Ultrasound-Induced Magnetic Imaging of Tumors Targeted by Biofunctional Magnetic Nanoparticles.

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.

Rapid and quantitative discrimination of tumour cells on tissue slices.

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.

Magnetic Clustering Effect during the Association of Biofunctionalized Magnetic Nanoparticles with Biomarkers.

We report herein an investigation into dynamic magnetic clustering that occurs during immunoassays as biofunctionalized magnetic nanoparticles (BMNs) become associated with biotargets. We measure the dynamic effective relaxation time τeff(t) and use scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to investigate the C-reactive protein (CRP) as it associates with the BMN Fe3O4-antiCRP to form the magnetic cluster Fe3O4-antiCRP-CRP. The results indicate that τeff(t) increases with increasing association time. In addition, the ration Δτeff/τ0 as a function of CRP concentration follows a characteristic logistic function, which provides a basis for estimating the quantity of biomolecules with a detection sensitivity close to 0.1 ppm. After the association, SEM and TEM images show that CRP and Fe3O4-antiCRP conjugate to form Fe3O4-antiCRP-CRP clusters hundreds of nanometers in size. The SEM and TEM images provide direct evidence of the formation of magnetic clustering.

Using bio-functionalized magnetic nanoparticles and dynamic nuclear magnetic resonance to characterize the time-dependent spin-spin relaxation time for sensitive bio-detection.

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.

Spatial repolarization heterogeneity detected by magnetocardiography correlates with cardiac iron overload and adverse cardiac events in beta-thalassemia major.

BACKGROUND: Patients with transfusion-dependent beta-thalassemia major (TM) are at risk for myocardial iron overload and cardiac complications. Spatial repolarization heterogeneity is known to be elevated in patients with certain cardiac diseases, but little is known in TM patients. The purpose of this study was to evaluate spatial repolarization heterogeneity in patients with TM, and to investigate the relationships between spatial repolarization heterogeneity, cardiac iron load, and adverse cardiac events. METHODS AND RESULTS: Fifty patients with TM and 55 control subjects received 64-channel magnetocardiography (MCG) to determine spatial repolarization heterogeneity, which was evaluated by a smoothness index of QTc (SI-QTc), a standard deviation of QTc (SD-QTc), and a QTc dispersion. Left ventricular function and myocardial T2* values were assessed by cardiac magnetic resonance. Patients with TM had significantly greater SI-QTc, SD-QTc, and QTc dispersion compared to the control subjects (all p values<0.001). Spatial repolarization heterogeneity was even more pronounced in patients with significant iron overload (T2*<20 ms, n = 20) compared to those with normal T2* (all p values<0.001). Loge cardiac T2* correlated with SI-QTc (r = -0.609, p<0.001), SD-QTc (r = -0.572, p<0.001), and QTc dispersion (r = -0.622, p<0.001), while all these indices had no relationship with measurements of the left ventricular geometry or function. At the time of study, 10 patients had either heart failure or arrhythmia. All 3 indices of repolarization heterogeneity were related to the presence of adverse cardiac events, with areas under the receiver operating characteristic curves (ranged between 0.79 and 0.86), similar to that of cardiac T2*. CONCLUSIONS: Multichannel MCG demonstrated that patients with TM had increased spatial repolarization heterogeneity, which is related to myocardial iron load and adverse cardiac events.

QTc Heterogeneity in Rest Magnetocardiography is Sensitive to Detect Coronary Artery Disease: In Comparison with Stress Myocardial Perfusion Imaging.

