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Background: The stability of Alzheimer’s disease (AD) biomarkers in plasma, measured by immunomagnetic reduction (IMR) after long-term storage at –80°C, has not been established before. Method: Ninety-nine human plasma samples from 53 normal controls (NCs), 5 patients with amnestic mild cognitive impairment (aMCI), and 41 AD patients were collected. Each plasma sample was aliquoted and stored as single-use aliquots at –80°C. The baseline measurements for Aβ1–40, Aβ1–42, and total Tau protein (T-Tau) concentrations for each sample were done within 3 months of blood draw by IMR. They are referred to as baseline concentrations. A separate aliquot from each sample was assayed with IMR to assess the stability of the measured analytes during storage at –80°C between 1.1 and 5.4 years. This is referred to as a repeated result. Results: IMR shows that plasma levels of Aβ1–40 and Aβ1–42 exhibit stability over 5-year storage at –80°C and that plasma levels of T-Tau are less stable (approximately 1.5 years). Conclusion: Although the measured concentrations of T-Tau in human plasma may alter during storage, the diagnostic utility of the results are only slightly affected when the product of Aβ1–42 and T-Tau concentrations are used. The results show that the overall agreement between baseline and repeated measurements in the ability of discriminating NCs from aMCI/AD patients is higher than 80%.

Introduction Concentrations of plasma biomarkers associated with Alzheimer’s disease have been reported to be as low as several tens of picograms/milliliter (pg/ml). However, in assays measuring these biomarkers, it is likely that repeated measurements are necessary to obtain reliable values. Methods We performed assays as a single test or as duplicate, quadruplicate, fivefold and tenfold repeated tests, on samples spiked with different concentrations of amyloid β 1–40 (Aβ1–40; 1–1000 pg/ml), Aβ1–42 (1–30,000 pg/ml) and total Tau protein (T-Tau; 0.1–1000 pg/ml), with the aim to to calculate the coefficients of variation (CVs). Results The results demonstrated common changes in the CVs with changes in the number of tests for a given sample: the CVs decreased with increases in the number of tests from one to ten. All CV values were distributed within the range of 0.35 to 15.5%; as such, the CV values were all lower than the acceptable value of 20%. Conclusion Based on this study, a single assay of Aβ1–40, Aβ1–42 and T-Tau, respectively, provides reliable results in terms of the measurement of that plasma biomarker.

ZnO nanowires (NWs) were directly grown on ductile zinc foil by thermal oxidation at 500 °C. The highly crystalline ZnO NWs exhibited bidirectional growth preferentially oriented in the [101] orientation. The ZnO NWs were highly resistant to hydroxyl groups and water compared with Zn foil that was oxidized naturally. The narrow excitonic photoluminescence (PL) peak combined with strongly suppressed visible emission demonstrated the high optical quality of the NWs. The binding energies of the donor bands and an acceptor band were obtained through temperature-dependent PL analysis. The NWs would be suitable for flexible planar UV device applications.

ZnO nanowires (NWs) were directly grown on ductile zinc foils through a two-step process: (a) large, thin, and ductile Zn foils were fabricated from a mixture of Zn and ZnO powders; and (b) ZnO NWs were produced by thermal oxidation at temperatures of 300–600 °C. The ZnO NWs presented preferential growth in the [101] orientation. The highly crystalline NWs synthesized at 500 °C exhibited a bidirectional mode with an angle of approximately 60° between their longitudinal axes. On foils oxidized at 600 °C, the NWs evolved into nanotowers. The photoluminescence (PL) spectra showed strong peaks at approximately 368 nm and weaker peaks at approximately 374 nm in the UV region; moreover, a broad deep-level-related green emission peak was recorded at approximately 520 nm in the visible region. The PL green emission line was strongly suppressed for the samples produced at higher oxidation temperatures, which indicated good optical qualities. These good optical qualities, combined with the bidirectional mode and the ductility of the foil, are expected to be useful for flexible planar device applications. The electrical properties of a single ZnO NW were investigated. I–V measurements revealed the Schottky characteristics of the NWs and the resistivity of the ZnO NWs was measured to be ∼93 Ω cm.

