; Dixon C.; Wheeler A.R.; Sikanen T.M. A Digital-to-Channel Microfluidic Interface via Inkjet Printing of Silver and UV Curing of Thiol–Enes. Adv. Mat. Tech. 2020, 5 (10). 10.1002/admt.202000451

Sathyanarayanan G. et al. demonstrated integration of DMF with in-channel separation systems using only low-cost and accessible (non-cleanroom) manufacturing techniques compatible with our DropBot.

Swyer I.; Fobel R.; Wheeler A.R. Velocity Saturation in Digital Microfluidics. Langmuir. 2019, 35 (15), 5342-5352. 10.1021/acs.langmuir.9b00220

Swyer, Fobel, & Wheeler (2019) used force-velocity plots to characterize droplet movement in DMF, which was found to be consistent with a simple theoretical framework for understanding dissipation effects for droplets in two-plate, air-filled devices.

von der Ecken S.; Sklavounos A.A.; Wheeler A.R. Vertical Addressing of 1-Plane Electrodes for Digital Microfluidics. Adv. Mat. Tech. 2022, 7 (7). 10.1002/admt.202101251

von der Ecken, S et al. developed a new method to produce DMF devices using vertical addressing of 1-plane electrodes (VAPE-DMF) to allow higher throughput compared to our standard chip designs. Their proof-of-concept device with an array of 336 electrodes to handle 48 droplets to run 24 reactions in parallel.