BACKGROUND: Stress nuclear myocardial perfusion imaging (MPI) is an established method for diagnosis and prognosis of coronary artery disease (CAD). However, radiation exposure limits its clinical application. Magnetocardiography (MCG) has been proposed as a non-contact, rapid and non-radiation technique with high reproducibility. The aim of the study was to evaluate the diagnostic efficacy of rest MCG in CAD comparing to stress MPI. METHODS: We prospectively enrolled 55 patients with suspected CAD (64 ± 10 years) who were scheduled for coronary angiography (CA). MCG, stress (201)Tl MPI and CA were performed within 3 months. The spatial distribution maps of QTc interval (21 × 21 in resolution) were derived from a 64-channel MCG system (KRISS, Korea). T-wave propagation mapping, repolarization heterogeneity index with QTc dispersion and smoothness index of QTc (SI-QTc) were analyzed, and the diagnostic criteria for CAD were developed based on the receiver operating characteristic (ROC) curve analysis. RESULTS: Patients with significant CAD (≥ 70% luminal stenosis, n = 36) had higher QTc dispersion and SI-QTc than controls (both p < 0.05). The diagnostic sensitivity and specificity were 0.8330, 0.6842 for QTc dispersion ≥ 79 ms; 0.7778, 0.6842 for SI-QTc ≥ 9.1 ms; and 0.8611, 0.6842 for combination. There was no difference of area under ROC curve by using criteria of QTc dispersion ≥ 79 ms, SI-QTc ≥ 9.1 ms or combination (0.7588, 0.7310, 0.7727, p = NS), and non-inferior to stress MPI (p = NS). CONCLUSIONS: The QTc heterogeneity parameters of rest MCG yield a good sensitivity and acceptable specificity for detection of CAD, and may provide an alternative to stress MPI without stress and radiation. KEY WORDS: Coronary artery disease (CAD); Magnetocardiography (MCG); Myocardial perfusion imaging (MPI); Repolarization.

Anti-CEA-functionalized superparamagnetic iron oxide nanoparticles for examining colorectal tumors in vivo.

Although the biomarker carcinoembryonic antigen (CEA) is expressed in colorectal tumors, the utility of an anti-CEA-functionalized image medium is powerful for in vivo positioning of colorectal tumors. With a risk of superparamagnetic iron oxide nanoparticles (SPIONPs) that is lower for animals than other material carriers, anti-CEA-functionalized SPIONPs were synthesized in this study for labeling colorectal tumors by conducting different preoperatively and intraoperatively in vivo examinations. In magnetic resonance imaging (MRI), the image variation of colorectal tumors reached the maximum at approximately 24 h. However, because MRI requires a nonmetal environment, it was limited to preoperative imaging. With the potentiality of in vivo screening and intraoperative positioning during surgery, the scanning superconducting-quantum-interference-device biosusceptometry (SSB) was adopted, showing the favorable agreement of time-varied intensity with MRI. Furthermore, biological methodologies of different tissue staining methods and inductively coupled plasma (ICP) yielded consistent results, proving that the obtained in vivo results occurred because of targeted anti-CEA SPIONPs. This indicates that developed anti-CEA SPIONPs owe the utilities as an image medium of these in vivo methodologies.

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 Alzheimer's disease (AD). These biomarkers include Aß-40, Aß-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 Aß-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 Aß-42 and tau protein in differentiating MCI from AD are all around 0.9 (0.88-0.97). However, neither plasma Aß-42 nor tau-protein concentration is an adequate parameter to distinguish MCI from AD. A parameter is proposed, which is the product of plasma Aß-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.

A temperature-stable cryo-system for high-temperature superconducting MR in-vivo imaging.

To perform a rat experiment using a high-temperature superconducting (HTS) surface resonator, a cryostat is essential to maintain the rat's temperature. In this work, a compact temperature-stable HTS cryo-system, keeping animal rectal temperature at 37.4°C for more than 3 hours, was successfully developed. With this HTS cryo-system, a 40-mm-diameter Bi2Sr2Ca2Cu3Ox (Bi-2223) surface resonator at 77 K was demonstrated in a 3-Tesla MRI system. The proton resonant frequency (PRF) method was employed to monitor the rat's temperature. Moreover, the capacity of MR thermometry in the HTS experiments was evaluated by correlating with data from independent fiber-optic sensor temperature measurements. The PRF thermal coefficient was derived as 0.03 rad/°C and the temperature-monitoring architecture can be implemented to upgrade the quality and safety in HTS experiments. The signal-to-noise ratio (SNR) of the HTS surface resonator at 77 K was higher than that of a professionally made copper surface resonator at 300 K, which has the same geometry, by a 3.79-fold SNR gain. Furthermore, the temperature-stable HTS cryo-system we developed can obtain stable SNR gain in every scan. A temperature-stable HTS cryo-system with an external air-blowing circulation system is demonstrated.

