Lecture 1 Flashcards
Why Biosensors?
- Advances in biosensing technologies have coincided with increased life expectancy and substantial improvements in the treatment and management of diseases, especially those associated with aging.
- Using biosensors for early diagnosis of diseases, like cancer, leads to significantly better clinical outcomes for patients and lower economic burdens
- Using biosensors for monitoring (as in the case of Type I diabetes), especially outside the clinic, leads to better quality of life, less demand on acute healthcare, and lower likelihood of complications.
What challenges Biosensors face?
achieving greater analytical performance, simplicity, and cost-effectiveness of clinical biosensors with the ultimate aim of providing point-of-care testing.
How many classes of material in biosensor are there? what are they?
- Hydrogels, nano materials, stimuli-responsive materials, polymers, fibrous materials
Explain two ways of creating hydrogel materials for biosensors?
Creating physical crosslinks between molecule by:
1) hydrogen bondings between O-H
2) adding calcium
What are some examples of nano materials used in biosensors?
- Carbon dots
- Ultra small MXene
- quantum dots
- metal nanostructures
- poulymers NPs
What are some examples of triggers for stimule-responsive materials used in biosensors?
- Heat
- frequency?
Explain two ways of creating polymeric materials for biosensors?
- exposing hydrophilic polymers to irradiation
- radical polymerization of hydrophilic monomers through multifunctional cross linkers.
What are some examples of Fibrous materials used in biosensors?
- Nitrocellulose
- glass fiber
- silk
What are biosensors?
Biosensorsare (1) analytical tools or devices that (2) measure biological or chemical reactions and (3) generate signals proportional to the concentration of atarget analyteor biomarker in a sample.
What are the types of biosensors?
(1) research-based biosensors
(2) point of care (POC)
What is a biomarker?
(1) a biological characteristic that is (2) objectively measured and evaluated as (3) an indicator of normal biological processes, pathogenic processes, or pharmacological response to a therapeutic intervention.”
What are the types of biomarkers?
(1) Nucleic acids: DNA (SNPs, mutations) & RNA (mRNA, uRNA, etc)
(2) proteins: prostate-specific antigen & enzymes
(3) others: exosomes, cells, hormones
What are the 4 clinical classifications of biomarkers?
based on clinical role:
(1) diagnostic
(2) prognostic
(3) predictive
(4) monitoring
What type of biomarkers answer the following: “ Who has the disease and what is its type or grade?”
Diagnostic biomarkers
Explain diagnostic biomarkers (uses and specificity)
(1) used to detect the presence of disease or to identify disease subtypes.
(2) can be present at any stage during disease development
(3) may be specific to various factors such as disease stage, tissue type, and patient age
(4) Diagnostic tests may also be based on a set of biomarkers
a 20-gene assay is used to classify patients with diffuse large B-cell lymphoma into subgroups of different tumor cell-of-origin signatures. What type of biomarker is this?
Diagnostic biomarker
Human Papillomavirus (HPV) is used to detect uterine and cervical cancers, as it is found in over 90% of cancer lesions. What type of biomarker is this?
Diagnostic biomarker
What type of biomarkers answer the following: “ What is the most likely clinical outcome without therapy”
Prognostic biomarkers
Explain Prognostic biomarkers (uses)
(1) can predict the probable course of disease including the likelihood of a clinical event like death, disease progression, or reoccurrence
(2) influence the aggressiveness and type of therapy administered
Give examples on prognostic biomarkers.
(1) traditional: assessment of clfinicopathologic characteristics like tumor size, number of positive lymph nodes (with tumor cells), and evidence of metastasis.
(2) molecular indicators: BRCA 1 and BRCA2 for breast cancer, TP53 gene for leukemia
BRCA1 and BRCA2 gene mutations are used to assess the likelihood of developing a contralateral breast cancer after diagnosis with a primary breast cancer. What type of biomarker is this?
Prognostic biomarkers for breast cancer,P
TP53 gene mutation, used to assess likelihood of death in patients with chronic lymphocytic leukemia. What type of biomarker is this?
Prognostic biomarker.
What type of biomarkers answer the following: “What is the most effective therapy?”
Predictive (response) biomarker
Explain predictive (response) biomarker
used to predict the effect of administering a therapy, aiding clinicians in selecting the most effective treatment for a patient
Her2/Neu (HER2) protein is guides clinicians to administer hercaptin for patients with over-expression of this gene and tamoxifen for other patients. What type of biomarker is HER2?
Predictive (Response) Biomarkers
The presence of specific mutations in the epidermal growth factor receptor (EGFR) gene is used to predict whether to administrate erlotinib or gefitinib for lung cancer therapy. What type of biomarker is EGFR.
Predictive (Response) Biomarkers
What type of biomarkers answer the following: “Is the therapy effective and will the disease reoccur?”
Monitoring Biomarkers
Explain Monitoring Biomarkers
(1) used to evaluated serially over time to investigate the state or extent of a disease, or the effect of a therapeutic drug or treatment.
(2) The time-dependent nature of this measurement focuses on change in a biomarker’s levels as a sign of a patient’s current or future medical condition;
(2) thus, the measurement must be interpreted as relative to normal changes in the biomarker values due to physiological and temporal fluctuations
cancer antigen 125 (CA-125) is used to assess the status of ovarian cancer or the response to treatment. What type of biomarkers is CA-125?
Monitoring Biomarkers
Can one biomarker fall into more than one category?
Yes. For example Prostate specific antigen (PSA) is used to screen for prostate cancer (PC) (diagnostic), assessment of PC status and/or burden (monitoring), and the likelihood of progression (prognostic)
How does biosensing happen?
(1) A sample is collected,
(2) the analyte is extracted containing the target biomarker and potentially impurities.
(3) The target will interact with the bioreceptor immobilized on a substrate.
(4) the affinity interaction is transduced into a measurable signal, which can be optical, mass based, or electrochemical.
What are the main components of biosensors?
(1) sensning/recognition element (bioreceptor)
(2) transducing element
(3) signal processor (reader)
What is the role of bioreceptors in biosensing?
Capturing or binding to targets (biomarkers)
What is the role of the transducing elemnet in biosensing?
converts analyte-receptor recognition event into measurable signal
What is the role of the signal processor or reader in biosensing?
interprets the emitted signal and outputs a quantifiable result.
What are the criteria for Bioreceptors?
Depending on target biomarker. Ideally, this element should bind the target biomarker with both high affinity and high specificity.
Give an example for bioreceptors.
(1) Antibodies are most commonly used for sensing biomarkers belonging to the families of proteins, viruses, or cells.
(2) Oligonucleotides such as DNA or RNA strands or oligonucleotide analogs such as peptide nucleic acids (PNA) are typically used for sensing of nucleic acid biomarkers.
What is a transducer?
key element that helps convert the measured signal and dictates the type of detector that will be required based on the nature of the output signal generated.
For each type of output signal, various detection platforms can be selected depending on the sensor’s intended use and purpose.
What are the different modes of detection (readouts)
(1) piezoelectric -> changes in mas
(2) electro-mechanical -> change in electric distribution.
(3) optical -> change in light intensity
(4) calorimetric -> change in heat
What is the most common type of optical readout?
fluorescent sensors (using small molecules and nanoparticles)
Why Optical Readouts for Biosensing?
(1) In fluorescent biosensors, changes in intensity or wavelength oflight emittedafter excitation can be linked quantitatively to the presence or absence of atarget analyte. These characteristic responses can be affected in an often predictable and quantitative manner upon binding to specific target analytes.
(2) For colorimetric biosensors, the readouts can be interpreted visually without the need for expensive instrumentation – making them amenable for POC devices
