UMBC Center for Advanced Sensor Technology (CAST)

Permanent URI for this collectionhttp://hdl.handle.net/11603/7875

The Center for Advanced Sensor Technology promotes the development of optical based sensors for biomedical, bioprocess, environmental and homeland defense applications. We are a multidisciplinary group of chemists, molecular biologists, electrical engineers and chemical and biochemical engineers. Our main objective is to create innovative sensor technology that is high throughput and low-cost amenable for transfer to industry counterparts.

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Completely noninvasive multi-analyte monitoring system for cell culture processes
(Springer, 2024-08-20) Rahmatnejad, Vida; Tolosa, Michael; Ge, Xudong; Rao, Govind
Although online monitoring of dissolved O₂, pH, and dissolved CO₂ is critical in bioprocesses, nearly all existing technologies require some level of direct contact with the cell culture environment, posing risks of contamination. This study addresses the need for an accurate, and completely noninvasive technique for simultaneous measurement of these analytes. A “non-contact” technique for simultaneous monitoring of dissolved O₂, pH, and dissolved CO₂ was developed. Instead of direct contact with the culture media, the measurements were made through permeable membranes via either a sampling port in the culture vessel wall or a flow cell. The efficacy of the “non-contact” technique was validated in Escherichia coli (E.coli), Chinese hamster ovary (CHO) culture processes, and dynamic environments created by sparging gases in cell culture medium. The measurements obtained through the developed techniques were comparable to those obtained through control methods. The noninvasive monitoring system can offer accurate, and contamination-minimized monitoring of critical process parameters including dissolved O₂, pH, and dissolved CO₂. These advancements will enhance the control and optimization of cell culture processes, promising improved cell culture performance.
Investigating Laser Ablation Process Parameters for the Fabrication of Customized Microneedle Arrays for Therapeutic Applications
(MDPI, 2024-06-30) Aldawood, Faisal Khaled; Andar, Abhay; Desai, Salil
Microneedles are an innovation in the field of medicine that have the potential to revolutionize drug delivery, diagnostics, and cosmetic treatments. This innovation provides a minimally invasive means to deliver drugs, vaccines, and other therapeutic substances into the skin. This research investigates the design and manufacture of customized microneedle arrays using laser ablation. Laser ablation was performed using an ytterbium laser on a polymethyl methacrylate (PMMA) substrate to create a mold for casting polydimethylsiloxane (PDMS) microneedles. An experimental design was conducted to evaluate the effect of process parameters including laser pulse power, pulse width, pulse repetition, interval between pulses, and laser profile on the desired geometry of the microneedles. The analysis of variance (ANOVA) model showed that lasing interval, laser power, and pulse width had the highest influence on the output metrics (diameter and height) of the microneedle. The microneedle dimensions showed an increase with higher pulse width and vice versa with an increase in pulse interval. A response surface model indicated that the laser pulse width and interval (independent variables) significantly affect the response diameter and height (dependent variable). A predictive model was generated to predict the microneedle topology and aspect ratio varying from 0.8 to 1.5 based on the variation in critical input process parameters. This research lays the foundation for the design and fabrication of customized microneedles based on variations in specific input parameters for therapeutic applications in dermal sensors, drug delivery, and vaccine delivery.
Novel design for a microfluidic-based platform for yeast replicative lifespan (RLS) analysis
(Elsevier, 2023-05-13) Kaprou, Georgia D.; Andar, Abhay; Shah, Pranjul; Linster, Carole L.; Paczia, Nicole
Microfluidic devices hold enormous potential for the development of cost-effective and faster alternatives to existing traditional methods across life science applications. Here we demonstrate the feasibility of fabricating a microfluidic device by means of photolithography comprising a single cell trap, a delay structure and a chamber defined by micropillars. This device is aimed to be used for biological applications such as replicative lifespan determination (RLS) of yeast cells, where single cell trapping, and cell counting are essential. The novelty of the present work lies on the integration of the above-mentioned microfluidic structures in a single device by means of the established method of photolithography by fine-tuning critical parameters needed to achieve the desired high aspect ratio (1:5) employing commercially available resins. The fine-tuning of the fabrication parameters in combination with appropriately selected resins allows for patterning reproducibly micron-sized features. The design of the proposed device ultimately aims at replacing the very cumbersome assays still commonly used today for RLS determination in budding yeast by a methodology that is drastically simpler and more time efficient.
