Prima Dewi Sinawang

All Publications

• A microneedle device for rapid dermal interstitial fluid sampling. Science advances Hung, A. H., Kamat, N. U., Bermudez, A., Boczek, S. M., Garcia-Marqués, F. J., Tan, Y. L., Hwang, J. L., Sinawang, P. D., Ilyin, D., Jacobson, G. B., Demirci, U., Poplack, S. P., Pitteri, S. J., DeSimone, J. M. 2025; 11 (39): eadx5492

  Abstract

  Dermal interstitial fluid (ISF) offers a promising alternative to invasive blood tests and opportunities for skin diagnostics. Progress in both the understanding and adoption of ISF tests is hindered by sampling challenges, including lengthy collection times, non-negligible failure rates, variable collection volumes, and inconsistent bioanalyte levels. The causes of many of these issues are not well understood. We demonstrate a microneedle device that is several times faster than state of the art, collecting an average of 15.5 mg of ISF in 5 minutes in humans with near-zero failure rate. This improvement was achieved by designing the spatial pressure gradient driving ISF flow. The influence of penetration depth, collection time, pressure, and age on ISF collection was elucidated, with Darcy's law explaining multiple observations. A data-driven acceptance criterion of <1% blood contamination for ISF is proposed. The device and findings presented will empower researchers to better conduct robust studies in the development of ISF diagnostics.

  View details for DOI 10.1126/sciadv.adx5492

  View details for PubMedID 40991687

  View details for PubMedCentralID PMC12459406

• Extracellular Vesicles in Serum Carry Trop2 Protein as a Potential Molecular Indicator in Prostate Cancer. Journal of extracellular biology Sinawang, P. D., Ozen, M. O., Liu, S., Hsu, E. C., Akin, D., Ding, E., Nolley, R., Brooks, J. D., Stoyanova, T., Demirci, U. 2025; 4 (9): e70083

  Abstract

  Extracellular vesicles (EVs) are lipid nano-to-micro-sized vesicles increasingly studied for their role in intercellular communication and their potential as minimally invasive molecular indicators in various diseases. However, challenges remain in characterizing specific surface molecules on EVs due to cargo heterogeneity and the lack of convenient quantification methods. In this study, we show the isolation, characterization, detection, and quantification of Trop2-carrying EVs (EV-Trop2) in serum of prostate cancer patients. This work combines the unique advantages of our EV isolation method with ELISA to enable surface-protein-specific EV analysis directly from serum. This is, to our knowledge, the first demonstration to isolate and quantify EV-Trop2 from prostate cancer patient serum to study its expression patterns in relation to prostate cancer status. Analysis of serum samples from three patient groups: high-risk prostate cancer (n = 22), low-risk prostate cancer (n = 23), and cancer-free groups (n = 21), revealed significantly different levels of EV-Trop2 expression between the high-risk and low-risk patient groups (p = 0.0015) and between high-risk patient and cancer-free groups (p < 0.0001). Multivariate modeling further showed that EV-Trop2 contributed to improved classifier metrics across the three sample groups. These findings highlight a strategy for probing EV-associated surface targets and suggest broader applicability of this approach across multiple cancers.

  View details for DOI 10.1002/jex2.70083

  View details for PubMedID 40994721

  View details for PubMedCentralID PMC12456249

• Plasma Preparation Strategies for Extracellular Vesicle-Based Biomarkers in Metastatic Castration-Resistant Prostate Cancer. Journal of extracellular biology Sinawang, P. D., Multani, P., Ozen, M. O., Wong, J., Akin, D., Hanson, C., Larsen, M., Ampaw, E., Rondina, M. T., Tolley, N. D., Wang, L., Cunningham, B. T., Kohli, M., Demirci, U. 2025; 4 (8): e70071

  Abstract

  Extracellular vesicles (EVs) offer a minimally invasive approach for cancer detection and monitoring. However, the lack of standardized methods for clinical biospecimen preparation and EV isolation limits the clinical utility of EV-based biomarker assessments. A targeted need exists for detailed analysis of plasma EV content. Our study investigates the impact of clinical sample preparation and our ExoTIC device on the quality of plasma-derived EVs and their RNA/protein cargo in metastatic castration-resistant prostate cancer (mCRPC) patients. We assessed sample preparation variables: blood anti-coagulant choice (EDTA or sodium citrate), type of plasma platelet fraction (platelet-rich or platelet-poor), and use of protease inhibitors. EVs were isolated via ExoTIC device, followed by EV characterization and biomarker analysis using nanoparticle tracking analysis (NTA), cryogenic electron microscopy, Western blot, and digital PCR (dPCR). We detected mCRPC-relevant proteins (ARv7 and PSMA) in EVs from all plasma sample types with different sample preparation variables. Additionally, our findings indicate that platelet-poor plasma (PPP) is optimal for detecting EV- and biologically associated mCRPC biomarker miR-375. In this pilot study (n = 3), elevated EV miR-375 levels in PPP samples from mCRPC patients experiencing disease progression during docetaxel treatment were associated with poor therapeutic response to docetaxel chemotherapy, which aligns with our preceding in vitro and in vivo study. Optimal biospecimen preparation for EV analysis could enhance detection accuracy and patient management, highlighting detection of plasma EV-associated mCRPC-specific marker proteins (ARv7 and PSMA) and microRNA miR-375.

