Combining the excellent electrical and optical properties of nanomaterials with biological or synthetic molecules as receptors to detect selectively any kind of analyte, nanobiosensors are a valuable alternative to conventional diagnostic tools. 

- Graphene-based Field-Effect Transistor (FET) Biosensor

- Dual-Functional Plasmonic Biosensor

Paper/nanomaterial-based sensors, in general, and, particularly, NP-based lateral-flow devices that are observed with the naked eye or operated through a smartphone are now the most reported testing platforms for the analysis of COVID-19-related biomarkers. Nanopaper and nanochannels may also offer cost-efficient alternatives for detection of viruses and related biomarkers. 

Nanomaterials for COVID-19 Diagnosis

Islam, M. M., Mahmud, S., Muhammad, L. J., Islam, M. R., Nooruddin, S., & Ayon, S. I. (2020). Wearable Technology to Assist the Patients Infected with Novel Coronavirus (COVID-19). SN computer science, 1(6), 320. https://doi.org/10.1007/s42979-020-00335-4

Wearable Technology to Assist the Patients Infected with Novel Coronavirus (COVID-19)


Existing wearable monitoring devices:
- respiration rate
- heart rate
- temperature
- oxygen saturation 
Respiratory support systems:
- ventilators
- CPAP devices
- oxygen therapy

Existing medical devices for COVID-19

Smith College

Medical devices encompass essentially all health care products that do not mainly use chemical (pharmaceutical) or biological (vaccines) approaches to diagnose, monitor, and treat patients with COVID-19. Examples include medical imaging, implants, bionics/artificial organs, and biomedical sensors.

- Medical Ventilators for COVID-19

- Medical Ventilator Alternatives for COVID-19

- Biosenors for COVID-19

- Personal Protective Equipment (PPE) for COVID-19

- CT imaging for COVID-19

- Prophylactic Dressings for COVID-19

- Continuous Positive Airway Pressure (CPAP) Devices for COVID-19

Medical Devices for COVID-19

- Isothermal Nucleic Acid Amplification
- RPA
- CRISPR
- Cas13a Assay
- Next Generation Sequencing 
- Nanomaterials (nanotrap particles, etc.)
- Wondfo Qualitative Rapid Chromatographic Immunoassay (RCI)

Emerging Methods for Diagnosis of SARS-CoV-2

Weiss C, Carriere M, Fusco L, et al. Toward Nanotechnology-Enabled Approaches against the COVID-19 Pandemic. ACS Nano. 2020;14(6):6383-6406. doi:10.1021/acsnano.0c03697

Toward Nanotechnology-Enabled Approaches against the COVID-19 Pandemic

Ventilators supply air/oxygen mixture to coronavirus patients suffering from various levels of lung damage due to COVID-19. Existing ventilators vary in their designs and uses.

Medical Ventilators for COVID-19

Due to ventilator shortages across the nation, biomedical engineers have been developing more efficient designs for medical ventilators and investigating alternative solutions to deliver oxygen to COVID-19 patients experiencing respiratory failure.

- Ventilator Splitting Design Proposals

- Extracorporeal Membrane Oxygenation (ECMO)


Medical Ventilator Alternatives for COVID-19

Biosensors for COVID-19

According to the CDC, personal protective equipment (PPE) is used every day by healthcare personnel (HCP) to protect themselves, patients, and others when providing care. PPE helps protect HCP from many hazards encountered in healthcare facilities. However, the sudden surge in cases has lead to a spike in the demand for PPEs, leading to shortages all around the world.

Personal Protective Equipment (PPE) and COVID-19

Imaging tests cannot be used as the only reliable diagnostic tool to detect infection due to its lack of sensitivity. However, it can be useful in medical settings with limited resources where the virus is prevalent.

- Chest Radiograph
- Ultrasound
- Computed Tomography

Radiographics Test / CT Imaging for COVID-19

The weight of the head is held up by the head; however COVID-19 patients placed in a prone position may experience pressure ulcers resulting from prolonged exposure/contact of the surface with the skin. Prophylactic dressing is a multi-layered silicone foam dressing which can be applied to the resting surface to relieve the stress and strain of the body weight on the soft tissue. This reduces the chances of a pressure ulcer especially for COVID-19 patients with low mobility. 