Giant nanomechanical energy storage capacity in twisted single-walled carbon nanotube ropes
(Nature, 2024-04-16) Utsumi, Shigenori; Ujjain, Sanjeev Kumar; Takahashi, Satoshi; Shimodomae, Ryo; Yamaura, Tae; Okuda, Ryosuke; Kobayashi, Ryuichiro; Takahashi, Oga; Miyazono, Satoshi; Kato, Naoki; Aburamoto, Keiichi; Hosoi, Yuta; Ahuja, Preety; Furuse, Ayumi; Kawamata, Yuma; Otsuka, Hayato; Fujisawa, Kazunori; Hayashi, Takuya; Tománek, David; Kaneko, Katsumi
A sustainable society requires high-energy storage devices characterized by lightness, compactness, a long life and superior safety, surpassing current battery and supercapacitor technologies. Single-walled carbon nanotubes (SWCNTs), which typically exhibit great toughness, have emerged as promising candidates for innovative energy storage solutions. Here we produced SWCNT ropes wrapped in thermoplastic polyurethane elastomers, and demonstrated experimentally that a twisted rope composed of these SWCNTs possesses the remarkable ability to reversibly store nanomechanical energy. Notably, the gravimetric energy density of these twisted ropes reaches up to 2.1 MJ kg⁻¹, exceeding the energy storage capacity of mechanical steel springs by over four orders of magnitude and surpassing advanced lithium-ion batteries by a factor of three. In contrast to chemical and electrochemical energy carriers, the nanomechanical energy stored in a twisted SWCNT rope is safe even in hostile environments. This energy does not deplete over time and is accessible at temperatures ranging from −60 to +100 °C.
Bioburden detection on surface and water samples in a rapid, ultra-sensitive and high-throughput manner
(Wiley, 2024-03-17) Hasan, Md Sadique; Sundberg, Chad Alan; Gilotte, Elias; Ge, Xudong; Kostov, Yordan; Rao, Govind
Bioburden detection is crucial for food, water, and biopharmaceutical applications as it can directly impact public health. The objective of this study is to develop and validate an assay and protocol for detecting bioburden on solid surfaces, as well as in water, with high sensitivity and accuracy in a rapid manner. Henceforth, a resazurin-based assay optimized for detecting bioburden has been integrated with a previously developed portable multichannel fluorometer. The microbes were isolated from solid surfaces in different laboratory settings by swabbing technique, and stream water was collected for contamination analysis. Based on the results, the assay and protocol can successfully detect bioburden as low as 20 CFU/cm² and 10 CFU/mL present in both surface and water samples, respectively.
Recent Developments in Bioprocess Monitoring Systems
(Springer, 2024-01-11) Rahmatnejad, Vida; Wei, Yunqian; Rao, Govind
Bioprocess monitoring systems are essential tools for achieving an optimal manufacturing process for pharmaceuticals. In recent years, there have been advancements in the development of these systems. One of the most notable developments in bioprocess monitoring systems is the use of biosensors, which can detect and measure biological molecules such as enzymes and proteins. The use of imaging technologies, such as microscopy and flow cytometry, has allowed for the non-invasive monitoring of cell culture, providing valuable information for process optimization. Other non-invasive monitoring systems are being developed with the aim of reducing the risk of contamination. Another important advancement is the use of machine learning and artificial intelligence in bioprocess monitoring systems. These technologies have the ability to learn from historical data and predict future outcomes, which can be beneficial for optimizing bioprocesses in real-time. Overall, recent advancements in sensor technology can help in improving the efficiency and effectiveness of bioprocessing. The integration of advanced sensing technologies, and machine learning can provide valuable insights and improve the ability to monitor and control bioprocesses online. In this chapter, we will discuss recent advancements in bioprocess monitoring systems, specifically for monoclonal antibody and cell and gene therapy manufacturing processes.
