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The diagnosis of liquid and solid biopsies by different instruments makes the clinic loading difficult in many aspects. Given the compositions of magnetic particles (MPs) with diverse characterizations and the innovative acoustic type of vibration sample magnetometer (VSM), the versatile, accessible magnetic diagnosis platform was proposed to meet clinical demands, such as low loading for multiple biopsies. In liquid biopsies of alpha-fetoprotein (AFP) standard solutions and subject serums, molecular concentration was analyzed from saturation magnetization by the soft type of Fe3O4 MPs with AFP bioprobe coating. In the phantom mixture simulated as bounded MPs in tissue, the bounded MPs was evaluated from the area of the hysteresis loop by hard type of cobalt MPs without bio-probes coating. Not only a calibration curve was founded for many hepatic cell carcinoma stages, but also microscale images verified the Ms increase due to magnetic protein clusters, etc. Hence, its wide populations in clinics could be expected.

Infections of orchids by the Odontoglossum ringspot virus or Cymbidium mosaic virus cause orchid disfiguration and are a substantial source of economic loss for orchid farms. Although immunoassays can identify these infections, immunoassays are expensive, time consuming, and labor consuming and limited to sampling-based testing methods. This study proposes a noncontact inspection platform that uses a spectrometer and Android smartphone. When orchid leaves are illuminated with a handheld optical probe, the Android app based on the Internet of Things and artificial intelligence can display the measured florescence spectrum and determine the infection status within 3 s by using an algorithm hosted on a remote server. The algorithm was trained on optical data and the results of polymerase chain reaction assays. The testing accuracy of the algorithm was 89%. The area under the receiver operating characteristic curve was 91%, thus, the platform with the algorithm was accurate and convenient for infection screening in orchids.

Background Although the powerful clinical effects of radiofrequency and microwave ablation have been established, such ablation is associated with several limitations, including a small ablation size, a long ablation time, the few treatment positioning, and biosafety risks. To overcome these limitations, biosafe and efficient magnetic ablation was achieved in this study by using biocompatible liquid gallium as an ablation medium and a contrast medium for imaging. Results Magnetic fields with a frequency (f) lower than 200 kHz and an amplitude (H) × f value lower than 5.0 × 109 Am−1 s−1 were generated using the proposed method. These fields could generate an ablation size of 3 cm in rat liver lobes under a temperature of approximately 300 °C and a time of 20 s. The results of this study indicate that biomedical gallium can be used as a contrast medium for the positioning of gallium injections and the evaluation of ablated tissue around a target site. Liquid gallium can be used as an ablation medium and imaging contrast medium because of its stable retention in normal tissue for at least 3 days. Besides, the high anticancer potential of gallium ions was inferred from the self-degradation of 100 µL of liquid gallium after around 21 days of immersion in acidic solutions. Conclusions The rapid wireless ablation of large or multiple lesions was achieved through the simple multi-injection of liquid gallium. This approach can replace the currently favoured procedure involving the use of multiple ablation probes, which is associated with limited benefits and several side effects. Methods Magnetic ablation was confirmed to be highly efficient by the consistent results obtained in the simulation and in vitro tests of gallium and iron oxide as well as the electromagnetic specifics and thermotherapy performance comparison detailed in this study Ultrasound imaging, X-ray imaging, and magnetic resonance imaging were found to be compatible with the proposed magnetic ablation method. Self-degradation analysis was conducted by mixing liquid gallium in acidic solutions with a pH of approximately 5–7 (to imitate a tumour-containing microenvironment). X-ray diffraction was used to identify the gallium oxides produced by degraded gallium ions.

