Susan Braunhut's Research Laboratory

Research

Medical Device Development 

Nanodiagnostics and Nanotherapeutics

Over the past decade, the lab team has focused on improving the diagnosis and treatment of cancer patients. These efforts have led to the development of four different medical device applications.

Radiation Therapy and Medical Countermeasures for Radiological Terrorism

In collaboration with Dr. Meetha Medhora at the Medical College of Wisconsin and Dr. Mark Tries in the UMass Lowell Physics department, we are conducting research to develop ways to predict and mitigate injuries resulting from neutron/gamma radiation exposure there by reducing injury in victims of radiological terrorist attach, a nuclear reactor accident or in patients receiving radiation therapy for cancers.  The research will test innovative "biomakers" that can potentially predict radiation injuries to the lungs, weeks before symptoms become apparent.  

Quartz Crystal Microbalance

In collaboration with Dr. Kenneth Marx in the UMass Lowell Chemistry Department and Dr. Joel Therrien in the UMass Lowell Electrical & Computer Engineering Department, we have developed the Quartz Crystal Microbalance (QCM) for use with living cells. We’ve discovered that, as the cells attach and spread in the QCM, we can monitor cell behavior in a novel way. When we compare the behaviors of normal cells to cancer cells, there are distinct differences over the first 24 hours of monitoring. By using small numbers of cells from a patient biopsy sample, we’ve been able to distinguish samples that only contain normal cells from those that have tumor cells. 

Nanotoxicology Biosensor

Using this same device but in a modified way, we’ve adapted the QCM as a whole cell biosensor for the detection of toxins and other physiological changes within the cell as a result of exposure to nanomaterials. 

 Drug Response Biosensors

Using this same device but in a modified way, we’ve adapted the QCM  as a drug response predictor. Today, when a patient is diagnosed with cancer, the therapy regime is surgical removal of the bulk of the tumor, radiation of the local area and if the tumor cells have entered the surrounding tissue or blood stream a regimen of chemotherapeutics begins. There are many choices of chemotherapeutics, each with their adverse effects, yet currently there’s no way to predict which drug is best for the treatment of a particular patient’s tumor. We have placed patient’s tumor cells in the QCM and are able to simultaneously compare the response of the cells to several different drugs outside the body. We can rapidly distinguish the drugs that work and those that don’t for that patient’s tumor. Using this device, we hope to provide the managing oncologist with a way to better choose the treatment for each patient. 

 The Smart Bandage

Also in collaboration with Dr. Kenneth Marx, we’ve developed a medical device for the treatment of wounds and burns called the Smart Bandage. We’ve been studying the use of electrical potential to release growth factors from cell free extracellular matrices. All living cells synthesize a thick mat of proteins to survive both in vivo and in vitro. Different cells use different proteins when they construct this matrix. Some cells enrich the matrix with potent wound healing growth factors as the matrix is being made. These growth factors are longer lived when stored in the matrix and are more potent when released with matrix molecules. We’ve invented a way to trick cells into synthesizing a matrix enriched with the growth factors we want for either the treatment of a burn or of a common laceration or a bite. We’ve invented a way to remove the cells leaving the matrix intact so it can be stored for long periods of time. We’ve also discovered a way to release just the growth factors we want on demand. 

 Supraparamagnetic Nanoparticles

In collaboration with a private company in Aduro Biotech (formerly Triton Biosystems), the lab team has assisted in developing a novel treatment for breast cancer. Using supraparamagnetic nanoparticles, we’ve bound these particles to antibodies. The antibodies were selected because they are capable of only binding to tumor cells and not to normal cells. The antibody therefore delivers the nanaoparticle to the surface of the tumor cell and binds there. The nanoparticles are benign until exposed to magnetic fields, at which time they become very hot and burn a hole in the membrane of the tumor cell, thus killing it. We can inject the antibody tagged with the nanoparticle into the vein of an animal, and the antibody finds the tumor cells in the animal within a primary tumor and within metastatic lesions. If we expose the animal to brief magnetic field, the tumor cells are killed at both primary and metastatic locations.