Sensor Web and Internet of Things (IoT) (SW-IoT) have been attracting attention from various fields. Both of them deploy networks of embedded devices to monitor physical properties (i.e., sensing capability) or to be controlled (i.e., tasking capability). One of the most important tasks to realize the SW-IoT vision is to establish an open and interoperable architecture, across the device layer, gateway layer, service layer, and application layer. To achieve this objective, many organizations and alliances propose standards for different layers. Among the standards, Open Geospatial Consortium (OGC) SensorThings API is arguably one of the most complete and flexible service standards. However, the SensorThings API only address heterogeneity issues in the service layer. Embedded devices following proprietary protocols need to join closed ecosystems and then link to the SensorThings API ecosystem via customized connectors. To address this issue, one could first follow another device layer and gateway layer open standards and then perform data model mapping with the SensorThings API. However, the data model mapping is not always straightforward as the standards were designed independently. Therefore, this research tries to propose a more direct solution to unify the entire SW-IoT architecture by extending the SensorThings API ecosystem to the gateway layer and the device layer. To be specific, this research proposes SW-IoT Plug and Play (IoT-PNP) to achieve an automatic registration procedure for embedded devices. The IoT-PNP contains three main components: (1) A description file describing device metadata and capabilities, (2) a communication protocol between the gateway layer and the device layer for establishing connections, and (3) an automatic registration procedure for both sensing and tasking capabilities. Overall, we believe the proposed solution could help achieve an open and interoperable SW-IoT end-to-end architecture based on the OGC SensorThings API.

Long-range electronic interaction between Bismuth (Bi) adatoms on graphene formed on a 4H-SiC (0 0 0 1) substrate are clearly observed at room temperature (T = 300 K). Using scanning tunneling microscopy (STM) and density functional theory (DFT) calculations, we have demonstrated that such oscillatory interaction results mainly from the mediation of graphene Dirac-like electrons and the effect of the corrugated surface of SiC substrate. These two factors cause the observed oscillatory interaction with characteristic distribution distances and linear arrangements of Bi adatoms. The present study sheds light on understanding and controlling the nucleation of adatoms and subsequent growth of nanostructures on graphene surface.

In this paper, a high-T c SQUID-based nuclear magnetic resonance (NMR) spectrometer was set up in National Taiwan University Hospital to discriminate liver tumor. In order to overcome the surrounding noise, a four-layer Al shielded box and a cylindrical magnetic shield were employed to avoid the electromagnetic noise in the coils part and the SQUID part, respectively. For NMR measurement, the larmor frequency is varying with time due to the variation of static field in hospital. Therefore, the time-domain frequency adjusted average method guided by a fluxgate was used to correct the frequency variation and average the NMR signal in the time domain. For tumor discrimination, the T 1 relaxation times of normal tissue and tumor tissue were demonstrated. Our high-T c SQUID-based low-field MRI system shows the feasibility for biomedical application in a clinic environment.

Immunomagnetic reduction (IMR), which involves the use of antibody-functionalized magnetic nanoparticles to specifically label target biomarkers, was utilized to develop an assay for total tau protein in human plasma. The analytic properties of the IMR assay on tau protein were investigated. The limit of detection was found to be 0.026 pg/ml. Other properties such as Hook effect, assay linearity, dilution recovery range, reagent stability, interference test, and spiked recovery were also characterized. The ultra-sensitive IMR assay was applied to detect the plasma tau protein levels of subjects with prevalent neurodegenerative diseases, such as Alzheimer’s disease (AD), mild cognitive impairment (MCI) due to AD, Parkinson’s disease (PD), frontotemporal dementia (FTD) and vascular dementia (VD). The concentrations of plasma tau protein in patients with VD, PD, MCI due to AD, FTD, and AD patients were higher than that of healthy controls. Using an ROC curve analysis, the cutoff value for discriminating dementia patients from healthy controls was 17.43 pg/ml, resulting in 0.856 and 0.727 for clinical sensitivity and specificity, respectively. The area under the ROC curve was 0.908. These results imply that the IMR plasma tau assay would be useful to screen for prevalent neurodegenerative diseases.