Global nuclear radiation monitoring using plants
(SPIE, 2015-05-13) Islam, Mohammad; Romero-Talamás, Carlos; Kostov, Dan; Wang, Wanpeng; Liu, Zhongchi; Hussey, Daniel S.; Baltic, Eli; Jacobson, David L.; Gu, Jerry; Choa, Fow-Sen
Plants exhibit complex responses to changes in environmental conditions such as radiant heat flux, water quality, airborne pollutants, soil contents. We seek to utilize the natural chemical and electrophysiological response of plants to develop novel plant-based sensor networks. Our present work focuses on plant responses to high-energy radiation – with the goal of monitoring natural plant responses for use as benchmarks for detection and dosimetry. For our study, we selected a plants cactus, Arabidopsis, Dwarf mango (pine), Euymus and Azela. We demonstrated that the ratio of Chlorophyll a to Chlorophyll b of the leaves has changed due to the exposure gradually come back to the normal stage after the radiation die. We used blue laser-induced blue fluorescence-emission spectra to characterize the pigment status of the trees. Upon blue laser excitation (400 nm) leaves show a fluorescence emission in the red spectral region between 650 and 800nm (chlorophyll fluorescence with maxima near 690nm and 735 nm). Sample tree subjects were placed at a distance of 1m from NIST-certified 241AmBe neutron source (30 mCi), capable of producing a neutron field of about 13 mrem/h. This corresponds to an actual absorbed dose of ~ 1 mrad/h. Our results shows that all plants are sensitive to nuclear radiation and some take longer time to recover and take less. We can use their characteristics to do differential detection and extract nuclear activity information out of measurement results avoid false alarms produced environmental changes. Certainly the ultimate verification can be obtained from genetic information, which only need to be done when we have seen noticeable changes on plant optical spectra, mechanical strength and electrical characteristics.
Rapid Bacterial Detection and Identification of Bacterial Strains Using Machine Learning Methods Integrated With a Portable Multichannel Fluorometer
(IEEE, 2023-08-09) Hasan, Md Sadique; Sundberg, Chad; Hasan, Hasibul; Kostov, Yordan; Ge, Xudong; Choa, Fow-Sen; Rao, Govind
Rapid and sensitive bioburden detection is of paramount importance in different applications including public health, and food and water safety. To overcome the traditional limitations of bacterial detection i.e., lengthy culture time, and complicated procedure, a low-cost, portable multichannel fluorometer coupled with machine learning (ML) has been implemented in this study. Five different strains of bacterial samples were tested along with the negative control for time-series fluorescence data collection and analysis. We applied different conventional unsupervised and supervised machine learning techniques with extracted features followed by preprocessing of the data. Initially, machine learning algorithms were applied for the qualitative detection of bacteria by binary classification followed by regression analysis to predict the level of contamination for E. coli. The multiclass classification was used to identify gram-positive, and gram-negative bacterial strains and differentiate all the bacterial strains tested. Our results show that around 97.9% accuracy can be achieved for bacterial contamination detection for as low as 1 CFU/mL while 92.1% accuracy can be achieved for differentiating the gram-positive and gram-negative strains. Additionally, with 1 minute of data, high accuracy is obtained for detecting bioburden, proving the multichannel fluorometer’s rapid detection capability. The multichannel fluorometer integrated with ML analytics is capable of automating data analysis and determining accurate and rapid bacterial detection on-site with the prediction of bioburden levels and differentiating bacterial strains and the protocol can be applied to the biosensors with a similar data type.
Tuning of antimicrobial property of commercial drugs by use of bio- synthesized noble metal nanoparticles
(2014-02) Srinivasan, Venkatesh; Vedantam, Pallavi; Ramkumar, C. B.; Ramamurthy, Sai Sathish
Silver nanoparticles are known to have antimicrobial and antifungal properties. Here we explore the effect of biogenic silver (AgNPs) and gold nanoparticles (AuNPs) on the antimicrobial property of drugs namely Vancomycin, Ampicillin and Tetracyclin, by measuring their zone of inhibition in disk diffusion studies against Escherichia coli, Enterococcus faecalis and Staphylococcus aureus. The different AuNPs and AgNPs used were synthesized using aqueous extracts of floral parts of Tecoma stans, Caesalpinia sappan, Tagetus erecta. The bacterial strains were spread on agar plates and the disks impregnated with known concentration of drug were used for disk diffusion studies and well diffusion studies. 20nm & 200nm commercially available AuNPs and AgNPs were also used along with drugs for disk diffusion studies and the results were compared. Different nanoparticles had different effect on drug's antimicrobial activity. The range of tunability of antimicrobial activity of drug achieved by using the biogenic nanoparticles was more than that of commercial nanoparticles. E.coli and S.aureus are known to gain resistance against Ampicilin and Vancomysin respectively. In this work, the effect of Ampicillin on E.coli and the effect of Vancomysin on S.aureus could be restored by using it along with our nanoparticles. Thus we propose a safe and simple method to increase or decrease drug's activity against specific microbe.
