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A novel multifunctional microfluidic chip integrated with blood centrifugation, ATPS mixing, VEGF165 enrichment, and fluorescence detection.

Microfluidic technology and a deep learning model are combined to automatically recognize and classify RBCs with different morphologies.

A sensor with heterostructured nanochannels consisting of a porous Nafion membrane and a DNA functionalized AAO membrane was designed for the sensitive detection of mercury ions with LOD of 1 pM due to the change of rectified ionic currents.

A simple strategy was developed to detect ultra-trace level of mercury ions using the co-precipitation method in aqueous sample solution, which had good selectivity, a linear range of 5–100 nM and a LOD as low as 0.1 nM.

Background: More and more evidences have suggested that Corynebacterium kroppenstedtii is associated with some cases of granulomatous mastitis, mostly based on pathology or microbiology. We aimed to find the clinical characteristics and treatment regimens for granulomatous mastitis with Corynebacterium kroppenstedtii infection. Understanding these clinical features is essential for patient care. Methods: We retrospectively collected 201 patients who were diagnosed as granulomatous mastitis pathologically and had microbiological results either Corynebacterium kroppenstedtii or no bacterial growth, recorded and analyzed their demographics and clinical characteristics, clinical outcome. Results: There were 107 patients in CK group, 94 patients in negative group. Sinus formation (x2=13.028, p=0.000), time to complete remission at the first treatment periods (Z=-3.027, p=0.002), diameter of breast mass at first-time medical consultancy (Z=-2.539, p=0.011) and recurrence (x2=4.953, p=0.026) were statistically significant. Age (Z=-1.046, p=0.295), laterality (x2=4.217, p=0.121), delivery way (x2=0.098, p=0.755), time to presentation since last delivery (x2=0.028, p=0.868), BMI (Z=-0.947, p=0.344), lactating time (Z=-1.378, p=0.168), parity (x2=1.799, p=0.180), gravida (Z=-0.144, p=0.885), history of lactational mastitis or abscess (x2=0.115, p=0.734), local trauma (x2=0.982, p=0.322), hyperprolactinemia (x2=0.706, p=0.401), erythema nodosum (x2=0.292, p=0.589), nipple discharge (x2=0.281, p=0.596) did not demonstrate a statistically significance. As to recurrence related to therapeutic strategy, except for surgery combined with immunosuppressants (x2=9.110, p=0.003) was statistically significant, none of the other treatment regimens reached statistical significance. Recurrence rate of patients in CK group using rifampicin in their treatment course was 22.0% (x2=4.892, p=0.027). Conclusions: Granulomatous mastitis accompanied by Corynebacterium kroppenstedtii is easier to form sinus and has higher recurrence rate. Both of the clinical characteristics may prove Corynebacterium kroppenstedtii plays an important role in the development and progression of granulomatous mastitis. Lipophilic antibiotics may be essential for GM with Corynebacterium kroppenstedtii infection.

Exploration of wearable strain sensors in diverse application scenarios is one global requirement for shaping the future of our intelligent community. However, state-of-the-art wearable devices still face challenges such as interference under humid conditions and chemical/mechanical fragility. Here, a facile and fluorine-free approach is introduced to realize a sensitive, robust and superhydrophobic strain sensor via the in situ formation of microcilia on the PDMS surface, followed by a two-step swelling process. The swelling process facilitates the penetration of carbon black nanoparticles into the PDMS matrix to render the conductive network suitable for strain sensing, while the decoration of silica nanoparticles along with the microcilia forms a hierarchical architecture for water repellency. The sensing performance was optimized, including the sensitivity (gauge factor of 354), working range (up to 250%), and long-term stability (>10 000 cycles). The superhydrophobic surface exhibits excellent resistance to mechanical abrasion, chemical corrosion, and high-speed water impact, etc. Demonstrations, such as body motion perception, wireless and underwater communications, Morse code generation, underwater jet impact, reveal the potential of the sensor as a robust platform for broad applications not only in air but also for underwater or under harsh condition uses.

