Hsin Hsien Chen

Time-Evolution contrast of target MRI using high-stability antibody functionalized magnetic nanoparticles: an animal model

In this work, high-quality antibody functionalized Fe3O4 magnetic 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 (mMċs)-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.

Combined Plasma Biomarkers for Diagnosing Mild Cognition Impairment and Alzheimer’s Disease

A highly sensitive immunoassay, the immunomagnetic reduction, is used to measure several biomarkers for plasma that is related to Alzheimers 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.

Enhancement of nuclear magnetic resonance in microtesla magnetic field with prepolarization field detected with high-Tc superconducting quantum interference device

We applied prepolarization field and high-Tc superconducting quantum interference device (SQUID) detector to enhance nuclear magnetic resonance signal in a microtesla magnetic field. The minimum measuring magnetic field is 8.9μT at which the proton resonance frequency is 380Hz. The specificity instrumentation and the difficulty of using a high-Tc SQUID with prepolarization field were investigated. We applied gradient field to perform one-dimensional proton imaging in a microtesla magnetic field. Additionally, low field high-Tc SQUID-based NMR systems are promising in biomagnetic research due to its use, for example, in imaging with hyperpolarized noble gas.

Characterization of tumors using high-Tc superconducting quantum interference device-detected nuclear magnetic resonance and imaging

The characterization of cancerous livers in rats using nuclear magnetic resonance and magnetic resonance imaging (NMR/MRI) based on high-Tc superconducting quantum interference devices (SQUIDs) is presented. The T1−1 were observed to be 6.5±0.5 s−1 for controlled livers and 2.85±0.2 s−1 for cancerous livers, which indicate that the T1 can be used to distinguish the cancerous tissues from controlled liver tissues. The intensity ratio for tap water, cancerous tissue, and controlled tissue, respectively, is 1:1.15:0.56 at TBp=1 s. The SQUID-detected NMR/MRI exhibits potential applications in research and clinics.

Effect of molecule-particle binding on the reduction in the mixed-frequency alternating current magnetic susceptibility of magnetic bio-reagents

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.

Enhancement in low field nuclear magnetic resonance with a high-Tc superconducting quantum interference device and hyperpolarized H3e

In this work, we present a design that improves signals produced by nuclear magnetic resonance (NMR) and magnetic resonance imaging by using optical pumping and a high-Tc superconducting quantum interference device (SQUID) magnetometer. In our design for a NMR detection system, a pickup coil is coupled to the spin procession of a H3e nucleus; the input coil is coupled to a high-Tc SQUID magnetometer; and the capacitor is connected in series to form a tank circuit resonating at the Larmor frequency of the H3e nucleus in the measuring field. A signal-to-noise ratio gain of 2.67 over a conventional Faraday detection coil was obtained with the high-Tc SQUID detection system in a measuring magnetic field equaling 0.1128 mT, at which the central frequency was 3.66 kHz for H3e nucleus. The improvement in the NMR signal for large-size, hyperpolarized H3e coupled to a high-Tc SQUID-based spectrometer in low magnetic fields at room temperature is significant compared to that without flux coupling. This result may b...

A study of J-coupling spectroscopy using the Earth’s field nuclear magnetic resonance inside a laboratory

In this paper, an instrumentation of the Earths field nuclear magnetic resonance (EFNMR) inside a laboratory is presented. A lock-in analysis (LIA) technique was proposed to enhance the signal-to-noise ratio (SNR). A SNR of 137.8 was achieved in a single measurement for 9 ml tap water, and the LIA technique significantly enhanced the SNR to 188 after a 10-average in a noisy laboratory environment. The proton-phosphorus coupling in trimethyl phosphate ((CH(3)O)(3)PO) with J-coupling J[H,F]=(10.99±0.013) Hz has been demonstrated. The LIA technique improves the SNR, and a 2.6-fold improvement in SNR over that of the frequency-adjusted averaging is achieved. To reduce the noise in EFNMR, it was suggested that the LIA technique and the first order gradient shim be used to achieve a subhertz linewidth.

Use of immunomagnetic reduction for C-reactive protein assay in clinical samples

Background: 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.

Time-dependent phase lag of biofunctionalized magnetic nanoparticles conjugated with biotargets studied with alternating current magnetic susceptometor for liquid phase immunoassays

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, chemica...

Plasma α-synuclein predicts cognitive decline in Parkinson's disease

Objective 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. Methods 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. Results 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; p<0.0001). 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, p<0.01) and were negatively correlated with Mini-Mental State Examination scores (R2-adjusted=0.3004, p<0.001), even after confounder adjustment. Conclusions Our 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.