Motivated by healthcare and biomedical research needs, Sarioglu Lab is developing technologies to investigate and manipulate biological systems on the micro and nanoscale. Using advanced fabrication techniques, we build devices that utilize microfluidics, microelectromechanical systems (MEMS), optics, electronics and signal processing. Through multidisciplinary collaborations, we use these technologies as clinical microdevices for disease detection and monitoring and as bioanalytical instruments for high-throughput molecular and cellular analysis.

Lab-on-a-Chip Devices with Integrated Electronic Readout

Numerous biophysical and biochemical assays rely on spatial manipulation of particles/cells as they are processed on lab-on-a-chip devices. Analysis of spatially distributed particles on these devices typically requires microscopy negating the cost and size advantages of microfluidic assays.

CODES_Fig2-01We have recently developed a scalable electronic sensor that utilizes code division multiple access (CDMA) a spread spectrum telecommunications technique, for orthogonal detection of particles in multiple microfluidic channels from a single electrical output. We call this technology Microfluidic Coded Orthogonal Detection by Electrical Sensing or Microfluidic CODES in short. We use microfabrication techniques to create coplanar electrodes such that particles passing over these electrodes produce bipolar digital codes, similar to the digital codes used in CDMA communication networks to differentiate between cell phone users. These codes are specifically designed to be orthogonal to each other so that they can easily be distinguished through computation even when they overlap.

Microfluidic CODES offers a simple, all-electronic interface for tracking particles on microfluidic devices and is particularly well suited to create integrated, low-cost lab-on-a- chip devices for cell- or particle-based assays that are needed for point-of-care tests in resource-limited settings.

Biomedical Microdevices for Disease Detection and Monitoring

Many physiological and pathological conditions are diagnosed and monitored primarily through blood sampling and analysis. Microsystems are poised to revolutionize blood analysis with higher sensitivity and smaller sample requirements. Fig-1_v3Leveraging these advantages, one of our research interests is in developing integrated microsystems for disease detection and monitoring through blood analysis. Our current efforts are focused on developing microfluidic systems for antigen-independent isolation of extremely rare circulating tumor cells (CTCs) from patient blood. CTCs disseminate from the primary tumor to distant organs and initiate metastasis, an event that is responsible for more than 90% of cancer-related deaths. Therefore, isolation and analysis of CTCs hold great promise not only in clinic for early cancer detection and noninvasive monitoring of disease progression, but also for understanding the molecular basis of cancer metastasis at the cellular level.

We have recently developed a microfluidic chip designed to specifically isolate clusters of CTCs from unprocessed patient blood samples. The CTCs embedded within clusters appear to have greatly enhanced metastatic propensity over single tumor cells, yet, the lack of isolation technologies optimized to detect these cellular aggregates led to their rare detection and precluded detailed studies of their role on metastasis for a long time. CTC Cluster Chip enables not only non-destructive, antigen-independent isolation of CTC clusters but also viable retrieval of CTC clusters in solution for downstream molecular assays. We collaborate with clinicians and molecular biologists to apply the technology on samples from patients with various metastatic cancer types such as non-small cell lung cancer, melanoma, breast and prostate cancers.

Leveraging our expertise in MEMS sensors and clinical microfluidics, we are currently developing BioMEMS platforms that employ a variety of sensing mechanisms (i.e., optical, mechanical, chemical, electrical). We envision that these platforms will change how we detect, monitor and manage diseases like cancer, diabetes and neurological disorders and will ultimately improve human life.

Technologies for Biomolecular Sensing and Spectroscopy

Nanoscale processes are fundamental to biology. Biological macromolecules and their interactions are at the core of biological function so that a malfunction at molecular level (i.e., mutations, protein misfolding or virus infection) can trigger a cascade of multi-scale events that may lead to diseases such as cancer, Alzheimer’s or AIDS. As such, it is crucial to interrogate biological systems at a molecular scale not only to understand life at its fundamental level but also to develop effective diagnostic and therapeutic strategies. RS_Fig2One of our research goals is to develop nanoscale sensing and spectroscopy technologies for high-throughput detection and characterization of biomolecules. To achieve this, we use advanced microfabrication technologies to build devices that exploit the unique mechanical, optical and electrical phenomena on the nanoscale. By combining these devices with advanced signal processing, our goal is to develop highly sensitive platforms that will allow physiological and pathological conditions to be diagnosed with higher accuracy and minimal sample requirements.

For example, we have developed a high-bandwidth nanomechanical spectroscopy technique for quantitative material characterization based on tapping-mode atomic force microscopy (AFM). We have developed specialized micromachined probes with interferometric high-bandwidth force sensor that can resolve nonlinear tip-sample interaction forces with microsecond time resolution. We also built an analog front-end, real-time data acquisition system and computational algorithms to integrate this probe in any commercial atomic force microscope. Such a technology has the potential to impact genomics and proteomics, where there is a demand for high content screening tools that can rapidly characterize biological molecules and interactions between molecules with high spatial resolution and sensitivity.