Circulating tumor cells (CTCs), which have extremely low density in whole blood, are an important indicator of primary tumor metastasis. Isolation and enumeration of these cells are critical for clinical applications. Separation of CTCs from massive blood cells without labeling and addition of synthetic polymers is challenging. Herein, a novel well-defined co-flow microfluidic device is presented and used to separate CTCs in viscous blood by applying both inertial and viscoelastic forces. Diluted blood without any synthetic polymer and buffer solution were used as viscoelastic fluid and Newtonian fluid, respectively, and they were co-flowed in the designed chip to form a sheath flow. The co-flow system provides the function of particle pre-focusing and creates a tunable shear rate region at the interface to adjust the migration of particles or cells from the sample solution to the buffer solution. Successful separation of CTCs from viscous blood was demonstrated and enumeration was also conducted by image recognition after separation. The statistical results indicated that a recovery rate of cancer cells greater than 87% was obtained using the developed method, which proved that the direct separation of CTCs from diluted blood can be achieved without the addition of any synthetic polymer to prepare viscoelastic fluid. This method holds great promise for the separation of cells in viscous biological fluid without either complicated channel structures or the addition of synthetic polymers.

For the rapid and sensitive detection of vascular endothelial growth factor 165 (VEGF

The effects of organic and inorganic additives on crystal morphology have been extensively studied in various materials. However, the basic fundamentals behind the morphology control are still unde...

Recently, flexible devices that can implement both pressure and shear force monitoring have attracted abundant interest. Even though flexible sensors with optimized pressure monitoring have been widely explored, the shear branch is yet to be fully addressed as it is restricted by the device assembly and structural features. Herein, we present the magnetic field-assisted in situ formation of spine arrays as the dielectric layer for a capacitive sensor that can respond to both normal pressure and shear force. The template-free and facile approach can not only induce a spine-shaped dielectric as a highly compressible medium for pressure sensing but can also simultaneously realize the device assembly for sustainable shear force monitoring. The capacitive sensor exhibits sensitive pressure monitoring with a detection limit of 2 Pa and possesses reliable and recoverable shear perception with a sensitivity of 0.0752 N−1 (0.015–0.50 N) and 0.0177 N−1 (0.50–1.30 N). As a proof of concept, the device was applied as a wearable motion indicator, artificial intelligence, and body force sensor in terms of pressure and shear force recognition. We believe that the demonstrated methodology can be promising for future wearable electronics thanks to the advantages such as facile production, competitive detection performance, and capability of pressure-shear monitoring.

The clean and reproducible conditions provided by microfluidic devices are ideal sample environments for in situ analyses of chemical and biochemical reactions and assembly processes. However, the small size of microchannels makes investigating the crystallization of poorly soluble materials on-chip challenging due to crystal nucleation and growth that result in channel fouling and blockage. Here, we demonstrate a reusable insert-based microfluidic platform for serial X-ray diffraction analysis and examine scale formation in response to continuous and segmented flow configurations across a range of temperatures. Under continuous flow, scale formation on the reactor walls begins almost immediately on mixing of the crystallizing species, which over time results in occlusion of the channel. Depletion of ions at the start of the channel results in reduced crystallization towards the end of the channel. Conversely, segmented flow can control crystallization, so it occurs entirely within the droplet. Consequently, the spatial location within the channel represents a temporal point in the crystallization process. Whilst each method can provide useful crystallographic information, time-resolved information is lost when reactor fouling occurs and changes the solution conditions with time. The flow within a single device can be manipulated to give a broad range of information addressing surface interaction or solution crystallization.

This article reviews several categories of electronic skins (e-skins) for monitoring signals involved in human health. It covers advanced candidate materials, compositions, structures, and integrate strategies of e-skin, focusing on stretchable and wearable electronics. In addition, this article further discusses the potential applications and expected development of e-skins. It is possible to provide a new generation of sensors which are able to introduce artificial intelligence to the clinic and daily healthcare.

