84
5 Gone with the Flow: Miniaturization and Safer Chemistry
in complex chemical synthesis. Reactors composed of multiple compartments can
be assembled into small machines with complete automation, integrating ultrasonic
transducers in critical points to prevent solid formation and ensuring kinetic control.
Ultrasound can be used with several parameters (frequency, acoustic pressure) that
allow the fine-tuning of many physico-chemical effects (radical production, sonoluminescence). With the right knowledge, it is possible to discriminate when only
mechanical or chemical effects are desired, and similarly, into motion-inducing or
static. While this is going to enable us to standardize numerous protocols in synthesis and processing, other applications of acoustofluidics have also shown enormous
versatility in particle separation, cell disruption or crystallization to name a few. In
a reference to this chapter’s title, we expect that the times where microfluidics and
ultrasound were overlooked are now gone. We also hope that its combination will be
a step forward towards a digitized, safer and greener chemistry.
References
Aljbour S, Yamada H, Tagawa T (2009) Ultrasound-assisted phase-transfer catalysis in a capillary
microreactor. Chem Eng Process 48:1167–1172
Banaszak-Léonard E, Mangin F, Len C (2016) Barton decarboxylation under ultrasonic continuous
flow. New J Chem 40:7414–7420
Bolaños-Jiménez R, Rossi M, Fernandez Rivas D, Kähler CJ, Marin A (2017) Streaming flow
by oscillating bubbles: quantitative diagnostics via particle tracking velocimetry. J Fluid Mech
820:529–548
Britton J, Jamison TF (2017) The assembly and use of continuous flow systems for chemical
synthesis. Nat Protoc 12:2423–2446
Britton J, Raston CL (2017) Multi-step continuous flow synthesis. Chem Soc Rev 46:1250–1271
Bruggeman PJ, Kushner MJ, Locke BR, Gardeniers JGE, Graham WG, Graves DB et al (2016)
Plasma-liquid interactions: a review and roadmap. Plasma Sources Sci Technol 25:053002 (1–59)
Bruus H (2012) Acoustofluidics 10: scaling lows in acoustophoresis. Lab Chip 12:1578–1586
Calcio Gaudino E, Carnaroglio D, Boffa L, Cravotto G, Moreira EM, Nunes MAG, Dressler VL,
Flores EMM (2014) Efficient H 2 O 2 /CH 3 COOH oxidative desulfurization/denitrification of liquid
fuels in sonochemical flow-reactors. Ultrason Sonochem 21:283–288
Cantillo D, Damm M, Dallinger D, Bauser M, Berger M, Kappe CO (2014) Sequential nitration/hydrogenation protocol for the synthesis of triaminophloroglucinol: safe generation and
use of an explosive intermediate under continuous-flow conditions. Org Process Res Dev
18:1360–1366
Castro F, Kuhn S, Jensen KF, Ferreira A, Rocha F, Vicente A, Teixeira JA (2013) Continuous-flow
precipitation of hydroxyapatite in ultrasonic microsystems. Chem Eng J 215–216:979–987
Chatel G (2017) Sonochemistry. New opportunities for green chemistry. World Scientific Publishing,
London, Chap. 4, pp 51–57, Chap. 6, p 151
Cintas P, Mantegna S, Calcio Gaudino E, Cravotto G (2010) A new pilot flow reactor for highintensity ultrasound irradiation. Application to the synthesis of biodiesel. Ultrason Sonochem
17:985–989
Elvira KSI, Solvas XC, Wooton RCR, Demello AJ (2013) The past, present and potential for
microfluidic reactor technology in chemical synthesis. Nat Chem 5:905–915
Fernandez Rivas D, Kuhn S (2016) Synergy of microfluidics and ultrasound. Process intensification,
challenges and opportunities. Top Curr Chem 374:70 (1–30)
5 Gone with the Flow: Miniaturization and Safer Chemistry
in complex chemical synthesis. Reactors composed of multiple compartments can
be assembled into small machines with complete automation, integrating ultrasonic
transducers in critical points to prevent solid formation and ensuring kinetic control.
Ultrasound can be used with several parameters (frequency, acoustic pressure) that
allow the fine-tuning of many physico-chemical effects (radical production, sonoluminescence). With the right knowledge, it is possible to discriminate when only
mechanical or chemical effects are desired, and similarly, into motion-inducing or
static. While this is going to enable us to standardize numerous protocols in synthesis and processing, other applications of acoustofluidics have also shown enormous
versatility in particle separation, cell disruption or crystallization to name a few. In
a reference to this chapter’s title, we expect that the times where microfluidics and
ultrasound were overlooked are now gone. We also hope that its combination will be
a step forward towards a digitized, safer and greener chemistry.
References
Aljbour S, Yamada H, Tagawa T (2009) Ultrasound-assisted phase-transfer catalysis in a capillary
microreactor. Chem Eng Process 48:1167–1172
Banaszak-Léonard E, Mangin F, Len C (2016) Barton decarboxylation under ultrasonic continuous
flow. New J Chem 40:7414–7420
Bolaños-Jiménez R, Rossi M, Fernandez Rivas D, Kähler CJ, Marin A (2017) Streaming flow
by oscillating bubbles: quantitative diagnostics via particle tracking velocimetry. J Fluid Mech
820:529–548
Britton J, Jamison TF (2017) The assembly and use of continuous flow systems for chemical
synthesis. Nat Protoc 12:2423–2446
Britton J, Raston CL (2017) Multi-step continuous flow synthesis. Chem Soc Rev 46:1250–1271
Bruggeman PJ, Kushner MJ, Locke BR, Gardeniers JGE, Graham WG, Graves DB et al (2016)
Plasma-liquid interactions: a review and roadmap. Plasma Sources Sci Technol 25:053002 (1–59)
Bruus H (2012) Acoustofluidics 10: scaling lows in acoustophoresis. Lab Chip 12:1578–1586
Calcio Gaudino E, Carnaroglio D, Boffa L, Cravotto G, Moreira EM, Nunes MAG, Dressler VL,
Flores EMM (2014) Efficient H 2 O 2 /CH 3 COOH oxidative desulfurization/denitrification of liquid
fuels in sonochemical flow-reactors. Ultrason Sonochem 21:283–288
Cantillo D, Damm M, Dallinger D, Bauser M, Berger M, Kappe CO (2014) Sequential nitration/hydrogenation protocol for the synthesis of triaminophloroglucinol: safe generation and
use of an explosive intermediate under continuous-flow conditions. Org Process Res Dev
18:1360–1366
Castro F, Kuhn S, Jensen KF, Ferreira A, Rocha F, Vicente A, Teixeira JA (2013) Continuous-flow
precipitation of hydroxyapatite in ultrasonic microsystems. Chem Eng J 215–216:979–987
Chatel G (2017) Sonochemistry. New opportunities for green chemistry. World Scientific Publishing,
London, Chap. 4, pp 51–57, Chap. 6, p 151
Cintas P, Mantegna S, Calcio Gaudino E, Cravotto G (2010) A new pilot flow reactor for highintensity ultrasound irradiation. Application to the synthesis of biodiesel. Ultrason Sonochem
17:985–989
Elvira KSI, Solvas XC, Wooton RCR, Demello AJ (2013) The past, present and potential for
microfluidic reactor technology in chemical synthesis. Nat Chem 5:905–915
Fernandez Rivas D, Kuhn S (2016) Synergy of microfluidics and ultrasound. Process intensification,
challenges and opportunities. Top Curr Chem 374:70 (1–30)