Dementia frequently occurs in Down syndrome (DS) patients, and early intervention is important in its management. We have previously demonstrated a positive correlation of plasma β-amyloid Aβ42 levels and negative correlations of Aβ40 and tau levels with dementia in DS. In this study, we examined more cases and constructed composite scores with both tau and amyloids to correlate with dementia in DS. Plasma Aβ42, Aβ40, and tau proteins were measured by an immunomagnetic reduction assay in DS patients. Data were randomly and repeatedly split into training and validating sets, and logistic regression was applied to calculate the area under the curve (AUC) for each biomarker. A total of 73 DS patients (among them, 23 had neurodegeneration) and 77 controls were recruited. In DS patients without dementia, plasma Aβ40 and tau levels were highly elevated, but Aβ42 levels were lower than those of the healthy controls. DS patients with dementia, compared with DS patients with no dementia, had a large decline in Aβ40 and tau but a rise in Aβ42. For biomarker scores correlating with dementia, Aβ40 revealed an AUC of 0.912; the composite score of Aβ40 × tau revealed an AUC of 0.953; and a combined composite score of 0.1 for Aβ40 × Tau +0.9 Tau × Aβ40/Aβ42 achieved the highest AUC of 0.965. Therefore, composite biomarker scores including both plasma tau and β-amyloid levels correlate with dementia in DS better than using individual biomarker scores. The pattern of tau decline and Aβ42 rise in DS patients with dementia are also different from previous findings in Alzheimer's disease.

ObjectiveTo examine whether plasma neurofilament light chain (NfL) levels were associated with motor and cognitive progression in Parkinson disease (PD).MethodsThis prospective follow-up study enrolled 178 participants, including 116 with PD, 22 with multiple system atrophy (MSA), and 40 healthy controls. We measured plasma NfL levels with electrochemiluminescence immunoassay. Patients with PD received evaluations of motor and cognition at baseline and at a mean follow-up interval of 3 years. Changes in the Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score and Mini-Mental State Examination score were used to assess motor and cognition progression.ResultsPlasma NfL levels were significantly higher in the MSA group than in the PD and healthy groups (35.8 ± 6.2, 17.6 ± 2.8, and 10.6 ± 2.3 pg/mL, respectively, p < 0.001). In the PD group, NfL levels were significantly elevated in patients with advanced Hoehn-Yahr stage and patients with dementia (p < 0.001). NfL levels were modestly correlated with UPDRS part III scores (r = 0.42, 95% confidence interval 0.46–0.56, p < 0.001). After a mean follow-up of 3.4 ± 1.2 years, a Cox regression analysis adjusted for age, sex, disease duration, and baseline motor or cognitive status showed that higher baseline NfL levels were associated with higher risks for either motor or cognition progression (p = 0.029 and p = 0.015, respectively).ConclusionsPlasma NfL levels correlated with disease severity and progression in terms of both motor and cognitive functions in PD.Classification of evidenceThis study provides Class III evidence that plasma NfL level distinguishes PD from MSA and is a surrogate biomarker for PD progression.

Magnetic tools here are defined as the nanotechnologies for medical diagnosis, including in vitro diagnostics, ex vivo examination, and in vivo imaging by using magnetic nanoparticles (MNPs). In this chapter, we describe the mechanism, instrumentation, and medical results of different advanced magnetic tools.

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.

Biofunctional magnetic nanoparticles (MNPs) have been widely applied in biomedical engineering. MNPs are used as a contrast medium in magnetic imaging. Current methods of magnetic imaging, such as magnetic particle imaging and magnetic relaxometry, use small amounts of MNPs at target points far from the surface of the patient's body; these methods always consume considerable power to produce magnetic fields of high uniformity or gradient excitations. Some drawbacks, such as a limited imaging region, imaging system shielding, and complex algorithms based on assumptions of MNP properties or environmental factors, also limit the application of MNP methods in clinics. Therefore, this work proposes an interdisciplinary methodology of ultrasound-induced magnetic imaging that lacks these drawbacks. In the proposed imaging method, magnet sets were designed with uniform magnetic fields to magnetize MNPs. Besides, magnetized MNPs are subjected to ultrasound vibrations; the motion of the MNPs induces weak induction voltages at the imaging pickup coils. The highly sensitive scanning superconducting quantum interference device biosusceptometry with three sets of ultrasound focus chips was developed to construct magnetic tomography at three depths. A phantom test showed favorable consistency between the visual photos and the magnetic images of alpha-fetoprotein antibody (anti-AFP) MNP distribution on gauzes. In animal tests, rats with liver tumors were imaged at the pre-injection and post-injection of anti-AFP MNPs. The consistent results of magnetic images and ultrasound images implied that the proposed method has high clinical potential.

