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The fusion of microfluidic technologies (digital microfluidics, continuous-flow microfluidics, and droplet microfluidics, just to name a few) presents great potential for overcoming the inherent limitations of each approach, while also elevating their respective strengths. This work exploits the combination of digital microfluidics (DMF) and droplet microfluidics (DrMF) on a single substrate, where DMF enables droplet mixing and further acts as a controlled liquid supplier for a high-throughput nano-liter droplet generator. Droplet generation is performed at a flow-focusing region, operating on dual pressure: negative pressure applied to the aqueous phase and positive pressure applied to the oil phase. We evaluate the droplets produced with our hybrid DMF\u2013DrMF devices in terms of droplet volume, speed, and production frequency and further compare them with standalone DrMF devices. Both types of devices enable customizable droplet production (various volumes and circulation speeds), yet hybrid DMF\u2013DrMF devices yield more controlled droplet production while achieving throughputs that are similar to standalone DrMF devices. These hybrid devices enable the production of up to four droplets per second, which reach a maximum circulation speed close to 1540 \u00b5m\/s and volumes as low as 0.5 nL.<\/jats:p>","DOI":"10.3390\/s23104927","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T02:00:27Z","timestamp":1684720827000},"page":"4927","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Hybrid Digital-Droplet Microfluidic Chip for Applications in Droplet Digital Nucleic Acid Amplification: Design, Fabrication and Characterization"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3359-3773","authenticated-orcid":false,"given":"Beatriz","family":"Coelho","sequence":"first","affiliation":[{"name":"CENIMAT|i3N, Department of Materials Science, NOVA School of Science and Technology, Campus de Caparica, NOVA University of Lisbon and CEMOP\/UNINOVA, 2829-516 Caparica, Portugal"},{"name":"UCIBIO, I4HB, Department of Life Sciences, NOVA School of Science and Technology, Campus de Caparica, NOVA University of Lisbon, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7237-8916","authenticated-orcid":false,"given":"Joana","family":"Neto","sequence":"additional","affiliation":[{"name":"CENIMAT|i3N, Department of Materials Science, NOVA School of Science and Technology, Campus de Caparica, NOVA University of Lisbon and CEMOP\/UNINOVA, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0809-6150","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Sieira","sequence":"additional","affiliation":[{"name":"CENIMAT|i3N, Department of Materials Science, NOVA School of Science and Technology, Campus de Caparica, NOVA University of Lisbon and CEMOP\/UNINOVA, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4090-9329","authenticated-orcid":false,"given":"Andr\u00e9","family":"Moura","sequence":"additional","affiliation":[{"name":"CENIMAT|i3N, Department of Materials Science, NOVA School of Science and Technology, Campus de Caparica, NOVA University of Lisbon and CEMOP\/UNINOVA, 2829-516 Caparica, Portugal"}]},{"given":"Elvira","family":"Fortunato","sequence":"additional","affiliation":[{"name":"CENIMAT|i3N, Department of Materials Science, NOVA School of Science and Technology, Campus de Caparica, NOVA University of Lisbon and CEMOP\/UNINOVA, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1997-7669","authenticated-orcid":false,"given":"Rodrigo","family":"Martins","sequence":"additional","affiliation":[{"name":"CENIMAT|i3N, Department of Materials Science, NOVA School of Science and Technology, Campus de Caparica, NOVA University of Lisbon and CEMOP\/UNINOVA, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5255-7095","authenticated-orcid":false,"given":"Pedro","family":"Baptista","sequence":"additional","affiliation":[{"name":"UCIBIO, I4HB, Department of Life Sciences, NOVA School of Science and Technology, Campus de Caparica, NOVA University of Lisbon, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6608-3422","authenticated-orcid":false,"given":"Rui","family":"Igreja","sequence":"additional","affiliation":[{"name":"CENIMAT|i3N, Department of Materials Science, NOVA School of Science and Technology, Campus de Caparica, NOVA University of Lisbon and CEMOP\/UNINOVA, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7350-649X","authenticated-orcid":false,"given":"Hugo","family":"\u00c1guas","sequence":"additional","affiliation":[{"name":"CENIMAT|i3N, Department of Materials Science, NOVA School of Science and Technology, Campus de Caparica, NOVA University of Lisbon and CEMOP\/UNINOVA, 2829-516 Caparica, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30011","DOI":"10.3390\/s151229783","article-title":"Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications","volume":"15","author":"Luka","year":"2015","journal-title":"Sensors"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102208","DOI":"10.1016\/j.cis.2020.102208","article-title":"Multiphase Flow in Microfluidics: From Droplets and Bubbles to the Encapsulated Structures","volume":"282","author":"Sattari","year":"2020","journal-title":"Adv. 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