Non-invasive on-skin sensors for brain machine interfaces with epitaxial graphene

Abstract Brain-machine interfaces are key components for the development of hands-free, brain -controlled devices. Electroencephalogram (EEG) electrodes are particularly attractive for harvesting the neural signals in a non-invasive fashion. Here, we explore the use of epitaxial graphene grown on silicon carbide on silicon for detecting the electroencephalogram signals with high sensitivity. This dry and non-invasive approach exhibits a markedly improved skin contact impedance when benchmarked to commercial dry electrodes, as well as superior robustness, allowing prolonged and repeated use also in a highly saline environment. In addition, we report the newly -observed phenomenon of surface conditioning of the epitaxial graphene electrodes. The prolonged contact of the epitaxial graphene with the skin electrolytes functionalize the grain boundaries of the graphene, leading to the formation of a thin surface film of water through physisorption and consequently reducing its contact impedance by more than 75%. This effect is primed in highly saline environments, and could be also further tailored as pre-conditioning to enhance the performance and reliability of the epitaxial graphene sensors.

Download Full-text

Self-Abrading Servo Electrode Helmet for Electrical Impedance Tomography

Sensors ◽

10.3390/s20247058 ◽

2020 ◽

Vol 20 (24) ◽

pp. 7058

Author(s):

James Avery ◽

Brett Packham ◽

Hwan Koo ◽

Ben Hanson ◽

David Holder

Keyword(s):

Acute Stroke ◽

Electrical Impedance Tomography ◽

Large Scale ◽

Electrical Impedance ◽

Applied Pressure ◽

High Sensitivity ◽

Haemorrhagic Stroke ◽

Contact Impedance ◽

Impedance Tomography ◽

Skin Contact

Electrical Impedance Tomography (EIT) is a medical imaging technique which has the potential to reduce time to treatment in acute stroke by rapidly differentiating between ischaemic and haemorrhagic stroke. The potential of these methods has been demonstrated in simulation and phantoms, it has not yet successfully translated to clinical studies, due to high sensitivity to errors in scalp electrode mislocation and poor electrode-skin contact. To overcome these limitations, a novel electrode helmet was designed, bearing 32 independently controlled self-abrading electrodes. The contact impedance was reduced through rotation on an abrasive electrode on the scalp using a combined impedance, rotation and position feedback loop. Potentiometers within each unit measure the electrode tip displacement within 0.1 mm from the rigid helmet body. Characterisation experiments on a large-scale test rig demonstrated that approximately 20 kPa applied pressure and 5 rotations was necessary to achieve the target 5 kΩ contact impedance at 20 Hz. This performance was then replicated in a simplified self-contained unit where spring loaded electrodes are rotated by servo motors. Finally, a 32-channel helmet and controller which sequentially minimised contact impedance and simultaneously located each electrode was built which reduced the electrode application and localisation time to less than five minutes. The results demonstrated the potential of this approach to rapidly apply electrodes in an acute setting, removing a significant barrier for imaging acute stroke with EIT.

Download Full-text

Non-invasive detection of acquired resistance to FGFR inhibition in patients with cholangiocarcinoma harboring FGFR2 alterations.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.4096 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 4096-4096 ◽

Cited By ~ 2

Author(s):

Anna M. Varghese ◽

Juber Ahamad A Patel ◽

Yelena Yuriy Janjigian ◽

Fanli Meng ◽

S Duygu Selcuklu ◽

...

Keyword(s):