Ultra-Amplification of Surface Plasmon Coupled Emission Using an Engineered Graphene-Silver Thin Film Hybrid
(Optica, 2012-12-12) Mulpur, Pradyumna; Vemu, Sai Krishna; Lingam, Kiran; Srinivasan, Venkatesh; Ramamurthy, Sai Sathish; Kamisetti, Venkataramaniah; Rao, Apparao M
We report the selective ultra-amplification of the Surface Plasmon Coupled Emission by synergistic plasmon coupling on incorporating a novel hybrid thin film stacking of graphene on silver.
Novel Synthesis of Nanoparticles for Enhancements in Surface Plasmon Coupled Emission
(Optica, 2014-12-16) Srinivasan, Venkatesh; Srikanth, M.; Nayak, Lisa; Ramamurthy, Sai Sathish; Neeleshwar, S.
We report a novel synthesis route for nanomaterials namely SnSe and SnTe and their application as a simple thin film spacers for achieving 30–45 fold fluorescence enhancements using Surface Plasmon Coupled Emission platform.
Back Cover: Ag-CNT Architectures for Attomolar Dopamine Detection and 100-Fold Fluorescence Enhancements with Cellphone-Based Surface Plasmon-Coupled Emission Platform (ChemPhysChem 18/2016)
(Wiley, 2016-09-14) Badiya, Pradeep Kumar; Srinivasan, Venkatesh; Jayakumar, Tejkiran Pindi; Ramamurthy, Sai Sathish
Spacer layer engineering for ultrasensitive Hg(II) detection on surface plasmon-coupled emission platform
(De Gruyter, 2017-06-15) Badiya, Pradeep Kumar; Jayakumar, Tejkiran Pindi; Srinivasan, Venkatesh; Ramamurthy, Sai Sathish
In this work, we demonstrate for the first time the ultrasensitive detection of Hg²⁺ ions with femtomolar sensitivity in water samples with the use of the surface plasmon-coupled emission (SPCE) platform. The use of portable network diagnostic tools for water security and integrated water shed management is a topic of recent research interest. In this context, the current study explores Hg²⁺ monitoring using a rhodamine-6G (Rh6G) derivative bearing a monothiospirolactone mounted onto a SPCE substrate. Thus far, the limit of detection for mercury ions by the conventional fluorescence technique has been 0.15 nm. However, we have achieved 1 fm Hg²⁺ detection using silver nanoparticle-based spacer layer engineering on an SPCE sensor chip. Using this technology, a field device can be fabricated for rapid, ultrasensitive, multi-analyte detection (of contaminants) in water samples.
An approach to rapid distributed manufacturing of broad spectrum anti-viral griffithsin using cell-free systems to mitigate pandemics
(2022-12-20) Borhani, Shayan G.; Levine, Max Z.; Krumpe, Lauren H.; Wilson, Jennifer; Henrich, Curtis J.; O’Keefe, Barry R.; Lo, Donald; Sittampalam, G. Sitta; Godfrey, Alexander G.; Lunsford, R. Dwayne; Mangalampalli, Venkata; Tao, Dingyin; LeClair, Christopher A.; Thole, Aaron; Frey, Douglas; Swartz, James; Rao, Govind
This study describes the cell-free biomanufacturing of a broad-spectrum antiviral protein, griffithsin (GRFT) such that it can be produced with consistent purity and potency in less than 24 hours. We demonstrate GRFT production using two independent cell-free systems, one plant and one microbial. Griffithsin purity and quality were verified using standard regulatory metrics. Efficacy was demonstrated in vitro against SARS-CoV-2 and HIV-1 and was nearly identical to that of GRFT expressed in vivo. The proposed production process is efficient and can be readily scaled up and deployed anywhere in the world where a viral pathogen might emerge. The current emergence of viral variants has resulted in frequent updating of existing vaccines and loss of efficacy for front-line monoclonal antibody therapies. Proteins such as GRFT with its efficacious and broad virus neutralizing capability provide a compelling pandemic mitigation strategy to promptly suppress viral emergence at the source of an outbreak.
