Proton-ELISA: Electrochemical immunoassay on a dual-gated ISFET array

Publication date: 15 October 2018
Source:Biosensors and Bioelectronics, Volume 117
Author(s): Duane S. Juang, Ching-Hui Lin, Yi-Ren Huo, Chia-Yu Tang, Chun-Ren Cheng, Hua-Shu Wu, Shih-Fen Huang, Alexander Kalnitsky, Chun-Cheng Lin
Here we report an electrochemical immunoassay platform called Proton-ELISA (H-ELISA) for the detection of bioanalytes. H-ELISA uniquely utilizes protons as an immunoassay detection medium, generated by the enzyme glucose oxidase (GOx) coupled with Fenton's reagent in a proton amplification reaction cascade that results in a highly amplified signal. A proton-sensitive dual-gated ion-sensitive field effect transistor (DG-ISFET) sensor was also developed for sensitive and accurate detection of the proton signal in H-ELISA. The DG-ISFET sensor comprises of a 128 × 128 array of 16,384 sensing transistors each with an individually addressable back gate to allow for a very high signal throughput and improved accuracy. We then demonstrated that the platform could detect C-reactive protein and immunoglobulin E down to concentrations of 12.5 and 125 pg/mL, respectively. We further showed that the platform is compatible with complex biological sample conditions such as human serum, suggesting that the platform is sufficiently robust for potential diagnostic applications.

Graphical abstract

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Interferon gamma transcript detection on T cells based on magnetic actuation and multiplex double-tagging electrochemical genosensing

Publication date: 15 October 2018
Source:Biosensors and Bioelectronics, Volume 117
Author(s): Soledad Carinelli, Cristina Xufré, Mercè Martí, María Isabel Pividori
Interferon-γ is a proinflammatory cytokine, and its production is related with effective host defense against intracellular pathogens. Therefore, the level of interferon-γ is considered a good biomarker for intracellular infections. It is also useful for the assessment, treatment progression and follow-up of non-communicable diseases, including cancer and autoimmune disorders, among others. This work addresses the development of a novel interferon-γ release assay (IGRA) to evaluate the expression of interferon-γ transcripts as biomarker produced by isolated T cells, as a main advantage. The method sequentially combined three different types of magnetic separation, including the immunomagnetic separation of the T cells performed on antiCD3 modified magnetic particles, the retrotranscription and multiplex double-tagging PCR on polydT-modified magnetic particles and, finally, the electrochemical genosensing on streptavidin magnetic particles as a support. This approach is able to quantify the levels of cellular interferon-γ produced by as low as 150 T cells with outstanding analytical features. The detection of interferon-γ transcripts is performed from only 100 μL of whole blood which can be potentially obtained by fingerprick, demonstrating a further clear advantage to be considered as a promising strategy for the quantification of this important biomarker in several clinical applications.



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Double eyelid surgery using palpebral marginal incision technique in Asians

Approximately 50% of Asians do not have upper eyelid creases. To create a double eyelid, full-incision methods may leave obvious scars, and buried-suture methods cannot remove excess tissues. The new palpebral marginal incision technique hided the incision at upper palpebral margin, and removed the excess tissue, achieving scarless and natural double-eyelids.

https://ift.tt/2l7G53n

Anatomic approximation approach to correction of transverse facial clefts

Transverse clefts of the oral cavity have significant impacts on both form and function. Many methods of repair have been described but there is no consensus on optimal approach. In addition, dissatisfaction with scars, distortion of form, and recurrent deformity have led to complex surgical designs that are difficult to understand and to reproduce. We describe a simple approach to repair that is based upon anatomic approximation of lip components and accurate repair of muscle.Twenty patients have undergone repair by the senior author, who devised the approach, and the corresponding author, who adopted it.