Targeted Therapy ◽

Acquired Resistance ◽

High Sensitivity ◽

Circulating Tumor Dna ◽

Resistance Mechanisms ◽

Tumor Evolution ◽

Background Error ◽

Tumor Biopsy ◽

Invasive Approach ◽

Non Invasive

4096 Background: FGFR2 alterations are present in 14% of cholangiocarcinomas (CCA) and are promising targets of investigational FGFR-directed therapies. Cell-free DNA profiling has emerged as a non-invasive approach to monitor disease and longitudinally characterize tumor evolution. We describe the use of circulating tumor DNA (ctDNA) among patients (pts) with FGFR2-altered CCA receiving FGFR-targeted therapy in the identification of acquired FGFR2 mutations (mut) at resistance. Methods: Serial blood samples were collected from 8 pts with FGFR-altered CCA for ctDNA isolation and next generation sequencing. Plasma ctDNA collected at baseline and resistance to FGFR-targeted therapy were sequenced using a custom ultra-deep coverage cfDNA panel, MSK-ACCESS, incorporating dual index primers and unique molecular barcodes to enable background error suppression and high-sensitivity mut detection. The assay was enhanced to include all protein-coding exons and relevant introns of FGFR2. In 5/8 pts, genomic profiling of an initial tumor biopsy was performed. Results: 8 pts with FGFR2-altered CCA (7 gene fusions, 1 amplification) were treated with FGFR-targeted therapies. 7/8 pts exhibited stable disease or partial response. 19 total acquired mut in FGFR2 were detected at resistance in 5/8 pts (between 1-9 unique mut identified in each sample). All mut were located in the kinase domain. Conclusions: Acquired mut in FGFR2 are seen in pts who have developed resistance to targeted therapy. CtDNA can be used to identify these mut at the time of acquired resistance. The multitude of FGFR2 mut observed within individual pts suggest heterogeneity and evolutionary convergence of resistance mechanisms. Our results illustrate the utility of ctDNA as a less invasive way to monitor for signs of resistance and to identify other potential targetable alterations. [Table: see text]

Download Full-text

BIOM-35. MULTI ANALYTE ASSAY FOR NON-INVASIVE DIAGNOSIS OF BRAIN TUMORS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.034 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii9-ii9

Author(s):

Dadasaheb Akolkar ◽

Darshana Patil ◽

Pooja Fulmali ◽

Sneha Puranik ◽

Sachin Apurwa ◽

...

Keyword(s):

Histopathological Examination ◽

Brain Biopsy ◽

High Sensitivity ◽

Tissue Samples ◽

Invasive Approach ◽

Non Invasive ◽

Droplet Pcr ◽

Asymptomatic Individuals ◽

Diagnostic Work ◽

Work Up

Abstract The diagnosis of Central Nervous System (CNS) malignancies such as Gliomas in individuals presenting with Intracranial Space Occupying Lesions (ICSOL) is based on histopathological examination (HPE) of tumor tissue obtained by an invasive brain biopsy. However, brain biopsies are resource intensive and are associated with procedural risks such as haemorrhage, morbidity and mortality. The present study evaluated a non-invasive approach for diagnosis of CNS-M in symptomatic individuals based on evaluation of circulating tumor analytes in peripheral blood. The non-invasive multi-platform approach for diagnosis of CNS-M included Immunocytochemistry (ICC) profiling and Fluorescence in situ Hybridization (FISH) of Circulating Tumor Cells (CTCs) and Digital Droplet PCR (ddPCR) of cell-free tumor DNA (ctDNA) and exosomal mRNA. Performance characteristics of each platform were evaluated using blood and tissue samples from 445 individuals including 227 known cases of CNS-M, 47 known cases of benign CNS conditions (CNS-B), 141 known cases of other cancers with brain metastases (OTH-M) and 30 asymptomatic individuals (ASYM). In a set of 37 samples from individuals with radiological ICSOL, suspected of malignancy (CNS-S) complete diagnostic work-up was performed with ICC, FISH and ddPCR. Glial CTCs were detected in 88.8% of 227 CNS-M and undetectable in 89.4% of 47 CNS-B or 100% of 141 OTH-M, indicating high sensitivity and specificity, respectively. The multi-analyte approach discerned CNS-M from CNS-B as well as OTH-M with 91.7% accuracy and accurately inferred lineage in 84.6% of cases. This non-invasive multi-analyte approach can diagnose CNS-M with an accuracy not inferior to standard HPE, can substitute invasive biopsies in most cases and is particularly helpful in cases where a biopsy is not viable.

Download Full-text

Salivary cortisol as a non-invasive approach to assess stress in dystocic dairy calves

Scientific Reports ◽

10.1038/s41598-021-85666-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Levente Kovács ◽

Fruzsina Luca Kézér ◽

Szilárd Bodó ◽

Ferenc Ruff ◽

Rupert Palme ◽

...

