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.

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 SerumSci. Trans. Med., 2009, 1, 1ra2. Supporting Info