Active Micropump-Mixer for Rapid Antiplatelet Drug Screening in Whole Blood

Szydzik, Crispin; Brazilek, Rose J.; Akbaridoust, Farzan; Silva, Charitha de; Moon, Mitchell J.; Marušić, Ivan; Ooi, Andrew; Nandurkar, Harshal; Hamilton, Justin Raymond; Mitchell, Arnan; Nesbitt, Warwick Scott

doi:10.1021/acs.analchem.9b02486

Cited by 9 publications

(8 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These miniaturized microdevices are in sub-millimeter dimension ( Chiu et al, 2017 ), which only require a small volume of blood sample in the scale of microliters ( Convery and Gadegaard, 2019 ) to render reliable results. More recently, the integrated microfluidics with micro-pumps and mixers enable high-throughput, automated disease and drug screening in much shorter turnaround time ( Mayr and Bojanic, 2009 ; Szydzik et al, 2019 ).…”

Section: Novel Microfluidic Approaches For Platelet Function Assessment and Anti-platelet Drug Screeningmentioning

confidence: 99%

“…(F) A chaotic mixer from Berry et al (2021) ; Top: Schematic of the chaotic mixer; Bottom: Confocal images of platelets (and leukocytes) and fibrin in EDTA-quenched channel (left) and the eptifibatide channel (right). (G) An active micropump mixer with micropump valve chambers and pneumatic actuation chambers from Szydzik et al (2019) . (H) Droplet microfluidics from Jongen et al (2020) ; Top: Schematic of the droplet generator design.…”

Section: Novel Microfluidic Approaches For Platelet Function Assessment and Anti-platelet Drug Screeningmentioning

confidence: 99%

See 1 more Smart Citation

Platelet Mechanobiology Inspired Microdevices: From Hematological Function Tests to Disease and Drug Screening

et al. 2022

View full text Add to dashboard Cite

Platelet function tests are essential to profile platelet dysfunction and dysregulation in hemostasis and thrombosis. Clinically they provide critical guidance to the patient management and therapeutic evaluation. Recently, the biomechanical effects induced by hemodynamic and contractile forces on platelet functions attracted increasing attention. Unfortunately, the existing platelet function tests on the market do not sufficiently incorporate the topical platelet mechanobiology at play. Besides, they are often expensive and bulky systems that require large sample volumes and long processing time. To this end, numerous novel microfluidic technologies emerge to mimic vascular anatomies, incorporate hemodynamic parameters and recapitulate platelet mechanobiology. These miniaturized and cost-efficient microfluidic devices shed light on high-throughput, rapid and scalable platelet function testing, hematological disorder profiling and antiplatelet drug screening. Moreover, the existing antiplatelet drugs often have suboptimal efficacy while incurring several adverse bleeding side effects on certain individuals. Encouraged by a few microfluidic systems that are successfully commercialized and applied to clinical practices, the microfluidics that incorporate platelet mechanobiology hold great potential as handy, efficient, and inexpensive point-of-care tools for patient monitoring and therapeutic evaluation. Hereby, we first summarize the conventional and commercially available platelet function tests. Then we highlight the recent advances of platelet mechanobiology inspired microfluidic technologies. Last but not least, we discuss their future potential of microfluidics as point-of-care tools for platelet function test and antiplatelet drug screening.

show abstract

Section: Novel Microfluidic Approaches For Platelet Function Assessment and Anti-platelet Drug Screeningmentioning

confidence: 99%

Section: Novel Microfluidic Approaches For Platelet Function Assessment and Anti-platelet Drug Screeningmentioning

confidence: 99%

Platelet Mechanobiology Inspired Microdevices: From Hematological Function Tests to Disease and Drug Screening

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Furthermore, single-layered microfluidics can emulate more complex vessel structures, such as bifurcation ( 39 ), 2D stenosis ( 46 ), network ( 47 ), and micropost array ( 40 ) to recapitulate flow disturbance induced platelet activation, adhesion, contraction and aggregation ( 48 , 49 ). The mechanical stimuli investigated include elevated shear stress ( 50 , 51 ), shear rate gradient ( 52 – 54 ), vorticity ( 7 ) and turbulence ( 8 , 55 ) at different locations of the microchannel. Moreover, lining the microchannel with endothelial cells enables the investigation of prothrombotic synergistic effects of hemodynamic forces, blood cells and the vessel wall ( 56 , 57 ).…”

