Minhong Jeun

Electrical signaling of enzyme-linked immunosorbent assays with an ion-sensitive field-effect transistor.

Optical laboratory-based immunoassays, such as enzyme-linked immunosorbent assay (ELISA) give a high sensitivity and specificity of various fatal diseases. However, these assays are no longer efficient in on-spot diagnostics of wide-spreading and contagious infections. At this point in time, portable and handhold devices play a pivotal role in infectious diseases with quick diagnostics at or near the site of the disease propagation. In this paper, we demonstrated a novel electrical immunoassay of ELISA that was not based on optical signaling but on electrical signaling. This was done by combining an ion-sensitive field-effect transistor (ISFET) with ELISA. By harnessing the catalytic reaction of alkaline phosphatase that precipitated silver particles, we effectively overcame the chronic Debye screening length issue of the ISFET. Ultimately, small signal ranging from 1 pg/mL to 10 ng/mL was immensely amplified with the ALP label, regardless of buffer conditions. The sensor platform herein surpassed a sensing capability of conventional ELISA that is considered to have a LOD on the order of ~1 ng/mL. The results were compared with those of horseradish peroxidase label, which is generally used for optical analyses in ELISA. Our newly developed ISFET-based portable sensor holds a large potential for point-of-care tools in a variety of diseases, without being limited by the need for expensive equipment such as spectrophotometers.

Diagnosis of prostate cancer via nanotechnological approach

Prostate cancer is one of the leading causes of cancer-related deaths among the Caucasian adult males in Europe and the USA. Currently available diagnostic strategies for patients with prostate cancer are invasive and unpleasant and have poor accuracy. Many patients have been overly or underly treated resulting in a controversy regarding the reliability of current conventional diagnostic approaches. This review discusses the state-of-the-art research in the development of novel noninvasive prostate cancer diagnostics using nanotechnology coupled with suggested diagnostic strategies for their clinical implication.

Zebrafish models for Functional and Toxicological Screening of Nanoscale Drug Delivery Systems: Promoting Preclinical Applications

Preclinical screening with animal models is an important initial step in clinical translation of new drug delivery systems. However, establishing efficacy, biodistribution, and biotoxicity of complex, multicomponent systems in small animal models can be expensive and time-consuming. Zebrafish models represent an alternative for preclinical studies for nanoscale drug delivery systems. These models allow easy optical imaging, large sample size, and organ-specific studies, and hence an increasing number of preclinical studies are employing zebrafish models. In this review, we introduce various models and discuss recent studies of nanoscale drug delivery systems in zebrafish models. Also in the end, we proposed a guideline for the preclinical trials to accelerate the progress in this field.

A strategy to minimize the sensing voltage drift error in a transistor biosensor with a nanoscale sensing gate

An ion-sensitive field-effect transistor (ISFET) biosensor is thought to be the center of the next era of health diagnosis. However, questions are raised about its functions and reliability in liquid samples. Consequently, real-life clinical applications are few in number. In this study, we report a strategy to minimize the sensing signal drift error during bioanalyte detection in an ISFET biosensor. A nanoscale SnO2 thin film is used as a gate oxide layer (GOL), and the surface of the GOL is chemically modified for improving bioanalyte-specific binding and for reducing undesirable ion reactions in sample solutions. The ISFET biosensor with surface-modified GOL shows significantly reduced sensing signal error compared with an ISFET with bare GOL in both diluted and undiluted phosphate buffered saline solutions.

Detection of Avian Influenza Virus from Cloacal Swabs Using a Disposable Well Gate FET Sensor

Current methods to detect avian influenza viruses (AIV) are time consuming and lo inw sensitivity, necessitating a faster and more sensitive sensor for on-site epidemic detection in poultry farms and urban population centers. This study reports a field effect transistor (FET) based AIV sensor that detects nucleoproteins (NP) within 30 minutes, down to an LOD of 103 EID50 mL-1 from a live animal cloacal swab. Previously reported FET sensors for AIV detection have not targeted NPs, an internal protein shared across multiple strains, due to the difficulty of field-effect sensing in a highly ionic lysis buffer. The AIV sensor overcomes the sensitivity limit with an FET-based platform enhanced with a disposable well gate (DWG) that is readily replaceable after each measurement. In a single procedure, the virus-containing sample is immersed in a lysis buffer mixture to expose NPs to the DWG surface. In comparison with commercial AIV rapid kits, the AIV sensor is proved to be highly sensitive, fast, and compact, proving its potential effectiveness as a portable biosensor.

Self-Normalized Detection of ANXA3 from Untreated Urine of Prostate Cancer Patients without Digital Rectal Examination

A noninvasive quantitative assay that is capable of identifying prostate cancer biomarkers in untreated urine is an attractive diagnosis tool, but this method is subject to various obstacles. Difficulties presented by untreated urine include varying salt concentrations, and pH levels that may be different even though they are from the same patient. Untreated urine also presents interference from other biomolecules and possesses a fewer number of cancer biomarkers than can be found in serum. As a result, urine preconditioning processes and digital rectal examination (DRE) to increase biomarker secretion are mandatory in current urine assays. To address these challenges, an ion-responsive urine sensor (IRUS) that measures differential electrical signals is proposed as a self-normalized detection method. The proposed IRUS is based on a FET biosensor with a disposable sensing gate and has the capability to detect the prostate cancer antigen ANXA3 in untreated patient urine. The IRUS can detect ANXA3 at <1 fg mL-1 with high reliability. In addition, it is found that ANXA3 levels in urine show clinically significant correlation with real tumor volumes. This paper provides a guideline in developing a clinically ready accurate noninvasive platform, which is capable of predicting prostate cancer using untreated urine without DRE.

Field-Effect Biosensors for On-Site Detection: Recent Advances and Promising Targets

There is an explosive interest in the immediate and cost-effective analysis of field-collected biological samples, as many advanced biodetection tools are highly sensitive, yet immobile. On-site biosensors are portable and convenient sensors that provide detection results at the point of care. They are designed to secure precision in highly ionic and heterogeneous solutions with minimal hardware. Among various methods that are capable of such analysis, field-effect biosensors are promising candidates due to their unique sensitivity, manufacturing scalability, and integrability with computational circuitry. Recent developments in nanotechnological surface modification show promising results in sensing from blood, serum, and urine. This report gives a particular emphasis on the on-site efficacy of recently published field-effect biosensors, specifically, detection limits in physiological solutions, response times, and scalability. The survey of the properties and existing detection methods of four promising biotargets, exosomes, bacteria, viruses, and metabolites, aims at providing a roadmap for future field-effect and other on-site biosensors.

Highly sensitive detection of protein biomarkers via nuclear magnetic resonance biosensor with magnetically engineered nanoferrite particles

Magnetic-based biosensors are attractive for on-site detection of biomarkers due to the low magnetic susceptibility of biological samples. Here, we report a highly sensitive magnetic-based biosensing system that is composed of a miniaturized nuclear magnetic resonance (NMR) device and magnetically engineered nanoferrite particles (NFPs). The sensing performance, also identified as the transverse relaxation (R2) rate, of the NMR device is directly related to the magnetic properties of the NFPs. Therefore, we developed magnetically engineered NFPs (MnMg-NFP) and used them as NMR agents to exhibit a significantly improved R2 rate. The magnetization of the MnMg-NFPs was increased by controlling the Mn and Mg cation concentration and distribution during the synthesis process. This modification of the Mn and Mg cation directly contributed to improving the R2 rate. The miniaturized NMR system, combined with the magnetically engineered MnMg-NFPs, successfully detected a small amount of infectious influenza A H1N1 nucleoprotein with high sensitivity and stability.