Background: Changes in beta-amyloids and tau proteins have been noted in patients with Alzheimer’s disease (AD) and patients with both Down syndrome (DS) and AD. However, reports of changes in the early stage of regression, such as behavioral and psychological symptoms of dementia (BPSD), in DS are sparse. Methods: Seventy-eight controls, 62 patients with AD, 35 with DS, and 16 with DS with degeneration (DS_D), including 9 with BPSD and 7 with dementia, were enrolled. The levels of beta-amyloids 40 and 42 (Abeta-40, Abeta-42) and tau protein in the blood were analyzed using immunomagnetic reduction. The Adaptive Behavior Dementia Questionnaire (ABDQ) was used to evaluate the clinical status of the degeneration. Results: The Abeta-40 and tau levels were higher and the Abeta-42 level and Abeta-42/Abeta-40 ratio were lower in DS than in the controls (all p < 0.001). Decreased Abeta-40 and increased Abeta-42 levels and Abeta-42/40 ratios were observed in DS_D compared with DS without degeneration (all p < 0.001). The ABDQ score was negatively correlated with the Abeta-40 level (rho= -0.556) and the tau protein level (rho= -0.410) and positively associated with the Abeta-42 level (rho= 0.621) and the Abeta-42/40 ratio (rho= 0.544) (all p < 0.05). Conclusions: The Abeta-40 and Abeta-42 levels and the Abeta-42/Abeta-40 ratio are considered possible biomarkers for the early detection of degeneration in DS. The elevated Abeta-40 and tau levels in DS may indicate early neurodegeneration. The increased Abeta-42 in DS_D may reflect the neurotoxicity of Abeta-42. The paradox of the tau decreases in DS_D could be explained by a burnout phenomenon during long-term neurodegeneration. The different patterns of the plasma beta amyloids and tau protein may imply a different pathogenesis between Down syndrome with degeneration and Alzheimer’s disease in the general population, in spite of their common key pathological features.

Previous studies have typically indicated that only one composition factor, such as wick structures or working fluids, affects the thermal resistance or critical heat flux of heat pipes. In this study, the composition factors influencing thermal performance, such as wick structures, working fluids, the modulation fields of working fluids, and combinations of these factors, were thoroughly investigated. The evaluated materials comprised microgrooved, sintered, and wickless heat pipes; magnetic nanofluids exhibiting volumetric fractions (vol.) of 0.16%–3.20%; and deionized water. A strong magnetic field of 200 Oe was applied. The results indicated that combining grooved heat pipes and a 0.80% vol. of magnetic nanofluids or sintered heat pipes and a 0.16% vol. of magnetic nanofluids yielded the optimal promotions: the thermal resistance was reduced by approximately 80% and the critical heat flux was enhanced 2.7-fold compared with general wickless heat pipes filled with deionized water. These findings should serve as a valuable reference when designing heat pipe exchangers for use in air-conditioning systems.

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.

Neurofibrillary tangles are associated with cognitive dysfunction, and hippocampal atrophy with increased CSF tau markers. However, the plasma tau levels of Alzheimer's disease (AD) have not been well studied. We investigated plasma tau by using an immunomagnetic reduction assay in 20 patients with mild cognitive impairment (MCI) due to AD, 10 early AD dementia, and 30 healthy eld- ers (HE). All received a 3D-brain MRI scan and a set of cognitive function test. We explored their rela- tionships with both brain structure and cognitive functions. Images were analyzed to determine the brain volumes and gray matter densities. Patients with MCI or early AD had significantly increased plasma tau levels compared with HE. Plasma tau levels were negatively associated with the perform- ance of logical memory, visual reproduction, and verbal fluency; also negatively associated with vol- ume of total gray matter, hippocampus, amygdala; and gray matter densities of various regions.

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.

