Wide-field optical detection of nanoparticles using on-chip microscopy and self-assembled nanolenses

The direct observation of nanoscale objects is a challenging task for optical microscopy because the scattering from an individual nanoparticle is typically weak at optical wavelengths. Electron microscopy therefore remains one of the gold standard visualization methods for nanoparticles, despite its high cost, limited throughput and restricted field-of-view. Here, we describe a high-throughput, on-chip detection scheme that uses biocompatible wetting films to self-assemble aspheric liquid nanolenses around individual nanoparticles to enhance the contrast between the scattered and background light. We model the effect of the nanolens as a spatial phase mask centred on the particle and show that the holographic diffraction pattern of this effective phase mask allows detection of sub-100 nm particles across a large field-of-view of >20 mm^2. As a proof-of-concept demonstration, we report on-chip detection of individual polystyrene nanoparticles, adenoviruses and influenza A (H1N1) viral particles.

 

 

Lensfree Holographic Microscope

A lensless on-chip microscope weighing 46 grams with dimensions smaller than 4.2 cm × 4.2 cm × 5.8 cm that achieves sub-cellular resolution over a very large field of view of 24 mm^2 

It has orders-of-magnitude improved light collection efficiency and is very robust to mechanical misalignments, therefore it may offer a cost-effective tool especially for telemedicine applications involving various global health problems in resource limited settings.


Lensfree Microscopy on a Cell-phone

A lensfree cell-phone microscope which achieves sub-cellular spatial-resolution over an imaging field-of-view (FOV) that is an order-of-magnitude larger than conventional microscopes and provides an alternative medical tool to rapidly monitor various bodily fluids such as blood, urine, sputum, etc. as well as water/food samples.  An inexpensive and light-weight (~38 grams) attachment is required to run microscopy on a commercially-available cell-phone. This high-throughput and mobile microscope exhibits a rapid and digital medical diagnostic tool for improved healthcare delivery to the field settings and can contribute to surveillance of various preventable epidemics in resource-poor environments.




Integrated Smart Rapid Diagnostic Test (RDT) Reader Platform on a Cell-phone

A cell-phone based RDT reader platform that can work with various lateral flow immuno-chromatographic assays and similar tests to sense the presence of a target analyte in a sample.

This cost-effective digital RDT reader, weighing only ~65 grams, mechanically attaches to the existing camera unit of a cell-phone, where various types of RDTs can be inserted to be imaged in reflection or transmission modes under LED based illumination. A smart application running on the cell-phone then transmits the resulting data, which presents the diagnostic results on a world-map through geo-tagging.

Providing real-time spatio-temporal statistics for the prevalence of various infectious diseases, this smart RDT reader platform running on cell-phones might assist health-care professionals and policy makers to track emerging epidemics worldwide and help epidemic preparedness.



 

LUCAS: Lensless Ultra-wide Field-of-view Cell Monitoring Array Platform based on Shadow Imaging
A high-throughput on-chip imaging platform that can rapidly monitor and characterize various cell types within a heterogeneous solution over a depth-of-field of 4 mm and a field-of-view of 18 cm^2.

This powerful system can rapidly image/monitor multiple layers of cells without the need for any lenses, microscope-objectives or any mechanical scanning.




Lensfree super-resolution holographic microscopy using wetting films on a chip

"Micro Lens Effect on Lensfree Microscopy"

Formation of an ultra-thin wetting film over the specimen effectively creates a micro-lens effect over each object, which significantly improves the signal-to-noise-ratio and therefore the resolution of our lensfree images.

We validated the performance of this approach through lensfree on-chip imaging of various objects having fine morphological features (with dimensions of e.g., ≤0.5 µm) such as Escherichia coli (E. coli), human sperm, Giardia lamblia trophozoites, polystyrene micro beads as well as red blood cells. These results are especially important for the development of highly sensitive field-portable microscopic analysis tools for resource limited settings.



Screening of Malaria using Holographic Pixel super-resolution microscopy

This wide-field and high-resolution on-chip microscope, being compact and light-weight, would be important for global health problems such as diagnosis of infectious diseases in remote locations.

Toward this end, we validated the performance of this field-portable microscope by imaging human malaria parasites (Plasmodium falciparum) in thin blood smears. Our results constitute the first-time that a lensfree on-chip microscope has successfully imaged malaria parasites.


Towards Faster and Cheaper HIV Testing: “Lensfree holographic imaging of antibody microarrays for high-throughput detection of leukocyte numbers and function"

Describing tandem use of Ab microarrays and lensfree holographic imaging, this platform paves the way for future development of miniature cytometry devices for multi-parametric blood analysis at the point of care or in a resource-limited setting.


 

 

 

Detection of waterborne parasites using field-portable and cost-effective lensfree microscopy

We investigated the use of a field-portable and cost-effective lensfree holographic microscope to image and detect pathogenic protozoan parasites such as Giardia Lamblia and Cryptosporidium Parvum at low concentration levels.

It may provide an important high-throughput analysis tool for combating waterborne diseases especially in resource limited settings.






High-throughput Lensfree Blood Analysis On a Chip

We demonstrated the measurement of the hemoglobin concentration of whole blood samples as well as automated counting of white blood cells, also yielding spatial resolution at the subcellular level sufficient to differentiate granulocytes, monocytes, and lymphocytes from each other. These results uncover the prospects of lensfree holographic on-chip imaging to provide a useful tool for global health problems, especially by facilitating whole blood analysis in resource-poor environments.