In this work, high-quality antibody functionalized Fe3O4magnetic nanoparticles are synthesized. Such physical characterizations as particle morphology, particle size, stability, and relaxivity of magnetic particles are investigated. The immunoreactivity of biofunctionalized magnetic nanoparticles is examined by utilizing immunomagnetic reduction. The results show that the mean diameter of antibody functionalized magnetic nanoparticles is around 50 nm, and the relaxivity of the magnetic particles is 145 (mM·s)−1. In addition to characterizing the magnetic nanoparticles, the feasibility of using the antibody functionalized magnetic nanoparticles for the contrast medium of target magnetic resonance imaging is investigated. These antibody functionalized magnetic nanoparticles are injected into mice bearing with tumor. The tumor magnetic-resonance image becomes darker after the injection and then recovers 50 hours after the injection. The tumor magnetic-resonance image becomes the darkest at around 20 hours after the injection. Thus, the observing time window for the specific labeling of tumors with antibody functionalized magnetic nanoparticles was found to be 20 hours after injecting biofunctionalized magnetic nanoparticles into mice. The biopsy of tumor is stained after the injection to prove that the long-term darkness of tumor magnetic-resonance image is due to the specific anchoring of antibody functionalized magnetic nanoparticles at tumor.

The nucleation and sintering characteristics of Co on ZnO(1010) during annealing were investigated by scanning tunneling microscopy (STM). The extent of coverage and annealing temperature were varied to modify the size of the Co nanoclusters. Temperature-dependent X-ray photoemission spectra of the Co chemical state reveal that metallic Co dominates the annealing procedure on ZnO(1010) and is more thermally stable than Co on both ZnO(0001) and ZnO(0001). The effects of annealing time and the distribution of Co adatoms were elucidated by STM. The results have potential implications for the thermal stability of Co/ZnO(1010) in real catalytic processes.

α-Synuclein is critical to the pathogenesis of Parkinson's disease (PD). Few studies examined the plasma levels of α-synuclein due to the exceptionally low level of α-synuclein in plasma compared with cerebrospinal fluid. We aimed to investigate plasma α-synuclein in patients with PD of different disease severity.There were total 114 participants, including 80 patients with PD and 34 controls, in the study. Participants received a complete evaluation of motor and non-motor symptoms, including cognitive function. We applied immunomagnetic reduction-based immunoassay to measure plasma levels of α-synuclein.Plasma levels of α-synuclein were significantly higher in patients with PD compared with controls (median: 1.56 pg/mL, 95% CI 1.02 to 1.98 pg/mL vs 0.02 pg/mL, 95% CI 0.01 to 0.03 pg/mL; p0.0001). Although there was a significant increase in plasma α-synuclein levels in PD patients with a higher Hoehn-Yahr (H-Y) stage, there was no correlation with motor symptom severity, as assessed by Unified Parkinson's Disease Rating Scale part III scores, after confounders (age, gender, and disease duration) were taken into account. However, plasma α-synuclein levels were significantly higher in PD patients with dementia (PDD) than in PD patients with mild cognitive impairment (PD-MCI) or normal cognition (0.42 pg/mL, (95% CI 0.25 to 0.93) for PD with normal cognition; 1.29 pg/mL (95% CI 0.76 to 1.93) for PD-MCI and 4.09 pg/mL (95% CI 1.99 to 6.19) for PDD, p0.01) and were negatively correlated with Mini-Mental State Examination scores (ROur data suggest that plasma α-synuclein level correlates with cognitive decline but not motor severity in patients with PD. Plasma α-synuclein could serve as a surrogate biomarker for patients at risk of cognitive decline.

This study elucidates the epitaxial growth structure and chemical state of Co on the ZnO(1010) surface by using scanning tunneling microscopy, reflection high-energy electron diffraction, X-ray photoelectron spectroscopy, and ultraviolet photoelectron spectroscopy. The well-ordered cobalt oxide (CoOx)(2 × 1) structure is formed at 0.5 ML Co coverage. Increasing the Co coverage from 0.7 to 1 ML allows for the surface characterization by the Co stripe structure, while the Co metallic clusters are clearly developed above 3 ML Co coverage. Coverage-dependent measurements of the Co chemical state indicate that the initial Co mixed oxidation and metallic state exists at submonolayer and gradually transfers to a metallic Co-dominated state. The results also suggest that the initial growth mode is two-dimensional-like and bridged to three-dimensional at higher Co coverages.

