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Lung cancer is one of the leading causes of death worldwide. Fifteen percent of lung cancer patients will present with malignant pleural effusion initially, and up to 50% will have malignant pleural effusion throughout the course of the disease. In this study, we developed a spiral microfluidic device that can rapidly isolate cancer cells and improve their purity through fluid dynamics. This label-free, high-throughput device continuously isolates cancer cells and other unrelated molecules from pleural effusion. Most of the background cells that affect interpretation are flushed to outlets 1 to 3, and cancer cells are hydrodynamically concentrated to outlet 4, with 90% of lung cancer cells flowing to this outlet. After processing, the purity of cancer cells identified in pleural effusion by CD45 and epithelial cell adhesion molecule (EpCAM) antibodies in flow cytometry will be increased by 6 to 24 times. The microfluidic device presented here has the advantages of rapid processing and low cost, which are conducive to rapid and accurate clinical diagnosis.

Proper orientation of probes and the binding capacity of surfaces will determine the performance of bio-applications. It has been reported that immobilizing through bio-/chemical affinity is an efficient but gentle strategy to solve the above-mentioned issue. Herein, we introduce a total self-assembly approach

Peripheral blood lymphocytes (PBLs) are mature lymphocytes that circulate in the blood rather than being localized to organs. A reliable label-free collection approach that can viably and appropriately isolate PBLs to establish in vitro culture systems is crucial for basic research and clinical requirements. However, isolation of PBLs from whole blood is difficult, and so the development of a rapid and safe method to perform this task is required. Microfluidic technology offers opportunities that challenge the performance of macroscale methods. In this study, we proposed a simple spiral microfluidic chip for efficient and high-throughput isolation of lymphocytes from a sample with prelysed RBCs. This spiral microfluidic platform does not rely on antibodies or biological markers for labeling cells of interest while isolating lymphocytes but rather enriches B and T lymphocytes through the different physical properties that are intrinsic to lymphocytes and other blood cells. The device was used to achieve high-throughput (~1.3 × 105 cells/min) separation of lymphocytes with high viability (>95%). Compared with previous approaches, our device provided rapid, label-free, high-throughput, and safe lymphocyte separation.

Summary Sweat-based wearable devices have attracted increasing attention by providing abundant physiological information and continuous measurement through noninvasive healthcare monitoring. Sweat pressure generated via sweat glands to the skin surface associated with osmotic effects may help to elucidate such parameters as physiological conditions and psychological factors. This study introduces a wearable device for measuring secretion sweat pressure through noninvasive, continuous monitoring. Secretion pressure is detected by a microfluidic chip that shows the resistance variance from a paired electrode pattern and transfers digital signals to a smartphone for real-time display. A human study demonstrates this measurement with different exercise activities, showing the pressure ranges from 1.3 to 2.5 kPa. This device is user-friendly and applicable to exercise training and personal health care. The convenience and easy-to-wear characteristics of this device may establish a foundation for future research investigating sweat physiology and personal health care., Graphical Abstract, Highlights • A wearable device sensing secreted sweat pressure for personal health care • A noninvasive method for real-time pressure monitoring displayed on a smartphone • Widely adopted in different individuals for ionic and temperature calibrations • Successful in situ measurements with exercise for 30 min, Sensor; Electronic Engineering; Biomedical Engineering; Electronic Materials

Extreme point-of-care testing (POCT) is a medical test performed at or near patients at a resource-limited condition. POCT technology has advantages over traditional medical lab tests for molecular detection and infection diagnosis, such as being simple, portable, low-cost, and user-friendly. However, some POCT devices might rely on bulky equipment, and some might be easily influenced by components in biofluid, which might result in higher prices and lower accuracy. In this paper, we demonstrated a low-cost method for detecting bacterial infection in the early stage. We designed a hand-powered centrifugal microfluidic (CMF) disc with magnetic chitosan beads (MCBs) to detect specific circulating antibodies in human whole blood. Nine identical units was used for calibration curve plotting and sample testing. The MCBs, generated with another microfluidic chip and coated with MBL proteins (biomarker of drug-resistant Streptococcus pneumoniae, DRSP, taken as an example for bacterial infection), were served as the substrate of sandwich-structured enzyme-linked immunosorbent assays (ELISA) and as the micro stirring sphere at the same time. The limit of detection (LOD) in PBS and human whole blood were 22.67 ng/mL and 24.83 ng/mL, respectively. The comparison between calibration curves from the antibody spiked in human whole blood and that in PBS was shown to prove the high compatibility and low interference of biofluid, and the recovery rate was 92 %. In conclusion, since our low-cost, time-saving, and user-friendly hand-powered CMF device with minimally consumed electricity detected the target antibody precisely, we believe that other similar assays would be feasible as well. Therefore, we are firmly convinced that this alternative POCT device may lead to the development of next-generation healthcare diagnoses.

