Indirect 3D Bioprinting of a Robust Trilobular Hepatic Construct with Decellularized Liver Matrix Hydrogel.

The liver exhibits complex geometrical morphologies of hepatic cells arranged in a hexagonal lobule with an extracellular matrix (ECM) organized in a specific pattern on a multi-scale level. Previous studies have utilized 3D bioprinting and microfluidic perfusion systems with various biomaterials to develop lobule-like constructs. However, they all lack anatomical relevance with weak control over the size and shape of the fabricated structures.

Layer-by-Layer Cellulose Nanofibrils: A New Coating Strategy for Development and Characterization of Tumor Spheroids as a Model for In Vitro Anticancer Drug Screening.

Three-dimensional multicellular spheroids (MCSs) are complex structure of cellular aggregates and cell-to-matrix interaction that emulates the in-vivo microenvironment. This research field has grown to develop and improve spheroid generation techniques. Here, we present a new platform for spheroid generation using Layer-by-Layer (LbL) technology.

3D Bioprinting of Multi-Material Decellularized Liver Matrix Hydrogel at Physiological Temperatures.

Bioprinting is an acclaimed technique that allows the scaling of 3D architectures in an organized pattern but suffers from a scarcity of appropriate bioinks. Decellularized extracellular matrix (dECM) from xenogeneic species has garnered support as a biomaterial to promote tissue-specific regeneration and repair. The prospect of developing dECM-based 3D artificial tissue is impeded by its inherent low mechanical properties.

Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients.

Detection of tuberculosis at the point-of-care (POC) is limited by the low sensitivity of current commercially available tests. We describe a diagnostic accuracy field evaluation of a prototype urine Tuberculosis Lipoarabinomannan Lateral Flow Assay (TB-LAM LFA) in both HIV-positive and HIV-negative patients using fresh samples with sensitivity and specificity as the measures of accuracy. This prototype combines a proprietary concentration system with a sensitive LFA.

High throughput viscoelastic particle focusing and separation in spiral microchannels.

Passive particle manipulation using inertial and elasto-inertial microfluidics have received substantial interest in recent years and have found various applications in high throughput particle sorting and separation. For separation applications, elasto-inertial microfluidics has thus far been applied at substantial lower flow rates as compared to inertial microfluidics. In this work, we explore viscoelastic particle focusing and separation in spiral channels at two orders of magnitude higher Reynolds numbers than previously reported.

Multi-layer assembly of cellulose nanofibrils in a microfluidic device for the selective capture and release of viable tumor cells from whole blood.

According to reports by the World Health Organization (WHO), cancer-related deaths reached almost 10 million in 2018. Nearly 65% of these deaths occurred in low- to middle-income countries, a trend that is bound to increase since cancer diagnostics are not currently considered a priority in resource-limited settings (RLS). Thus, cost-effective and specific cancer screening and diagnostics tools are in high demand, particularly in RLS.

Microfluidic Immunoaffinity Basophil Activation Test for Point-of-Care Allergy Diagnosis.

Background: The flow cytometry-based basophil activation test (BAT) is used for the diagnosis of allergic response. However, flow cytometry is time-consuming, requiring skilled personnel and cumbersome processing, which has limited its use in the clinic. Here, we introduce a novel microfluidic-based immunoaffinity BAT (miBAT) method.

A flow-through nanoporous alumina trypsin bioreactor for mass spectrometry peptide fingerprinting.

Unlabelled: Mass spectrometry-based proteomics benefits from efficient digestion of protein samples. In this study, trypsin was immobilized on nanoporous anodized alumina membranes to create an enzyme reactor suitable for peptide mass fingerprinting. The membranes were derivatized with 3-aminopropyltriethoxysilane and the amino groups were activated with carbonyldiimidazole to allow coupling of porcine trypsin via ε-amino groups.

Elasto-inertial microfluidics for bacteria separation from whole blood for sepsis diagnostics.

Background: Bloodstream infections (BSI) remain a major challenge with high mortality rate, with an incidence that is increasing worldwide. Early treatment with appropriate therapy can reduce BSI-related morbidity and mortality. However, despite recent progress in molecular based assays, complex sample preparation steps have become critical roadblock for a greater expansion of molecular assays.

Microfluidic-Based Bacteria Isolation from Whole Blood for Diagnostics of Blood Stream Infection.

Bacterial blood stream infection (BSI) potentially leads to life-threatening clinical conditions and medical emergencies such as severe sepsis, septic shock, and multi organ failure syndrome. Blood culturing is currently the gold standard for the identification of microorganisms and, although it has been automated over the decade, the process still requires 24-72 h to complete. This long turnaround time, especially for the identification of antimicrobial resistance, is driving the development of rapid molecular diagnostic methods.

Acoustic micro-vortexing of fluids, particles and cells in disposable microfluidic chips.

We demonstrate an acoustic platform for micro-vortexing in disposable polymer microfluidic chips with small-volume (20 μl) reaction chambers. The described method is demonstrated for a variety of standard vortexing functions, including mixing of fluids, re-suspension of a pellet of magnetic beads collected by a magnet placed on the chip, and lysis of cells for DNA extraction. The device is based on a modified Langevin-type ultrasonic transducer with an exponential horn for efficient coupling into the microfluidic chip, which is actuated by a low-cost fixed-frequency electronic driver board.

Microfluidic-based isolation of bacteria from whole blood for sepsis diagnostics.

Blood-stream infections (BSI) remain a major health challenge, with an increasing incidence worldwide and a high mortality rate. Early treatment with appropriate antibiotics can reduce BSI-related morbidity and mortality, but success requires rapid identification of the infecting organisms. The rapid, culture-independent diagnosis of BSI could be significantly facilitated by straightforward isolation of highly purified bacteria from whole blood.

Dean flow-coupled inertial focusing in curved channels.

Passive particle focusing based on inertial microfluidics was recently introduced as a high-throughput alternative to active focusing methods that require an external force field to manipulate particles. In inertial microfluidics, dominant inertial forces cause particles to move across streamlines and occupy equilibrium positions along the faces of walls in flows through straight micro channels. In this study, we systematically analyzed the addition of secondary Dean forces by introducing curvature and show how randomly distributed particles entering a simple u-shaped curved channel are focused to a fixed lateral position exiting the curvature.

Lab-on-DVD: standard DVD drives as a novel laser scanning microscope for image based point of care diagnostics.

We present a novel "Lab-on-DVD" system and demonstrate its capability for rapid and low-cost HIV diagnostics by counting CD4+ cells isolated from whole blood. We show that a commercial DVD drive can, with certain modifications, be turned into an improved DVD-based laser scanning microscope (DVD-LSM). The system consists of a multi-layered disposable polymer disc and a modified commercial DVD reader with rotational control for sample handling, temperature control for optimized bioassay, a photodiode array for detection, and software for signal processing and user interface - all the necessary components required for a truly integrated lab-on-a-chip system, with the capability to deliver high-resolution images down to 1 μm in size.

Evaluation of the sulfo-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate coupling chemistry for attachment of oligonucleotides to magnetic nanobeads.

The sulfo-SMCC (Succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate) coupling chemistry was evaluated for immobilization of oligonucleotides onto 130 nm sized magnetic nanobeads aimed for bio-detection in a magnetic readout assay. The chemistry was found to produce a high surface coverage of approximately 93 +/- 10 oligonucleotides per bead whereas stability tests showed that about 50% of the oligonucleotides detached from the bead surfaces after eight weeks of storage in a buffer solution. It was shown that bead aggregation prior to magnetic readout could be suppressed by incubating the samples at 70 degrees C for 30 min.