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Viability of a modified GoPro for Professional Surgical Videography

There are multiple aspects to consider when deciding upon the best method of filming a surgical procedure. A jib with a precision, remote controlled pan and tilt head is ideal, however these systems are not only expensive, but require the presence of a video operator and the inherent difficulty in maneuverability during surgery. Ease of use, simplicity, and usability of footage are therefore the main factors evaluated in previous papers.2-4 We evaluated common complications of current and previously tested systems to develop a method of high quality surgical videography using a modified GoPro HERO5 video camera from Back-Bone Gear Inc.

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Umbilical varices: A potential pitfall in gastrointestinal bleed scintigraphy interpretation

Sunny J Gandhi

Indian Journal of Nuclear Medicine 2018 33(3):245-247

Tc-99m labeled red blood cell (RBC) scintigraphy is commonly used in the evaluation of acute gastrointestinal (GI) bleeding. On Tc-99m RBC studies, GI bleeding is seen as an initial focus of increased radiotracer activity that on subsequent images increases in intensity and changes position in a pattern that confirms to segments of bowel. We report a case of a patient with multiple episodes of GI bleeding referred to detect the source of bleeding. A Tc-99m labeled RBC scan was performed and the findings showed a focal abnormal hot spot in the mid quadrant of the abdomen, seen promptly in initial dynamic images. Subsequent static and single-photon emission computed tomography-CT (SPECT-CT) images found it to be umbilical varices. Most varices fill promptly as in this case and should not be misinterpreted as a focus of hemorrhage. SPECT-CT should be used in such cases so that that false-positive interpretation can be avoided.

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Bladder leiomyoma: A rare differential and a potential pitfall in the evaluation for a bladder mass in 18F-Fluorodeoxyglucose-positron emission tomography/computed tomography

Abhishek Sharma, Shelvin Kumar Vadi, Ashwani Sood, Santosh Kumar, Uttam Kumar Mete, Mayur Parkhi, Bhagwant Rai Mittal

Indian Journal of Nuclear Medicine 2018 33(3):264-265

18F-Fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG PET/CT) has shown an increasing role in the evaluation of urinary bladder cancer, though benign pathological processes of the urinary bladder can also result in increased FDG uptake. Leiomyomas of urinary bladder are benign mesenchymal neoplasms and a very rare bladder tumor comprising <0.5% of all bladder tumors. Here, we present the low-grade 18FDG uptake in urinary bladder leiomyoma on PET/CT done for the clinical suspicion of bladder cancer, which can be a rare differential for bladder carcinoma.

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Role of 18F-Fluorodeoxyglucose positron-emission tomography/computed tomography scan in primary staging of breast cancer compared to conventional staging

Naveen Kumar Reddy Akepati, Zakir Ali Abubakar, Prathyusha Bikkina

Indian Journal of Nuclear Medicine 2018 33(3):190-193

Aim: In newly diagnosed carcinoma breast cancer patients, comparing conventional staging and 18F-fluorodeoxyglucose positron-emission tomography–computed tomography (18F-FDG PET/CT) staging. Materials and Methods: This was a retrospective observational study. A total of 171 new diagnosed carcinoma breast patients who underwent staging 18F-FDG PET/CT scan and routine conventional imaging including mammosonography of breast and axilla, chest X-ray, ultrasound sonography abdomen, and bone scan were included in the study. Staging was done according to the American Joint Committee on Cancer staging (tumor-node-metastasis). Changes in staging and management with 18F-FDG PET/CT scan were assessed. Results: Overall PET/CT upstaged in 22.2% of cases and changed management in 15.78% of cases. PET/CT upstaged in three of eight cases in Stage IA patients but changed management in only one case. In Stage IIA, of 31 patients PET/CT upstaged in two patients (6.45%). In Stage IIB, of 45 patients PET/CT upstaged in six patients (13.3%). In Stage IIIA, of 22 patients PET/CT upstaged in six patients (27.2) and in five patients there is a change in management. In Stage IIIB, of 43 patients PET/CT upstaged in 21 patients (48.8%) with change in management in 13 patients (25.5%). Conclusion: 18F-FDG PET/CT scan can be helpful in a significant number of patients with Stage IIB and above in upstaging and changing management.

