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The mechanical properties of cells are harmless biomarkers for cell identification and disease diagnosis. Although many systems have been developed to evaluate the static mechanical properties of cells for biomedical research, their robustness, effectiveness, and cost do not meet clinical requirements or the experiments with a large number of cell samples. In this paper, we propose an approach for on-chip cell mechanical characterization by analyzing the dynamic behavior of cells as they pass through multiple constrictions. The proposed serpentine microfluidic channel consisted of 20 constrictions connected in series and divided into five rows for tracking cell dynamic behavior. Assisted by computer vision, the squeezing time of each cell through five rows of constrictions was automatically collected and filtered to evaluate the cell's mechanical deformability. We observed a decreasing passage time and increasing dynamic deformability of the cells as they passed through the multiple constrictions. The deformability increase rate of the HeLa cells was eight times greater than that of MEF cells. Moreover, the weak correlation between the deformability increase rate and the cell size indicated that cell recognition based on measuring the deformability increase rate could hardly be affected by the cell size variation. These findings showed that the deformability increase rate of the cell under on-chip sequential squeezing as a new index has great potential in cancer cell recognition.
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Microfluídica , Tamanho Celular , Células HeLa , HumanosRESUMO
To investigate substitution effects on excited-state intermolecular proton transfer (ESPT) reactions as well as acidity of proton donating fragments in the ground state, we synthesized substituted anthracen-2-yl-3-phenylurea derivatives that form a hydrogen bonds with acetate anions and undergo ESPT reaction. Fluorescence lifetime measurements and their kinetic analyses revealed that the trifluoromethyl group on the phenyl ring as an electron-withdrawing group caused a slow ESPT reaction despite an increase in the acidity of the N-H fragment in the ground state. In contrast, the methoxy group as a donating group leads to a fast ESPT reaction despite a reduction of the acidity of the N-H fragment in the ground state. These effects of substituents on ESPT reaction are due to their influence on the charge transfer reaction, which occurs from the N-H fragment to the anthryl ring to increase the acidity of N-H followed by ESPT reaction, over the urea unit by a combination of resonance and inductive effects. These opposing effects of substituents on the acidity of the urea unit in the ground and excited states provide an important insight in balancing the reactivity of proton transfer reaction in both the excited and ground states.
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INTRODUCTION: The objectives of this study were to identify what is reflected in cortical speed of sound (cSOS) measured by a cortical quantitative ultrasound (cortical QUS) device we have developed, and to investigate cSOS measurements in healthy individuals and dialysis patients. METHODS: The cSOS and the SOS were measured by cortical QUS and conventional QUS in 20 volunteers, and the correlations between these measurements and areal bone mineral density measured by dual-energy X-ray absorptiometry and bone microstructural parameters on high-resolution peripheral quantitative computed tomography were analyzed. The cSOS and the SOS were measured in 91 young adults (47 men, 44 women), 64 elderly people (30 men, 33 women), and 64 dialysis patients (33 men, 31 women). The period of hemodialysis and intact parathyroid hormoneevels were also investigated in the dialysis patients. RESULTS: cSOS was correlated with cortical tissue mineral density (tibia: râ¯=â¯0.74, radius: râ¯=â¯0.72) on high-resolution peripheral quantitative computed tomography, reflecting the degree of minaralization and microporosity of cortical bone. There was no correlation with the thickness of cortical bone, suggesting that it measured the bone quality rather than bone mass. Elderly women had lower cSOS than young adults (3865 ± 74 vs 3971 ± 63 m/s, p < 0.01). Many of dialysis patients showed very low cSOS and it was related to higher intact parathyroid hormone levels (male: ß = -0.67, female: ß = -0.60). CONCLUSIONS: Our cortical QUS device is capable of evaluating the qualitative degradation of cortical bone, which cannot be assessed by conventional QUS, and its use in combination with conventional QUS may provide a better understanding of fracture risk.