Microwave induced thermally assisted solvent-based bonding of biodegradable thermoplastics: an eco-friendly rapid approach for fabrication of microfluidic devices and analyte detection
(Nature, 2022-09-27) Hasan, Md Sadique; Borhani, Shayan; Ramamurthy, Sai Sathish; Andar, Abhay; Ge, Xudong; Choa, Fow-Sen; Kostov, Yordan; Rao, Govind
There is an increasing interest in low-cost, facile and versatile thermoplastic bonding for microfluidic applications that can be easily transitioned from laboratory prototyping to industrial manufacturing. In addition, owing to the surge in the usage of thermoplastic microfluidics and its adverse effect on the environment, it is prudent to source alternative materials that are biodegradable, providing a sustainable, green approach. To address the problems, here we introduce an environment friendly, low-cost and safe welding technology used in the fabrication of microcassettes from biodegradable cellulose acetate (CA) thermoplastics. The thermally assisted solvent based bonding of the thermoplastics was accomplished in a domestic microwave oven with the aid of a polyether ether ketone (PEEK) vise. To characterize the quality of the bonding, our in-house technique was compared with a conventional thermally assisted solvent bonding configuration using a heat press machine and tested under different conditions. Our microwave induced bonding of CA presents three times reduced bonding time with higher bonding strength, good reliability and does not necessitate the use of cumbersome instrumentation. Finally, we demonstrate an electrophoresis application and vitamin C detection accomplished using this biodegradable microcassette presenting comparable results with traditional techniques, illustrating the potential of this fabrication technique in different microfluidic applications.
Rapid ultra-sensitive and high-throughput bioburden detection: Microfluidics and instrumentation
(ACS, 2022-06-06) Hasan, Md Sadique; Marsafari, Monireh; Tolosa, Michael; Andar, Abhay; Ramamurthy, Sai Sathish; Ge, Xudong; Kostov, Yordan; Rao, Govind
Contamination detection often requires lengthy culturing steps to detect low-level bioburden. To increase the rate of detection and decrease the limit of detection (LOD), a system featuring microfluidics and a multichannel fluorometer has been developed. The eight-channel fluorometer enables parallel testing of multiple samples with the LOD as low as <1 cfu/mL. This low-cost system utilizes the slope of fluorescence intensity that serves as the criterion for bioburden detection. The redox indicator dye resazurin is used to monitor the presence of viable cells in this study and is reduced to resorufin with a high quantum yield at 585 nm. The sample under investigation is spiked with resazurin and loaded in a special-design microfluidic cassette, and the rate of change is observed via the fluorometer. The method was validated using primary Escherichia coli culture in comparison with a spectrophotometer which served as the gold standard. An optimized assay based on Luria–Bertani medium was developed. The impact on the assay sensitivity based on incubation and filtration steps was also explored. The assay is shown to pick up inadvertent contamination from test tubes and pipette tips showing its applicability in real-world settings. The data analysis demonstrated a comparable performance of the multichannel fluorometer vis-a-vis the conventional plate reader. The multichannel system is shown to detect bioburden presence in as low as 20 s for bacterial concentrations ≥5 cfu/mL after 6 h of incubation. Considering its portability, low cost, simplicity of operation, and relevant assay sensitivity, the system is well positioned to detect low-level bioburden in the laboratory, pharmaceutical, and field settings.