After a needle biopsy, immunohistochemistry is generally used to stain tissue slices for clinically confirming tumours. Currently, tissue slices are immersed in a bioprobe-linked fluorescent reagent for several minutes, washed to remove the unbound reagent, and then observed using a fluorescence microscope. However, the observation must be performed by experienced pathologists, and producing a qualitative analysis is time consuming. Therefore, this study proposes a novel scanning superconducting quantum interference device biosusceptometry (SSB) method for avoiding these drawbacks. First, stain reagents were synthesised for the dual modalities of fluorescent and magnetic imaging by combining iron-oxide magnetic nanoparticles and the currently used fluorescent reagent. The reagent for the proposed approach was stained using the same procedure as that for the current fluorescent reagent, and tissue slices were rapidly imaged using the developed SSB for obtaining coregistered optical and magnetic images. Analysing the total intensity of magnetic spots in SSB images enables quantitatively determining the tumour cells of tissue slices. To confirm the magnetic imaging results, a traditional observation methodology entailing the use of a fluorescence microscope was also performed as the gold standard. This study determined high consistency between the fluorescent and magnetic spots in different regions of the tissue slices, demonstrating the feasibility of the proposed approach, which will benefit future clinical pathology.

Although there is a consensus on the reduced levels of Aβ1-42 in the CSF of patients with AD, studies of plasma Aβ levels were inconsistent and have limited clinical value. We developed an immunomagnetic reduction assay (IMR) to determine the plasma levels of Aβ. We surveyed patients with varying AD severity (CDR = 0.5, n=16; CDR ≥ 1, n=18) and controls (n=26). Significant group differences were apparent in the levels of Aβ1-42 (F = 5.54, p = 0.002) and the Aβ1-42/Aβ1-40 ratio (F = 24.198, p < 0.001). Post-hoc analyses showed significant differences in the Aβ1-42 levels of controls and AD patients (p = 0.001) and in the Aβ1-42/Aβ1-40 ratio of control, MCI and AD subjects (all p ≤ 0.001). Regression analysis of Aβ1-42/Aβ1-40 ratios on dementia severity showed an adjusted R2 of 0.553 (p = 0.001). We identified a cut-off of 16.1 pg/ml for Aβ1-42 to differentiate control subjects from patients (both AD and MCI) with 85.3% sensitivity and 88.5% specificity. We also obtained a cut-off value of 0.303 for Aβ1-42/Aβ1-40 ratios with 85.3% sensitivity and 96.2% specificity. APOE e4 carriers had significantly higher Aβ1-42/Aβ1-40 ratios than the non-carriers (F = 4.839, p = 0.015). An independent group of case-control subjects validated both cut-off values for Aβ1-42/Aβ1-40 (100% sensitivity and 83.3% specificity) and for Aβ1-42 (100% sensitivity and 75.3% specificity). In a subgroup of longitudinal follow- up study, we found that the plasma Aβ was relatively stable with an interval of approximately 3 months. In conclusion, we found that the plasma Aβ1-42 is a useful biomarker for AD. The Aβ1-42/Aβ1-40 ratio improves the diagnostic power of the plasma Aβ biomarkers. The iron nanoparticles and IMR provides a novel method to measure plasma Aβ and could serve as an important clinical tool for the diagnosis of neurodegenerative diseases.

Magnetic nanoparticles biofunctionalized with antibodies against β-amyloid-40 (Aβ-40) and Aβ-42, which are promising biomarkers related to Alzheimer's disease (AD), were synthesized. We characterized the size distribution, saturated magnetizations, and stability of the magnetic nanoparticles conjugated with anti-Aβ antibody. In combination with immunomagnetic reduction technology, it is demonstrated such biofunctionalized magnetic nanoparticles are able to label Aβs specifically. The ultralow-detection limits of assaying Aβs in vitro using the magnetic nanoparticles via immunomagnetic reduction are determined to a concentration of ∼10 ppt (10 pg/mL). Further, immunomagnetic reduction signals of Aβ-40 and Aβ-42 in human plasma from normal samples and AD patients were analyzed, and the results showed a significant difference between these two groups. These results show the feasibility of using magnetic nanoparticles with Aβs as reagents for assaying low-concentration Aβs through immunomagnetic reduction, and also provide a promising new method for early diagnosis of Alzheimer's disease from human blood plasma.