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Densidade Óssea , Diálise Renal , Absorciometria de Fóton , Idoso , Osso e Ossos , Osso Cortical/diagnóstico por imagem , Feminino , Humanos , Masculino , Ultrassonografia , Adulto JovemRESUMO
Wearable auxiliary devices for visually impaired people are highly attractive research topics. Although many proposed wearable navigation devices can assist visually impaired people in obstacle avoidance and navigation, these devices cannot feedback detailed information about the obstacles or help the visually impaired understand the environment. In this paper, we proposed a wearable navigation device for the visually impaired by integrating the semantic visual SLAM (Simultaneous Localization And Mapping) and the newly launched powerful mobile computing platform. This system uses an Image-Depth (RGB-D) camera based on structured light as the sensor, as the control center. We also focused on the technology that combines SLAM technology with the extraction of semantic information from the environment. It ensures that the computing platform understands the surrounding environment in real-time and can feed it back to the visually impaired in the form of voice broadcast. Finally, we tested the performance of the proposed semantic visual SLAM system on this device. The results indicate that the system can run in real-time on a wearable navigation device with sufficient accuracy.
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Pessoas com Deficiência Visual , Dispositivos Eletrônicos Vestíveis , Humanos , SemânticaRESUMO
A magnetically-guided capsule endoscope, embedding flexible force sensors, is designed to measure the capsule-tissue interaction force. The flexible force sensor is composed of eight force-sensitive elements surrounding the internal permanent magnet (IPM). The control of interaction force acting on the intestinal wall can reduce patient's discomfort and maintain the magnetic coupling between the external permanent magnet (EPM) and the IPM during capsule navigation. A flexible force sensor can achieve this control. In particular, by analyzing the signals of the force sensitive elements, we propose a method to recognize the status of the motion of the magnetic capsule, and provide corresponding formulas to evaluate whether the magnetic capsule follows the motion of the external driving magnet. Accuracy of the motion recognition in Ex Vivo tests reached 94% when the EPM was translated along the longitudinal axis. In addition, a method is proposed to realign the EPM and the IPM before the loss of their magnetic coupling. Its translational error, rotational error, and runtime are 7.04 ± 0.71 mm, 3.13 ± 0.47∘, and 11.4 ± 0.39 s, respectively. Finally, a control strategy is proposed to prevent the magnetic capsule endoscope from losing control during the magnetically-guided capsule colonoscopy.
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Cápsulas Endoscópicas , Fenômenos Mecânicos , Desenho de Equipamento , Humanos , Imãs , Movimento (Física)RESUMO
Traumatic nerve injury activates cell stress pathways, resulting in neuronal death and loss of vital neural functions. To date, there are no available neuroprotectants for the treatment of traumatic neural injuries. Here, we studied three important flavanones of citrus components, in vitro and in vivo, to reveal their roles in inhibiting the JNK (c-Jun N-terminal kinase)-JUN pathway and their neuroprotective effects in the optic nerve crush injury model, a kind of traumatic nerve injury in the central nervous system. Results showed that both neural injury in vivo and cell stress in vitro activated the JNK-JUN pathway and increased JUN phosphorylation. We also demonstrated that naringenin treatment completely inhibited stress-induced JUN phosphorylation in cultured cells, whereas nobiletin and hesperidin only partially inhibited JUN phosphorylation. Neuroprotection studies in optic nerve crush injury mouse models revealed that naringenin treatment increased the survival of retinal ganglion cells after traumatic optic nerve injury, while the other two components had no neuroprotective effect. The neuroprotection effect of naringenin was due to the inhibition of JUN phosphorylation in crush-injured retinal ganglion cells. Therefore, the citrus component naringenin provides neuroprotection through the inhibition of the JNK-JUN pathway by inhibiting JUN phosphorylation, indicating the potential application of citrus chemical components in the clinical therapy of traumatic optic nerve injuries.
