# Chemical-selective real-time laser precision control of biomolecules

> **NIH NIH R35** · PURDUE UNIVERSITY · 2022 · $325,482

## Abstract

PROJECT SUMMARY
The capability to precisely control behaviors of biomolecules in living cells is a challenging task. Current methods
can be classified into chemical-based and laser-based approaches. For example, small molecule inhibitors or
activators can be introduced into the biological system for manipulating enzyme activities. However, it is
impossible to control the interaction locations with high precision, which poses off-target effects. Protein control
using genetic methods such as gene silencing or editing might selectively impact a targeted protein, but requires
transfection and incubation, and cannot be performed in real-time. Optical techniques such as optical tweezers
can manipulate small targets at the laser focus, but can only interact with a few targets at a time. Current laser
manipulation and ablation methods usually require a pre-acquired image together with a manual selection of
target locations on samples. This method is not only time-consuming but also unsuitable to apply to highly
dynamic living biological samples. Optogenetic methods can control neuron functions using light radiation and
light-sensitive ion channels, but only at the single-cell level. There’s no existing technology that can select
molecular targets in cells and control only these targets at sub-micron resolution in real-time.
In this application, we develop a real-time precision opto-control (RPOC) platform that can selectively and
precisely control biomolecules only at the desired interaction site using lasers. RPOC is based on a high-speed
laser scanning system. First, during the laser scanning, an optical signal is generated at a specific pixel from the
target molecule. Then, this optical signal will be compared with a preset threshold and to send out an electronic
signal to control an acousto-optic modulator which is used as a fast switch to couple another laser beam to
interact with the same pixel. The optical signal detection, processing, and laser control happen within 20 ns,
much faster than the pixel dwell time. Digital logic circuits will also be designed with the comparator circuits to
control the interaction laser beam based on the logic output from multiple signal channels. We will use photo-
switchable proteins and design photo-convertible inhibitors and activators to demonstrate precision control of
enzyme activities on site. Furthermore, we will use multiple continuous-wave lasers and acousto-optic tunable
filters to design a portable and multicolor RPOC that can operate outside an optical lab. RPOC can accurately
control and manipulate biomolecules in real-time without affecting other biomolecules in the system. It is highly
chemical selective since the optical signal can be selected from fluorescence, Raman, or absorption signals. It
will allow biologists to control and interrogate only the biomolecules of interest during laser scanning without
affecting other parts of the sample with sub-micron precision. RPOC would be widely applied to ...

## Key facts

- **NIH application ID:** 10501038
- **Project number:** 1R35GM147092-01
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Chi Zhang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $325,482
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501038

## Citation

> US National Institutes of Health, RePORTER application 10501038, Chemical-selective real-time laser precision control of biomolecules (1R35GM147092-01). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10501038. Licensed CC0.

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