Welcome to the Centre for BioSystems Science and Engineering. The Centre for BioSystems Science and Engineering (BSSE) at the Indian
Institute of Science (IISc) was founded on June 4th, 2015, based on the critical mass that became evident due to the Interdisciplinary PhD programme in Bioengineering
that started in August 2012 and a large grant from DBT entitled 'Bioengineering and Biodesign Initiative'. BSSE brings together biologists, engineering, and those who
are trained as bioengineers. It is also extending its reach to medical doctors, agricultural scientists, and biomedical industries. The approach to research in BSSE is
two-pronged. The first is to conduct discovery-oriented research in biology using engineering principles. This is a complementary approach that dovetails with extensive
biology research being conducted in IISc. Increasing number of biologists are getting involved with BSSE. The second is to engineer biological systems, biomedical
instruments, and human-assistive devices for improving human healthcare and agricultural practices. BSSE currently hosts 4 permanent faculty, 12 associate faculty,
1 INSPIRE fellow and 37 PhD students.
The BSSE Research Symposium is our platform to showcase, deliberate and improve the research at BSSE. We take great pleasure
in inviting you for the "6th BSSE Annual Research Symposium" to be held on the 24th and 25th of January, 2020. In addition to this, we are also excited to host
a pre-symposium event, "Workshop on Theoretical and Computational Biology" on 23rd January, 2020.
This year, symposium is preceded by a one-day workshop
on "Theoretical and Computational Biology". Lectures comprise of concepts introduced to audience in a chalk talk mode followed by a short research presentation and an
interactive discussion. This is followed by a two-day symposium which is divided into theme-based sessions to highlight the multifaceted nature of interdisciplinary
research performed in BSSE. We conclude the symposia with an interesting panel discussion on "Behind the scenes: Untold failed stories of research". We hope that the
workshop and symposium excites you as much as we are delighted in bringing it to you.
Venue: CES Seminar Hall, 3rd Floor, Biological Sciences Building, IISc. We are here.
Click here to navigate our beautiful campus.
Detailed schedule and abstracts here.
Programme, Day 0 (23rd Jan.)
Workshop on Theoretical and Computational Biology : 9 AM to 5:30 PM
Dynamical Systems in Biology
I will discuss our efforts to understand the yeast metabolic cycle, a very robust oscillation that is
observed when yeast cells are grown in a well mixed chemostat. The yeast cells oscillate between long periods of quiescence,
followed by short burst of growth and division. I will demonstrate how tools from nonlinear dynamical systems can be used to
understand this oscillation. In particular, I will touch on the concepts of negative and positive feedback, multistability,
and frustrated bistability as a means to engineer oscillations.
Stochastic Processes in Biology
Biological processes are often subject to strong stochastic effects because of the small copy numbers of the
molecular players involved. For instance, a single protein molecule may be involved in catalyzing a crucial reaction underlying
cell fate decisions. Classical, mass action-based methods of describing such processes then will not apply. Alternative
techniques based on the chemical master equation and its stochastic realization using the popular Gillespie algorithm are
typically used in such scenarios. In this talk, examples of strong stochastic effects governing biological processes will be
presented along with an exposition of the Gillespie algorithm.
Large scale human whole genome data analysis to understand disease susceptibilities: practical guide
In order to truly integrate personalized medicine into healthcare, knowledge from human whole genome sequence data at population level
is of utmost importance. The rate at which human genomes are being sequenced and large population level or disease cohorts are being
genotyped is accelerating every day. This entails tremendous high-performance computing and data storage requirements. Large scale
genome wide association studies in populations and families are required to shed insights into genetic underpinnings of complex diseases,
that are on the rise in developed and developing nations. This talk will focus on the analytical aspects of human whole genome data
that can derive knowledge from sequence information. This will ultimately help pave the way for adopting actionable measures that can
benefit human health.