Via immunomagnetic reduction assay, bio-molecules can be quantitatively detected with the aid of bio-functionalized magnetic nanoparticles, which are used as labeling markers for specific bio-molecules. To achieve an ultra-high sensitivity in the detection of bio-molecules, the superconducting quantum interference device (SQUID) looks very promising as a sensor for the magnetic signal that are related to the concentration of the detected bio-molecules. We had developed a single channel SQUID-based magnetosusceptometer, but for increasing the detection through-put, we have developed a multi-channel SQUID-based magnetosusceptometer. In this work, the design and the working principle of a 4-channel SQUID-based magnetosusceptometer are introduced. By utilizing scanning technology, 4 samples can be logged into a SQUID-based magnetosusceptometer simultaneously. Be noted that only one single SQUID magnetometer has been used in the magnetosusceptometer. The precision and the sensitivity of detecting bio-molecules by using a 4-channel SQUID-based magnetosusceptometer have been investigated. The detected bio-molecules are biomarkers for Alzheimer's disease.

To determine the iron concentration of administrated magnetic nano-particles in animals is essential for evaluation of arrival efficiency in target regions in biomagnetism studies. In this work, a high Tc superconucting quantum interference devices (SQUID) biosusceptometry with a scanning coil set is developed. The measurement principal is based on the AC susceptibility of magnetic nano-particles, and the low noise of 8 pT/√Hz at 400 Hz is characterized in unshielded environment. The dextran-coated magnetic nano-particle of 50 nm in diameter is administrated intravenously into Wistar male rats to demonstrate the in-vivo and fast examination feasibility of this instrument. The in-vivo results of heart region and liver region explained the reasonable biological phenomenon of magnetic nano-particles in animals. Good correlation of concentration-time curve between the induction-coupled-plasma (ICP) and in-vivo examination by AC susceptibility measurement in rat liver region until 4 hours after injection of magnetic naoparticle validates the in-vivo measurement of iron concentration. After 4 hrs post magnetic nanoparticle injection, the phagocyted magnetic nano-particles in liver tissue shows antiferromagnetism properties and explain the difference between the low in-vivo intensity by AC susceptibility measurement and high intensity by ICP.

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.

An alternating-current magnetosusceptometer of antibody-functionalized magnetic nanoparticles (MNPs) was developed for immunomagnetic reduction (IMR). A high-sensitivity, high-critical-temperature superconducting quantum interference device was used in the magnetosusceptometer. Minute levels of biomarkers of early-stage neurodegeneration diseases were detectable in serum, but measuring each biomarker required approximately 4 h. Hence, an eight-channel platform was developed in this study to fit minimal screening requirements for Alzheimer's disease. Two consistent results were measured for three biomarkers, namely Aβ40, Aβ42, and tau protein, per human specimen. This paper presents the instrument configuration as well as critical characteristics, such as the low noise level variations among channels, a high signal-to-noise ratio, and the coefficient of variation for the biomarkers' IMR values. The instrument's ultrahigh sensitivity levels for the three biomarkers and the substantially shorter total measurement time in comparison with the previous single- and four-channels platforms were also demonstrated in this study. Thus, the eight-channel instrument may serve as a powerful tool for clinical high-throughput screening of Alzheimer's disease.

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.

The accredited biomarker alpha-fetoprotein (AFP) offers limited sensitivity and specificity in the early detection of hepatocellular carcinoma (HCC). To improve the screening performance, des-gamma-carboxy prothrombin (DCP) has been identified as another promising biomarker of HCC, combined with AFP biomarkers. The results of the commercial optical enzyme-linked immunosorbent assay (ELISA) kit easily have the interference problem due to the optical methodology. The immunomagnetic reduction (IMR) assay based on the magnetic measurement was utilized to assay DCP biomarkers without the excellent antiinterference performances. A DCP magnetic reagent, composed of iron-oxide (Fe3O4 ) magnetic nanoparticles coated with anti-DCP antibodies solved in phosphoryl-buffer solution, was synthesized and characterized. In the test of standard DCP antigens, superior antiinterference and sensitivity than optical ELISA were proved. In the animal test, the results indicate good agreement between the IMR assay findings and the tumor sizes of HCC rats at all time points after the HCC implantation. The feasibility of the developed DCP magnetic reagent with the IMR for the detection of DCP is verified, and demonstrates the high potential for future clinical applications.

