Bekir Yenilmez

3D-printed microfluidic devices

Microfluidics is a flourishing field, enabling a wide range of biochemical and clinical applications such as cancer screening, micro-physiological system engineering, high-throughput drug testing, and point-of-care diagnostics. However, fabrication of microfluidic devices is often complicated, time consuming, and requires expensive equipment and sophisticated cleanroom facilities. Three-dimensional (3D) printing presents a promising alternative to traditional techniques such as lithography and PDMS-glass bonding, not only by enabling rapid design iterations in the development stage, but also by reducing the costs associated with institutional infrastructure, equipment installation, maintenance, and physical space. With the recent advancements in 3D printing technologies, highly complex microfluidic devices can be fabricated via single-step, rapid, and cost-effective protocols, making microfluidics more accessible to users. In this review, we discuss a broad range of approaches for the application of 3D printing technology to fabrication of micro-scale lab-on-a-chip devices.

Towards Single-Step Biofabrication of Organs on a Chip via 3D Printing

Organ-on-a-chip engineering employs microfabrication of living tissues within microscale fluid channels to create constructs that closely mimic human organs. With the advent of 3D printing, we predict that single-step fabrication of these devices will enable rapid design and cost-effective iterations in the development stage, facilitating rapid innovation in this field.

Advancing cancer research using bioprinting for tumor-on-a-chip platforms

There is an urgent for a novel approach to cancer research with 1.7 million new cases of cancer occurring every year in the United States of America. Tumor models offer promise as a useful platform for cancer research without the need for animal models, but there remains a challenge to fabricate a relevant model which mimics the structure, function and drug response of human tumors. Bioprinting can address this need by fabricating three-dimensional constructs that mimic tumor heterogeneity, vasculature and spheroid structures. Furthermore, bioprinting can be used to fabricate tissue constructs within microfluidic platforms, forming tumor-on-a-chip devices which are ideal for high-throughput testing in a biomimetic microenvironment. Applications of tumors-on-a-chip include facilitating basic research to better understand tumor development, structure and function as well as drug screening to improve the efficiency of cancer drug discovery.

Continuous-Ink, Multiplexed Pen-Plotter Approach for Low-Cost, High-Throughput Fabrication of Paper-Based Microfluidics

There is an unmet need for high-throughput fabrication techniques for paper-based microanalytical devices, especially in limited resource areas. Fabrication of these devices requires precise and repeatable deposition of hydrophobic materials in a defined pattern to delineate the hydrophilic reaction zones. In this study, we demonstrated a cost- and time-effective method for high-throughput, easily accessible fabrication of paper-based microfluidics using a desktop pen plotter integrated with a custom-designed multipen holder. This approach enabled simultaneous printing with multiple printing heads and, thus, multiplexed fabrication. Moreover, we proposed an ink supply system connected to commercial technical pens to allow continuous flow of the ink, thereby increasing the printing capacity of the system. We tested the use of either hot- or cold-laminating layers to improve (i) the durability, stability, and mechanical strength of the paper-based devices and (ii) the seal on the back face of the chromatography paper to prevent wetting of the sample beyond the hydrophilic testing region. To demonstrate a potential application of the paper-based microfluidic devices fabricated by the proposed method, colorimetric urine assays were implemented and tested: nitrite, urobilinogen, protein, blood, and pH.

High-throughput rapid-prototyping of low-cost paper-based microfluidics

Paper-based micro analytical devices offer significant advantages compared to the conventional microfluidic chips including cost-effectiveness, ease of fabrication, and ease of use while preserving critical features including strong capillary action and biological compatibility. In this work, we demonstrate an inexpensive, rapid method for high-throughput fabrication of paper-based microfluidics by patterning hydrophobic barriers using a desktop pen plotter integrated with a custom-made, low-cost paper feeder. We tested various types of commercial permanent markers and compared their water-resistant capabilities for creating hydrophobic barriers. Additionally, we studied the performance of markers with different types of paper, plotting speeds, and pattern dimensions. To verify the effectiveness of the presented fabrication method, colorimetric analysis was performed on the results of a glucose assay.

Smart-phone attachable, flow-assisted magnetic focusing device

Detection and sorting of particles and cells in a continuous flow stream is of great importance to downstream biological studies and high-throughput screening. Many particle separation techniques require peripheral devices, complex channel designs or setups that can limit the process and its applications. Here, we present a smart-phone attachable continuous flow magnetic focusing device as an inexpensive and portable tool for reproducible, real-time detection and sorting of particles in high-volume samples based on their volumetric mass density. Diamagnetic particles were suspended in a paramagnetic medium and pumped through a microcapillary located between two permanent magnets. Appropriate flow rate allows each particle to be confined at a vertical equilibrium height. A magnifying lens is placed between the smart-phone camera and capillary to capture images of micro-objects illuminated by an LED. A custom-developed Android application is used for adjusting the focal plane and other imaging parameters, and communicating with a microcontroller to control the pump and LED intensity. The effects of magnet length and flow rate on the particle sorting performance of the setup have been investigated. This device offers a portable, low-cost, digital, and versatile method for identifying, sorting, and quantifying particles on the basis of their volumetric mass densities.

Magnetic Levitation Coupled with Portable Imaging and Analysis for Disease Diagnostics

Currently, many clinical diagnostic procedures are complex, costly, inefficient, and inaccessible to a large population in the world. The requirements for specialized equipment and trained personnel require that many diagnostic tests be performed at remote, centralized clinical laboratories. Magnetic levitation is a simple yet powerful technique and can be applied to levitate cells, which are suspended in a paramagnetic solution and placed in a magnetic field, at a position determined by equilibrium between a magnetic force and a buoyancy force. Here, we present a versatile platform technology designed for point-of-care diagnostics which uses magnetic levitation coupled to microscopic imaging and automated analysis to determine the density distribution of a patients cells as a useful diagnostic indicator. We present two platforms operating on this principle: (i) a smartphone-compatible version of the technology, where the built-in smartphone camera is used to image cells in the magnetic field and a smartphone application processes the images and to measures the density distribution of the cells and (ii) a self-contained version where a camera board is used to capture images and an embedded processing unit with attached thin-film-transistor (TFT) screen measures and displays the results. Demonstrated applications include: (i) measuring the altered distribution of a cell population with a disease phenotype compared to a healthy phenotype, which is applied to sickle cell disease diagnosis, and (ii) separation of different cell types based on their characteristic densities, which is applied to separate white blood cells from red blood cells for white blood cell cytometry. These applications, as well as future extensions of the essential density-based measurements enabled by this portable, user-friendly platform technology, will significantly enhance disease diagnostic capabilities at the point of care.