Behavioral modeling meets computational neuroimaging
How do stimulus representations and task goals in the brain interact to produce behavioral choices? As a
first step toward answering this question, I will introduce signal detection theory (SDT) -- a highly successful behavioral
framework for modeling simple perceptual decisions. Next, I will describe a recently developed multidimensional SDT model
which has found increasing application in modeling complex behaviors, like attention. Finally, I will present an example of
how combining multidimensional SDT with computational neuroimaging (diffusion MRI) has provided unique insights into the involvement
of specific brain regions in attention. The broad goal will be to develop mathematical intuitions for analyzing a broad class
of choice behaviors.
Programme, Day 1 (24th Jan.)
Sanjay K. Biswas Memorial Lecture : "Engineering Stem Cells" by Prof. Maneesha Inamdar from JNCASR at 9:15 AM
In her own words : Stem cells have the innate capacity to build tissues, organs or even the whole organism. The ability to isolate and grow stem cells
in the laboratory has opened up a wide range of possible applications in diagnostics, healthcare and clinical interventions. However the challenge lies in
generating sufficient numbers of these cells, controlling their properties and directing their construction of desired structures. While great strides have
been made in understanding the biology of stem cells and their genetic manipulation, translation of benchtop knowledge to products and therapies requires
scale-up and automation. Cross-disciplinary science and engineering solutions are increasingly being applied to achieve the goals of regenerative medicine.
This talk will give an overview of the field of stem cell biology and put in perspective local and global efforts in this area.
Immunoengineering : 10:15 AM to 12:55 PM
Exciting inter disciplinary research for diseases with public health implications
Our research strategy has been to encourage discovery that is inspired by societal need and innovation which is
driven by new knowledge or synthesis of existing knowledge, in order to create applications that can go back to the society. With
this philosophy, maternal and child health is critical because it is a key determinant of the health of a society. Maternal, U5 and
infant mortality rates continue to be alarmingly high.
Despite decades of research there are no effective solutions for some
critical public health diseases in this domain and this is largely because of large knowledge gaps. It is evident that deep
interdisciplinary knowledge is required for innovative applications.
The talk will summarize our attempt to develop unique
large interdisciplinary research programs that bridge classical epidemiology with modern science to find solutions for diseases that
have major public health significance in the country. These programs facilitate development of knowledge-based interventions and
public health tools for national and global policy.
The CAR journey in India
CAR-T cell therapy has demonstrated remarkable success in long-term remission of relapsed or refractory B-ALL.
Recently two drugs (KymriahTM and YescartaTM) against CD19 malignancies have been approved by FDA after phase I/II clinical trials.
However, there is a global disparity in availability of CAR T cell treatment. This “intent to cure” therapeutic platform is not yet
available in India. Considering socioeconomic conditions of patients in our country, the current CAR-T-cell therapy will be unaffordable
to majority of them due to high cost. To harness this technology and bringing it to the clinic in India at affordable-cost, there is a
clear need of developing indigenous CAR-T cell technology platform. In this talk I will discuss about some of the work we have been doing
to develop anti-CD19 CAR T cells. In addition, we have scaled up manufacturing platform as per the industry standard and validated assays
for product quality control. The data obtained from our work will set the foundation of first in-human clinical trials for CD19 positive B
cell malignancies (r/rB-ALL, DLBCL and FL) in India, which will start soon in India.
Dry powder micro-carriers for treatment of Tuberculosis
by Pallavi Sharma, BSSE
Tuberculosis affects an estimated 10 million people globally leading to significant mortality, making it the
leading cause of death due to a single infectious agent. The current treatment strategies involve oral dosing of a combination
of drugs for 6-12 months. This approach is being rendered ineffective because of low patient compliance and emergence of
antibiotic-resistant strains. Hence, there is a pressing need to develop more effective treatment regimens.
are viruses that specifically infect their host bacteria and cause lysis. They are emerging as promising candidates to manage
antibiotic-resistant infections. Inhalation based dry powder delivery is a patient compliant method that directly targets the
lungs and can be used to increase TB patient compliance. However, phages cannot deposit deep in the lungs via inhalation, where
the bacteria resides. Hence for effective delivery, it is necessary to use polymeric carriers for deep lung targeting where they
can be taken up by alveolar macrophages. Enhanced targeting to Mtb-infected macrophages and the intracellular niche can be achieved
by engineering particle properties such as size, surface charge or attaching a ligand. Thus, polymeric carriers can potentially
serve as effective vehicles for delivering potent bactericidal agents. Here, we report engineering of PLGA microparticles for
optimal delivery to Mtb-infected human macrophages that can be used to translate phage therapy.