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Facial dysmorphism due to multiple brown tumors secondary to large parathyroid adenoma, diagnosed on 99mTC-sestamibi parathyroid scintigraphy

Ashwin Singh Parihar, Sanjay Bhadada, Anish Bhattacharya, Bhagwant Rai Mittal

Indian Journal of Nuclear Medicine 2018 33(3):255-256

Brown tumors are an uncommon entity associated with hyperparathyroidism. Initially described with primary hyperparathyroidism, with the widespread use of dialysis, they were also seen to be associated with secondary and tertiary hyperparathyroidism. These are lytic, expansile lesions causing bony pains, and depending on the size and extent, skeletal dysmorphism. The present case illustrates the detection of parathyroid adenoma with multiple brown tumors on 99mTc-sestamibi parathyroid scintigraphy in a patient presenting with facial dysmorphism and multiple bony pains.

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Comparative study of positron emission tomography/computed tomography and computed tomography in the evaluation of post-treatment carcinoma cervix patients

Saurabh Pantola, Sanjay Kala, Chayanika Kala, Santhosh Sampath, Mukesh Shukla

Indian Journal of Nuclear Medicine 2018 33(3):194-201

Purpose of Study: To evaluate and compare imaging findings using computed tomography (CT) alone and positron emission tomography/CT (PET/CT) fusion imaging in posttreatment carcinoma cervix patients for recurrence. Subjects and Methods: From June 2014 to May 2016, 50 posttreatment carcinoma cervix patients were referred to our institution for PET/CT imaging. In all 50 of these patients referred for evaluation, a reliable reference standard was available. The reference standard was established by histopathological examination of accessible locoregional and nodal/distant metastatic involvement or follow-up of patients. CT and PET/CT were performed and analyzed for locoregional, pelvic nodal, and distant metastasis involvement in posttreatment carcinoma cervix cases. Results: In the evaluation of locoregional involvement, CT alone was found to have a sensitivity of 75% and specificity of 90% while PET/CT was found to have a sensitivity of 95% and specificity of 100%. Furthermore, in evaluation of pelvic nodal involvement, CT alone was found to have a sensitivity of 72% and specificity of 92.6% while PET/CT was found to have a sensitivity of 95.5% and specificity of 92.9%. In context to distant metastasis involvement (including para-aortic nodes), CT alone was found to have a sensitivity of 91.7% and specificity of 96.2% while PET/CT was found to have a sensitivity of 95.8% and specificity of 100%. PET/CT fusion in comparison to CT alone is better in sensitivity and specificity in the detection of locoregional involvement, pelvic node invasion, and distant metastasis in posttreatment carcinoma cervix cases.

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F-18 FDG PET-CT versus contrast enhanced ct in detection of extra nodal involvement in patients with lymphoma

Aboelmagd Alnouby, Ibraheem Mansour Ibraheem Nasr, Ismail Ali, Mahmoud Rezk

Indian Journal of Nuclear Medicine 2018 33(3):183-189

Aim and Objectives: The aim of this study is to assess the added value of hybrid fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the evaluation of extranodal involvement in patients with lymphoma in comparison to contrast-enhanced CT (CECT). Patients and Methods: All patients had lymphoma, proved by histopathological and immunophenotyping examinations. They underwent CECT and F-18 FDG PET–CT studies. Both CECT and PET/CT studies were done within 30 days. Results: The study included 144 patients 92 (63.9%) males and 52 (36.1%) females with mean age 49.3 years (range 18–80 years). A total of 102 (70.8%) patients had non-Hodgkin lymphoma and 42 patients (18.1%) had Hodgkin disease, diffuse large B-cell lymphoma subtype had the highest prevalence 52.8% (76/144), whereas lymphocytic predominance was the least prevalent 1.4% (2/144) followed by mucosa-associated lymphoid tissue lymphoma 2.8% (4/144) and small lymphocytic type 4.2% (6/144), mixed cellularity (MC), T-cell, and follicular type were equally distributed 6.9% (10/144 each). The lung was the most common site as it was involved in 34 patients followed by bone and bone marrow 32 patients, spleen 18, liver 16, nasopharynx 8, stomach 6, cutaneous and subcutaneous tissue 6, peritoneum, cecum, small intestine, brain, and intramuscular four patients each. However, the parotid and pancreas were the least common sites two patients each. The overall sensitivity, specificity PPV, NPV, and accuracy of PET/CT and CECT are 97%, 20% 94.2%, 33.3% and 91.7% and 89.6%, 60%, 96.8%, 30% and 87.5%, respectively. Conclusion: F-18 FDG-PET/CT can accurately monitor the extranodal lymphoma, it can detect metabolically-active lesions without CT structural changes and identify viable tumor in normal size lymph nodes. FDG-PET/CT is more effective than CECT in evaluating extra nodal lymphomatous infiltration, especially in the spleen, bone, and bone marrow.