Keyword(s):

Birth Weight ◽

Body Condition ◽

Salivary Cortisol ◽

Sampling Period ◽

Dairy Calves ◽

Birth Process ◽

Invasive Approach ◽

Non Invasive ◽

Saliva Cortisol ◽

Cortisol Levels

AbstractThe intensity and the magnitude of saliva cortisol responses were investigated during the first 48 h following birth in newborn dairy calves which underwent normal (eutocic, EUT, n = 88) and difficult (dystocic, DYS, n = 70) calvings. The effects of parity and body condition of the dam, the duration of parturition, the time spent licking the calf, the sex and birth weight of the calf were also analyzed. Neonatal salivary cortisol concentrations were influenced neither by factors related to the dam (parity, body condition) nor the calf (sex, birth weight). The duration of parturition and the time spent licking the calf also had no effect on salivary cortisol levels. Salivary cortisol concentrations increased rapidly after delivery in both groups to reach their peak levels at 45 and 60 min after delivery in EUT and DYS calves, respectively supporting that the birth process means considerable stress for calves and the immediate postnatal period also appears to be stressful for newborn calves. DYS calves exhibited higher salivary cortisol concentrations compared to EUT ones for 0 (P = 0.022), 15 (P = 0.016), 30 (P = 0.007), 45 (P = 0.003), 60 (P = 0.001) and 120 min (P = 0.001), and for 24 h (P = 0.040), respectively. Peak levels of salivary cortisol and the cortisol release into saliva calculated as AUC were higher in DYS than in EUT calves for the 48-h of the sampling period (P = 0.009 and P = 0.003, respectively). The greater magnitude of saliva cortisol levels in DYS calves compared to EUT ones suggest that difficult parturition means severe stress for bovine neonates and salivary cortisol could be an opportunity for non-invasive assessment of stress during the early neonatal period in cattle.

Download Full-text

Role of MRI evaluation in acute secondary inability to walk in children

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-021-00417-0 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

K. H. Sedeek ◽

K. Aboualfotouh ◽

S. M. Hassanein ◽

N. M. Osman ◽

M. H. Shalaby

Keyword(s):

Transverse Myelitis ◽

High Sensitivity ◽

Acute Disseminated Encephalomyelitis ◽

Limb Weakness ◽

Non Invasive ◽

Highly Sensitive ◽

Common Causes ◽

Bilateral Lower Limb ◽

Severity Of The Disease

Abstract Background Acute bilateral lower limb weakness is a common problem in children which necessitates a rapid method for diagnosis. MRI is a non-invasive imaging technique that produces high-quality images of the internal structure of the brain and spinal cord. Results MRI was very helpful in reaching rapid and prompt diagnosis in children with acute inability to walk. Acute disseminated encephalomyelitis (ADEM), Guillain–Barré syndrome (GBS), and acute transverse myelitis (ATM) were the most common causes in our study. MRI proved to be of high sensitivity in detecting the lesions and reaching the diagnosis in ADEM and GBS; however, there was no significant relation between the lesions’ size, enhancement pattern, and severity of the disease or prognosis, yet in ATM the site of the lesion and number of cord segment affection were significantly related to the severity of the disease and prognosis. Conclusion MRI is a quick tool to reach the diagnosis of children with acute secondary inability to walk, and to eliminate other differential diagnosis which is essential for proper treatment and rapid full recovery. It is highly sensitive in detecting the lesions, their site and size.

Download Full-text

Through thick and thin: Diagnosis of transthyretin cardiac amyloidosis through non-invasive multimodality imaging

Proceedings of Singapore Healthcare ◽

10.1177/20101058211006146 ◽

2021 ◽

pp. 201010582110061

Author(s):

Raja Ezman Raja Shariff ◽

Hafisyatul Aiza Zainal Abidin ◽

Sazzli Kasim

Keyword(s):