We report a peptide-based sensor that involves a multivalent interaction with L-ascorbate 6-phosphate lactonase (UlaG), a protein marker of Streptococcus pneumonia. By integrating the antifouling feature of the sensor, we significantly improved the signal-to-noise ratio of UlaG detection. The antifouling surface was fabricated via electrodeposition using an equivalent mixture of 4-amino-N,N,N-trimethylanilinium and 4-aminobenzenesulfonate. This antifouling layer not only effectively reduces the non-specific adsorption on the biosensor but also decreases the charge transfer resistance (Rct) of the screen-printed carbon electrode. The aniline-modified S7 peptide, an UlaG-binding peptide, was pre-synthesized and further electrochemically modified to bind onto the antifouling layer. Bio-electrochemical analysis confirms that the antifouling S7-peptide sensor binds strongly to the UlaG with a dissociation constant (Kd) = 0.5 nM. This strong interaction can be attributed to a multivalent interaction between the biosensor and the heximeric form of UlaG. To demonstrate the potential for clinical application, further detection of Streptococcus pneumonia from 50 to 5 × 10 4 CFU/mL were successfully performed in 25% human serum.

Blood tests provide crucial diagnostic information regarding several diseases. A key factor that affects the precision and accuracy of blood tests is the interference of red blood cells; however, the conventional methods of blood separation are often complicated and time consuming. In this study, we devised a simple but high-efficiency blood separation system on a self-strained microfluidic device that separates 99.7% of the plasma in only 6 min. Parameters, such as flow rate, design of the filter trench, and the relative positions of the filter trench and channel, were optimized through microscopic monitoring. Moreover, this air-difference-driven device uses a cost-effective and easy-to-use heater strip that creates a low-pressure environment in the microchannel within minutes. With the aforementioned advantages, this blood separation device could be another platform choice for point-of-care testing.

Diabetes has become a chronic metabolic disorder, and the growing diabetes population makes medical care more important. We investigated using a portable and noninvasive contact lens as an ideal sensor for diabetes patients whose tear fluid contains glucose. The key feature is the reversible covalent interaction between boronic acid and glucose, which can provide a noninvasive glucose sensor for diabetes patients. We present a phenylboronic acid (PBA)-based HEMA contact lens that exhibits a reversible swelling/shrinking effect to change its thickness. The difference in thickness can be detected in a picture taken with a smartphone and analyzed using software. Our novel technique offers the following capabilities: (i) non-enzymatic and continuous glucose detection with the contact lens, (ii) no need for an embedded circuit and power source for the glucose sensor, and (iii) the use of a smartphone to detect the change in thickness of the contact lens with no need for additional photo-sensors. This technique is promising for a noninvasive measurement of the glucose level and simple implementation of glucose sensing with a smartphone.