Patents:

Acoustic wave (aw) sensing devices using live cells
Application number: 20140087451
Abstract: In one embodiment according to the invention, there is provided a method of sensing a response of a living cell or virus to a change in conditions. The method comprises applying an essentially constant external electromotive force that causes oscillation of an acoustic wave device at essentially constant amplitude and frequency under steady state conditions. The acoustic wave device has attached at least one living cell or virus. A combined oscillating system including the acoustic wave device and the living cell or virus exhibits a fundamental frequency and at least one harmonic frequency of the combined oscillating system.
Type: Application
Filed: August 20, 2013
Issued: March 27, 2014
Assignee: University of Massachusetts
Inventors: Joel M. Therrien, Susan J. Braunhut, Kenneth A. Marx, Gang Wang, Malavika Vashist, Abiche H. Dewilde, Jianping Zhang, Hongwei Sun, Lian Dai, Sai Liu


Acoustic wave (aw) sensing devices using live cells
Application number: 20120258444
Abstract: In one embodiment according to the invention, there is provided a method of sensing a response of a living cell or virus to a change in conditions. The method comprises applying an essentially constant external electromotive force that causes oscillation of an acoustic wave device at essentially constant amplitude and frequency under steady state conditions. The acoustic wave device has attached at least one living cell or virus. A combined oscillating system including the acoustic wave device and the living cell or virus exhibits a fundamental frequency and at least one harmonic frequency of the combined oscillating system.
Type: Application
Filed: November 18, 2011
Issued: October 11, 2012
Inventors: Joel M. Therrien, Susan J. Braunhut, Kenneth A. Marx, Gang Wang, Malavika Vashist, Abiche H. Dewilde, Jianping Zhang, Hongwei Sun, Lian Dai, Sai Liu


Synthesis of oligo/poly(catechins) and methods of use
Patent number: 8143308
Abstract: A method for synthesizing a biocompatible, water-soluble oligo/polyflavanoid, includes polymerizing an optionally substituted flavanoid with a polymerization agent in the presence of a biocompatible polymerization solubilizer, thereby producing the biocompatible, soluble oligo/polyflavanoid. Also included is a biocompatible, soluble, oligo/polyflavanoid or a pharmaceutically acceptable salt, solvate, or complex thereof. Also included are methods of treating a subject for cancer, cardiac damage, viral infection, and obesity.
Type: Grant
Filed: October 29, 2007
Issued: March 27, 2012
Assignees: University of Massachusetts Lowell, The United States of America, as represented by the Secretary of the Army
Inventors: Ferdinando F. Bruno, Jayant Kumar, Subhalakshmi Nagarajan, Susan J. Braunhut, Ramaswamy Nagarajan, Lynne A. Samuelson, Donna McIntosh, Klaudia Foley


Selective whole cell quartz crystal microbalance biosensors
Patent number: 7566531
Abstract: Selective whole cell QCM biosensors are disclosed. Also disclosed are methods of making and using such whole cell QCM biosensors, e.g., to screen drugs and diagnose diseases.
Type: Grant
Filed: March 3, 2004
Issued: July 28, 2009
Assignee: University of Massachusetts
Inventors: Kenneth A. Marx, Susan J. Braunhut, Tiean Zhou, Anne Rugh


Synthesis of oligo/poly(catechins) and methods of use
Application number: 20090170928
Abstract: A method for synthesizing a biocompatible, water-soluble oligo/polyflavanoid, includes polymerizing an optionally substituted flavanoid with a polymerization agent in the presence of a biocompatible polymerization solubilizer, thereby producing the biocompatible, soluble oligo/polyflavanoid. Also included is a biocompatible, soluble, oligo/polyflavanoid or a pharmaceutically acceptable salt, solvate, or complex thereof. Also included are methods of treating a subject for cancer, cardiac damage, viral infection, and obesity.
Type: Application
Filed: October 29, 2007
Issued: July 2, 2009
Inventors: Ferdinando F. Bruno, Jayant Kumar, Subhalakshmi Nagarajan, Susan J. Braunhut, Ramaswamy Nagarajan, Lynne A. Samuelson, Donna McIntosh, Klaudia Foley


Thermotherapy via targeted delivery of nanoscale magnetic particles
Patent number: 6997863
Abstract: Disclosed are therapeutic methods for the treatment of disease material involving administration of a thermotherapeutic magnetic composition, which contains single-domain magnetic particles attached to a target-specific ligand, to a patient and application of an alternating magnetic field to inductively heat the thermotherapeutic magnetic composition. Also disclosed are methods of administering the thermotherapeutic magnetic material composition. The thermotherapeutic methods may be used where the predetermined target is associated with diseases, such as cancer, diseases of the immune system, and pathogen-borne diseases, and undesirable targets, such as toxins, reactions associated with organ transplants, hormone-related diseases, and non-cancerous diseased cells or tissue.
Type: Grant
Filed: July 19, 2002
Issued: February 14, 2006
Assignee: Triton BioSystems, Inc.
Inventors: Erik S. Handy, Robert Ivkov, Diane Ellis-Busby, Allan Foreman, Susan J. Braunhut, Douglas U. Gwost, Blair Ardman