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Citrus/química , Lesões por Esmagamento/enzimologia , Flavanonas/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Compressão Nervosa , Neurônios/patologia , Nervo Óptico/patologia , Proteínas Proto-Oncogênicas c-jun/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Lesões por Esmagamento/patologia , Células HEK293 , Humanos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neuroproteção/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Estresse Fisiológico/efeitos dos fármacosRESUMO
In recent decades, cell immobilization using microfluidic chips has facilitated significant advancements in biological analyses at the single-cell level. However, the efficient capture of multiple cells as a cluster in adjustable quantities for cell-cell interaction has not been achieved. In this paper, aiming to monitor the cell-cell interaction at the single-cell level, we proposed a novel method for the efficient immobilization of adjustable quantities of cells on the basis of passive hydrodynamics so that different cell-cell interaction patterns could be generated. Experiments were conducted to characterize the key geometric parameters of the chip to optimize the efficiency of trapping different quantities of cells. In the microfluidic chips optimized for immobilizing one to five cells, the trapping success rates (TSRs) were up to 97%, 87%, 84%, 58%, and 54%, respectively. Furthermore, the throughput was over 200 cells min-1 with a minimum cell density of 350 cells mm-2. Finally, in the experiments of applying the proposed multicell immobilization chips to cell-cell interaction monitoring, calcein-AM transfer between multiple cells under different patterns has been studied through quantifying the local fluorescent intensity. The results demonstrated that the proposed method could be a promising opportunity in the widening field of biological research at the single-cell level.
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Comunicação Celular/fisiologia , Técnicas Analíticas Microfluídicas/instrumentação , Microfluídica/instrumentação , Análise de Célula Única/instrumentação , Células 3T3 , Animais , Células Cultivadas , Células Imobilizadas/metabolismo , Técnicas de Cocultura , Dimetilpolisiloxanos/química , Equipamentos e Provisões , Fluoresceínas/metabolismo , Células HT29 , Células HeLa , Humanos , Hidrodinâmica , Camundongos , Modelos QuímicosRESUMO
1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU), which forms weak hydrogen bonds despite the high basicity caused by its hindered structure, was used to investigate tautomer formation via excited-state intermolecular proton-transfer (ESPT) reactions. The kinetics of the ESPT reactions of anthracen-2-yl-3-phenylurea (2PUA) in the presence of DBU were compared to that observed for the acetate anion (Ac) using time-resolved fluorescence measurement. Based on the association constants in the ground state, the intermolecular hydrogen bond between 2PUA and DBU was less stable than the bond between 2PUA and Ac due to steric hindrance and the geometry of the hydrogen bond. In the fluorescence spectra, 2PUA-DBU displayed prominent tautomeric emission in chloroform (CHCl3), whereas 2PUA-Ac exhibited distinct tautomeric emissions in dimethyl sulfoxide (DMSO). Kinetic analysis revealed that the rate constant of the ESPT reaction of 2PUA-DBU remarkably decreased when the proton-accepting ability of the solvent increased whereas the reaction of 2PUA-Ac was linked to the solvent polarity rather than proton-accepting ability. These results indicated that moderate hydrogen bonds due to steric hindrance were influenced by the type of solvent present, particularly if the solvents exhibited proton-accepting capabilities like DMSO. This, in turn, affected the rate constant of tautomer formation.
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A noncontact method that can achieve immobilization, transportation, and rotation in the microscale is desired in biological micromanipulation. A multifunctional noncontact micromanipulation method is proposed here based on a vibration-generated whirling flow. Resonance of a cantilever structure is utilized to extend the straight vibration of a single piezo actuator to the 2D circular vibration of a micropipette. The circular vibration in fluids can generate the whirling flow featured with low pressure in the core area and flow velocity gradient. The low pressure can immobilize the objects nearby and transport them together with the micropipette, and the flow velocity gradient is utilized to form a torque to rotate the immobilized object. Experiments of the microbeads are conducted to evaluate the claimed functions and quantify the key parameters that influence the rotation velocity. The cell spheroid is immobilized and rotated for 3D observation, and by assessing the viability of the cells containing in the spheroid, the proposed method is proved noninvasive to living cells. Finally, another important application in operations of mouse egg cells is shown, which indicates that the proposed method is a potential valuable tool in biological micromanipulation.