In applications of silicon nanowire field-effect transistors (SiNW-FETs) as biosensors, the SiNW-FETs conventionally are all area modified (AAM), with receptors covering not only the minute SiNW surface area but also the relatively large surrounding substrate area. In this study, using a bottom-up technique, we successfully fabricated selective surface modified (SSM) SiNW-FETs with the receptors on the SiNW sensing surface only. In this approach, the strategy was to modify the SiNWs with a chemical linker of 3-aminopropyltrimethoxysilane (APTMS) prior to photolithographic fabrication of the device. The APTMS molecules modifying the SiNWs survived the harsh photolithographic processes, including coating with photoresist, washing with organic solvent, and thermal annealing. These SSM SiNW-FETs also exhibited desirable electrical characteristics such as ohmic contact and high transconductance. Using the biotin-avidin binding system, we showed that the faster response time and smaller sample requirements of the SSM SiNW-FETs, relative to the conventional AAM SiNW-FETs, clearly show that restricting the surface modification of the SiNW-FETs substantially improves their detection sensitivity. Detection with a SSM boronic acid-modified SiNW-FET of the dopamine released under high-K(+) buffer stimulation from living PC12 cells also demonstrates that SiNW-FETs can serve as highly sensitive biosensors for biomedical diagnosis. In binding affinity measurements with SiNW-FETs, the dissociation constants (Kd) of the biotin-avidin and dopamine-boronic acid complexes were determined to be 15 ± 1 fM and 33 ± 8 fM, respectively.

Understanding how proteins interact with each other is the basis for studying the biological mechanisms behind various physiological activities. Silicon nanowire field-effect transistors (SiNW-FETs) are sensitive sensors used to detect biomolecular interactions in real-time. However, the majority of the applications that use SiNW-FETs are for known interactions between different molecules. To explore the capability of SiNW-FETs as fast screening devices to identify unknown interacting molecules, we applied mass spectrometry (MS) to analyze molecules reversibly bound to the SiNW-FETs. Calmodulin (CaM) is a Ca(2+)-sensing protein that is ubiquitously expressed in cells and its interaction with target molecules is Ca(2+)-dependent. By modifying the SiNW-FET surface with glutathione, glutathione S-transferase (GST)-tagged CaM binds reversibly to the SiNW-FET. We first verified the Ca(2+)-dependent interaction between GST-CaM and purified troponin I, which is involved in muscle contraction, through the conductance changes of the SiNW-FET. Furthermore, the cell lysate containing overexpressed Ca(2+)/CaM-dependent protein kinase IIα induced a conductance change in the GST-CaM-modified SiNW-FET. The bound proteins were eluted and subsequently identified by MS as CaM and kinase. In another example, candidate proteins from neuronal cell lysates interacting with calneuron I (CalnI), a CaM-like protein, were captured with a GST-CalnI-modified SiNW-FET. The proteins that interacted with CalnI were eluted and verified by MS. The Ca(2+)-dependent interaction between GST-CalnI and one of the candidates, heat shock protein 70, was re-confirmed via the SiNW-FET measurement. Our results demonstrate the effectiveness of combining MS with SiNW-FETs to quickly screen interacting molecules from cell lysates.

Summary Silicon nanowire field-effect transistors (SiNW-FETs) have recently drawn tremendous attention as a promising tool in biosensor design because of their ultrasensitivity, selectivity, and label-free and real-time detection capabilities. Here, we review the recently published literature that describes the device fabrication and biomedical applications of SiNW-FET sensors. For practical uses, SiNW-FETs can be delicately designed to be a reusable device via a reversible surface functionalization method. In the fields of biological research, SiNW-FETs are employed in the detections of proteins, DNA sequences, small molecules, cancer biomarkers, and viruses. The methods by which the SiNW-FET devices were integrated with these representative examples and advanced to virus infection diagnosis or early cancer detection will be discussed. In addition, the utilization of SiNW-FETs in recording the physiological responses from cells or tissues will also be reviewed. Finally, the novel design of a three dimensional (3D) nano-FET probe with kinked SiNWs for recording intracellular signals will be highlighted in this review.

Silicon nanowire field effect transistors (SiNW-FETs) have shown great promise as biosensors in highly sensitive, selective, real-time and label-free measurements. While applications of SiNW-FETs for detection of biological species have been described in several publications, less attention has been devoted to summarize the conjugating methods involved in linking organic bio-receptors with the inorganic transducer and the strategies of improving the sensitivity of devices. This article attempts to focus on summarizing the various organic immobilization approaches and discussing various sensitivity improving strategies, that include (I) reducing non-specific binding, (II) alignment of the probes, (III) enhancing signals by charge reporter, (IV) novel architecture structures, and (V) sensing in the sub-threshold regime.