Usefulness of magnetocardiography to detect coronary artery disease and cardiac allograft vasculopathy.

BACKGROUND: Electrophysiological information as well as anatomic information are important for the detection of coronary artery lesions. The aim of this study was to assess the efficacy of resting magnetocardiography (MCG) in stable coronary artery disease (CAD) and cardiac allograft vasculopathy (CAV). METHODS AND RESULTS: MCG and coronary angiography were performed within 1 month in 75 patients with suspected CAD and in 26 subjects after orthotopic heart transplantation (OHT). Plaque volumes were additionally measured on intravascular ultrasound in OHT recipients. The spatially distributed QT(c) interval maps were constructed with 64-channel MCG. A T-wave propagation map and QT(c) heterogeneity index including QT(c) dispersion and smoothness index of QT(c) (SI-QT(c)) were derived for ischemia detection and localization. CAD patients had higher QT(c) dispersion and SI-QT(c). Receiver operating characteristic curve analysis identified SI-QT(c) ≥9 ms, QT(c) dispersion ≥79 ms as the optimal cut-off for detecting CAD (diagnostic accuracy, 0.7953, 0.7819), better than T-wave propagation (0.6594, P<0.05). There was no significant difference of QT(c) dispersion between CAD and OHT subjects. In OHT recipients, QT(c) dispersion positively correlated with plaque volume, and SI-QT(c) progressively increased after transplantation. Using T-wave propagation mapping, regionally increased dispersion could be demonstrated in CAD patients, but increased dispersion was noted in fewer OHT recipients. CONCLUSIONS: MCG is clinically feasible as a non-invasive tool for diagnosis of CAD, and could be used as a surrogate marker of CAV.

A noninvasive method to determine the fate of Fe(3)O(4) nanoparticles following intravenous injection using scanning SQUID biosusceptometry.

Magnetic nanoparticles (MNPs) of Fe(3)O(4) have been widely applied in many medical fields, but few studies have clearly shown the outcome of particles following intravenous injection. We performed a magnetic examination using scanning SQUID biosusceptometry (SSB). Based on the results of SSB analysis and those of established in vitro nonmagnetic bioassays, this study proposes a model of MNP metabolism consisting of an acute metabolic phase with an 8 h duration that is followed by a chronic metabolic phase that continues for 28 d following MNP injection. The major features included the delivery of the MNPs to the heart and other organs, the biodegradation of the MNPs in organs rich with macrophages, the excretion of iron metabolites in the urine, and the recovery of the iron load from the liver and the spleen. Increases in serum iron levels following MNP injection were accompanied by increases in the level of transferrin in the serum and the number of circulating red blood cells. Correlations between the in vivo and in vitro test results indicate the feasibility of using SSB examination for the measurement of MNP concentrations, implying future clinical applications of SSB for monitoring the hematological effects of MNP injection.

Discriminating hepatocellular carcinoma in rats using a high-Tc SQUID detected nuclear resonance spectrometer in a magnetic shielding box.

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.

In vivo screening of hepatocellular carcinoma using AC susceptibility of anti-alpha fetoprotein-activated magnetic nanoparticles.

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.

Enlargement of the field of view and maintenance of a high signal-to-noise ratio using a two-element high-Tc superconducting array in a 3T MRI.

This study examines the enlargement of the field of view (FOV) and the maintenance of a high signal-to-noise ratio (SNR) through the use of two high-temperature superconducting (HTS) resonators in a 3T MRI. Two Bi(2)Sr(2)Ca(2)Cu(3)O(x) (Bi-2223) surface resonators, each of 4-cm diameter, were used in a 3T MRI. Professionally made copper resonators operate at 300 K, but each Bi-2223 resonator, operated at 77 K and demonstrated a 3.75 fold increase in SNR gain. For the same scanning time, the SNR of the images of a rat's brain and back, obtained using two small Bi-2223 surface resonators, was higher than that obtained using a single 8-cm surface resonator.

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.

Characteristics of magnetic labeling on liver tumors with anti-alpha-fetoprotein-mediated Fe3O4 magnetic nanoparticles.

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 Fe(3)O(4) 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.

Feasibility studies for assaying alpha-fetoprotein using antibody-activated magnetic nanoparticles.