Nuclear magnetic resonance and imaging (NMR/MRI) of optically pumped (OP) hyperpolarized 3He were studied by using a high-Tc SQUID magnetometer device in microtesla magnetic fields. The OP cell was filled with a few milligrams of Rb metal, 0.0798 bar N2 gas and 0.705 bar 3He gas. The 3He cell had been hyperpolarized at an optical pumping system for 5 ~ 6 hours first; then it was moved to the SQUID-detected nuclear magnetic resonance and imaging system to measure. An appropriate B1 pulse level and time duration generated a 5° low flip angle of polarization. The free induction decay NMR signals were measured. The spin-lattice relaxation time (T1) of 3He was 4.7 hours. We improved the line width of NMR spectrum to 0.8 Hz by compensating the inhomogeneous gradient field of environment. The filtered back projection image of hyperpolarized 3He could show a clear image in one shot. The SQUID-detected NMR/MRI would be a great interest for biological imaging.

In this work, a study of hepatocellular carcinoma and normal livers in rats using nuclear magnetic resonance (NMR) based on superconducting quantum interference devices (SQUIDs) was presented. The time domain free induction decay signals, Sy(t), of cancerous liver tissue and control liver tissue of rats were measured to study the respective longitudinal relaxation rate T1-1 . The NMR data were fitted to [1-exp(-TBp/T1)] to derive the longitudinal relaxation times T1 for cancerous liver tissue and control liver tissue. It is found that T1, cancer of cancerous liver tissues is 2.3 times higher than T1, control of control liver tissues. Statistically the data suggest that T1, cancer/T1, control can be used to discriminate cancerous liver tissue from control tissue. Furthermore, differentiating cancerous tissues from control tissues was demonstrated using magnetic fluid phantoms as phantoms for cancerous and control tissues. The SQUID-detected NMR/MRI exhibits potential applications in clinical research.

The fabrication processes for step-edge high- Tc superconducting-quantum-interference-device (SQUID) magnetometers have been developed. A magnetometer consists of three SQUIDs, which can be activated either individually or in series. Thus, the transfer function can be manipulated by activating a single SQUID or multiple SQUIDs in series. Furthermore, such a SQUID magnetometer is benefited by that if one of the three SQUIDs is broken, the other two SQUIDs are still workable. In addition to characterizing the SQUID magnetometer, the application of the SQUID magnetometer in the low-field nuclear magnetic resonance (NMR) has also been investigated. The results has shown a clear NMR signal of 4230 Hz for the water under 99.3 μT.

Background It is difficult to discriminate healthy subjects and patients with Parkinson disease (PD) or Parkinson disease dementia (PDD) by assaying plasma α-synuclein because the concentrations of circulating α-synuclein in the blood are almost the same as the low-detection limit using current immunoassays, such as enzyme-linked immunosorbent assay. In this work, an ultra-sensitive immunoassay utilizing immunomagnetic reduction (IMR) is developed. The reagent for IMR consists of magnetic nanoparticles functionalized with antibodies against α-synuclein and dispersed in pH-7.2 phosphate-buffered saline. A high-Tc superconducting-quantum-interference-device (SQUID) alternative-current magnetosusceptometer is used to measure the IMR signal of the reagent due to the association between magnetic nanoparticles and α-synuclein molecules. Results According to the experimental α-synuclein concentration dependent IMR signal, the low-detection limit is 0.3 fg/ml and the dynamic range is 310 pg/ml. The preliminary results show the plasma α-synuclein for PD patients distributes from 6 to 30 fg/ml. For PDD patients, the concentration of plasma α-synuclein varies from 0.1 to 100 pg/ml. Whereas the concentration of plasma α-synuclein for healthy subjects is significantly lower than that of PD patients. Conclusions The ultra-sensitive IMR by utilizing antibody-functionalized magnetic nanoparticles and high-Tc SQUID magnetometer is promising as a method to assay plasma α-synuclein, which is a potential biomarker for discriminating patients with PD or PDD.

