Publications by authors named "Piyush Raj"

5 Publications

  • Page 1 of 1

Raman and quantitative phase imaging allow morpho-molecular recognition of malignancy and stages of B-cell acute lymphoblastic leukemia.

Biosens Bioelectron 2021 Oct 12;190:113403. Epub 2021 Jun 12.

Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA; The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA; Department of Oncology, Johns Hopkins University, Baltimore, MD, 21287, USA. Electronic address:

Acute lymphoblastic leukemia (ALL) is one of the most common malignancies that account for nearly one-third of all pediatric cancers. The current diagnostic assays are time-consuming, labor-intensive, and require expensive reagents. Here, we report a label-free approach featuring diffraction phase imaging and Raman microscopy that can retrieve both morphological and molecular attributes for label-free optical phenotyping of individual B cells. By investigating leukemia cell lines of early and late stages along with the healthy B cells, we show that phase images can capture subtle morphological differences among the healthy, early, and late stages of leukemic cells. By exploiting its biomolecular specificity, we demonstrate that Raman microscopy is capable of accurately identifying not only different stages of leukemia cells but also individual cell lines at each stage. Overall, our study provides a rationale for employing this hybrid modality to screen leukemia cells using the widefield QPI and using Raman microscopy for accurate differentiation of early and late-stage phenotypes. This contrast-free and rapid diagnostic tool exhibits great promise for clinical diagnosis and staging of leukemia in the near future.
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http://dx.doi.org/10.1016/j.bios.2021.113403DOI Listing
October 2021

Utilizing pulse dynamics for non-invasive Raman spectroscopy of blood analytes.

Biosens Bioelectron 2021 May 26;180:113115. Epub 2021 Feb 26.

Department of Metrology and Optoelectronics, Faculty of Electronics, Telecommunications, and Informatics, Gdańsk University of Technology, G. Narutowicza 11/12, 80-233, Gdańsk, Poland.

Non-invasive measurement methods offer great benefits in the field of medical diagnostics with molecular-specific techniques such as Raman spectroscopy which is increasingly being used for quantitative measurements of tissue biochemistry in vivo. However, some important challenges still remain for label-free optical spectroscopy to be incorporated into the clinical laboratory for routine testing. In particular, non-analyte-specific variations in tissue properties introduce significant variability of the spectra, thereby preventing reliable calibration. For measurements of blood analytes such as glucose, we propose to decrease the interference from individual tissue characteristics by exploiting the known dynamics of the blood-tissue matrix. We reason that by leveraging the natural blood pulse rhythm, the signals from the blood analytes can be enhanced while those from the static components can be effectively suppressed. Here, time-resolved measurements with subsequent pulse frequency estimation and phase-sensitive detection are proposed to recover the Raman spectra correlated with the dynamic changes at blood-pulse frequency. Pilot in vivo study results are presented to establish the benefits as well as outline the challenges of the proposed method in terms of instrumentation and signal processing.
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http://dx.doi.org/10.1016/j.bios.2021.113115DOI Listing
May 2021

Furin-Mediated Self-Assembly of Olsalazine Nanoparticles for Targeted Raman Imaging of Tumors.

Angew Chem Int Ed Engl 2021 02 26;60(8):3923-3927. Epub 2021 Jan 26.

The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Olsalazine (Olsa) is a broad-spectrum anti-cancer agent acting as a DNA-methylation inhibitor. When conjugated to 2-cyano-6-aminobenzothiazole and a peptide substrate specific for the tumor-overexpressed enzyme furin, it can self-assemble into nanoparticles that can be detected by chemical-exchange saturation-transfer magnetic-resonance imaging (CEST MRI). We report here that these nano-assemblies can also be detected with high specificity in furin-overexpressing tumor cells by Raman spectroscopy with a distinct scattering signature and demonstrate the utility of this sensing mechanism in vitro and in vivo. Our findings suggest that Raman spectroscopy could be used for high-resolution image-guided surgery to precisely delineate tumor margins during and after resection in real-time as well as to determine microscopic tumor invasion and multifocal locoregional tumor spread, which are currently impossible to visualize with available imaging technologies, including CEST MRI.
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http://dx.doi.org/10.1002/anie.202014839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902394PMC
February 2021

Coarse Raman and optical diffraction tomographic imaging enable label-free phenotyping of isogenic breast cancer cells of varying metastatic potential.

Biosens Bioelectron 2021 Mar 27;175:112863. Epub 2020 Nov 27.

Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA; The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA; Department of Oncology, Johns Hopkins University, Baltimore, MD, 21287, USA. Electronic address:

Identification of the metastatic potential represents one of the most important tasks for molecular imaging of cancer. While molecular imaging of metastases has witnessed substantial progress as an area of clinical inquiry, determining precisely what differentiates the metastatic phenotype has proven to be more elusive. In this study, we utilize both the morphological and molecular information provided by 3D optical diffraction tomography and Raman spectroscopy, respectively, to propose a label-free route for optical phenotyping of cancer cells at single-cell resolution. By using an isogenic panel of cell lines derived from MDA-MB-231 breast cancer cells that vary in their metastatic potential, we show that 3D refractive index tomograms can capture subtle morphological differences among the parental, circulating tumor cells, and lung metastatic cells. By leveraging its molecular specificity, we demonstrate that coarse Raman microscopy is capable of rapidly mapping a sufficient number of cells for training a random forest classifier that can accurately predict the metastatic potential of cells at a single-cell level. We also perform multivariate curve resolution alternating least squares decomposition of the spectral dataset to demarcate spectra from cytoplasm and nucleus, and test the feasibility of identifying metastatic phenotypes using the spectra only from the cytoplasmic and nuclear regions. Overall, our study provides a rationale for employing coarse Raman mapping to substantially reduce measurement time thereby enabling the acquisition of reasonably large training datasets that hold the key for label-free single-cell analysis and, consequently, for differentiation of indolent from aggressive phenotypes.
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http://dx.doi.org/10.1016/j.bios.2020.112863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847362PMC
March 2021

Microwave power induced resonance shifting of silicon ring modulators for continuously tunable, bandwidth scaled frequency combs.

Opt Express 2020 Apr;28(9):13032-13042

We demonstrate a technique to continuously tune center frequency and repetition rate of optical frequency combs generated in silicon microring modulators and bandwidth scale them. We utilize a drive frequency dependent, microwave power induced shifting of the microring modulator resonance. In this work, we demonstrate center frequency tunability of frequency combs generated in silicon microring modulators over a wide range (∼8nm) with fixed number of lines. We also demonstrate continuously tunable repetition rates from 7.5GHz to 15GHz. Further, we use this effect to demonstrate a proof-of-principle experiment to bandwidth scale an 8-line (20dB band) comb generated from a single ring modulator driven at 10GHz to a comb with 12 and 15 lines by cascading two and three ring modulators, respectively. This is accomplished by merging widely spaced ring modulator resonances to a common location, thus coupling light simultaneously into multiple cascaded ring modulators.
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http://dx.doi.org/10.1364/OE.386810DOI Listing
April 2020
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