3D printed auto-mixing chip enables rapid smartphone diagnosis of anemia

Plevniak, Kimberly; Campbell, Matthew; Myers, Timothy; Hodges, Abby M; He, Mei

doi:10.1063/1.4964499

Cited by 56 publications

(40 citation statements)

References 57 publications

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“…The mold printing followed the reported protocols. [22][23] Freshly printed molds were cleaned using isopropyl alcohol in sonication and followed with 30-min post cure under UV light. A 20nm thick palladium or gold coating was deposited onto the surface of the 3D-printed mold using a sputter coater (DENTON, DESK II).…”

Section: Methodsmentioning

confidence: 99%

3D-printing Enabled Micro-assembly of Microfluidic Electroporation System for 3D Tissue Engineering

Zhu

Hamilton

2019

Preprint

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Electro-transfection is an essential workhorse tool for regulating cellular responses and engineering cellular materials in tissue engineering. However, existing approaches, including microfluidic platforms and bench top methods, are only able to study monolayer cell suspensions in vitro, and are incapable of clinical translation within in vivo tissue microenvironment.Knowledge regarding the three-dimensional (3D) electric field distribution and mass transport in a tissue microenvironment is lacking. However, building a 3D electro-transfection system that is compatible with 3D cell culture for mimicking in vivo tissue microenvironment is challenging, due to the substantial difficulties in control of 3D electric field distribution as well as the cellular growth. To address such challenges, we introduce a novel 3D micro-assembling strategy assisted by 3D printing, which enables the molding of 3D microstructures as LEGO® parts from 3D-printed molds. The molded PDMS LEGO  bricks are then assembled into a 3D-cell culture chamber interconnected with vertical and horizontal perfusion microchannels as a 3D channel network. Such 3D perfusion microchannel network is unattainable by direct 3D printing or other microfabrication approaches, which can facilitate the high-efficient exchange of nutrition and waste for 3D cell growth.Four flat electrodes are mounted into the 3D culture chamber via a 3D-printed holder and controlled by a programmable power sequencer for multi-directional electric frequency scanning (3D -electro-transfection). This multi-directional scanning not only can create transient pores all over the cell membrane, but also can generate local oscillation for enhancing mass transport and improving cell transfection efficiency. As a proof-of-concept, we electro-delivered pAcGFP1-C1 vector to 3D cultured HeLa cells within peptide hydrogel scaffolding. The expressed GFP level from transfected HeLa cells reflects the transfection efficiency. We found two key parameters including electric field strength and plasmid concentration playing more important roles than manipulating pulse duration and duty cycles. The results showed an effective transfection efficiency of ~15% with ~85% cell viability, which is a 3-fold increase compared to the conventional benchtop 3D cell transfection. This 3D -electrotransfection system was further used for genetically editing 3D-cultured Hek-293 cells via direct delivery of CRISPR/Cas9 plasmid which showed successful transfection with GFP expressed in the cytoplasm as the reporter. The 3D-printing enabled micro-assembly allows facile creation of novel 3D culture system for electro-transfection which can be employed for versatile gene delivery and cellular engineering, as well as building in-vivo like tissue models for fundamentally studying cellular regulatory mechanisms. the orientation of cells to the electric fields and so on. [16][17] Thus, the clinical in vivo gene delivery faces tremendous problems. 3,18 Although the in vitro cellular spheroid model is often applied to study t...

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Section: Methodsmentioning

confidence: 99%

3D-printing Enabled Micro-assembly of Microfluidic Electroporation System for 3D Tissue Engineering

Zhu

Hamilton

2019

Preprint

Self Cite

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“…Less than one second of mixing allowed of the blood sample with the oxidizing agent; generated colorimetric signal detected with a smartphone. Reproduced with permission from [71].…”

Section: Flow Controlmentioning

confidence: 99%

“…Plevniak et al proposed a 3D printed microfluidic mixer for diagnosis of anemia ( Figure 7A). In their work they were able to integrate the device with smartphone-aided colorimetric signal detection to overcome distance barrier for efficient anemia screening [71]. The device can analyze a finger prick of blood (~5µL) driven by capillary force into the mixing chamber where it is mixed with an oxidizing agent in less than 1 sec with cost 50 cents/chip.…”

Section: Microfluidic Mixersmentioning

confidence: 99%

3D Printed Biosensor Arrays for Medical Diagnostics

Sharafeldin¹,

Jones²,

Rusling³

2018

Preprint

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While the technology is relatively new, low cost 3D printing has impacted many aspects of human life. 3D printers are being used as manufacturing tools for a wide variety of devices in a spectrum of applications ranging from diagnosis to implants to external prostheses. The ease of use and availability of 3D design software and low cost has made 3D printing an accessible manufacturing and fabrication tool in many research laboratories. 3D printers can print materials with varying density, optical character, strength and chemical properties providing platforms for a huge number of strategies that can be chosen for user's needs. In this review, we focus on applications in biomedical diagnostics and how this revolutionary technique is facilitating development of low cost, sensitive and often geometrically complex tools. 3D printing in fabrication of microfluidics, supporting equipment, optical and electronic components of diagnostic devices is presented. Emerging diagnostic 3D bioprinting as a tool to incorporate living cells or biomaterials into 3D printing is also discussed.

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“…Plevniak et al . developed a capillary‐driven auto‐mixing platform for rapid diagnosis of anemia. The oxidizing agents were mixed with blood by capillary force and a colorimetric analysis was implemented on the mixture with the assistance of smartphone.…”

Section: Introductionmentioning

confidence: 99%

A rapid, maskless 3D prototyping for fabrication of capillary circuits: Toward urinary protein detection

et al. 2018

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Proteinuria is an established risk marker for progressive renal function loss and patients would significantly benefit from a point-of-care testing. Although extensive work has been done to develop the microfluidic devices for the detection of urinary protein, they need the complicated operation and bulky peripherals. Here, we present a rapid, maskless 3D prototyping for fabrication of capillary fluidic circuits using laser engraving. The capillary circuits can be fabricated in a short amount of time (<10 min) without the requirements of clean-room facilities and photomasks. The advanced capillary components (e.g., trigger valves, retention valves and retention bursting valves) were fabricated, enabling the sequential liquid delivery and sample-reagent mixing. With the integration of smartphone-based detection platform, the microfluidic device can quantify the urinary protein via a colorimetric analysis. By eliminating the bulky and expensive equipment, this smartphone-based detection platform is portable for on-site quantitative detection.

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3D printed auto-mixing chip enables rapid smartphone diagnosis of anemia

Cited by 56 publications

References 57 publications

3D-printing Enabled Micro-assembly of Microfluidic Electroporation System for 3D Tissue Engineering

3D-printing Enabled Micro-assembly of Microfluidic Electroporation System for 3D Tissue Engineering

3D Printed Biosensor Arrays for Medical Diagnostics

A rapid, maskless 3D prototyping for fabrication of capillary circuits: Toward urinary protein detection

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