The formation of bacterial biofilms is a key factor in the emergence of chronic infections due to the strong resistance of biofilms to conventional antibiotics. There is an urgent need to develop an effective strategy to control the formation of biofilms. In this study, a nanocomposite of tannic acid and silver (Tannin-AgNPs) was designed and successfully prepared based on the quorum sensing (QS) inhibitory activity of tannic acid and the anti-bacterial activity of silver. The dynamic light scattering and SEM observations indicated that the obtained Tannin-AgNPs were spherical with a mean particle size of 42.37 nm. Tannic acid was successfully modified on the surface of silver nanoparticles and characterized via Fourier transform infrared (FTIR) spectroscopy. The prepared Tannin-AgNPs demonstrated a more effective anti-bacterial and anti-biofilm activity against E. coli than the unmodified AgNPs or tannic acid. In addition, the Tannin-AgNPs can modulate the formation process of E. coli biofilms, shorten the growth period of biofilms and extend the dispersion period of biofilms. Tannin-AgNPs also showed the function of decreasing the production of the QS signal molecule. The proposed strategy of constructing a nanocomposite using AgNPs and natural components with QS inhibitory activity is effective and promising for inhibiting the formation of biofilms.

A microfluidic SERS chip integrated with blood separation and in-situ detection was designed and fabricated for the rapid detection of clinical blood samples. Each functional unit in the microfluidic SERS chip consist of separation-decantation cavity based on centrifugal separation principle, mixing channels and SERS detection chamber built with integrated nano-Au on Ag film microstructure. The serum creatinine was selected as a typical sample to demonstrate the capability of microfluidic SERS chip. It was found that the creatinine SERS characteristic peaks at 678 cm−1 can be effectively identified and the detection limit could be as low as 4.42 × 10−3 μmol mL−1 in water. The blood samples were also tested in microfluidic SERS chip. The whole separation and test process could be completed within 2 min, which is a significant improvement in the field of creatinine detection. The whole blood of six cases clinical blood samples were also tested, and the results were consistent with the enzymatic results. The developed microfluidic SERS chip has advantages including reduction of the required quantity of blood sample, reusable and easy to operate. It is expected to provide a new method for rapid diagnostics.

Developing sensitive and miniaturized biosensors for the detection of microRNAs (miRNAs) is highly desirable due to their association with early cancer diagnosis and prognosis. Here, a new microfluidic-based biosensor, combined with multifunctional nanosurface and DSN-assisted target recycle amplification strategy, is designed for the detection of miRNA-21. The design of nanosurface includes gold nanoparticles on porous anodic aluminum oxide (AAO) for surface enhanced Raman scattering (SERS) substrate, Au

Sealing is one of the inevitable process in microfluidic chip fabrication to form complex networks for the biosensing applications. Currently, only a few materials can be used in microfluidic biosensor due to the lack of reliable bonding technique for most materials. To solve the problem of versatility for chip sealing, a novel adhesive bonding method as simple as “tear off–paste on” is developed. PDMS is mixed with a small amount of polyethylenimine solution to prepare a sticky thin layer, which works like a tape to paste on different materials. Various substrates including glass, plastic, metal and ceramics are used for preparation of microfluidic chips with good bonding strength. This method is appealing for its compatibility to traditional replication method using PDMS and SU8 channel mold while the small surface structures of channel walls can be retained. This method is reliable and versatile for microfluidic biosensor sealing, especially for those with biological sensitive recognition elements on the surfaces since neither aggressive chemicals, high temperature nor high-energy plasma is used. The applicability of the developed method is demonstrated to fabricate a novel long-term cell culture 3D microfluidic chip which keeps bacteria viable for more than 7 days.