Immune Responses in Diabetic Foot Ulcers: characterization and approaches for modulation
by Jayashree V Raghavan, BSSE
Diabetic foot ulcers (DFUs), a common complication in individuals with Type 2 diabetes, shows delayed wound healing
and chronic inflammation. Wound management through frequent dressing changes, and topical application of antibiotics are the most common
strategies for treatment. While this may be sufficient in some individuals, in many healing does not occur naturally, and eventually the
limb needs to be amputated. The question that remains unanswered is why some diabetic ulcers heal while others do not. We hypothesized
that innate immune cells, specifically neutrophils, may be alternately activated in individuals whose ulcers do not heal. To test this
hypothesis, peripheral venous blood and biopsy of the ulcer site was collected from about 60 DFU patients. Peripheral venous blood was
also collected from a small number of diabetic individuals with no foot ulcer. Phenotype of immune cells in blood was characterized through
antibody-staining of specific cell surface markers followed by flow cytometry. In addition, the functional activity of neutrophils in terms
of their phagocytic capacity as well as ability to produce ROS was determined. Results from all these experiments will be discussed in the
talk, with a focus on use of dimensionality reduction techniques to identify clusters of immune cell populations that may be different
between stages of ulcers as well as controls.
If differences are observed, we also hypothesized that an approach to assist healing
in DFU patients would be to design a drug delivery system that may sequentially release an neutrophil-immunomodulatory agent followed by
release of tissue growth factors. The first set of agents are likely to convert the inflammatory environment into an immunosuppressive
environment, and the growth factors may then support re-growth of normal tissue. I will present data in my talk that describes the development
of such a sequential release system. We believe that such an approach of temporally controlled drug release may accelerate wound healing in
DFU patients, thereby serving as a new therapeutic strategy to treat early stage DFUs.
Resolvin nanocarriers for treatment of Osteoarthritis
by Ameya Dravid, BSSE
Osteoarthritis (OA) is the most common joint affliction and is characterized by degradation of cartilage, damage to
subchondral bone, loss of function of the affected joint and subsequent pain. In this disease, an initiating damage to the cartilage releases
damage associated molecular patterns (DAMPs) in the surrounding synovial fluid. These DAMPs are recognized by cells in the joint, like
synovial macrophages. These cells subsequently release pro-inflammatory cytokines like IL-1β, TNF-𝛂 and IL-6 which trigger more damage
to the cartilage. This results in a vicious cycle of damage and inflammation.
Conventionally prescribed therapies (like corticosteroids)
have several limitations due to low retention in body and poor targeting to the joints. A newer approach administers n-3 fatty acids to the body
to resolve the associated inflammation. One of the advantages of this approach is cell-level targeting instead of the molecular level
(as in case of most other approaches). This allows targeting of multiple pathways simultaneously. Recent reports suggest that RvD1, an n-3 fatty
acid, ameliorates symptoms of OA by resolving the associated inflammation. The therapeutic potential is, however, impaired due to its short in
vivo half-life. To overcome these obstacles, we have exploited the ability of nanoparticles to have increased intraarticular retention. Our
data shows that liposomes, our nanocarriers of choice, are retained in the knee joint for ~7 days compared to free dye. We hypothesize that
these resolvin D1-loaded liposomes will increase intraarticular retention of this molecule by generating a sustained release over an extended
period of time. We plan on testing the effect of these liposomes on surgically-induced OA in mice in the future.