To improve graphene-based multifunctional devices at nanoscale, a stepwise and controllable fabrication procedure must be elucidated. Here, a series of structural transition of bismuth (Bi) adatoms, adsorbed on monolayer epitaxial graphene (MEG), is explored at room temperature. Bi adatoms undergo a structural transition from one-dimensional (1D) linear structures to two-dimensional (2D) triangular islands and such 2D growth mode is affected by the corrugated substrate. Upon Bi deposition, a little charge transfer occurs and a characteristic peak can be observed in the tunneling spectrum, reflecting the distinctive electronic structure of the Bi adatoms. When annealed to ~500 K, 2D triangular Bi islands aggregate into Bi nanoclusters (NCs) of uniform size. A well-controlled fabrication method is thus demonstrated. The approaches adopted herein provide perspectives for fabricating and characterizing periodic networks on MEG and related systems, which are useful in realizing graphene-based electronic, energy, sensor and spintronic devices.

A highly sensitive immunoassay, the immunomagnetic reduction, is used to measure several biomarkers for plasma that is related to Alzheimer's disease (AD). These biomarkers include Aβ-40, Aβ-42, and tau proteins. The samples are composed of four groups: healthy controls (n=66), mild cognitive impairment (MCI, n=22), very mild dementia (n=23), and mild-to-serve dementia, all due to AD (n=22). It is found that the concentrations of both Aβ-42 and tau protein for the healthy controls are significantly lower than those of all of the other groups. The sensitivity and the specificity of plasma Aβ-42 and tau protein in differentiating MCI from AD are all around 0.9 (0.88-0.97). However, neither plasma Aβ-42 nor tau-protein concentration is an adequate parameter to distinguish MCI from AD. A parameter is proposed, which is the product of plasma Aβ-42 and tau-protein levels, to differentiate MCI from AD. The sensitivity and specificity are found to be 0.80 and 0.82, respectively. It is concluded that the use of combined plasma biomarkers not only allows the differentiation of the healthy controls and patients with AD in both the prodromal phase and the dementia phase, but it also allows AD in the prodromal phase to be distinguished from that in the dementia phase.

Nanomagnetically labeled immunoassays have been demonstrated to be promisingly applied in clinical diagnosis. In this work, by using antibody-functionalized magnetic nanoparticles and a high-temperature superconducting quantum interference device ac magnetosusceptometer, the assay properties for vascular endothelial growth factor (VEGF) in serum are investigated. By utilizing the assay method so-called immunomagnetic reduction, the properties of assaying VEGF are explored. In addition, the VEGF concentrations in serum samples of normal people and patients with either colorectal or hepatocellular cancer are detected. The experimental results show that the low-detection limit for assaying VEGF is 10 pg/mL, which is much lower than the clinical cut-off VEGF concentration of 50 pg/mL for diagnosing malignancy. Besides, there are no significant interference effects on assaying VEGF from hemoglobin, conjugated bilirubin, and triglyceride. The VEGF concentrations in serum samples donated by normal people and patients with hepatocellular carcinoma or colorectal cancer are detected. A clear difference in VEGF concentrations between these two groups is found. These results reveal the feasibility of applying nanomagnetically labeled immunoassay to clinics.