Droplet manipulations are critical for applications ranging from biochemical analysis, medical diagnosis to environmental controls. Even though magnetic actuation has exhibited great potential, the capability of high-speed, precise manipulation, and mixing improvement covering a broad droplet volume has not yet been realized. Herein, we demonstrated that the magnetic actuation could be conveniently achieved via decorating the magnetically responsive film with microcilia. Under magnetic field, the film can quickly response with localized deformation, along with the microcilia to realize the surface superhydrophobicity for droplet manipulation with velocity up to ∼173 mm/s covering a broad volume of 2-100 μL. The robust system further allows us to realize rapid and complete droplet mixing within ∼1.6 s. In addition, the microcilia decorated surface can preserve the robust superhydrophobicity after various stability tests, for example, normal pressing, chemical corrosion, and mechanical abrasion, exhibiting the possibility toward the long-term and real applications. With the multifunctional demonstrations such as obvious mixing improvement, parallel manipulation, and serial dilution, we believe that the methodology can open up a magnetic field-based avenue for future applications in digital microfluidics, and biochemical assays, etc.

The efficient detection of cancer markers has faced many challenges, such as severe interference, complicated and time-consuming operation, low sensitivity and so on. In this paper, a microfluidic chip integrated with electrodes for dielectrophoretic (DEP) separation, microchannels for electrochemical nanoprobes binding and differential pulse voltammetry (DPV) detection was proposed for the sensitive and rapid detection of prostate specific antigen (PSA) in whole blood. The functional units, which could realize cell separation, PSA derivatization (binding of electrochemical nanoprobes), capture and detection, were integrated on the microfluidic chip. The well-designed V-shaped interdigital electrode arrays provided DEP separation for blood cells with efficiency as high as 98%. Particularly, DEP effect significantly improved the sensitivity of PSA detection and reduced the detection limit by two orders of magnitude. In order to achieve sensitive detection of PSA, binding of electrochemical nanoprobes and then DPV detection was selected and integrated following the DEP separation. A sandwich structure based on electrochemical nanoprobes and dual-aptamers for on-chip DPV detection was proposed, which included self-synthesized electrochemical nanoprobes bovine serum albumin/detection aptamer 2/polythionine@gold nanoparticles (BSA/Apt2/PThi@Au NPs), target PSA, and sensing interface 6-mercaptohexanol/capture aptamer 1/gold nanoparticles on gold electrode (MCH/Apt1/Au NPs/Au). The method of quantitative detection of PSA in whole blood was then established. The excellent performance of the microfluidic chip allowed the determination of PSA in whole blood in the range of 1 pg/mL ∼10 ng/mL with an ultralow limit of detection of 0.25 pg/mL, which was better than the results obtained by conventional methods.

Electronic skins (e-skins) with monitoring capabilities have attracted extensive attention and are being widely employed in wearable devices for medical diagnosis. In particular, e-skins based on strain sensors have been reported extensively due to their simple structure and efficient performance in collecting human physiological information. Flexible sensors with high sensitivity, simplified fabrication, and low-cost are highly desired for human signal monitoring; this work provides a novel strain-sensing e-skin with micro-structures, which is simply made of modified polydimethylsiloxane (PDMS) and silver nanowires (AgNWs). The fabricated e-skin has great sensitivity towards strain changes, and its mechanical properties and sensitivity could be regulated by varying the micro-structures. Furthermore, the e-skin demonstrated significant capacity for monitoring human body movements, temperature changes, and spatial resolution, highlighting its great potential in personalized medicine.