  View details for DOI 10.1002/jex2.70071

  View details for PubMedID 40755906

  View details for PubMedCentralID PMC12311838

• Screw-Based Pill for Intelligent Robotic Extraction of Viscous Fluids in Medical Applications ADVANCED INTELLIGENT SYSTEMS Sinawang, P., Garcia-Gradilla, V., Soto, F., Akin, D., Braunreuther, M., Fuller, G. G., Demirci, U. 2025

  View details for DOI 10.1002/aisy.202500330

  View details for Web of Science ID 001527431300001

• PpIX-enabled fluorescence-based detection and photodynamic priming of platinum-resistant ovarian cancer cells under fluid shear stress. Photochemistry and photobiology Ruhi, M. K., Rickard, B. P., Overchuk, M., Sinawang, P. D., Stanley, E., Mansi, M., Sierra, R. G., Hayes, B., Tan, X., Akin, D., Chen, B., Demirci, U., Rizvi, I. 2024

  Abstract

  Over 75% percent of ovarian cancer patients are diagnosed with advanced-stage disease characterized by unresectable intraperitoneal dissemination and the presence of ascites, or excessive fluid build-up within the abdomen. Conventional treatments include cytoreductive surgery followed by multi-line platinum and taxane chemotherapy regimens. Despite an initial response to treatment, over 75% of patients with advanced-stage ovarian cancer will relapse and succumb to platinum-resistant disease. Recent evidence suggests that fluid shear stress (FSS), which results from the movement of fluid such as ascites, induces epithelial-to-mesenchymal transition and confers resistance to carboplatin in ovarian cancer cells. This study demonstrates, for the first time, that FSS-induced platinum resistance correlates with increased cellular protoporphyrin IX (PpIX), the penultimate downstream product of heme biosynthesis, the production of which can be enhanced using the clinically approved pro-drug aminolevulinic acid (ALA). These data suggest that, with further investigation, PpIX could serve as a fluorescence-based biomarker of FSS-induced platinum resistance. Additionally, this study investigates the efficacy of PpIX-enabled photodynamic therapy (PDT) and the secretion of extracellular vesicles under static and FSS conditions in Caov-3 and NIH:OVCAR-3 cells, two representative cell lines for high-grade serous ovarian carcinoma (HGSOC), the most lethal form of the disease. FSS induces resistance to ALA-PpIX-mediated PDT, along with a significant increase in the number of EVs. Finally, the ability of PpIX-mediated photodynamic priming (PDP) to enhance carboplatin efficacy under FSS conditions is quantified. These preliminary findings in monolayer cultures necessitate additional studies to determine the feasibility of PpIX as a fluorescence-based indicator, and mediator of PDP, to target chemoresistance in the context of FSS.

  View details for DOI 10.1111/php.14014

  View details for PubMedID 39189505

• Integrated "lab-on-a-chip" microfluidic systems for isolation, enrichment, and analysis of cancer biomarkers. Lab on a chip Surappa, S., Multani, P., Parlatan, U., Sinawang, P. D., Kaifi, J., Akin, D., Demirci, U. 2023

  Abstract

  The liquid biopsy has garnered considerable attention as a complementary clinical tool for the early detection, molecular characterization and monitoring of cancer over the past decade. In contrast to traditional solid biopsy techniques, liquid biopsy offers a less invasive and safer alternative for routine cancer screening. Recent advances in microfluidic technologies have enabled handling of liquid biopsy-derived biomarkers with high sensitivity, throughput, and convenience. The integration of these multi-functional microfluidic technologies into a 'lab-on-a-chip' offers a powerful solution for processing and analyzing samples on a single platform, thereby reducing the complexity, bio-analyte loss and cross-contamination associated with multiple handling and transfer steps in more conventional benchtop workflows. This review critically addresses recent developments in integrated microfluidic technologies for cancer detection, highlighting isolation, enrichment, and analysis strategies for three important sub-types of cancer biomarkers: circulating tumor cells, circulating tumor DNA and exosomes. We first discuss the unique characteristics and advantages of the various lab-on-a-chip technologies developed to operate on each biomarker subtype. This is then followed by a discussion on the challenges and opportunities in the field of integrated systems for cancer detection. Ultimately, integrated microfluidic platforms form the core of a new class of point-of-care diagnostic tools by virtue of their ease-of-operation, portability and high sensitivity. Widespread availability of such tools could potentially result in more frequent and convenient screening for early signs of cancer at clinical labs or primary care offices.

