Microfluidic blood processing is used in a range of applications from cancer therapeutics to infectious disease diagnostics. As these applications are being translated to clinical use, processing larger volumes of blood in shorter timescales with high-reliability and robustness is becoming a pressing need. In this work, we report a scaled, label-free cell separation mechanism called non-equilibrium inertial separation array (NISA). The NISA mechanism consists of an array of islands that exert a passive inertial lift force on proximate cells, thus enabling gentler manipulation of the cells without the need of physical contact. As the cells follow their size-based, deterministic path to their equilibrium positions, a preset fraction of the flow is siphoned to separate the smaller cells from the main flow. The NISA device was used to fractionate 400 mL of whole blood in less than 3 hours, and produce an ultrapure buffy coat (96.6% white blood cell yield, 0.0059% red blood cell carryover) by processing whole blood at 3 mL/min, or ∼300 million cells/second. This device presents a feasible alternative for fractionating blood for transfusion, cellular therapy and blood-based diagnostics, and could significantly improve the sensitivity of rare cell isolation devices by increasing the processed whole blood volume.

There are several emerging diagnostic and therapeutic applications of magnetic nanoparticles (mNPs) in medicine. This study examines the potential for developing an mNP imager that meets these emerging clinical needs with a low cost imaging solution that uses arrays of digitally controlled drive coils in a multiple-frequency, continuous-wave operating mode and compensated fluxgate magnetometers. The design approach is described and a mathematical model is developed to support measurement and imaging. A prototype is used to demonstrate active compensation of up to 185 times the primary applied magnetic field, depth sensitivity up to 2.5 cm (p < 0.01), and linearity over 5 dilutions (R2 > 0.98, p <0.001). System frequency responses show distinguishable readouts for iron oxide mNPs with single magnetic domain core diameters of 10 nm and 40 nm, and multi-domain mNPs with a hydrodynamic diameter of 100 nm. Tomographic images show a contrast-to-noise ratio of 23 for 0.5 ml of 12.5 mg Fe/ml mNPs at 1 cm depth. A demonstration involving the injection of mNPs into pork sausage shows the potential for use in biological systems. These results indicate that the proposed mNP imaging approach can potentially be extended to a larger array system with higher-resolution.

This study demonstrates a method for alternating current (AC) susceptibility imaging (ASI) of magnetic nanoparticles (mNPs) using low cost instrumentation. The ASI method uses AC magnetic susceptibility measurement to create tomographic images using an array of drive coils, compensation coils and fluxgate magnetometers. Using a spectroscopic approach in conjunction with ASI, a series of tomographic images can be created for each frequency measurement and is termed sASI. The advantage of sASI is that mNPs can be simultaneously characterized and imaged in a biological medium. System calibration was performed by fitting the in-phase and out-of-phase susceptibility measurements of an mNP sample with a hydrodynamic diameter of 100 nm to a Brownian relaxation model (R2 = 0.96). Samples of mNPs with core diameters of 10 and 40 nm and a sample of 100 nm hydrodynamic diameter were prepared in 0.5 ml tubes. Three mNP samples were arranged in a randomized array and then scanned using sASI with six frequencies between 425 and 925 Hz. The sASI scans showed the location and quantity of the mNP samples (R2 = 0.97). Biological compatibility of the sASI method was demonstrated by scanning mNPs that were injected into a pork sausage. The mNP response in the biological medium was found to correlate with a calibration sample (R2 = 0.97, p <0.001). These results demonstrate the concept of ASI and advantages of sASI.

The disease burden and healthcare costs of psychiatric diseases along with the pursuit to understand their underlying biochemical mechanisms have led to psychiatric biomarker investigations. Current advances in evaluating candidate biomarkers for psychiatric diseases, such as major depressive disorder (MDD), focus on determining a specific biomarker signature or profile. The origins of candidate biomarkers are heterogenous, ranging from genomics, proteomics, and metabolomics, while incorporating associations with clinical characterization. Prior to clinical use, candidate biomarkers must be validated by large multi-site clinical studies, which can be used to determine the ideal MDD biomarker signature. Therefore, identifying valid biomarkers has been challenging, suggesting the need for alternative approaches. Following validation studies, new technology must be employed to transition from biomarker discovery to diagnostic biomolecular profiling. Current technologies used in discovery and validation, such as mass spectroscopy, are currently limited to clinical research due to the cost or complexity of equipment, sample preparation, or measurement analysis. Thus, other technologies such as electrochemical detection must be considered for point-of-care (POC) testing with the needed characteristics for physicians’ offices. This review evaluates the advantages of using electrochemical sensing as a primary diagnostic platform due to its rapidity, accuracy, low cost, biomolecular detection diversity, multiplexed capacity, and instrument flexibility. We evaluate the capabilities of electrochemical methods in evaluating current candidate MDD biomarkers, individually and through multiplexed sensing, for promising applications in detecting MDD biosignatures in the POC setting.