Soft Matter : 1:45 PM to 5 PM
Re-entrant efficiency of phototaxis in Chlamydomonas reinhardtii cells
Phototaxis is one of the most fundamental stimulus-response behaviors in biology wherein motile
micro-organisms sense light gradients to swim towards the light source. We find surprisingly that the phototactic efficiency of
model algae Chlamydomonas reinhardtii has a minimum at a well-de fined number density, for a given light gradient, above which
the phototactic efficiency of a collection of cells can even exceed the performance obtainable from single isolated cells. We show
that the origin of enhancement of performance above the critical concentration lies in the slowing down of the cells which enables
them to sense light more effectively. We show that this phenomenon can be understood theoretically by modelling the phototactic
response as a density dependent torque acting on an active Brownian particle.
Multifunctional magnetic nanomotors as radiosensitizers
by Reshma V R, BSSE
Nanomotors are micro-nano sized particles that can be actuated by chemical, magnetic, acoustic
or biological methods which have potential applications in targeted drug delivery, precision surgery, medical diagnostics
and detoxification. Our helical magnetic nanomotors can be propelled by an externally applied rotating magnetic field
which is a scalable, non-invasive form of actuation with minimal effects on organisms. Spatiotemporal manipulation and
multifunctionality of these motors have been demonstrated for movement in blood, magnetic hyperthermia, active colloidal
manipulation, maneuverability inside living cells, and measurement of local viscosity. These properties of helical magnetic
nanomotors may be exploited for theranostics in live organisms.
Here, we look at the radiosensitization effects of
nanomotors on human breast cancer cells. In-vitro studies on MDA-MB-231 cells show radiosensitization effects of nanomotors.
We have developed a syngeneic breast tumor model in BALB/c mice for in-vivo experiments on radiosensitization. Further,
we explore the in-vivo biocompatibility and biodistribution of the nanomotors.
Phase transitions in active and living matter
Phase transitions are ubiquitous in active and living matter and the physics of these phenomena is of
fundamental interest. The control of phase transitions may serve as a unique probe: (i) in living systems, mechanisms encoding
the control of such transitions may be used a window to understand evolutionary dynamics/constraints and (ii) in synthetic
systems, they point to design principles to engineer novel phenomena.
After discussing this viewpoint briefly, I will
present two mechanisms that lead to the phase separation of active agents (i) Flow-Induced Phase Separation (FIPS) in self-propelled
particle populations, which we explore using a synthetic system of active particles and (ii) Motility-Induced Phase Separation
(MIPS) a complementary mechanism to FIPS which I will discuss in the context of fruiting body formation in Myxococcus Xanthus,
a soil bacterium.
Mechanistic insights into biofilm formation by Pseudomonas aeruginosa
by Divakar Badal, BSSE
Ventilator-associated pneumonia is one of the major causes of death in ICU patients. In these patients, respiratory
support is provided using a mechanical ventilator connected to an endotracheal tube (ETT) made of polyvinyl chloride. Ends of ETT in
the trachea often support biofilm formation by ESKAPE pathogens most notably Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter
baumanii, and Pseudomonas aeruginosa. Apart from bacteria, Cryptococcus neoformans, and Candida albicans were also found in patients
with pulmonary disorders. These microbes can form biofilm which is linked to their resistance against antimicrobial compounds. However,
the interaction between microbes at the site of infection is not well understood.
To begin with, we aimed to understand the
formation of biofilm by Pseudomonas aeruginosa (PA14) on the polystyrene surface, on the polycarbonate surface and on the endotracheal
tube. We looked at the initial attachment to the substratum. In the second part of the study, we have studied interactions of P. aeruginosa
with C. neoformans. We found that P. aeruginosa can kill C. neoformans in a manner that is dependent on ErdR response regulator of
Pseudomonas. ErdR regulates the oxidation of ethanol. We found that PA14::∆erdR mutant forms a better biofilm in the presence of 1%
alcohol on polystyrene. Further, using microscopy we show that P. aeruginosa cells chemotaxis towards C. neoformans cells and do not
allow the yeast to divide and grow. Whereas, In PA14::∆erdR mutants fail to kill yeast and allow them to grow. We conclude that ethanol
secreted by C. neoformans cells induces foraging motility in P. aeruginosa.