  View details for DOI 10.1039/d2lc01076c

  View details for PubMedID 37314731

• Methods to Evaluate Changes in Mitochondrial Structure and Function in Cancer. Cancers Rickard, B. P., Overchuk, M., Chappell, V. A., Kemal Ruhi, M., Sinawang, P. D., Nguyen Hoang, T. T., Akin, D., Demirci, U., Franco, W., Fenton, S. E., Santos, J. H., Rizvi, I. 2023; 15 (9)

  Abstract

  Mitochondria are regulators of key cellular processes, including energy production and redox homeostasis. Mitochondrial dysfunction is associated with various human diseases, including cancer. Importantly, both structural and functional changes can alter mitochondrial function. Morphologic and quantifiable changes in mitochondria can affect their function and contribute to disease. Structural mitochondrial changes include alterations in cristae morphology, mitochondrial DNA integrity and quantity, and dynamics, such as fission and fusion. Functional parameters related to mitochondrial biology include the production of reactive oxygen species, bioenergetic capacity, calcium retention, and membrane potential. Although these parameters can occur independently of one another, changes in mitochondrial structure and function are often interrelated. Thus, evaluating changes in both mitochondrial structure and function is crucial to understanding the molecular events involved in disease onset and progression. This review focuses on the relationship between alterations in mitochondrial structure and function and cancer, with a particular emphasis on gynecologic malignancies. Selecting methods with tractable parameters may be critical to identifying and targeting mitochondria-related therapeutic options. Methods to measure changes in mitochondrial structure and function, with the associated benefits and limitations, are summarized.

  View details for DOI 10.3390/cancers15092564

  View details for PubMedID 37174030

• Review of HIV Self Testing Technologies and Promising Approaches for the Next Generation. Biosensors Bacon, A., Wang, W., Lee, H., Umrao, S., Sinawang, P. D., Akin, D., Khemtonglang, K., Tan, A., Hirshfield, S., Demirci, U., Wang, X., Cunningham, B. T. 2023; 13 (2)

  Abstract

  The ability to self-test for HIV is vital to preventing transmission, particularly when used in concert with HIV biomedical prevention modalities, such as pre-exposure prophylaxis (PrEP). In this paper, we review recent developments in HIV self-testing and self-sampling methods, and the potential future impact of novel materials and methods that emerged through efforts to develop more effective point-of-care (POC) SARS-CoV-2 diagnostics. We address the gaps in existing HIV self-testing technologies, where improvements in test sensitivity, sample-to-answer time, simplicity, and cost are needed to enhance diagnostic accuracy and widespread accessibility. We discuss potential paths toward the next generation of HIV self-testing through sample collection materials, biosensing assay techniques, and miniaturized instrumentation. We discuss the implications for other applications, such as self-monitoring of HIV viral load and other infectious diseases.

  View details for DOI 10.3390/bios13020298

  View details for PubMedID 36832064

• Robotic Pill for Biomarker and Fluid Sampling in the Gastrointestinal Tract ADVANCED INTELLIGENT SYSTEMS Soto, F., Purcell, E., Ozen, M., Sinawang, P., Wang, J., Akin, D., Demirci, U. 2022

  View details for DOI 10.1002/aisy.202200030

  View details for Web of Science ID 000778957300001

• Progress and challenges in biomarker enrichment for cancer early detection Progress in Biomedical Engineering Sinawang, P., Soto, F., Ozen, M. O., Akin, D., Demirci, U. 2021; 3 (4)

  View details for DOI 10.1088/2516-1091/ac1ea3

• Cost-Effectiveness Analysis of Fenestrated Endovascular Aneurysm Repair Compared With Open Surgical Repair for Patients With Juxtarenal Abdominal Aortic Aneurysms George, E. L., Nardacci, L., Sinawang, P., Rao, I., Owens, D. K., Garcia-Toca, M. MOSBY-ELSEVIER. 2019: E244–E245

  View details for DOI 10.1016/j.jvs.2019.04.367

  View details for Web of Science ID 000469220300359

• TEMPO-based immuno-lateral flow quantitative detection of dengue NS1 protein SENSORS AND ACTUATORS B-CHEMICAL Sinawang, P., Fajs, L., Elouarzaki, K., Nugraha, J., Marks, R. S. 2018; 259: 354–63

  View details for DOI 10.1016/j.snb.2017.12.043

  View details for Web of Science ID 000424877600042

• Photoinducible silane diazirine as an effective crosslinker in the construction of a chemiluminescent immunosensor targeting a model E. coli analyte SENSORS AND ACTUATORS B-CHEMICAL Ye, K., Sinawang, P., Tok, A., Marks, R. S. 2018; 256: 234–42