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Microtecnologia/métodos , Reologia , Vibração , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Microesferas , Células NIH 3T3 , Oócitos/citologia , Rotação , Esferoides Celulares/citologiaRESUMO
In this paper, we report the solvent effect of excited state intermolecular proton transfer (ESIPT) reactions of urea compounds in the presence of tetrabutylammonium acetate (TBAAc). We prepared anthracene-urea compounds (9An and 2An), a pyrene-urea compound (Py) and an anthracene-diurea compound (9,10An), which have alkylsulfonyl groups to improve their solubility in various organic solvents. We investigated the solvent effects of the ESIPT reaction using absorption, fluorescence, and 1H NMR spectroscopy along with fluorescence decay measurements in dimethyl sulfoxide (DMSO), acetonitrile (MeCN), tetrahydrofuran (THF) and toluene. The tautomer fluorescence of 9An showed remarkable solvent dependence on the spectral red-shift compared with 2An, Py and 9,10An. As a result of the detailed spectroscopic investigations with regard to the solvent including kinetic analysis of the ESIPT for 9AnAcO-, we revealed that the energy gap between the normal and tautomer forms in the excited state depended on the hydrogen bond acceptor basicity (ß), which is one of the Kamlet-Taft solvent parameters. Finally, we discovered that the tautomer structures of aromatic-urea compounds were stabilized by hydrogen bond interactions.
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The demand for a harmless noncontact trapping and transportation method in manipulation and measurement of biological micro objects waits to be met. In this paper, a novel micromanipulation method named “Hydrodynamic Tweezers” using the vortex induced by oscillating a single piezoelectric actuator is introduced. The piezoelectric actuator is set between a micropipette and a copper beam. Oscillating the actuator at a certain frequency causes the resonance of the copper beam and extend 1D straight oscillation of the piezoelectric actuator to 2D circular oscillation of the micropipette, which induces a micro vortex after putting the micropipette into fluid. The induced vortex featuring low pressure in its core area can trap the object nearby. A robotic micromanipulator is utilized to transport the trapped objects together with the micropipette. Experiments of trapping and transportation microbeads are carried out to characterize the key parameters. The results show that the trapping force can be controlled by adjusting peak-peak voltage of the sinusoidal voltage input into the piezoelectric actuator.
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The photochemical properties of stilbene cored amphiphilic dendrimers (G0-G3) in THF and water were investigated. The solvation dynamics in water depended on the generation, while the behavior is almost the same in THF. Dendrimers G1 and G2 form molecular assemblies and undergo photodimerization reaction in addition to photoisomerization. G3 has enough TEG groups on the surface to cover the hydrophobic moiety within a single molecule. These dendrimers have free space around the core to undergo mutual isomerization even in water. This type of surface functional group is important for the dendritic effect in water.
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We report anthracene-diurea compounds which behave as anion sensors based on the fluorescence emission regulated by the substitution position on the anthracene ring. Anthracene-diurea compounds exhibit different excited-state intermolecular proton transfer (ESIPT) reactions depending on the pattern of the substituents. Three new anthracene-diurea compounds that have two phenylurea groups substituted at different positions on anthracene were synthesized. These compounds formed complexes with acetate ions through intermolecular hydrogen bonding between N-H and C[double bond, length as m-dash]O moieties in the ground state. The positions of the substituents greatly affected the excited-state intermolecular proton transfer. 1,5BPUA with urea groups at the 1 and 5 positions exhibited ESIPT reaction, which is energetically favorable for tautomer formation, in the presence of TBAAc. In contrast, 2,6BPUA with urea groups at low-electron-density positions (2 and 6 positions) showed no ESIPT reaction due to the inversion of the lowest unoccupied molecular orbital (LUMO) energy levels of the normal and tautomer states. Detailed spectroscopic measurements showed that the LUMO energy level of the normal form was lowered because the urea group acted as an electron-withdrawing group. In addition, 9,10BPUA exhibited strong electronic interactions between the two phenylurea moieties at the 9 and 10 positions, resulting in an ON1-OFF-ON2 response for acetate ions. Our findings offer guidelines for the molecular design of materials with anthracene moieties based on the substitution patterns of anthracene derivatives.