Some previous reports have already shown the characterizations of immunomagnetic reduction (IMR). The assay technology involves the utilities of biofunctionalized magnetic nanoparticles to label target biomolecules. However, the detection threshold and interference tests for IMR have not been investigated in detail. In this study, alpha-fetoprotein (AFP) was used as a target biomolecule. The signals for AFP solutions of various concentrations, or with interfering materials, were detected via IMR. These samples were also used for characterizing the detection threshold and interference with enzyme-linked immunosorbent assay (ELISA). The results of assaying AFP level with IMR and ELISA were compared. The detection threshold for assaying AFP with IMR was found to be 3 ng/mL, which is 15 times lower than that of ELISA, and definitely suppresses false negative. For the interfering materials noted commonly in serum such as hemoglobin, bilirubin, triglyceride, and vascular endothelial growth factor, there was no detectable interfering effect when assaying AFP with IMR. Several serum samples from normal people and liver-tumor-bearing patients were used for the detections of AFP concentration via IMR. These results reveal the feasibilities of assaying AFP in blood using IMR, as well as achieving high-sensitive and high-specific assay for AFP.

Whole body screening using high-temperature superconducting MR volume resonators: mice studies.

High temperature superconducting (HTS) surface resonators have been used as a low loss RF receiver resonator for improving magnetic resonance imaging image quality. However, the application of HTS surface resonators is significantly limited by their filling factor. To maximize the filling factor, it is desirable to have the RF resonator wrapped around the sample so that more nuclear magnetic dipoles can contribute to the signal. In this study, a whole new Bi(2)Sr(2)Ca(2)Cu(2)O(3) (Bi-2223) superconducting saddle resonator (width of 5 cm and length of 8 cm) was designed for the magnetic resonance image of a mouse's whole body in Bruker 3 T MRI system. The experiment was conducted with a professionally-made copper saddle resonator and a Bi-2223 saddle resonator to show the difference. Signal-to-noise ratio (SNR) with the HTS saddle resonator at 77 K was 2.1 and 2 folds higher than that of the copper saddle resonator at 300 K for a phantom and an in-vivo mice whole body imaging. Testing results were in accordance with predicted ones, and the difference between the predicted SNR gains and measured SNR gains were 2.4%∼2.7%. In summary, with this HTS saddle system, a mouse's whole body can be imaged in one scan and could reach a high SNR due to a 2 folds SNR gain over the professionally-made prototype of copper saddle resonator at 300 K. The use of HTS saddle resonator not only improves SNR but also enables a mouse's whole body screen in one scan.

Exploration of the relationship between the tumor burden and the concentration of vascular endothelial growth factor in liver-cancer-bearing animals using immunomagnetic reduction assay.

To achieve early-stage diagnosis, a high-sensitivity assay method is needed. As a biomarker, vascular endothelial growth factor (VEGF) has played a growing role in diagnosing and treating hepatocellular carcinoma (HCC). In this work, an immunomagnetic reduction (IMR) through bio-functionalized magnetic nanoparticles and a high-temperature superconducting-quantum-interference-device magnetometer were utilized for quantitative detection of low-concentration VEGF in serum from rats with HCC. The precision and accuracy of IMR on VEGF were characterized. Further, the results of assaying VEGF in the serum of rats were compared with those of using enzyme-linked immunosorbant assay (ELISA). It was found the correlations between the detected VEGF concentration in the rat serum and tumor burdens were 0.99 and 0.90 for IMR and ELISA, respectively, within the range from 2 pg/ml to 8000 pg/ml of VEGF concentration.

Biofunctionalized magnetic nanoparticles for specifically detecting biomarkers of Alzheimer's disease in vitro.

Magnetic nanoparticles biofunctionalized with antibodies against ß-amyloid-40 (Aß-40) and Aß-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-Aß antibody. In combination with immunomagnetic reduction technology, it is demonstrated such biofunctionalized magnetic nanoparticles are able to label Aßs specifically. The ultralow-detection limits of assaying Aßs 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 Aß-40 and Aß-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 Aßs as reagents for assaying low-concentration Aßs through immunomagnetic reduction, and also provide a promising new method for early diagnosis of Alzheimer's disease from human blood plasma.