Biofunctionalized magnetic nanoparticles (BMNs) that provide unique advantages have been extensively used to develop immunoassay methods. However, these developed magnetic methods have been used only for specific immunoassays and not in studies of magnetic characteristics of materials. In this study, a common vibration sample magnetometer (VSM) was used for the measurement of the hysteresis loop for different carcinoembryonic antigens (CEA) concentrations (Φ CEA) based on the synthesized BMNs with anti-CEA coating. Additionally, magnetic parameters such as magnetization (M), remanent magnetization (M R), saturation magnetization (M S), and normalized parameters (ΔM R/M R and ΔM S/M S) were studied. Here, ΔM R and ΔM s were defined as the difference between any ΦCEA and zero Φ CEA. The parameters M, ΔM R, and ΔM S increased with Φ CEA, and ΔM S showed the largest increase. Magnetic clusters produced by the conjugation of the BMNs to CEAs showed a ΔM S greater than that of BMNs. Furthermore, the relationship between ΔM S/M S and Φ CEA could be described by a characteristic logistic function, which was appropriate for assaying the amount of CEAs. This analytic ΔM S/M S and the BMNs used in general magnetic immunoassays can be used for upgrading the functions of the VSM and for studying the magnetic characteristics of materials.

Magnetic particle imaging was introduced to an noninvasive method for 3-dimensional imaging tool for tracing the distribution of magnetic particle in vivo. However the proposed method should not only applying a high strength AC magnetic field to induce the third harmonic magnetic signal form the nonlinear magnetized magnetic nanoparticles but also applying three strong gradient fields and three strong magnetic fields to construct a small field-free point (FFP) and scan the FFP for imaging. The strength of gradient field should be several T/m for a high spatial resolution about several mm. It limits the imaging size and the cost of high power supplies for strong scanning magnetic fields is expensive. Here, we propose a new magnetic particle imaging method by using pickup coil array and a strong ac exciting field instead of the gradient fields and scanning field. This method reaches the real time imaging and low cost and promise for the industrialization in the new future.

This article studies, experimentally and theoretically, the thermal performance of cold storage in thermal battery for air conditioning. Thermal battery utilizes the superior heat transfer characteristics of heat pipe and eliminates drawbacks found in the conventional thermal storage tank. Experimental investigations are first conducted to study the cold storage thermal performance in two experimental systems: the ratio of distance between heat pipes to outer diameter of heat pipe W/D=6 and 2. Different heat transfer mechanisms including nucleate boiling, geyser boiling and natural convection are identified in different experimental systems with various liquid fills. A theoretical model to determine the thermal characteristics of the thermal battery has also been developed. Comparisons of this theory with experimental data show good agreements in the nucleate boiling stage of cold storage process.

In this work, we report characterizations of biofunctionalized magnetic nanoparticles (BMNPs) associated with alpha-fetoprotein (AFP) for biomedical applications. The example BMNP in this study is anti-alpha-fetoprotein (anti-AFP) conjugated onto dextran-coated Fe3O4 labeled as Fe3O4-anti-AFP, and the target is AFP. We characterize magnetic properties, such as increments of magnetization ΔMH and effective relaxation time Δτeff in the reaction process. It is found that both ΔMH and Δτeff are enhanced when the concentration of AFP, ФAFP, increases. The enhancements are due to magnetic interactions among BMNPs in magnetic clusters, which contribute extra MH after the association with MH and in turn enhance τeff. The screening of patients carrying hepatocellular carcinoma (HCC) is verified via ΔMH/MH. The proposed method can be applied to detect a wide variety of analytes. The scaling characteristics of ΔMH/MH show the potential to develop a vibrating sample magnetometer system with low field strength for clinic applications.