Disposable low-cost cardboard incubator for thermoregulation of stable preterm infant – a randomized controlled non-inferiority trial
(Elsevier, 2020-12-07) Chandrasekaran, Ashok; Amboiram, Prakash; Balakrishnan, Umamaheswari; Abiramalatha, Thangaraj; Rao, Govind; Jan, Shaik Mohammad Shafi; Rajendran, Usha Devi; Sekar, Uma; Thiruvengadam, Gayathri; Ninan, Binu
Background Incubators and radiant warmers are essential equipment in neonatal care, but the typical 1,500 to 35,000 USD cost per device makes it unaffordable for many units in low and middle-income countries. We aimed to determine whether stable preterm infants could maintain thermoregulation for 48 h in a low-cost incubator (LCI). Methods The LCI was constructed using a servo-heater costing 200 USD and cardboard infant-chamber. We conducted this open-labeled non-inferiority randomized controlled trial in a tertiary level teaching hospital in India from May 2017 to March 2018. Preterm infants on full feeds and receiving incubator or radiant warmer care were enrolled at 32 to 36 weeks post-menstrual age. We enrolled 96 infants in two strata (Strata-1< 33 weeks, Strata-2 ≥ 33 weeks at birth). Infants were randomized to LCI or standard single-wall incubator (SSI) after negative incubator cultures and monitored for 48 h in air-mode along with kangaroo mother care. The incubator temperature was adjusted manually to maintain skin and axillary temperatures between 36.5 °C and 37.5 °C. During post-infant period after 48 h, SSI and LCI worked for 5 days and incubator temperatures were measured. The primary outcome was maintenance of skin and axillary temperatures with a non-inferiority margin of 0.2 °C. Failed thermoregulation was defined as abnormal axillary temperature (< 36.5 °C or >37.5 °C) for > 30 continuous-minutes. Secondary outcomes were incidence of hypothermia and required incubator temperature. Trial registration details: Clinical Trial Registry - India (CTRI/2015/10/006316). Findings Prior to enrollment 79(82%) infants were in radiant warmer and 17(18%) infants were in incubator care. Median weight at enrollment in Strata-1 and Strata-2 for SSI vs. LCI was 1355(IQR 1250–1468) vs. 1415(IQR 1280–1582) and 1993(IQR 1595–2160) vs. 1995(IQR 1632–2237) grams. Mean skin temperature in Strata-1 and Strata-2 for SSI vs. LCI was 36.8 °C ± 0.2 vs. 36.7 °C ± 0.18 and 36.8 °C ± 0.22 vs. 36.7 °C ± 0.19. Mean axillary temperature in Strata-1 and Strata-2 for SSI vs. LCI was 36.9 °C ± 0.19 vs. 36.8 °C ± 0.16 and 36.8 °C ± 0.2 vs. 36.8 °C ± 0.19. Mixed-effect model done for repeated measures of skin and axillary temperatures showed the estimates were within the non-inferiority limit; -0.07 °C (95% CI -0.11 to -0.04) and -0.06 °C (95% CI -0.095 to -0.02), respectively. Failed thermoregulation did not occur in any infants. Mild hypothermia occurred in 11 of 48(23%) of SSI and 16 of 48(33%) of LCI, OR 1.28 (95%CI 0.85 to 1.91). Incubator temperature in LCI was higher by 0.7 °C (95%CI 0.52 to 0.91). In the post-infant period SSI and LCI had excellent reliability to maintain set-temperature with intra-class correlation coefficient of 0.93 (95%CI 0.92 to 0.94) and 0.96 (95%CI 0.96 to 0.97), respectively. Interpretation Maintenance of skin and axillary temperature of stable preterm infants in LCI along with kangaroo mother care was non-inferior to SSI, but at a higher incubator temperature by 0.7 °C. No adverse events occurred and LCI had excellent reliability to maintained set-temperature.
Developments in Insulin Manufacturing Using Cell-Free Systems
Borhani, Shayan; Gurramkonda, Chandrasekhar; Frey, Douglas; Tolosa, Leah; Swartz, James; Rao, Govind
The primary aim of this method is to emulate the naturally occurring mechanisms which take place in vivo, when converting preproinsulin into metabolically active insulin (4). Figure 2, displays the binding of pre-proinsulin to a CM HiTrap FF column (pH 3.0) followed by cleavage and threonine addition to the terminal B29 residue. The final product is then eluted using a linear salt gradient.
Robust and easy macrofluidic connections in acrylic
(Royal Society of Chemistry, 2012-04-23) Horner, Nathalie; Henderson, Robert; Selock, Nick; Rao, Dr. Govind
Sensor Techknowledge: Sensors for Process Development: A Practical Guide
(UMBC Center for Advanced Sensor Technology and Department of Biochemical and Environmental Engineering, 2020-07-05) Rao, Govind

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