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Can early dynamic positron emission tomography/computed tomography obviate the need for postdiuresis image in 68Ga-PSMA-HBED-CC scan for evaluation of prostate adenocarcinoma?

Gazala Perveen, Geetanjali Arora, Nishikant Avinash Damle, Meghana Prabhu, Saurabh Arora, Madhavi Tripathi, Chandrasekhar Bal, Praveen Kumar, Rajeev Kumar, Prabhjot Singh, Chandan Jyoti Das, Averilicia Passah

Indian Journal of Nuclear Medicine 2018 33(3):202-208

Introduction: Forced diuresis technique is often adopted to wash out the high amount of urinary radioactivity that masks the foci of abnormal uptake in the pelvic region on 68Ga-PSMA-HBED-CC positron emission tomography/computed tomography (PET/CT) scan in prostate cancer (PC) patients. However, this method is time-consuming, makes the patient non/less compliant, and is not feasible in patients with renal dysfunction. We hypothesized that early dynamic imaging can obviate the need for a postdiuresis view as the urinary activity is expected to be low at the time. Materials and Methods: A total of 20 biopsy-proven PC patients who were referred to our department for a 68Ga-PSMA PET/CT for staging/restaging were prospectively studied. Dynamic PET/CT was done with on table intravenous (i.v.) injection of 2–3 mCi (74–111 MBq) of the radiotracer. Dynamic images were acquired over the pelvis with a frame time of 1 min for 10 min. Static images of 2 min/bed position were acquired between 45 and 60 min p.i. The patients were then administered i.v. furosemide and encouraged water intake and frequent urination. A static view of pelvic region was acquired at 5 min/bed at 120 min p.i. A three-dimensional volume of interest (3D-VOI) was plotted on the primary lesion, bladder, involved nodes if any, pelvic bones at involved and uninvolved sites, gluteal muscles, and artery. The sentence seems fine. This was to generate the Time activity curve for analysis. Results: Nine patients were referred for staging and 11 for restaging. Mean age of 20 patients was 64.6 years, and median prostate-specific antigen level was 21.4 ng/ml (range: 0.05–2180). Prostatic lesion was present in 20 patients, nodal involvement in 8, and bone involvement in 10 patients. Median maximum standardized uptake value (SUVmax) of the prostatic lesion (P) showed an ascending trend: 5.31 at 5 min, 10.65 at 60 min, and 10.52 at 120 min p.i. At the same time, median SUVmax of the bladder (B) also progressed steeply and then decreased postdiuresis: 1.01 at 5 min, 24.6 at 60 min, and 6.88 at 120 min. Despite forced diuresis, the bladder activity remained higher than that during early dynamic imaging. Median prostate-to-bladder (P/B) ratio was highest during early dynamic imaging at 5 min p.i. was 5.17, while at 60 min, P/B ratio was 0.42 (P = 0.002) and, at 120 min, it was 1.27 (P = 0.009). Further, all the nodal and bone lesions were clearly visualized on early dynamic images. Conclusion: The study results suggest that early dynamic imaging performs better than a postdiuresis view in terms of delineation of prostatic and regional lesions on 68Ga-PSMA scan. Further, it saves time and the patients are more compliant to this technique.