Chien-Hsi Chang,1 Zhi-Xian Lai,1 Hsiu-Li Lin,2 Che-Chuan Yang,3 Hsin-Hsien Chen,3,4 Shieh-Yueh Yang,5 Herng-Er Horng,3 Chin-Yih Hong,6 Hong-Chang Yang,4 Hsiu-Chen Lin1,71Department of Laboratory Medicine, Taipei Medical University Hospital, 2Department of Neurology, General Cathay Hospital, Sijhih Branch, 3Institute of Electro-optical Science and Technology, National Taiwan Normal University, 4Department of Physics, National Taiwan University, 5MagQu Co, Ltd, Sindian District, New Taipei City, 6Department of Mechanical Engineering, Nan-Kai University of Technology, Nan-tau County, 7Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, TaiwanBackground: Magnetic nanoparticles biofunctionalized with antibodies are able to recognize and bind to the corresponding antigens. In this work, anti-C-reactive protein (CRP) antibody was covalently conjugated onto the surface of magnetic nanoparticles to label CRP specifically in serum.Methods: The level of serum CRP was detected by immunomagnetic reduction (IMR) assay, which identifies the changes in the magnetic signal representing the level of interaction between antibody-conjugated magnetic nanoparticles and CRP proteins. To investigate the feasibility of IMR for clinical application, pure CRP solutions and 40 human serum samples were tested for IMR detection of CRP to characterize sensitivity, specificity, and interference.Results: In comparison with the immunoturbidimetry assay, the results of the IMR assay indicated higher sensitivity and had a high correlation with those of the current immunoturbidimetry assay.Conclusion: We have developed a novel and promising way to assay CRP in human serum using immunomagnetic reduction in clinical diagnosis.Keywords: magnetic nanoparticles, immunomagnetic reduction, C-reactive protein

In this study, we report the spin-lattice relaxation rate of hepatocellular carcinoma (HCC) and normal liver tissue in rats using a high-T(c) superconducting quantum interference device (SQUID) based nuclear magnetic resonance (NMR) spectrometer. The resonance spectrometer used for discriminating liver tumors in rats via the difference in longitudinal relaxation time in low magnetic fields was set up in a compact and portable magnetic shielding box. The frequency-domain NMR signals of HCC tissues and normal liver tissues were analyzed to study their respective longitudinal relaxation rate T(1) (-1). The T(1) (-1) of liver tissues for ten normal rats and ten cancerous rats were investigated respectively. The averaged T(1) (-1) value of normal liver tissue was (6.41±0.66) s(-1), and the averaged T(1) (-1) value of cancerous tissue was (3.38±0.15) s(-1). The ratio of T(1) (-1) for normal liver tissues and cancerous liver tissues of the rats investigated is estimated to be 1.9. Since this significant statistical difference, the T(1) (-1) value can be used to distinguish the HCC tissues from normal liver tissues. This method of examining liver and tumor tissues has the advantages of being convenient, easy to operate, and stable.

Based on in situ scanning probe microscopy/spectroscopy, this study investigates the stabilization of Zn-terminated ZnO polar plane using surface defects. O-terminated surface defects on a nanometer scale, which have two morphologies, i.e., hexagonal cavities and small pits, are observed at the submonolayer depth on the (0001)-Zn surface by applying medium-energy ${\text{Ar}}^{+}$ bombardment (2.5 keV) at a high temperature $(850\text{ }\ifmmode^\circ\else\textdegree\fi{}\text{C})$. Experimental results indicate that the local electronic structure of O-terminated surface defects exhibits upward band bending with respect to the Zn-terminated surface, which is consistent with the observations made using Kevin probe microscopy, in which the ZnO polar surface has a locally reversed electrostatic field. Moreover, pair-distribution analysis indicates that the O-terminated surface defects with diameters below 0.9 nm are charged with one electron per pit, thus helping to compensate for the internal polarization.

This work reports an enhanced polarization and mechanisms in optically pumped (OP) hyperpolarized $^{3}\mathrm{He}$ in the presence of $^{4}\mathrm{He}$. The cells contain Rb metal, 60-torr ${\mathrm{N}}_{2}$, and different pressures of $^{3}\mathrm{He}$ and $^{4}\mathrm{He}$. In the absence of $^{4}\mathrm{He}$, the polarization of $^{3}\mathrm{He}$ increases monotonically from 4.5% to 8% when the pressure of $^{3}\mathrm{He}$ is increased from 300 to 1500 torr. In the presence of 1850-torr $^{4}\mathrm{He}$ gas, the polarization of $^{3}\mathrm{He}$ is enhanced from 7% to 30% for a cell containing 600-torr $^{3}\mathrm{He}$ and 60-torr ${\mathrm{N}}_{2}$. The wall relaxation factors $X$ for OP cells with and without buffering $^{4}\mathrm{He}$ gas were derived. It was found that the $^{4}\mathrm{He}$ gas confines the $^{3}\mathrm{He}$ atoms to a diffusion-limited region which effectively reduces the wall relaxation factor $X$. Mechanisms contributed to relaxation are addressed and discussed.