An impedimetric aptasensor for the detection of endotoxin in a microfluidic chip was proposed, in which the Apt/AuNPs/SPCE sensing surface was fabricated in a screen-printed electrode with good biological activity and stability. The quantitative detection of endotoxin was accomplished by electrochemical impedance spectroscopy (EIS) measurement before and after exposing to samples. The impedance biosensor offers an ultrasensitive and selective detection of endotoxin down to 500 pg mL-1 with a wide linear range from 500 pg mL-1 to 200 ng mL-1. According to the Langmuir isotherm model, the interactions between the target molecules and the sensing surface had been analyzed and strong binding was concluded. Compared to the traditional static incubation methods, the microfluidic biosensor realizes the enrichment of endotoxin owing to the confined space and continuous flow nature, so that the lowest detection concentration is reduced from 5 ng mL-1 to 500 pg mL-1, which is much lower than the existing technology, and the total assay time is shortened from 1.0 h to 0.5 h. The proposed microfluidic impedance biosensor provides a new strategy for the design of an aptasensor to realize the rapid detection of target biomolecules with high sensitivity and it can be integrated into wearable medical devices due to its flexible properties.

In order to achieve real-time and in situ detection of endotoxin, which is an important and significant clinical test index, surface-enhanced Raman spectroscopy (SERS) chip integrated array microchambers within bioscaffold nanostructures and a SERS monitoring strategy were proposed in this paper. After sputtering of nanogold on the cicada wing, which was selected as a natural template, and polydimethylsiloxane bonding, array-type chambers within bioscaffold nanostructures were prepared for in situ bacterial culture and monitoring of endotoxin in the bacteriostasis process by SERS. Meanwhile, the SERS tag modified with the DNA aptamer was prepared and added into this complex biochemical reaction to further improve the sensitivity and selectivity. A new method for in situ detection of endotoxin was thus established. The detection time was shortened to 100 s, and the detection limit was as low as 6.25 ng/mL. Pseudomonas aeruginosa was cultured in situ in the chamber of the SERS chip with antimicrobial agents in 0-72 h. The endotoxin released in the antibacterial process was monitored by the designed SERS detection strategy. The results obtained by SERS analysis were consistent with those of the ELISA kit.

SERS enhancement factor calculation and the raw SERS spectra

We report a novel method to fabricate sectionalized hydrophobic/hydrophilic nanochannel. Photolithography, dry/wet etching, aligned anodic bonding and selective modification were utilized to fabric...

The sensitivity and linearity are critical parameters that can preserve the high pressure-resolution across a wide range and simplify the signal processing process of flexible tactile sensors. Although extensive micro-structured dielectrics have been explored to improve the sensitivity of capacitive sensors, the attenuation of sensitivity with increasing pressure is yet to be fully resolved. Herein, a novel dielectric layer based on the gradient micro-dome architecture (GDA) is presented to simultaneously realize the high sensitivity and ultrabroad linearity range of capacitive sensors. The gradient micro-dome pixels with rationally collocated amount and height can effectively regulate the contact area and hence enable the linear variation in effective dielectric constant of the GDA dielectric layer under varying pressures. With systematical optimization, the sensor exhibits the high sensitivity of 0.065 kPa-1 in an ultrabroad linearity range up to 1700 kPa, which is first reported. Based on the excellent sensitivity and linearity, the high pressure-resolution can be preserved across the full scale of pressure spectrum. Therefore, potential applications such as all-round physiological signal detection in diverse scenarios, control instruction transmission with combinatorial force inputs, and convenient Morse code communication with non-overlapping capacitance signals are successfully demonstrated through a single sensor device.