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The photodimerization reaction of anthracene derivatives was performed by capitalizing on intermolecular hydrogen bonds. Anthracene derivatives that can control the dimerization reaction depending on the substitution site were designed by using two anthryl moieties and one urea group, referred to as N,N'-dianthracen-n-ylurea, nDAU (n = 1, 2 and 9), which are symmetrically substituted by 1-anthryl, 2-anthryl and 9-anthryl groups, respectively. We investigated the excimer emission and photodimerization reaction of these anthracene-urea derivatives using absorption, emission, and (1)H NMR spectroscopy along with fluorescence decay measurements. All derivatives showed a concentration dependence of their fluorescence spectra and multiple fluorescence lifetime components even at 10(-6) M. Significantly, 9DAU resulted in an intermolecular photodimerization reaction. These differences in photoreactivity of nDAU may depend on variations in the overlap of the intermolecularly associated anthracene rings of nDAU by hydrogen bonding between intermolecular urea moieties. Furthermore, the dimerization quantum yield of 9DAU was reduced by the addition of tetrabutylammonium acetate (TBAAc). Consequently, we revealed that the substitution site and the addition of TBAAc affected the dimerization reaction of anthracene-urea derivatives.
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The mechanism of photosensitized protein damage byphosphorus(V) tetraphenylporphyrin derivatives (P(V)TPPs) wasquantitatively clarified. P(V)TPPs bound to human serum albumin(HSA), a water-soluble protein, and damaged its tryptophan residueduring photoirradiation. P(V)TPPs photosensitized singlet oxygen ((1)O(2))generation, and the contribution of (1)O(2) to HSA damage was confirmedby the inhibitory effect of sodium azide, a (1)O(2) quencher. However,sodium azide could not completely inhibit HSA damage, suggesting thecontribution of an electron transfer mechanism to HSA damage. Thedecrement in the fluorescence lifetime of P(V)TPPs by HSA supportedthe electron transfer mechanism. The contribution of these processes could be determined by the kinetic analysis of the effect ofsodium azide on the photosensitized protein damage by P(V)TPPs.
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Fósforo/química , Processos Fotoquímicos , Porfirinas/química , Albumina Sérica/química , Albumina Sérica/efeitos da radiação , Oxigênio Singlete/análise , Transporte de Elétrons , Humanos , Modelos Moleculares , Estrutura Molecular , Oxigênio Singlete/metabolismo , Azida Sódica/farmacologiaRESUMO
In this paper, a dynamic releasing approach is proposed for high-speed biological cell manipulation. A compact parallel mechanism for grasping and releasing microobjects is used to generate controllable vibration to overcome the strong adhesion forces between the end effector and the manipulated object. To reach the required acceleration of the end effector, which is necessary for the detachment of the target object by overcoming adhesion forces, vibration in the end effector is generated by applying sinusoidal voltage to the PZT actuator of the parallel mechanism. For the necessary acceleration, we focus on the possible range of the frequency of the PZT-actuator-induced vibration, while minimizing the amplitude of the vibration (14 nm) to achieve precise positioning. The effect of the air and liquid environments on the required vibration frequency for successful release is investigated. For the first time, release results of microbeads and biological cells are compared. Release of the biological cells with 100 % success rate suggests that the proposed active release method is an appropriate solution for adhered biological cells during the release task.