Guest Lecture : "Next-Generation Neuromonitoring Inside and Outside the Intensive Care Setting" by Prof. Thomas Heldt from MIT at 5 PM
In his own words : Compared to cardiorespiratory monitoring and assessment, very few technologies are currently in use to track brain health
in a quantitative, objective and longitudinal manner. Assessment of brain health and cognitive function largely relies on physician assessment of a patient.
Such assessment does not tend to be quantified and can be prone to inter-rater variability. My group is actively involved in developing novel neuromonitoring
approaches inside and outside the high-acuity setting of the intensive care unit.
In this talk, I will highlight our work in model-based signal processing
for improved neurocritical care to derive additional and clinically useful information from routinely available data streams. I will briefly present our
model-based approach to noninvasive, patient-specific and calibration free estimation of intracranial pressure. I will also highlight recent work in
automated emboli detection using transcranial ultrasound and recording of eye movements with consumer-grade electronic devices to track the progression
of neurodegenerative diseases.
Programme, Day 2 (25th Jan.)
Quantitative Biology : 9:00 AM to 12:50 PM
Gamma rhythm as a tool to investigate brain function in health and disease
Brain signals often show intrinsic oscillations at “gamma” frequency range (30-80 Hz), which can be induced by
presenting visual stimuli such as bars and gratings. Stimulus-induced gamma oscillations are modulated by high-level cognitive processes
such as attention and memory and are abnormal in patients suffering from mental disorders such as Autism and Schizophrenia. Gamma oscillations
thus provide ways to investigate neural processes in health and disease. I will discuss how stimulus induced gamma oscillations vary with
healthy ageing in a large cohort of elderly subjects (>50 years), and can be used as a biomarker in early diagnosis of Alzheimer’s Disease (AD).
Single-molecule imaging of cytoplasmic dynein in vivo reveals the mechanism of motor activation and cargo capture
by Nireekshit A T, BSSE
Cytoplasmic dynein is the major minus-end-directed motor required for transport of intracellular cargo. Dynein is activated
in vitro upon formation of a tripartite complex containing dynactin and cargo adaptors such as BicD2. However, how processive complexes come
together in the complex in vivo milieu is unknown. A prevalent hypothesis is EB1-driven formation of dynein-dynactin clusters at microtubule
plus-ends to capture cargo. To test this, we first improved HILO microscopy to visualize single dynein molecules in HeLa cells and observed
that only half of the dyneins binding to the microtubule moved in a processive fashion. The rest detached from the microtubule after a residence
time of ~1s. Then, we depleted the microtubule-binding dynactin subunit p150 and observed a reduction in the residence time of dynein on
microtubules and the proportion of molecules with the minus-end directed runs. Further, we employed high-resolution microscopy to unveil that
(i) dynein clusters are found at plus ends only in cells overexpressing dynein heavy chain and, (ii) both dynactin and cargo are closely
associated with the microtubules at all times. Taken together, we propose that cargo transport is achieved in vivo when single molecules
of dynein stochastically bind to dynactin-cargo complexes that are pre-anchored to microtubules.
Imaging life with programmable supramolecular interaction
Developing strategies to assemble molecular components within the complexities of cells and tissues is of great interest in
biology. It drives advancements in various domains of fundamental and medical research, including protein modification, assay development,
therapeutic targeting, and cell surface engineering. Importantly, such strategies play a crucial role in applications that require molecular
tagging or labeling, such as imaging. Supramolecular non-covalent structural motifs are particularly attractive for this purpose as it allows
molecular−level design approach to control properties of the systems in a manner that is life-like (i.e., dynamic behavior, environmental
responsiveness, and adaptability). However, the application of synthetic recognition motifs for programming molecular assemblies in living systems
remains a challenging task due to the chemical complexities of the living system and lack of selectivity in conventional non-covalent interactions.