In this work, we report the use of bio-functionalized magnetic nanoparticles (BMNs) and dynamic magnetic resonance (DMR) to characterize the time-dependent spin-spin relaxation time for sensitive bio-detection. The biomarkers are the human C-reactive protein (CRP) while the BMNs are the anti-CRP bound onto dextran-coated Fe3O4 particles labeled as Fe3O4-antiCRP. It was found the time-dependent spin-spin relaxation time, T2, of protons decreases as time evolves. Additionally, the ΔT2 of of protons in BMNs increases as the concentration of CRP increases. We attribute these to the formation of the magnetic clusters that deteriorate the field homogeneity of nearby protons. A sensitivity better than 0.1 μg/mL for assaying CRP is achieved, which is much higher than that required by the clinical criteria (0.5 mg/dL). The present MR-detection platform shows promise for further use in detecting tumors, viruses, and proteins.

The low limit of detection (LLD) plays an important role in biomolecular assays, especially for early-stage assays. Biomolecular detections usually involve the use of two main elements: a reagent and an analyzer, which both greatly contribute to the LLD. In this work, the relationships among the LLD and reagent-related factors are investigated. The to-be-detected biomolecule is c-reactive protein (CRP) as an example. The assay method is immunomagnetic reduction (IMR). The components of reagent are Fe(3)O(4) magnetic nanoparticles bio-functionalized with antibodies against CRP, dispersed in pH-7.4 phosphate buffered saline solution. Several key factors of the reagent, such as particle concentration, volume ratio of reagent to sample, and particle size, are manipulated to optimize the LLD of detecting CRP.

With antibody-mediated magnetic nanoparticles (MNPs) applied in cancer examinations, patients must pay at least twice for MNP reagents in immunomagnetic reduction (IMR) of in vitro screening and magnetic resonance imaging (MRI) of in vivo tests. This is because the high maintenance costs and complex analysis of MRI have limited the possibility of in vivo screening. Therefore, this study proposes novel methods for in vivo screening of tumors by examining the AC susceptibility of bound MNPs using scanning superconducting-quantum-interference-device (SQUID) biosusceptometry (SSB), thereby demonstrating high portability and improved economy. The favorable agreement between in vivo tests using SSB and MRI demonstrated the feasibility of in vivo screening using SSB for hepatocellular carcinoma (HCC) targeted by anti-alpha fetoprotein (AFP)-mediated MNPs. The magnetic labeling was also proved by in vitro tests using SSB and biopsy assays. Therefore, patients receiving bioprobe-mediated MNPs only once can undergo in vivo screening using SSB in the future.

Kai-Wen Huang,1 Jen-Jie Chieh,2 Herng-Er Horng,2 Chin-Yih Hong,3 Hong-Chang Yang41Department of Surgery and Hepatitis Research Center, National Taiwan University Hospital, Taipei, 2Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei, 3Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung, 4Department of Physics, National Taiwan University, Taipei, TaiwanAbstract: For preoperative and intraoperative detection of tumor distribution, numerous multimodal contrast agents, such as magnetic nanoparticles (MNPs) with several examination indicators, are currently in development. However, complex materials, configuration, and cost are required for multimodal contrast agents, accompanied by a high possibility of toxicity and low popularity in clinics. Nevertheless, the magnetic labeling of MNPs using bioprobes should be feasible not only in preoperative magnetic resonance imaging (MRI), but also in intraoperative examination based on other magnetic properties. In this study, anti-alpha-fetoprotein (AFP)-mediated Fe3O4 MNPs, injected into mice with liver tumors, were used to examine the characteristics of magnetic labeling. Using MRI and scanning superconducting-quantum-interference-device biosusceptometry (SSB), based on alternating current (AC) susceptibility, the magnetic labeling occurred significantly on the first day post-injection of anti-AFP magnetic fluid (MF), and then decreased over time. However, for both MF without antibodies and an anti-carcinoembryonic antigen MF, no magnetic labeling occured on the first day of their respective post-injection. The favorable agreement indicates that magnetic labeling possesses two magnetic characteristics: distortion of the imaging field and AC susceptibility. In addition, the results of the biopsy tests, anti-AFP staining, and Prussian blue staining show the same dynamics as those of magnetic methodologies and prove that bound MNPs on tumor tissue are rotatable by an AC magnetic field to express AC susceptibility. Therefore, with the simple configuration of antibody-mediated MNPs, magnetic labeling is also feasible for intraoperative examinations using SSB with high mobility and sensitivity.Keywords: alpha-fetoprotein, magnetic resonance imaging, scanning SQUID biosusceptometry