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Adesão Celular/fisiologia , Movimento Celular/fisiologia , Separação Celular/instrumentação , Sistemas Microeletromecânicos/instrumentação , Micromanipulação/instrumentação , Robótica/instrumentação , Células 3T3 , Animais , Desenho de Equipamento , Análise de Falha de Equipamento , Camundongos , Miniaturização , VibraçãoRESUMO
We report herein the selective preparation of normal, tautomeric, and dual-fluorescent molecules with a common ESIPT core. 2'-Hydroxyacetophenone (OHAP) is known as a typical molecule that undergoes excited-state intramolecular hydrogen transfer (ESIPT) to display fluorescence emission from the excited state of the tautomer. In this study, a series of ten OHAP-cored fluorescent molecules were prepared and their excited state properties have been explored. The bathochromic shift of the π-π* absorption band with π-extensions of substituents of these molecules indicates that the excitation energy of the normal form of the OHAP unit was reduced due to the substituents, while the energy of the excited tautomer appeared to be independent of the π-extension of the substituents. When pyrene or anthracene was connected at the end (molecules 4 and 5), only normal fluorescence appeared, and the tautomer fluorescence disappeared. An anthracene derivative (molecule 10) displayed dual fluorescence, indicating that the normal and the tautomer excited states were energetically "balanced". A fluorescence lifetime analysis revealed the ESIPT reaction rate of 10 to be much slower than those of other derivatives and that the normal and tautomer forms were in equilibrium in the excited state.
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A dipyrrin complex has been one of the most utilized fluorescent dyes, and a variety of dipyrrin complexes show intriguing functions based on the various coordination structures of the central element. We now report the synthesis, structure, and photophysical properties of germanium and stannane complexes of the N2O2-type tetradentate dipyrrin, L·Ge and L·Sn, which are heavier analogues of the previously reported dipyrrin silicon complex, L·Si. The central group-14 atoms of the monomeric complexes have geometries close to trigonal bipyramidal (TBP), in which the contribution of the square-pyramidal (SP) character becomes higher as the central atom is heavier. Interestingly, L·Sn formed a dimeric structure in the crystal. All complexes L·Si, L·Ge, and L·Sn showed a fluorescence in the red/NIR region. Fluorescence quantum yields of L·Ge and L·Sn are higher than that of L·Si. These results indicated that the central atom on the dipyrrin complexes contributes not only to the geometry difference but also to tuning the fluorescence properties.
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Complexos de Coordenação/química , Germânio/química , Pirenos/química , Silício/química , Estanho/química , Cristalografia por Raios X , Luminescência , Modelos MolecularesRESUMO
Introduction: This study aimed to elucidate the relationship between interactions with everyday objects (e.g., stationery, clothing, and tools) and one's connectedness with nature, environmentally conscious behavior, and life satisfaction. While previous research has predominantly explored the link between awareness of and behavior toward nature with direct education and experience related to the natural environment, we focused on the origins of the objects that surround us, which are inherently derived from nature. Methods: We conducted an online survey with 1,102 Japanese participants, who completed an object-interaction measure assessing the two dimensions of care and learning, and measures of connectedness with nature, pro-environmental behavior, and life satisfaction. Results: Interactions with everyday objects involving care and learning were significantly associated with a sense of connectedness with nature, pro-environmental behavior, and life satisfaction. Discussion: The study highlights that interactions with everyday artifacts are not isolated experiences but are related to broader awareness of and behavior toward the natural world, and with individual life satisfaction. Hence, environmental awareness and actions can extend beyond direct environmental experiences and encompass daily interactions with objects. Future research could examine how cultural factors shape the relationship between human-object interactions, connection with nature, environmentally conscious behavior, and life satisfaction.
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Acoustohydrodynamic micromixers offer excellent mixing efficiency, cost-effectiveness, and flexible controllability compared with conventional micromixers. There are two mechanisms in acoustic micromixers: indirect influence by induced streamlines, exemplified by sharp-edge micromixers, and direct influence by acoustic waves, represented by surface acoustic wave micromixers. The former utilizes sharp-edge structures, while the latter employs acoustic wave action to affect both the fluid and its particles. However, traditional micromixers with acoustic bubbles achieve significant mixing performance and numerous programmable mixing platforms provide excellent solutions with wide applicability. This review offers a comprehensive overview of various micromixers, elucidates their underlying principles, and explores their biomedical applications. In addition, advanced programmable micromixing with impressive versatility, convenience, and ability of cross-scale operations is introduced in detail. We believe this review will benefit the researchers in the biomedical field to know the micromixers and find a suitable micromixing method for their various applications.