In my talk, I will describe our recent success of programming molecular assemblies in the living system based on a synthetic host-guest system
featuring Cucurbituril (CB). We demonstrated that highly selective and ultrastable host-guest interaction in CB provides a non-covalent
mechanism for assembling imaging agents in cells and tissues. Importantly, we have shown that CB−ADA interaction fulfills the demands of
specificity and stability that is required for bioorthogonal assembly in the living cell. We demonstrated this by labeling and imaging the
distribution and dynamics of microtubule in HeLa cell. We used the dynamic nature of the supramolecular interaction to develop a new technique
for super-resolution imaging with ~20 nm resolution. This technique, which we call SPIN (Supramolecular Probe-based Interaction mediated Nanoscopy),
exploits repetitive and transient binding of the fluorescently labeled guest to complementary CB host to obtain stochastic switching between
fluorescence ON- and OFF-states. By connecting CB guest to targeting ligands, we demonstrated that this autonomous blinking enables
two-dimensional (2D) and 3D super-resolution imaging of biomolecules in cells. We expect that this simple and easy to implement strategies will
be easily applicable to address various questions in a wide range of biological and materials research.
Heterogeneity in arabinose inducible gene expression in bacteria
by Ratnasri K, BSSE
The arabinose inducible pBAD series of bacterial vectors is considered a tuneable and tightly regulated system with protein
expression increasing monotonically with arabinose concentration for a bacterial population. However, single cell studies have shown that the
arabinose expression vectors have an ‘all-or-none’ response. Initially attributed to the heterogeneity in the expression of the transporter AraE,
this heterogeneity persists in non-arabinose metabolizing cells with a constitutively expressed transporter.
To characterize this
heterogeneity and understand the underlying cause, a fast degrading(fd) version of GFP expression under the PBAD promoter was monitored by
flow cytometry and fluorescence microscopy. Upon arabinose induction at intermediate levels, only a fraction of cells initiate gene expression
resulting in a bimodal distribution of proteins per cell. Even with increasing amounts of arabinose, a large delay in initiation of gene expression
leads to an ‘all-or-none’ behaviour over long timescales (~1.5 hrs). Further, we employed a single molecule RNA quantification technique,
smRNA-FISH, to determine whether the observed protein heterogeneity stems from transcriptional heterogeneity at the single cell level. Our results
suggest that a ‘inducer-threshold’ model explains the observed heterogeneity in the bacterial arabinose inducible system.
Atomic force microscopy for addressing problems across scales: Single Molecules to Cells to Animal Models
As a chemist, I have always been interested in studying chemical reactions in novel ways. With the developments in force-based tools
(such as Atomic Force Microscope), we are able to manipulate individual molecules and probe them under tension. After successful attempts on
force-sensitive bi-molecular reactions such as biologically important disulfide reduction, I tried to switch my focus to unimolecular reactions,
such as conformational changes during ‘proline isomerization’ under the influence of stretching force. However, we could not perform reproducible
pulling experiments on polyproline molecules despite trying for months! This made me look for proline-rich molecules that occur naturally for the
study. In a casual converstation with my colleagues in the biology department, I came to know that such proline-rich molecules do exist in biological
systems and we chose a protein candidate on the surface of malarial parasite, which is called circumsporozoite protein (CSP). Then we went on to
study the mechanical properties of CSP and concluded that it might be acting as a lubricant for the parasite to navigate in the host. We extended
the study to cells and whole parasites to strengthen the hypothesis that this protein indeed has properties to enhance the parasite motility.
This research work emphasizes that how a failed chemistry experiment turned our attention to searching for molecules and addressed an important biology
. Aditya P. Patra, Shobhona Sharma, and Sri Rama Koti Ainavarapu*, Force spectroscopy of the Plasmodium falciparum vaccine candidate
circumsporozoite protein suggests a mechanically pliable repeat region, J. Biol. Chem., Vol. 292 (2017) p2110-2119.