In this work, the time-dependent phase lag θ of biofunctionalized magnetic nanoparticles (BMNs) conjugated with biotargets is studied with a home-made alternating current (ac) susceptometor for liquid phase immunoassays. The sensing unit of the ac susceptometor composed of excitation, pick-up, and compensation coils are balanced to 0.03 ppm. The BMNs are anti-goat C-reactive protein coated onto dextran-coated magnetic nanoparticles composed of Fe3O4, labeled as Fe3O4-antiCRP. The bio-targets are human CRP. As the human CRP is conjugated with reagents Fe3O4-antiCRP, the magnetic clusters of Fe3O4-antiCRP-CRP are formulated. Due to the clustering effect, the Brownian relaxation of BMNs will be depressed, which in turn enhances the effective relaxation time. By monitoring the dynamic phase lag, we demonstrate a sensitive platform of assaying human CRP. The detection platform is robust, easy to use and can be applied for assaying a wide variety of biotargets including viruses, proteins, tumor markers, chemicals, etc.

Resonant coupling schemes are commonly used in SQUID-based ultra-low field (ULF) nuclear magnetic resonance (NMR) systems to couple the spin relaxation signals from samples to the SQUID. Generally, in NMR systems, a resonant coupling scheme is composed of two solenoid coils which are made of enamel insulated wires and a capacitor connected in series. In this work, we tried to replace the metal solenoid input coil with a planar high-Tc superconducting spiral coil to improve the signal-to-noise ratio (SNR) of the ULF NMR signal. A measurement of the free induction decay signal of water protons was performed to demonstrate the improved performance of the system. This improvement is due to the fact that the planar superconducting spiral coil possesses a higher mutual inductance with the SQUID. Therefore, it is a promising way to enhance the SNR of high-Tc SQUID-based ULF NMR/MRI systems.

The HTS superconducting quantum interference devices (SQUID) magnetometers meets the requirement for the early-stage or hard-to-detect in-vitro diagnosis because of its ultrahigh sensitivity. For example, the demand for assaying the ultra-low-concentration biomarkers of tumors is always existing. It would be better to quantitatively detect the vascular endothelial growth factor (VEGF) at the concentration of 1 pg/ml for diagnosing the early-stage malignancy. In this work, by using the HTS SQUID-based ac magnetosusceptometer and biofunctionalized magnetic nanoparticles, the low-detection limit for VEGF is sub-pg/ml. Furthermore, the clear difference in the VEGF concentrations in sera was found between normal people and tumor patients. Another example to demonstrate the high sensitivity and high specificity of the immunoassay based on the HTS SQUID ac magnetosusceptometer is the detection of biomarkers for Alzheimer's Disease. The biomarkers for Alzheimer's Disease in plasma are very rare (around 1-100 pg/ml). It is hardly possible to assay the biomarkers in plasma. Here, it has been demonstrated that the HTS SQUID ac magnetosusceptometer can detect the biomarkers at very low concentrations ( ~ 1 pg/ml). Through the assays on the biomarkers in plasma of more than 100 people, the clinical accuracy is almost 90%. These results show the niches of clinical applications using the HTS SQUID ac magnetosusceptometer.

In this work, the relaxation rates of ferrofluids are characterized using a high-Tc SQUID-based nuclear magnetic resonance spectrometer in different field strengths and temperatures. It was found that the longitudinal relaxation rate, 1/T1, of ferrofluids measured in a high field strength is significantly higher than that measured in a low field strength. We attribute this to the magnetic-field gradients from the magnetization of magnetic nanoparticles that accelerate the T1-relaxation more in a high strength of magnetic fields than they are in a low strength of magnetic fields. Furthermore, T1 and T2 decrease when temperature increases, where T2 is the transverse relaxation time. This is due to the improved field-homogeneity seen by protons' spins at high temperatures, attributed to the enhanced Brownian motion of magnetic nanoparticles. Characterizing the relaxation rates will be helpful for further use of ferrofluids as contrast agents in low-field MR imagings.