Cardiac Amyloidosis ◽

Troponin T ◽

Multimodality Imaging ◽

High Sensitivity ◽

Dark Blood ◽

Non Invasive ◽

Doppler Study ◽

Alternative Means ◽

High Sensitivity Troponin T

Cardiac amyloidosis is a severely underdiagnosed cause of heart failure with preserved ejection fraction. We report a case of highly probable transthyretin (ATTR) cardiac amyloidosis (ATTR-CA) diagnosed through the assistance of non-invasive multimodality imaging. An 81-year-old man presented with worsening dyspnoea, reduced effort tolerance and limb swelling. Examination and bedside investigations demonstrated congestive cardiac failure. On arrival, N-terminal-pro B-type natriuretic peptide was 2400 ng/L, and high-sensitivity troponin T was 78 mmol/L. Echocardiography showed severe left and right ventricular hypertrophy, and a Doppler study revealed diastolic dysfunction. Cardiac magnetic resonance imaging revealed on non-conventional dark blood sequence an abnormal inversion time for nulling myocardium suggestive of infiltrative disease, including amyloidosis. The patient was referred for nuclear-based studies involving technetium-99m pyrophosphate which demonstrated changes highly diagnostic of ATTR-CA. Early diagnosis of ATTR-CA remains paramount due to the increasing availability of disease-modifying therapies. Current guidelines recognise the role of multimodality imaging in confidently recognising the disease without the need for histological evidence in the appropriate context, providing an alternative means of diagnosis.

Download Full-text

Fluorescent Probes for Live Cell Thiol Detection

Molecules ◽

10.3390/molecules26123575 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3575

Author(s):

Shenggang Wang ◽

Yue Huang ◽

Xiangming Guan

Keyword(s):

Fluorescent Probes ◽

Biological System ◽

High Sensitivity ◽

Intracellular Distribution ◽

Live Cell ◽

Live Cells ◽

High Demand ◽

Non Invasive

Thiols play vital and irreplaceable roles in the biological system. Abnormality of thiol levels has been linked with various diseases and biological disorders. Thiols are known to distribute unevenly and change dynamically in the biological system. Methods that can determine thiols’ concentration and distribution in live cells are in high demand. In the last two decades, fluorescent probes have emerged as a powerful tool for achieving that goal for the simplicity, high sensitivity, and capability of visualizing the analytes in live cells in a non-invasive way. They also enable the determination of intracellular distribution and dynamitic movement of thiols in the intact native environments. This review focuses on some of the major strategies/mechanisms being used for detecting GSH, Cys/Hcy, and other thiols in live cells via fluorescent probes, and how they are applied at the cellular and subcellular levels. The sensing mechanisms (for GSH and Cys/Hcy) and bio-applications of the probes are illustrated followed by a summary of probes for selectively detecting cellular and subcellular thiols.

Download Full-text

The Cat Mandible (II): Manipulation of the Jaw, with a New Prosthesis Proposal, to Avoid Iatrogenic Complications

Animals ◽

10.3390/ani11030683 ◽

2021 ◽

Vol 11 (3) ◽

pp. 683

Author(s):

Matilde Lombardero ◽

Mario López-Lombardero ◽

Diana Alonso-Peñarando ◽

María del Mar Yllera

Keyword(s):

Imaging Techniques ◽

Recovery Period ◽

Prosthesis Design ◽

Patient Specific ◽

Mandibular Fractures ◽

Rigid Fixation ◽

Invasive Approach ◽

Non Invasive ◽

Iatrogenic Complications ◽

Mandibular Body

The cat mandible is relatively small, and its manipulation implies the use of fixing methods and different repair techniques according to its small size to keep its biomechanical functionality intact. Attempts to fix dislocations of the temporomandibular joint should be primarily performed by non-invasive techniques (repositioning the bones and immobilisation), although when this is not possible, a surgical method should be used. Regarding mandibular fractures, these are usually concurrent with other traumatic injuries that, if serious, should be treated first. A non-invasive approach should also first be considered to fix mandibular fractures. When this is impractical, internal rigid fixation methods, such as osteosynthesis plates, should be used. However, it should be taken into account that in the cat mandible, dental roots and the mandibular canal structures occupy most of the volume of the mandibular body, a fact that makes it challenging to apply a plate with fixed screw positions without invading dental roots or neurovascular structures. Therefore, we propose a new prosthesis design that will provide acceptable rigid biomechanical stabilisation, but avoid dental root and neurovascular damage, when fixing simple mandibular body fractures. Future trends will include the use of better diagnostic imaging techniques, a patient-specific prosthesis design and the use of more biocompatible materials to minimise the patient’s recovery period and suffering.