A Hepacivirus, a Flavivirus and an Enterovirus walk into a cell
by Harsh Chhajer, BSSE
During cellular infection, the genome of apositive-sense single-strand RNA (+ssRNA) virus serves as the coding strand for translation,
template for replication as well as the cargo to be packaged into new viruses. Although coupled to each other, these processes are mutually
exclusive and compete for the common resource, +RNA strand. The regulation of resource allocation to lifecycle processes poses an important optimization
problem for these viruses and an important avenue for anti-viral strategies.
Certain groups of +ssRNA viruses have packaging signals
in their genome increasing the efficiency of viral assembly, whereas certain viruses mimic host mRNA for efficient translation. However, a feature of all
+RNA virus infection is the ability of viral proteins to induce host membrane alterations to spatially isolate viral replication reactants in
protected confinements. We developed a mathematical model to study intra-cellular viral dynamics during +RNA viral infections that captures this
viral lifecycle process-based description. Due to its board approach, the model is able to explain the dynamics observed during infections
due to Hepatitis C virus (HCV), Japanese Encephalitis Virus (JEV) and Poliovirus (PV) infections, well studied representatives of the three important
genera under +RNA virus class namely Hepacivirus, Flavivirus and Enterovirus, respectively. Model parameter estimates for these viruses
are consistent with specific mechanisms employed by them during different aspects of lifecycle, namely, translation initiation, replicase loading and packaging
signals. Our model further allows us to evaluate the effect of different combination of such lifecycle strategies on time span of infection and probability
of success of viral replication upon cellular infection.
Biomedical Devices : 1:45 PM to 3:45 PM
PathShodh: A Journey from Science to Product
In this talk, I will describe our fascinating journey in the last few years, traversing through scientific discovery, engineering innovation,
entrepreneurial venture and manufacturing scale-up to create one of its kind multi-analyte point of care diagnostic device for diabetes and its complications.
The device is currently capable of performing 5 blood tests (Hb, HbA1c, Serum Albumin, Glycated Albumin, Glucose) and 3 urine tests (Microalbuminuria, Urine
Creatinine and Urine ACR), using electrochemical bio-sensing technology. Based on my experience, I will also discuss the challenges involved in translating the
scientific discovery into product to create societal impact. The issues in scaling up the production and regulatory aspects to meet the stringent requirements
of medical diagnostics will also be presented.
A gripper to get a grip
SpOvum is a young medical device company started by two alumni of the Indian Institute of Science, Bangalore. The company is into developing
devices pertaining to the Assisted reproductive technology-ART. Currently, success (the rate at which the baby is taken home after the infertility is diagnosed)
is quite low ~30% and remained the same since some time now. It is reckoned that innovations are the need of the hour. Since our expertise is in design and we
started our journey by designing gripper as an alternative to a three-decade-old technology of micro-pipette based aspiration. It provides a host of benefits and
is to reign supreme to its alternative. Though it felt as a designer that we have solved something dear and significant, the real problem of providing better
outcomes or success-rate loomed largely due to lack of holistic viewing of the problem. This realization gave us both the grip of the challenge and an opportunity
to enter into different phases of the ART treatment, plan, and develop solutions that would improve the outcomes. The solutions include micro-manipulation, automation,
data analytics, digital platform. The talk shall provide snippets of the work and our learning.
Raising the Lid on Blood Pressure Measurement
In contrast to the measurement of motion and flow which do not require physical contact, the actual measurement of force and pressure cannot be
done from the outside. The clinical measurement of blood pressure usually relies on proxy or indirect measurements as you might see in a doctor’s office, where a
pneumatic cuff is used to compress the tissue around the artery accompanied by the observation of the flutter of instability when the artery borders on collapse
or full release – namely, the extrema of systolic and diastolic pressure values.