Serum creatinine is a key biomarker for the diagnosis and monitoring of kidney disease. Rapid and sensitive creatinine detection is thus important. Here, we propose a high-performance nano-Ag/Au@Au film composite SERS substrate for the rapid detection of creatinine in human serum. Au nanoparticles (AuNPs) and Ag nanoparticles (AgNPs) with uniform particle size were synthesized by a chemical reduction method, and the nano-Ag/Au@Au film composite SERS substrate was successfully prepared via a consecutive layer-on-layer deposition using an optimized liquid-liquid interface self-assembly method. The finite element simulation analysis showed that due to the multi-dimensional plasmonic coupling effect formed between the AuNPs, AgNPs, and the Au film, the intensity of the local electromagnetic field was greatly improved, and a very high enhancement factor (EF) was obtained. Experimental results showed that the limit of detection (LOD) of this composite SERS substrate for rhodamine 6G (R6G) molecules was as low as 1 × 10-13M, and the Raman EF was 15.7 and 2.9 times that of the AuNP and AgNP monolayer substrates respectively. The results of different batch tests and SERS mapping showed that the relative standard deviations of the Raman intensity of R6G at 612 cm-1were 12.5% and 11.7%, respectively. Finally, we used the SERS substrate for the label-free detection of human serum creatinine. The results showed that the LOD of this SERS substrate for serum creatinine was 5 × 10-6M with a linear correlation coefficient of 0.96. In conclusion, the SERS substrate has high sensitivity, good uniformity, simple preparation, and has important developmental potential for the rapid detection and application of disease biomarkers.

As crystallization processes are often rapid, it can be difficult to monitor their growth mechanisms. In this study, we made use of the fact that crystallization proceeds more slowly in small volumes than in bulk solution to investigate the effects of the soluble additives Mg2+ and poly(styrene sulfonate) (PSS) on the early stages of growth of calcite crystals. Using a “Crystal Hotel” microfluidic device to provide well‐defined, nanoliter volumes, we observed that calcite crystals form via an amorphous precursor phase. Surprisingly, the first calcite crystals formed are perfect rhombohedra, and the soluble additives have no influence on the morphology until the crystals reach sizes of 0.1–0.5 μm for Mg2+ and 1–2 μm for PSS. The crystals then continue to grow to develop morphologies characteristic of these additives. These results can be rationalized by considering additive binding to kink sites, which is consistent with crystal growth by a classical mechanism.

Fourier transform infrared micro-spectroscopy provides an effective means of performing rapid, non-destructive, and label-free analysis of specimens according to their vibrational modes. However, as water absorbs very strongly in the infrared region, analysis of aqueous solutions in transmission mode can suffer from problems with signal saturation. We here describe the fabrication of a novel microfluidic device that overcomes this problem. Devices with channel depths of just 3 μm were constructed from calcium fluoride using photolithography and hot embossing bonding, where calcium fluoride was selected due to its transparency in the IR region. The utility of this device was then demonstrated by employing it to follow the precipitation pathways of calcium sulfate and calcium carbonate using synchrotron FTIR micro-spectroscopy. Importantly, due to the high brightness provided by synchrotron radiation, and the fact that the reacting ions (HCO3-, CO32- and SO42-) and the different mineral polymorphs all have finger print spectra in the measured IR range, this method can be used to acquire time-resolved, hyperspectral maps of the mineral particles formed within the sample cell, and then study the interaction and evolution of particles. The data provide new insight into the formation pathway of a population of crystals in confined volumes, and demonstrate that this in situ, real-time detection system provides a powerful tool for studying crystallization processes.

Surface enhanced Raman spectroscopy (SERS) detection in microfluidics is an interesting topic for its high sensitivity, miniaturization and online detection. In this work, a SERS detection in microfluidics with the help of the Ag nanowire aggregating based on dielectrophoresis (DEP) is reported. The Raman intensities of molecule in microfluidics is greatly enhanced in the naturally generated nanogaps of Ag nanowire aggregating modulated by DEP. Firstly, the influence of DEP voltage and time on Ag nanowire aggregating is investigated to figure out the optimal condition for SERS. And then, the SERS intensities of methylene blue and rhodamine6G at various concentration with high reproducibility and uniformity are studied. Furthermore, the experiment data demonstrate this DEP-SERS system could be repeated used for different molecule detections. At last, the SERS of melamine is measured to explore its application on food safety. Our work anticipates this nanowire assisted repeatable DEP-SERS detection in microfluidics with high sensitivity could meet the emerging needs in environmental pollution monitoring, food safety evaluation, and so on.