Immunomagnetic reduction assay is used to quantitatively detect bio-molecules. Many reports show that the to-be-detected bio-molecular concentration dependent reduction in the alternative-current (ac) magnetic susceptibility of a reagent is governed by the logistic function, which is a four-parameter function. One of the parameters relates to the increase in the rate of the magnetic reduction signal when the concentration of to-be-detected bio-molecules is increased. Theoretically, this parameter is attributed to the clustering associations between to-be-detected bio-molecules and labeling particles in the reagent. In an immunomagnetic reduction assay, the bioactive labeling particles are anti-body-functionalized magnetic nanoparticles. However, there is no detailed information about the effect of the clustering associations on this parameter. In this work, the clustering association is manipulated by controlling the concentrations of anti-body-functionalized magnetic nanoparticles in the reagent. The experimental results show that higher values for this parameter are obtained with concentrated anti-body-functionalized magnetic nanoparticles in the reagent. This implies that particle clustering is enhanced by an increase in the concentration of the bio-functionalized magnetic particles. It is also demonstrated that the particle clustering effect dominates the increased rate of the magnetic reduction signal.

In this work, the spin-spin relaxation rate, 1/T2, and spin-lattice relaxation rate, 1/T1, of protons’ spins induced by biofunctionalized magnetic nanoparticles and ferrofluids are investigated using a high-Tc superconducting quantum interference device-detected magnetometer in ultra-low fields. The biofunctionalized magnetic nanoparticles are the anti-human C-reactive protein (antiCRP) coated onto dextran-coated superparamagnetic iron oxides Fe3O4, which is labeled as Fe3O4-antiCRP. The ferrofluids are dextran-coated iron oxides. It was found that both 1/T2 and 1/T1 of protons in Fe3O4-antiCRP are enhanced by the presence of magnetic nanoparticles. Additionally, both the 1/T1 and 1/T2 of Fe3O4-antiCRP are close to that of ferrofluids, which are dextran-coated Fe3O4 dispersed in phosphate buffer saline. Characterizing the relaxation of Fe3O4-antiCRP can be useful for biomedical applications.

In this paper, we report an enhanced liver tumor discrimination for rats using antibody-activated magnetic nanoparticles (MNs) and ultra-low-field magnetic resonance imaging ex vivo. It was found that the intensity ratio between the magnetic resonance image of tumor and normal liver tissues is 2–3 absence of antibody-activated MNs in rats. The intensity ratio rises to ∼100 when antibody-activated MNs are expressed in liver tumors through vein injection. Enhancing tumor discrimination using antibody-activated MNs is demonstrated using T1-weighted contrast imaging in ultra-low magnetic fields.

In this paper, we investigate the field-dependent T1-relaxation and T1-contrast imaging of ferrofluids using high-Tc superconducting quantum interference device (SQUID)-detected nuclear magnetic resonance and imaging in low magnetic fields, where T1 is the spin-lattice relaxation time. It was found that the 1/T1 of ferrofluids increases when the prepolarization field increases. We attribute this to the enhanced magnetic-field gradients generated from the induced magnetization that accelerates the T1-relaxation more in a high strength of fields in comparison to a low strength of fields. Using phantoms with different relaxation times, the T1-contrast images are demonstrated in low magnetic fields, which can be promising for discriminating tumors.

By specifically bio-functionalizing magnetic nanoparticles, magnetic nanoparticles are able to label target bio-molecules. This property can be applied to quantitatively detect molecules invitro by measuring the related magnetic signals of nanoparticles bound with target molecules. One of the magnetic signals is the reduction in the mixed-frequency ac magnetic susceptibility of suspended magnetic nanoparticles due to the molecule-particle association. Many experimental results show empirically that the molecular-concentration dependent reduction in ac magnetic susceptibility follows the logistic function. In this study, it has been demonstrated that the logistic behavior is originated from the growth of particle sizes due to the molecule-particle association. The analytic relationship between the growth of particle sizes and the reduction in ac magnetic susceptibility is developed.