In Intensive Care Units where continuous medical supervision is available,
direct measurement of blood pressure is performed by invasively reaching inside an artery (radial or femoral) using a fluid filled catheter. Such intra-arterial
blood pressure measurement gives continuous time recording of the pressure which contains much more information than the non-invasive measurement of extrema.
collaborative research between the departments of Physiology and Bioengineering we addressed two problems of human blood pressure measurement. The first is the
dynamic calibration and long-term measurement of intra-arterial blood pressure. The second is a method to non-invasively estimate the variation in blood pressure.
A fluid filled catheter used to measure blood pressure has a bandwidth that is barely wider than the spectrum of the blood pressure being measured. Using a data
recorder piggybacked on the standard catheter pressure measurement, we have been able to quantify the calibration of the system and also obtain long term measurement.
Our data shows that the pressure waveform exhibits considerable variation in the short term and in the medium term (of several minutes). This variation can be as much
as 20% of the average values. We have measured the rate and extent of the variations in both time and frequency domains. Our data shows that single pairs of extrema
measurement as conventionally done in the clinic can be incomplete and erroneous leading to improper treatment. Non-invasive methods of blood pressure waveforms have
been shown with tissue pressure controlled volume-clamps and also using variations of tonometry. However, these have several limitations. We have proposed a method of
optical flow measurement while controlling tissue pressure to estimate the variation in the systolic and diastolic (extrema) values of the blood pressure.
this talk, I will discuss methods of calibrating the dynamic system properties in situ during blood pressure measurement, and our method of non-invasive blood pressure
variation measurement; we will also look at the instrumentation used for the measurements. This discussion will be accompanied by simulation of the measurement methods,
and a simulation model for blood flow in the arterial system.
A Cancer Diagnosis Tool Integrated with Biochips for Rapid Phenotyping of Breast Biopsy Tissues: Developing a New Class of Biomedical Systems
by Anil Vishnu, BSSE
Breast cancer is the most commonly occurring cancer in women with over 2 million new cases in 2018. The gold standard diagnostic techniques for breast
cancer are immunohistochemistry and histopathology which look for the key biomarkers of breast cancer (ER, PR, HER2) and atypical morphology of cells. These techniques have
limited use inside the operation theatre (OT) for pre-operative staging during surgery owing to time constraints. Additionally, in cases of triple negative breast cancer
(TNBC) all the key markers are absent which makes the staging difficult. We report a cancer diagnosis tool integrated with biochips and electronic modules for label-free
and rapid phenotyping of breast biopsy tissues using electro-thermal modalities. The bio chips are fabricated on a silicon substrate using standard microfabrication
techniques such as e-beam evaporation, photolithography, wet etching, and deep reactive ion etching. The properties of the tissue that are profiled using the platform are
the surface and bulk electrical resistivity and thermal conductivity. Preliminary measurements from human breast biopsy tissue (cancer and adjacent normal from n=4 patients)
were carried out using the developed platform. The surface electrical resistivity of cancer was 193±14.01 Ω-m and for normal 134.69±4.09 Ω-m at 25 ℃. Similarly, the bulk
electrical resistivity of cancer was 200.1±29.65 Ω-m and normal 132.02±4.8 Ω-m at 25℃. The surface thermal conductivity of cancer was 0.19±0.009 W/m. ℃ and normal was
0.34±0.022 W/m. ℃. Similarly, the bulk thermal conductivity of cancer was 0.112±0.021 W/m. ℃ and normal was 0.42±0.061 W/m. ℃. These results show the capability of the
tool to delineate between cancer and normal. The next steps would be to understand changes in mechanical properties of normal and cancerous tissues and correlate
electro-thermo-mechanical(ETM) signatures with the gold standard and to measure ETM properties from the live biopsy tissues.
Panel discussion on "Behind the scenes: Untold failed stories of research" : 4 PM to 5 PM
Contact us @ firstname.lastname@example.org We hope to see you at the BSSE Symposium.