Section: Microfluidic Approaches For Investigating Platelet Mechanobiology and Platelet–circulatory System Interplaymentioning

confidence: 99%

“…The composite microsystems can support tissue coculture and the channel-channel interface, thereby enabling studies of bidirectional tissue signaling across the endothelial barrier ( 61 ). More importantly, external mechanical manipulation apparatus (e.g., stiff ECM matrices, actuation chambers) can be integrated for disease-specific studies and rapid drug screening ( 55 , 69 ). Although multiple-layered microfluidics incur higher fabrication requirements including precise alignment and assembly, they present physiologically relevant hemodynamic microenvironments for better biomimetic performance.…”

Section: Microfluidic Approaches For Investigating Platelet Mechanobiology and Platelet–circulatory System Interplaymentioning

confidence: 99%

Emerging Microfluidic Approaches for Platelet Mechanobiology and Interplay With Circulatory Systems

Zhang

Ramasundara

Preketes-Tardiani

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Understanding how platelets can sense and respond to hemodynamic forces in disturbed blood flow and complexed vasculature is crucial to the development of more effective and safer antithrombotic therapeutics. By incorporating diverse structural and functional designs, microfluidic technologies have emerged to mimic microvascular anatomies and hemodynamic microenvironments, which open the floodgates for fascinating platelet mechanobiology investigations. The latest endothelialized microfluidics can even recapitulate the crosstalk between platelets and the circulatory system, including the vessel walls and plasma proteins such as von Willebrand factor. Hereby, we highlight these exciting microfluidic applications to platelet mechanobiology and platelet–circulatory system interplay as implicated in thrombosis. Last but not least, we discuss the need for microfluidic standardization and summarize the commercially available microfluidic platforms for researchers to obtain reproducible and consistent results in the field.

show abstract

“…204,205 While numerous on-chip blood actuation methods are outlined in the literature, generally very little consideration is given to material hemocompatibility, or functional effects of the manipulation mechanisms regarding operational hemocompatibility, factors that may severely hamper application of on-chip blood handling systems. Recent advances in hemocompatible on-chip microfluidic control components including on-chip valves 206 and pumps 207 have been developed with a focus on operational hemocompatibility, and may pave the way to more complex and high throughput on-chip blood manipulation platforms.…”

Section: Microfluidic Technologies For On-chip Blood Manipulationmentioning

confidence: 99%

A Review of Design Considerations for Hemocompatibility within Microfluidic Systems

Szydzik

Brazilek

Nesbitt

2020

Semin Thromb Hemost

Self Cite

View full text Add to dashboard Cite

The manipulation of blood within in vitro environments presents a persistent challenge, due to the highly reactive nature of blood, and its multifaceted response to material contact, changes in environmental conditions, and stimulation during handling. Microfluidic Lab-on-Chip systems offer the promise of robust point-of-care diagnostic tools and sophisticated research platforms. The capacity for precise control of environmental and experimental conditions afforded by microfluidic technologies presents unique opportunities that are particularly relevant to research and clinical applications requiring the controlled manipulation of blood. A critical bottleneck impeding the translation of existing Lab-on-Chip technology from laboratory bench to the clinic is the ability to reliably handle relatively small blood samples without negatively impacting blood composition or function. This review explores design considerations critical to the development of microfluidic systems intended for use with whole blood from an engineering perspective. Material hemocompatibility is briefly explored, encompassing common microfluidic device materials, as well as surface modification strategies intended to improve hemocompatibility. Operational hemocompatibility, including shear-induced effects, temperature dependence, and gas interactions are explored, microfluidic sample preparation methodologies are introduced, as well as current techniques for on-chip manipulation of the whole blood. Finally, methods of assessing hemocompatibility are briefly introduced, with an emphasis on primary hemostasis and platelet function.

show abstract

Active Micropump-Mixer for Rapid Antiplatelet Drug Screening in Whole Blood

Cited by 9 publications

References 50 publications

Platelet Mechanobiology Inspired Microdevices: From Hematological Function Tests to Disease and Drug Screening

Platelet Mechanobiology Inspired Microdevices: From Hematological Function Tests to Disease and Drug Screening

Emerging Microfluidic Approaches for Platelet Mechanobiology and Interplay With Circulatory Systems

A Review of Design Considerations for Hemocompatibility within Microfluidic Systems

Contact Info

Product

Resources

About