Download Full-text

Metal Oxide Nanorods-Based Sensor Array for Selective Detection of Biomarker Gases

Sensors ◽

10.3390/s21051922 ◽

2021 ◽

Vol 21 (5) ◽

pp. 1922

Author(s):

Gwang Su Kim ◽

Yumin Park ◽

Joonchul Shin ◽

Young Geun Song ◽

Chong-Yun Kang

Keyword(s):

Real Time ◽

Sensor Array ◽

High Sensitivity ◽

Gas Analysis ◽

Diagnostic Methods ◽

Real Time Monitoring ◽

Non Invasive ◽

Sensitivity And Selectivity ◽

Breath Gas Analysis ◽

Angle Method

The breath gas analysis through gas phase chemical analysis draws attention in terms of non-invasive and real time monitoring. The array-type sensors are one of the diagnostic methods with high sensitivity and selectivity towards the target gases. Herein, we presented a 2 × 4 sensor array with a micro-heater and ceramic chip. The device is designed in a small size for portability, including the internal eight-channel sensor array. In2O3 NRs and WO3 NRs manufactured through the E-beam evaporator’s glancing angle method were used as sensing materials. Pt, Pd, and Au metal catalysts were decorated for each channel to enhance functionality. The sensor array was measured for the exhaled gas biomarkers CH3COCH3, NO2, and H2S to confirm the respiratory diagnostic performance. Through this operation, the theoretical detection limit was calculated as 1.48 ppb for CH3COCH3, 1.9 ppt for NO2, and 2.47 ppb for H2S. This excellent detection performance indicates that our sensor array detected the CH3COCH3, NO2, and H2S as biomarkers, applying to the breath gas analysis. Our results showed the high potential of the gas sensor array as a non-invasive diagnostic tool that enables real-time monitoring.

Download Full-text

Holistic description of new deep sea megafauna (Cephalopoda: Cirrata) using a minimally invasive approach

BMC Biology ◽

10.1186/s12915-021-01000-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Alexander Ziegler ◽

Christina Sagorny

Keyword(s):

Minimally Invasive ◽

Dna Barcoding ◽

Deep Sea ◽

Imaging Techniques ◽

Structural Complexity ◽

Micro Computed Tomography ◽

Invasive Approach ◽

Non Invasive ◽

Additional Support ◽

Holistic Description

Abstract Background In zoology, species descriptions conventionally rely on invasive morphological techniques, frequently leading to damage of the specimens and thus only a partial understanding of their structural complexity. More recently, non-destructive imaging techniques have successfully been used to describe smaller fauna, but this approach has so far not been applied to identify or describe larger animal species. Here, we present a combination of entirely non-invasive as well as minimally invasive methods that permit taxonomic descriptions of large zoological specimens in a more comprehensive manner. Results Using the single available representative of an allegedly novel species of deep-sea cephalopod (Mollusca: Cephalopoda), digital photography, standardized external measurements, high-field magnetic resonance imaging, micro-computed tomography, and DNA barcoding were combined to gather all morphological and molecular characters relevant for a full species description. The results show that this specimen belongs to the cirrate octopod (Octopoda: Cirrata) genus Grimpoteuthis Robson, 1932. Based on the number of suckers, position of web nodules, cirrus length, presence of a radula, and various shell characters, the specimen is designated as the holotype of a new species of dumbo octopus, G. imperator sp. nov. The digital nature of the acquired data permits a seamless online deposition of raw as well as derived morphological and molecular datasets in publicly accessible repositories. Conclusions Using high-resolution, non-invasive imaging systems intended for the analysis of larger biological objects, all external as well as internal morphological character states relevant for the identification of a new megafaunal species were obtained. Potentially harmful effects on this unique deep-sea cephalopod specimen were avoided by scanning the fixed animal without admixture of a contrast agent. Additional support for the taxonomic placement of the new dumbo octopus species was obtained through DNA barcoding, further underlining the importance of combining morphological and molecular datasets for a holistic description of zoological specimens.

Download Full-text