Biosensor for drug candidates
Application number: 20030008335
Abstract: The Quartz Crystal Microbalance (QCM) creates a piezoelectric biosensor utilizing living endothelial cells (ECs) as the biological signal transduction element. ECs adhere to the hydrophilically treated gold QCM surface under growth media containing serum. The EC QCM biosensor can be used for the study of EC attachment and to detect EC cytoskeletal alterations. The cellular biosensor can be used for real time identification or screening of classes of biologically active drugs or biological macromolecules that affect cellular attachment, regardless of their molecular mechanism of action.
Type: Application
Filed: May 13, 2002
Issued: January 9, 2003
Inventors: Kenneth A. Marx, Susan J. Braunhut, Tiean Zhou, Anne Montrone

Research

Medical Device Development 

Nanodiagnostics and Nanotherapeutics

Over the past decade, the lab team has focused on improving the diagnosis and treatment of cancer patients. These efforts have led to the development of four different medical device applications.

Radiation Therapy and Medical Countermeasures for Radiological Terrorism

In collaboration with Dr. Meetha Medhora at the Medical College of Wisconsin and Dr. Mark Tries in the UMass Lowell Physics department, we are conducting research to develop ways to predict and mitigate injuries resulting from neutron/gamma radiation exposure there by reducing injury in victims of radiological terrorist attach, a nuclear reactor accident or in patients receiving radiation therapy for cancers.  The research will test innovative "biomakers" that can potentially predict radiation injuries to the lungs, weeks before symptoms become apparent.  

Quartz Crystal Microbalance

In collaboration with Dr. Kenneth Marx in the UMass Lowell Chemistry Department and Dr. Joel Therrien in the UMass Lowell Electrical & Computer Engineering Department, we have developed the Quartz Crystal Microbalance (QCM) for use with living cells. We’ve discovered that, as the cells attach and spread in the QCM, we can monitor cell behavior in a novel way. When we compare the behaviors of normal cells to cancer cells, there are distinct differences over the first 24 hours of monitoring. By using small numbers of cells from a patient biopsy sample, we’ve been able to distinguish samples that only contain normal cells from those that have tumor cells. 

Nanotoxicology Biosensor

Using this same device but in a modified way, we’ve adapted the QCM as a whole cell biosensor for the detection of toxins and other physiological changes within the cell as a result of exposure to nanomaterials. 

 Drug Response Biosensors

Using this same device but in a modified way, we’ve adapted the QCM  as a drug response predictor. Today, when a patient is diagnosed with cancer, the therapy regime is surgical removal of the bulk of the tumor, radiation of the local area and if the tumor cells have entered the surrounding tissue or blood stream a regimen of chemotherapeutics begins. There are many choices of chemotherapeutics, each with their adverse effects, yet currently there’s no way to predict which drug is best for the treatment of a particular patient’s tumor. We have placed patient’s tumor cells in the QCM and are able to simultaneously compare the response of the cells to several different drugs outside the body. We can rapidly distinguish the drugs that work and those that don’t for that patient’s tumor. Using this device, we hope to provide the managing oncologist with a way to better choose the treatment for each patient. 

 The Smart Bandage

Also in collaboration with Dr. Kenneth Marx, we’ve developed a medical device for the treatment of wounds and burns called the Smart Bandage. We’ve been studying the use of electrical potential to release growth factors from cell free extracellular matrices. All living cells synthesize a thick mat of proteins to survive both in vivo and in vitro. Different cells use different proteins when they construct this matrix. Some cells enrich the matrix with potent wound healing growth factors as the matrix is being made. These growth factors are longer lived when stored in the matrix and are more potent when released with matrix molecules. We’ve invented a way to trick cells into synthesizing a matrix enriched with the growth factors we want for either the treatment of a burn or of a common laceration or a bite. We’ve invented a way to remove the cells leaving the matrix intact so it can be stored for long periods of time. We’ve also discovered a way to release just the growth factors we want on demand. 

 Supraparamagnetic Nanoparticles

In collaboration with a private company in Aduro Biotech (formerly Triton Biosystems), the lab team has assisted in developing a novel treatment for breast cancer. Using supraparamagnetic nanoparticles, we’ve bound these particles to antibodies. The antibodies were selected because they are capable of only binding to tumor cells and not to normal cells. The antibody therefore delivers the nanaoparticle to the surface of the tumor cell and binds there. The nanoparticles are benign until exposed to magnetic fields, at which time they become very hot and burn a hole in the membrane of the tumor cell, thus killing it. We can inject the antibody tagged with the nanoparticle into the vein of an animal, and the antibody finds the tumor cells in the animal within a primary tumor and within metastatic lesions. If we expose the animal to brief magnetic field, the tumor cells are killed at both primary and metastatic locations.