Prophylactic Dressings

- Journal of Pakistan Medical Association

- Lancet Respir Med

- Anaesthesia (Journal of Association of Anaesthetists)

- ACS Nano

- Radiology

- International Wound Journal

- World Health Organization

- JAMA Health Forum

Medical Devices for COVID-19 References by Journal/Organization

CPAP devices deliver positive pressure in each cycle of respiration. The pressure facilitates the alveoli to remain open during exhalation, which is very helpful for oxygenation and easy breathing. The device is properly suited for the initial treatment patients having mild respiratory problems. 

Continuous Positive Airway Pressure (CPAP) Devices for COVID-19

The development of a SENsitive Splint-based one-step isothermal RNA detection (SENSR) method for rapid and straightforward onsite detection of pathogen RNAs with high sensitivity and specificity offers great potential for SARS-CoV-2 diagnosis. 


SENSR consists of two simple enzymatic reactions: a ligation reaction by SplintR ligase and subsequent transcription by T7 RNA polymerase. The resulting transcript forms an RNA aptamer that induces fluorescence. Compared to the conventional culture-based or immunoassay-based approaches, a nucleic acid-based approach relies primarily on a strand-displacing polymerase or T7 RNA polymerase at a constant temperature. In particular, the SplintR ligase can efficiently ligate two DNA probes using a target single-stranded RNA as a splint, enabling the sequence-specific detection of RNA molecules. 


SENSR integrates all component reaction steps using the specially designed probes that contain all required functional parts: promoter, hybridization sequence to target, and an aptamer template. Even with the multifaceted features of the SENSR probes, the design process is systematic and straightforward. The probe design is unique in that two DNA probes are designed to expose single-stranded target recognition parts, enabling hybridization of the target RNA and the probes at 37°C. 


SENsitive Splint-based one-step isothermal RNA detection (SENSR)

This method amplifies a DNA or RNA target sequence, but unlike PCR, does not need thermal cycling. These assays use isothermal methods to allow for primer binding and then amplify the selected strands using a polymerase with stand displacement activity. The amplified gene products are then detected via photometry. 

Isothermal Nucleic Acid Amplification

This method detects the total viral RNA from a cell culture supernatant and 19 nasopharyngeal swab samples. Uses isothermal methods for reverse transcription and then uses recombinase activity to promote primer binding to the respective dsDNA sequence. This process also achieves 100% specificity and sensitivity and offers advantages over the typical RT-PCR in efficiency and portability allowing for clinical decisions to be made real time when a patient visits. 

Uses recently discovered crRNA guided detection that is specific to viral RNA. The Cas13a enzyme that recognizes and binds targeted RNAs in a sequence-specific manner for signal amplification and nucleic acid detection.   

CRISPR

Unlike CRISPR, the Cas13a protein needs to be purified and is recombinantly expressed. Target site-recognition activates reporter probes resulting in fluorescence to recognize viral RNA. Assays can be designed as a paper dipstick test which delivers in 30-60 minutes. 


Cas13a Assay

NGS can sequence 30,000 nucleotides of the viral genome. This method provides insight on environmental monitoring, surveillance testing, and origin of the strain to pinpoint the viral evolution. 

Next Generation Sequencing

Diagnostic Testing methods that amplify DNA using reverse transcriptase.
Nucleic Acid Amplification Tests include but are not limited to:

- RT-PCR
- RT-LAMP
- Next Generation Sequencing
- Isothermal Nucleic Acid Amplification
- RPA

NAAT

The Wondfo RCI functions by detecting IgM/IgG antibodies for SARS-CoV-2.  10 μL of plasma or serum are inserted into the testing device, and antibodies that fight against SARS-CoV-2 contained in the sample attach to recombinant antigens that cover colloidal gold particles, ultimately creating a complex of antigen-antibody/colloidal gold particles.  80 μL of buffer solution must also be inserted into the testing device under the sample cavity.  The results of the RCI can be read within 15 minutes.  A major limitation of RCI is that it is not capable of differentiating between acute disease and infection from the past.  


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