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18F-Fluorodeoxyglucose positron emission tomography-computed tomography imaging of inferior vena cava tumor thrombus extending into the right atrium in a patient with cholangiocarcinoma treated with 90Y-Microspheres

Luca Filippi, Annamaria Lacanfora, Roberto Cianni, Orazio Schillaci, Oreste Bagni

Indian Journal of Nuclear Medicine 2018 33(3):250-252

We present a case of a 42-year-old male patient affected by unresectable, chemorefractory cholangiocarcinoma, with prior placement of biliary stent. Because of the absence of extrahepatic metastases, he was submitted to liver-direct therapy with 90Y-microspheres. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) performed before the procedure showed intense tracer uptake in the hepatic lesion and along the biliary stent. The patient underwent radioembolization with 90Y-resin spheres (1.1 GBq). 18F-FDG PET-CT, acquired 6 weeks after the procedure, showed no response of the hepatic lesion and the appearance of an area of markedly increased uptake extending through the inferior vena cava into the right atrium, confirmed as extensive tumor thrombus at the enhanced multislice CT subsequently performed. 18F-FDG PET-CT proved to be a useful imaging tool not only for the evaluation of metabolic response but also for the early detection of extrahepatic progression after 90Y-radioembolization.

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Radiation exposure to the personnel performing robotic arm-assisted positron emission tomography/computed tomography-guided biopsies

Tamanna Lakhanpal, Bhagwant Rai Mittal, Rajender Kumar, Ankit Watts, Nivedita Rana, Harmandeep Singh

Indian Journal of Nuclear Medicine 2018 33(3):209-213

Purpose: The aim of the study was to estimate the radiation burden to personnel performing robotic arm-assisted positron emission tomography/computed tomography (PET/CT)-guided metabolic biopsies and to staff assisting the procedure in a PET/CT facility. Materials and Methods: We estimated the whole-body exposures to physicians and staff based on the dose rate measurement with an ionization chamber-based calibrated survey monitor and pocket dosimeters during the robotic arm-assisted 2-[F-18]-fluoro-2-deoxy-D-glucose PET/CT-guided biopsies from September 2016 to February 2017. In addition, we also noted the time to biopsy after injection and total biopsy time during which the staff was exposed to the radiation. Results: In this prospective study, PET/CT-guided biopsy was performed in 50 patients (males – 36, females – 14) with a mean age of 54 ± 15 years (range17–78 years). Of the 50 biopsy procedures, 18 were lung biopsies, 10 were bone biopsies, and 22 biopsies were from abdomen/pelvic lesions. The mean time taken for the procedure was 26 ± 11 min. The mean time elapsed between injection and procedure was 182 ± 85 min and mean injected activity of 138.38 ± 74 MBq. The mean whole-body exposure per procedure to an interventionist and an assistant was 1.88 ± 0.82 μSv and 1.04 ± 0.75 μSv, respectively. The mean exposure rates at 0-m and 1-m distance from the patient were 30.77 ± 14.61 μSv/h and 2.59 ± 1.49 μSv/h, respectively. Conclusion: We conclude that the interventionist received the highest mean effective dose as compared to the helping staffs. The occupational radiation exposure was found to be within the limits as specified by the regulatory authorities (International Commission on Radiological Protection-103), and PET/CT-guided biopsies were safe from radiation protection point of view.

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Carotid body tumor masquerading as metastatic cervical lymph node on fluorodeoxyglucose positron-emission tomography-computed tomography

Amit Nautiyal, Anirban Mukherjee, Deepanjan Mitra, Piyali Chatterjee, Anindya Roy

Indian Journal of Nuclear Medicine 2018 33(3):259-260

Carotid body tumors, although representing about 65% of head and neck paragangliomas, are rare neoplasms. Doppler ultrasonography, contrast-enhanced computed tomography (CECT), and MRI have been routinely used in the diagnosis of carotid body tumor. We hereby represent a case of 56-year-old male suspected to have lymph node metastasis from carcinoma pyriform sinus detected as carotid body tumor in fluorodeoxyglucose positron-emission tomography-CECT imaging and subsequently confirmed by histopathology.