  View details for DOI 10.1016/j.snb.2017.10.058

  View details for Web of Science ID 000414971100027

• Rapid and label-free electrochemical DNA biosensor for detecting hepatitis A virus BIOSENSORS & BIOELECTRONICS Manzano, M., Viezzi, S., Mazerat, S., Marks, R. S., Vidic, J. 2018; 100: 89–95

  Abstract

  Diagnostic systems that can deliver highly specific and sensitive detection of hepatitis A virus (HAV) in food and water are of particular interest in many fields including food safety, biosecurity and control of outbreaks. Our aim was the development of an electrochemical method based on DNA hybridization to detect HAV. A ssDNA probe specific for HAV (capture probe) was designed and tested on DNAs from various viral and bacterial samples using Nested-Reverse Transcription Polymerase Chain Reaction (nRT-PCR). To develop the electrochemical device, a disposable gold electrode was functionalized with the specific capture probe and tested on complementary ssDNA and on HAV cDNA. The DNA hybridization on the electrode was measured through the monitoring of the oxidative peak potential of the indicator tripropylamine by cyclic voltammetry. To prevent non-specific binding the gold surface was treated with 3% BSA before detection. High resolution atomic force microscopy (AFM) confirmed the efficiency of electrode functionalization and on-electrode hybridization. The proposed device showed a limit of detection of 0.65pM for the complementary ssDNA and 6.94fg/µL for viral cDNA. For a comparison, nRT-PCR quantified the target HAV cDNA with a limit of detection of 6.4fg/µL. The DNA-sensor developed can be adapted to a portable format to be adopted as an easy-to- use and low cost method for screening HAV in contaminated food and water. In addition, it can be useful for rapid control of HAV infections as it takes only a few minutes to provide the results.

  View details for DOI 10.1016/j.bios.2017.08.043

  View details for Web of Science ID 000416187600013

  View details for PubMedID 28865923

• Electrochemical impedimetric detection of stroke biomarker NT-proBNP using disposable screen-printed gold electrodes EUROBIOTECH JOURNAL Sinawang, P., Harpaz, D., Fajs, L., Seet, R., Tok, A., Marks, R. S. 2017; 1 (2): 165–76

  View details for DOI 10.24190/ISSN2564-615X/2017/02.09

  View details for Web of Science ID 000467955700009

• Electrochemical lateral flow immunosensor for detection and quantification of dengue NS1 protein BIOSENSORS & BIOELECTRONICS Sinawang, P., Rai, V., Ionescu, R. E., Marks, R. S. 2016; 77: 400–408

  Abstract

  An Electrochemical Lateral Flow Immunosensor (ELFI) is developed combining screen-printed gold electrodes (SPGE) enabling quantification together with the convenience of a lateral flow test strip. A cellulose glassy fiber paper conjugate pad retains the marker immunoelectroactive nanobeads which will bind to the target analyte of interest. The specific immunorecognition event continues to occur along the lateral flow bed until reaching the SPGE-capture antibodies at the end of the cellulosic lateral flow strip. The rationale of the immunoassay consists in the analyte antigen NS1 protein being captured selectively and specifically by the dengue NS1 antibody conjugated onto the immunonanobeads thus forming an immunocomplex. With the aid of a running buffer, the immunocomplexes flow and reach the immuno-conjugated electrode surface and form specific sandwich-type detection due to specific, molecular recognition, while unbound beads move along past the electrodes. The successful sandwich immunocomplex formation is then recorded electrochemically. Specific detection of NS1 is translated into an electrochemical signal contributed by a redox label present on the bead-immobilized detection dengue NS1 antibody while a proportional increase of faradic current is observed with increase in analyte NS1 protein concentration. The first generation ELFI prototype is simply assembled in a cassette and successfully demonstrates wide linear range over a concentration range of 1-25 ng/mL with an ultrasensitive detection limit of 0.5 ng/mL for the qualitative and quantitative detection of analyte dengue NS1 protein.

  View details for DOI 10.1016/j.bios.2015.09.048

  View details for Web of Science ID 000366766900058

  View details for PubMedID 26433352

• Lateral Flow Immunoassays - from Paper Strip to Smartphone Technology ELECTROANALYSIS Eltzov, E., Guttel, S., Kei, A., Sinawang, P., Ionescu, R. E., Marks, R. S. 2015; 27 (9): 2116–30

  View details for DOI 10.1002/elan.201500237

  View details for Web of Science ID 000362901800008

• Optimizing aerosolization efficiency of dry-powder aggregates of thermally-sensitive polymeric nanoparticles produced by spray-freeze-drying POWDER TECHNOLOGY Kho, K., Hadinoto, K. 2011; 214 (1): 169–76

  View details for DOI 10.1016/j.powtec.2011.08.010

  View details for Web of Science ID 000296126300023