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Dacryoscintigraphy: A pictorial essay

Shefali Madhur Gokhale

Indian Journal of Nuclear Medicine 2018 33(3):214-217

Dacryoscintigraphy is a noninvasive, simple, easy to perform imaging modality used in the evaluation of epiphora. However, it is an infrequently done study in nuclear medicine departments. A standardized protocol and a systematic interpretation of the scans help in answering the queries of the clinicians in cases of epiphora. We have attempted to build a pictorial essay of the various findings detected on dacryoscintigraphy.

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Reply by the author

Subramanian Kannan

Indian Journal of Nuclear Medicine 2018 33(3):266-267



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Thyroglobulin “nonsecretor” metastatic poorly differentiated thyroid carcinoma with noniodine concentrating disease and aggressive clinical course: A clinical case series

Ashwini Kalshetty, Sandip Basu

Indian Journal of Nuclear Medicine 2018 33(3):218-223

Poorly differentiated thyroid carcinomas (PDTC) are a subgroup of thyroid cancers with aggressive behavior and worse prognosis compared to the well DTC. Limited diagnostic tools and therapeutic options exist for such cases, and the appropriate management algorithm continues to evolve in this subgroup. They pose difficulty in clinical management due to their behavioral heterogeneity and increased occurrence of aggressive clinical behavior underlining the need for management individualization. In the present communication, a case series of three clinically challenging cases of PDTC (with low serum thyroglobulin (Tg) and iodine nonavidity) are presented with a discourse on their management intrigues, unresolved issues and the requirement of a distinctive management protocol. A small fraction of PDTCs may show low serum Tg values, with the questionable significance of its role for the assessment and monitoring of disease burden in this group of patients. Given uncommon occurrence, limited and variable literature data, management guidelines for "nonsecretor" PDTC needs to be more clearly defined based on scientific evidence. The present clinical case series of PDTC with low serum thyroglobulin in the context of noniodine concentrating metastatic disease and aggressive clinical course ("nonsecretor" status) was noteworthy from this viewpoint.

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Multifarious Ga-68 labeled PET radiopharmaceuticals in imaging various malignancies

Rakhee Vatsa, Abhiram Gopalajois Ashwathanarayana, Jaya Shukla, Shashank Singh, Priya Bhusari, Rajender Kumar, Harmandeep Singh, Bhagwant Rai Mittal

Indian Journal of Nuclear Medicine 2018 33(3):242-244

The gamut of gallium labeled radiopharmaceuticals contributes to augmented variety in molecular imaging approach for in vivo identification of tumor characteristics. The spectrum ranges from somatostatin receptor based target-specific imaging agents, to those used for tumor imaging based on specific receptor types extending into ones used for therapeutic monitoring. The versatility of gallium chemistry provides the needed advantage for imaging which is further exploited in clinical practice influences the specificity of tumor imaging. Ga-68 has revealed applicability in labeling compounds from nanoparticles to micro as well as macromolecules. We in this image, present variety of frequently and infrequently used gallium labeled radiopharmaceuticals, for imaging diverse malignancies other than conventional established tracers.

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Role of 18F-Fluorodeoxyglucose positron emission tomography/computed tomography scan in castleman's disease

Naveen Kumar Reddy Akepati, Zakir Ali Abubakar, Prathyusha Bikkina

Indian Journal of Nuclear Medicine 2018 33(3):224-226

Castleman's disease (CD) is a rare benign lymphoproliferative disorder. We are presenting three cases of CD of which one is unicentric CD, and the other two are an idiopathic multicentric CD. One of the two multicentric cases is associated with POEMS syndrome. The whole body 18F-Fluorodeoxyglucose positron-emission tomography–computed tomography scan plays a significant role in identifying the centricity, distribution of disease, response to therapy, and in early detection of remission.

https://ift.tt/2sPSe13